NHS Digital Data Release Register - reformatted

University Of Oxford

Project 1 — DARS-NIC-10496-Z3F9B

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/08.

Repeats: One-Off

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • Office for National Statistics Mortality Data

Benefits:

The provision of primary care services outside core contracted hours is fundamental to the operation of the NHS. On a national scale it is clear that out of hours care is an area of significant challenge, and a current focus for quality improvement; the 2014 Urgent Care Commission report ‘Urgent and important: the future for urgent care in a 24/7 NHS' issued a direct ‘call to action’ for improvement in out of hours primary care provision. If Out of hours primary care is a fertile research area, then end of life care is even more so. ‘Actions for End of Life Care’ (NHS England, 2014) clearly establishes improving end of life care as a key goal for the NHS. The contribution of out of hours primary care to end of life care is currently unknown. It is not known how many patients who have contact with OOH services die shortly after, and it is not known whether these deaths were expected or not. This study seeks to address those questions. In doing so the study is expected to contribute to improvements in healthcare in the following ways: - By providing crucial background information for further research to enable the development of out of hours primary care services that are better able to meet the needs of people at end of life in the community. - Identifying particular subgroups at risk of death has direct implications for patient safety and service design. Detailed analysis of the results, including use of deprivation indices might provide the basis for targeted local interventions in particular patient groups. - This study benefits from having direct links to the service it is based upon. A co-investigator on the study is the clinical lead for Urgent Care at Oxford Health NHS Foundation Trust (who runs the Oxfordshire OOH service). Having management so closely integrated within the study team provides an immediate route for dissemination of the findings of the study, for their discussion, and for changes to be identified and made if necessary. - The two nominated users have previously done research involving the Oxfordshire OOH service, results of which we have shared and discussed with clinicians working at the service at Research and Development meetings. These meetings informed the design of this study in its early stages. Study findings would be discussed in future meetings to share findings, and discuss how service change might result from these. - The aim is to publish the results of this study in appropriate peer reviewed journals, and to present findings at conferences. This contributes to a growing evidence base around out of hours primary care, and, through national collaboration may help to inform and understand regional variation in the UK. - Already underway is the process of setting up a local patient public involvement group (PPI) group for out of hours primary care (none currently exists). Results of the study would be shared with this group, and used as a basis for discussion of further research, and to gather service user views on how the results of the study could change local services.

Outputs:

When data processing is complete, the aim is to have established the proportion of patients who died over the course of a year in Oxfordshire who had seen the Oxfordshire OOH service in the 4 weeks prior to their death. Multivariable logistic regression will have been used to see whether any particularly high risk patient subgroups can be identified (hence the need for causes of death). Oxford University aim to have completed the study (including preparation of manuscripts for publication) within one year of receipt of data from the HSCIC/ONS. The findings will be published in academic journals such as the British Medical Journal (BMJ) and the British Journal of General Practice (BJGP) and shared with colleagues at conferences. A report will be written for the study funder, and this will be held in their archives. On completion of the study, the funder (Oxford Radcliffe Hospitals Charitable Funds charity) may report a summary of the study on their website. Outputs from this study (online, for the funder, and any others) will not include personal data and will only use aggregated data, with any small numbers supressed in line with the HES Analysis Guide. This data will not be used for any commercial purpose at any point.

Processing:

Mortality data provided by the HSCIC/ONS will be linked to OOH records for Oxfordshire held by the Oxford Health NHS Foundation Trust. Linkage will be performed by cross-referencing NHS numbers between the two data sets. Only employees of the University of Oxford will process the data at the Trust, before the data is transferred to the University. In this way, it can be established what proportion of people who died in Oxfordshire during the study period were seen by the OOH service in the 4 weeks prior to their death. This will identify the study population (patients who saw OOH services within 4 weeks of their death). Data from patients who died in Oxfordshire during the study period but who had not been seen by the OOH service within four weeks of their death will be securely disposed of at this point as this information plays no further part in the study. Data to be collected, together with an explanation of why this information is required, is detailed below. NHS numbers - required in initial HSCIC dataset to enable linkage with OOH dataset to establish proportion of patients dying in Oxfordshire who had seen the OOH service within 4 weeks of their death. Date of death - required to establish 4 week period prior to death. Cause of death - required for subgroup analysis seeking to establish any patient groups who might be at high risk of death following OOH contact. Date of birth (month and year) - Age of patient required for demographics/risk profiling. Postcode - District level postcode required for deprivation scoring. Gender - For demographics/risk profiling. This will form a dataset of all patients who had died in Oxfordshire between 1st January 2015 and 31st December 2015 and who had contacted the Oxfordshire Out of Hours service within four weeks of their death. This is the study population of interest. To minimise the use of identifiable data, study data will be pseudonymised at this point by replacing NHS numbers with a unique study number. Following pseudonymisation, data will be transferred to the Department of Primary Care Health Sciences at the University of Oxford for further analysis via secure electronic file transfer (SEFT). This subsequent analysis will include Multivariable logistic regression analyses with the data of patients who did die within four weeks of contact with the Oxfordshire OOH service, to identify any particular groups at particularly high risk of death.

Objectives:

This is a research study aiming to establish the proportion of patients dying over the course of a year in Oxfordshire who are assessed by the Oxfordshire Out of Hours (OOH) service in the 4 weeks prior to their death. The study also aims to evaluate whether there are clinical and demographic features which could help distinguish patient subgroups at higher risk of death within 4 weeks of contact with the OOH service.


Project 2 — DARS-NIC-13172-S1S3F

Opt outs honoured: Y

Sensitive: Non Sensitive, and Sensitive

When: 2017/06 — 2017/11.

Repeats: One-Off, Ongoing

Legal basis: Health and Social Care Act 2012, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Section 251 approval is in place for the flow of identifiable data

Categories: Anonymised - ICO code compliant, Identifiable

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • MRIS - Cause of Death Report
  • MRIS - Flagging Current Status Report

Benefits:

Clinical trials are a pivotal part of evidence-based medicine but their rising costs are problematic and hampering research. If this project’s results indicate that routinely collected healthcare data is as robust as clinical adjudication, this would potentially result in very substantial efficiency savings for future trials as; 1, Collection of trial events and trial event adjudication (which requires training and employment of skilled staff) will be greatly streamlined 2. The need for trial participants to attend study clinics (which can be onerous and expensive if travel costs are not reimbursed) may be reduced This in turn will enable such future research to be conducted on a greatly reduced budget, which is vital given the limited funding that national and charity funding bodies can typically offer. This may be particularly important for trials of generic drugs in common conditions (e.g. aspirin in cancer prevention) which do not currently attract industry funding. Such methodological research is becoming increasingly important to the efficiency, design and data collection strategies of future trials and studies, and hence will be of benefit to public health at home and abroad. In summary, expected benefits include; Researchers/health and social care; 1. reduced costs 2. Greater efficiency leading to increased throughput of research and associated enhancement of evidence based medicine, with impact upon national clinical guidelines 3. Increased awareness of the potential for routinely collected data to augment existing understanding and knowledge of a therapeutic area Patients; 1. Reduction in the demands upon trial participants in terms of time and inconvenience in attending study visits 2. Increased knowledge which will be used to inform healthcare decisions leading to improved quality of patient care

Outputs:

Results of the analyses will be presented at relevant international scientific meetings, such as the International Clinical Trials Methodology Conference and in peer reviewed journals, e.g. Clinical Trials, CJASN (Clinical Journal of the American Society of Nephrology) and NDT (Nephrology Dialysis Transplantation). These will be targeted to ensure that the results are disseminated widely among the clinical trials community, including the MRC Hub for Trial Methodology Research and UK Kidney Research Consortium Clinical Trial Network. The results of these analyses will be posted on the SHARP website (http://www.sharpinfo.org/) in a similar manner to multiple previous SHARP-related publications. The target time frame for publication of the results of analyses is 2019-2021.

Processing:

The data will be accessed only by substantive employees of Oxford University and only for the purposes described in this document. NHSDigital already hold the cohort data and will link this in a one off extract with mortality, cancer and HES data Data supplied by NHS Digital will be psuedonymised HES data, identifiable mortality and cancer data all supplied with a study ID. The researchers will compare the NHS Digital data with the existing SHARP trial analysis database which includes: • Unique study Patient ID • Clinical data on clinical events • Laboratory results • Study treatment The data supplied for the purpose described in this document will not be linked to the data being held for the post trial follow up held under Data Sharing Agreement NIC 147782. University of Oxford will adhere to the Office for National Statistics standard terms and conditions as described in the special conditions in the Data Sharing Agreement.

Objectives:

The Clinical Trial Service Unit has extensive experience in developing and running large-scale streamlined randomized trials, many of which have significantly changed clinical practice and majorly influenced national and international guidelines. One of these trials was the Study of Heart and Renal Protection (SHARP), which is the largest trial to date worldwide in patients with chronic kidney disease (CKD), and involved >9000 participants. The SHARP trial was carried out in 18 countries with 1,987 people in the United Kingdom being randomized. It assessed the effect of lowering LDL cholesterol with a combination of simvastatin 20mg plus ezetimibe 10mg versus a matching placebo on serious vascular disease (e.g. heart attacks, strokes) and renal disease (e.g. starting dialysis) events. Participants were followed regularly in study clinics, with all serious adverse events being recorded. Those events which were pre-specified as study outcomes were confirmed by central review of hospital notes by study doctors. This process is referred to as clinical adjudication. Such outcome measure adjudication is typically seen as the ‘gold standard’ for assessment of study outcomes. However it is very resource intensive and expensive, and took a team of trained clinicians two years to complete for the SHARP trial. Such increasing cost of research is a contemporary major issue for all researchers conducting trials. If it can be demonstrated that reports from routine healthcare data-sets are complete and reliable compared with nurse reported events and/or the final adjudicated outcomes, future trials could be designed which follow-up participants solely through routine healthcare data. There are examples where routinely collected healthcare data has been compared to study outcomes previously and they have demonstrated that using routinely collected data to record study outcomes can be reliable which could greatly simplify future trial design, and as such benefit patients and the public. However, there are limited such examples in people with renal disease, where complex disease presentations make some researchers doubt the reliability and therefore utility of routinely collected healthcare data. Moreover, people with chronic kidney disease – who have substantially increased morbidity and mortality compared with the general population - are often excluded from large randomized trials. Consequently, in renal disease, there is a mismatch between high clinical need and levels of evidence on which to base clinical care. There is, therefore, a particular need to develop novel ways of conducting affordable trials of both old and new treatments in this patient group. An example is the NIHR-funded SIMPLIFIED trial http://www.phpc.cam.ac.uk/pcu/research/research-projects-list/other-projects/simplified/) which is assessing the effect of high-dose native vitamin D versus standard of care in dialysis patients. The primary outcome is all-cause mortality, however such a trial could become much more informative if the value of routinely collected hospitalisation data can be confirmed by this proposed study, and so the effect of high dose vitamin D on other non-fatal outcomes such as vascular disease, can be tested. The SHARP trial dataset is in a unique position to validate such methods for both SIMPLIFIED and other future renal trials. This project seeks to obtain all relevant registry associated outcomes from healthcare data sources at NHS Digital so as to compare the outcome data collected and adjudicated during SHARP with those collected as part of routine practice. To ensure the completeness of the comparison, in addition to hospital episode statistics (HES), all relevant death and cancers data are also requested. Methods: This study aims to compare the validity of registry data with both the nurse-led reporting of adverse events, as well as clinically adjudicated outcomes. The main focus will be on non-fatal outcomes (where there is more doubt of validity) derived from registry data including: • major cardiac events • stroke and its subtypes • revascularisation procedures • end-stage renal disease events • admissions with acute kidney injury and • a range of infections including opportunistic infections unique to immunosuppressed transplant recipients and more common infections This will involve an evaluation of the specificity and sensitivity of registry data derived outcomes, looking at both the occurrence of events and the time frame in which they occurred. Results of the original trial will be compared against replicated results using registry data derived outcomes.


Project 3 — DARS-NIC-147757-8SVGP

Opt outs honoured: N

Sensitive: Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data, Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

The study aims to randomise at least 30,000 (6,500 in the UK) aged 50 years or older with pre-existing vascular disease, to receive either anacetrapib 100mg daily or matching placebo for a median of 4 years' follow up. The primary aim is to assess the effect of lipid-modification with anacetrapib on major coronary events (MCE - defined as coronary death, myocardial infarction or coronary revascularization).


Project 4 — DARS-NIC-147782-0D7TX

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2018/02.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Identifiable

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration

Objectives:

SHARP was a large-scale randomised controlled trial involving almost 9500 volunteers aged 40 or over which assessed the effects of lowering LDL-cholesterol in participants with chronic kidney disease (CKD). Patients with CKD are at high risk of substantial cardiovascular mortality and morbidity, and there is a great public need for reliable medical evidence regarding effective therapies for this group of patients. SHARP’s key objective was the assessment of the effect of the combination of simvastatin 20mg and ezetimibe 10mg daily versus placebo on the time to a first ‘major atherosclerotic event’ (MAE) (defined as non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke or revascularisation). Between 2003 and 2006, 9438 patients were randomised world-wide (of which 1987 were from 65 UK centres). The final study visits occurred in August 2010, resulting in a median follow-up of 4.9 years. The main results were published last year (The Lancet 2011; 377: 2181-92) and showed a highly significant 17% reduction in the risk of developing MAEs (95% confidence interval 0.74-0.94, p=0.0022). The study Sponsor was the University of Oxford. All 1987 UK patients in this randomised trial gave their consent for follow-up of their health by our coordinating centre at the University of Oxford. A further 5 year follow-up study of SHARP survivors is planned. Such extended follow-up will be imperative to answer the following questions: • Whether the benefits seen in the main results persists in future years • Whether the study treatment has any effect on renal disease progression i.e. whether statins are reno-protective in the longer term • Whether there is any latent safety signal (e.g. effect on cancer, since it has previously been suggested that one of the study drugs - ezetimibe - might be associated with an increased risk of cancer) that did not emerge during the trial’s initial follow-up period • Whether the intervention is cost-effective (long-term health economic analyses)


Project 5 — DARS-NIC-147808-3F9FR

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration

Objectives:

To relate mortality from a wide range of specific diseases and the incidence of cancer to smoking habits and to characterize the effects of stopping smoking.


Project 6 — DARS-NIC-147885-0TV66

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

Background Large-scale randomized trial to access the clinical effects of a combined daily tablet of niacin 2g plus MK-0524 40 mg (MK-0524A) on the risk of heart attack or coronary death, stroke, or the need for atrial bypass procedures in people with a history of circulatory problems. Aims The study will include 20,000 patients aged 50-80 years, 7,500 from around the UK plus (at least 7,500 from China and 5,000 from Scandinavia) with a history of circulatory problem.


Project 7 — DARS-NIC-147931-DT25Y

Opt outs honoured: Y

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: Ongoing, One-Off

Legal basis: Section 251 approval is in place for the flow of identifiable data, Section 42(4) of the Statistics and Registration Service Act (2007) as amended by section 287 of the Health and Social Care Act (2012)

Categories: Identifiable

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Members and Postings Report
  • Hospital Episode Statistics Admitted Patient Care
  • MRIS - Flagging Current Status Report

Benefits:

The aim of the trial is to assess reliably the risks and benefits of additional NHS invitations for breast screening before age 50 and, separately, after age 70. The results are expected to help determine future NHS policy on age at breast screening. The main results are not expected before the mid-2020s but interim results will be reviewed and the trial end date may be brought forward if the evidence is clear before then. Public Health England will use the findings to inform government and influence policy. This will affect breast screening policy in the UK and influence policy in much of the rest of the world for decades after the results have published. The benefits of interim analyses are that these will be used to monitor the protection and safety of trial participants in addition to feeding into the wider trial aims.

Outputs:

The primary output of the study will be findings disseminated by publications in peer-reviewed open-access journals and presented at medical conferences to academics, NHS national policy makers and on the web. The results are expected to help determine future NHS policy on breast cancer screening outside the 50-70 age group. The main results are not expected before the mid-2020s. Outputs will include only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. As with any clinical trial, it is necessary to gather evidence incrementally throughout the course of the trial in order to check that the trial itself is not exposing participants to increased risk of harm or, conversely, to check for evidence of benefits. The trial end date is not fixed and may be brought forward if at any stage, sufficient evidence is obtained. The outputs from the interim analyses will be annual reports to the Data Ethics and Monitoring Committee who may also request additional analyses within the scope of the clinical trial’s objectives if they identify the need. The Data Ethics and Monitoring Committee report any concerns about the trial or findings to the trial management group.

Processing:

To date, identifiable details have been supplied to NHS Digital (formerly known as HSCIC) in separate batches for flagging on NHS Digital's MIDAS system and NHS Digital has supplied periodic updates on deaths, cancers and exits from NHS registration. Approximately 2 million cohort members have been flagged to date with the number to rise to 2.5m. Further batches of trial participants will be supplied as new participants are randomised into the trial on an ongoing basis. In addition to the ongoing supply of notifications, NHS Digital will perform further linkage to Hospital Episode Statistics data and supply the linked data to the CEU. All data received from NHS Digital is linked with trial participants’ records from the National Breast Screening System and PHE cancer outcome datasets. The purpose for collecting the data is to assess the short-term and long-term effects of the additional screening on: patterns of investigation; detection and treatment of breast lesions; breast cancer incidence; breast cancer mortality; hospital admissions, and overall mortality. The data will be held exclusively at the Cancer Epidemiology Unit (CEU) at the University of Oxford and used solely for the purpose of this project. All data (core trial data, including personal details, flagging information, deaths, cancers, externally linked data, some admin data) is held in a central database. Several internal ID's exist so that data can be appropriately structured. No statistical analyses of the data are performed directly on this database. Direct access to the entire database is limited to the database manager. Access to personal identifiers is required to process externally linked data, and to prepare datasets for external linkage to HES, ONS, Cancer Registration, NHS Registration and NHS Screening records. Pseudonymised analysis data is extracted from the database, either as database views or via text files. When accessing views directly, appropriate roles exist to limit access to the required view(s) only. Analysis datasets will have no individual level identifiers but may have a group identifier e.g. year recruited or site recruited. Analysis datasets will never contain any personally identifiable data e.g. name, NHS number etc. ONLY linkage datasets will require this information. If required year and month of birth will be used instead of full date of birth or death.

Objectives:

Evaluating the age extension of the NHS Breast Screening Programme To evaluate the effects of a) offering women one additional screen at age 47-49 years and b) offering women one additional screen at age 71-73 years, within the existing NHS Breast Screening Programme which currently offers women seven 3-yearly screens between the ages of 50 and 70 years. To date there is limited evidence on the net benefit of extending the age range for breast screening; no trial has looked at the added value of one extra screen within an existing screening programme. This trial provides a unique opportunity to assess the effects of adding an extra screening invitation to an existing screening programme. The results have the potential to inform future screening policy in the UK and elsewhere.


Project 8 — DARS-NIC-147940-WVXJF

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

Legal basis: Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Identifiable

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Personal Demographics Service

Objectives:

The purpose of the audit is to establish whether the age women are when first invited for routine mammogram by the NHS Breast Screening programme affects mortality from breast cancer. The finding of this audit will inform screening policy and practice regarding the age at first routine mammogram. The findings of this audit will inform screening policy and practice regarding the age at first routine mammogram. They will, therefore, have the potential to reduce the risk of dying from breast cancer. The audit will contribute to the NHSBSP's ongoing mission to provide as effect a service as possible.


Project 9 — DARS-NIC-147957-4444C

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2017/05.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

We aim to carry out several investigations of different aspects of DSH that will inform and assess national strategies on DHS and suicide prevention. One of these is on mortality following DSH. Some studies will be carried out in Oxford on Oxford data alone, and others as part of a multicentre collaborative project on DSH (coordinated by Oxford, together with groups in Manchester, Leeds and Derby). Aims of the multicentre mortality studies are: (i) To determine current risk of suicide following DSH over time and in gender and age subgroups; (ii) To identify risk factors for suicide that can inform assessment procedures; (iii) To provide data on risk of death from non-suicidal causes; and (iv) To provide information on mortality following DSH in important subgroups e.g. black, minority and ethnic groups, older people, and people who misuse alcohol


Project 10 — DARS-NIC-148069-ZB4GM

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/08.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Scottish NHS / Registration
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

The data supplied will be used only for the approved medical research project MR542 - MRC/BHF HEART PROTECTION STUDY


Project 11 — DARS-NIC-148130-46N08

Opt outs honoured: Y, N

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration

Objectives:

The data supplied by the NHSIC to Clinical Trail Service Unit will be used only for the approved Medical Research project MR261.


Project 12 — DARS-NIC-148137-YQCFB

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/09 — 2016/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Scottish NHS / Registration
  • MRIS - Cohort Event Notification Report

Objectives:

The data supplied will be used only for the approved medical research project - MR240: FERTILITY STUDY


Project 13 — DARS-NIC-148171-LGV0V

Opt outs honoured: Y, N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

The data supplied to the Clinical Trial Service Unit (CTSU) will be used only for the approved medical research project - MR200 Leukaemia Trials (CLL2)


Project 14 — DARS-NIC-148204-7B1XT

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2017/02.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

The data supplied by the NHSIC to Clinical Trial Service Unit (CTSU) will be used only for the approved Medical Research project MR360.


Project 15 — DARS-NIC-148220-FSJM5

Opt outs honoured: N

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/08.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Members and Postings Report
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

The 3C Study is investigating two possible strategies that could improve the lifespan of kidney transplants: firstly, is Campath-based induction treatment superior to standard basilixmab-based treatment; secondly, is sirolimus-based maintenance treatment superior to standard tacrolimusbased treatment. Although the primary outcomes of the study are relatively short-term, there is considerable scientific interest in the long-term (i.e. 5-20 year) outcomes from this study. In particular, there is uncertainty about the safety of such treatments with malignancy being one complication of transplantation that often occurs late.


Project 16 — DARS-NIC-148267-W26RZ

Opt outs honoured: Y, N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2017/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Benefits:

The aim of the study is to improve information on diet in relation to the risk of cancer and cardiovascular disease and offers potential for improvements in public health in the UK. The results are published in peer-reviewed publications and presented at conferences, and are also reported through national media. University of Oxford research relates directly to the health of 1.2 million people in the UK who follow vegetarian diets (NHS 2014). The long-term effects on cancer of a vegetarian diet are not well understood, and little is known about the health effects of a vegan diet. Our previous research has demonstrated lower risks of obesity (50%), heart disease (30%), stomach cancer (60%) and haematological cancers (36%) in vegetarians compared with non-vegetarians (Key and Davey 1996, Crowe et al 2013, Key et al 2009, 2014), and further study is likely to reveal other associations between diet and cancer risk. As well as peer-reviewed scientific publications, where appropriate, University of Oxford will also communicate with the NHS and other organisations such as the National Cancer Intelligence Network within Public Health England and other health providers in the UK, where the outputs from the study will provide information to underpin their health advice to the public. For example: The PI of this study sits on the Scientific Advisory Committee on Nutrition (SACN) which reports to Public Health England and other UK government organisations. Conclusions from this committee are used to formulate government and NHS policy on diet and thus reduce the risk of disease and the burden on the NHS. In a current SACN update, the fortification of the UK food supply for folic acid to prevent neural tube defects included a key piece of evidence including data from the Oxford Vegetarian Study, related to the safety of folic acid with respect to cancer risk. (https://www.gov.uk/government/consultations/consultation-on-draft-sacn-update-on-folic-acid). Future work will look at heart disease (further analyses with more data), death from stroke and risk of prostate cancer, as well as the protective impact of vegetarian diets in preventing the development of obesity. In the planned new analyses of ischaemic heart disease and stroke, the study will use their data on diet to estimate the impacts on health of replacing energy (calories) from red and processed meat with energy from plant foods which can be used to replace these foods, such as legumes (beans, peas and lentils) and nuts. The NHS Choices website (http://www.nhs.uk/Livewell/Vegetarianhealth/Pages/Vegetarianhealthqanda.aspx#what) states that “a vegetarian diet can be very healthy” and reports on an NHS patient who comments “I feel much healthier on a vegan diet”, but includes few specific statements about the benefits. The research will provide the robust information needed to include more specific facts and advice on the NHS website and thus enable the public to improve their health and reduce the burden on the NHS. As well as peer-reviewed scientific publications, where appropriate, University of Oxford will also communicate with the NHS and other organisations such as the National Cancer Intelligence Network within Public Health England where the outputs from the study will provide information to underpin their health advice to the public. This study will directly benefit health care through the NHS by providing clinicians and other NHS health care professionals with up-to-date evidence-based guidance on the effects of diet on cancer and the risk of death. This will improve clinical health care and inform planners and policy makers to address demands on health and social care in the present and future. The robust, reliable knowledge on vegetarian diets and risk of chronic disease will provide the evidence to underpin the judgements made by decision-makers on the future direction of NHS policy in relation to dietary advice, thus acting as an enabler. For example, the NHS reported in 2013 that a vegetarian diet brings a range of health benefits and is linked to longer lifespan (12% in risk of death from any cause, see http://www.nhs.uk/news/2013/06June/Pages/Vegetarian-diet-linked-to-longer-lifespan.aspx). This NHS assessment noted that the study concerned had a relatively short follow-up of six years, this is quite short to address how dietary patterns might affect the risk of death. In University of Oxford analyses, there is a follow-up of over thirty years which will provide the NHS with much more reliable information on the long-term health of people following a vegetarian diet. This reliable evidence will be available in publications in late 2017 and 2018, enabling updating of NHS sources during 2018. In the link http://www.nhs.uk/news/2013/01january/pages/does-a-veggie-diet-lead-to-a-healthier-heart.aspx The researchers concluded that vegetarians had a 32% lower risk of IHD than non-vegetarians, and that this is likely due to “reduced levels of well-established risk factors for IHD, such as non-HDL cholesterol concentrations and systolic blood pressure”. This large and impressive prospective cohort study suggests that a vegetarian diet may benefit your heart; reducing the risk of IHD. This was a well-conducted, large long-term study that suggests there are heart healthy benefits to a vegetarian diet. The NHS will be able to continue to use University of Oxford data to update their websites accessible to the general public. This NHS provided advice, based on OVS data, to their stakeholders. This will enable commissioners to implement appropriate policies in relation to diet, thus reducing the financial burden of dietary related diseases. More recently one of the named researchers attended the inaugural workshop of the Cancer and Nutrition NIHR infrastructure collaboration http://cancerandnutrition.nihr.ac.uk/wp-content/uploads/2016/06/Cancer-Nutrition-Full-Report-FINAL_03-06-16.pdf . OVS and EPIC will be part of this initiative. The Cancer and Nutrition NIHR infrastructure collaboration will improve cancer prevention and care for clinicians and patients. Selected publications: Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr 2016;103:218-30. Key TJ, Appleby PN, Crowe FL, Bradbury KE, Schmidt JA, Travis RC. Cancer in British vegetarians: updated analyses of 4998 incident cancers in a cohort of 32,491 meat eaters, 8612 fish eaters, 18,298 vegetarians, and 2246 vegans. Am J Clin Nutr 2014;100 Suppl 1:378S-85S. San Joaquin MA, Appleby PN, Key TJ. Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation of 10998 vegetarians and non-vegetarians in the United Kingdom. Br J Cancer 2004;90:118-21.

Outputs:

Publications are produced on an ongoing basis, all outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide. Examples of publications are: Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain. Thorogood M, Carter R, Benfield L, McPherson K, Mann JI. British Medical Journal 1987;295:351-353. Relationship of body mass index, weight and height to plasma lipid levels in people with different diets in Britain. Thorogood M, McPherson K, Mann J. Community Medicine 1989;11:230-233. Dietary intake and plasma lipid levels: lessons from a study of the diet of health conscious groups. Thorogood M, Roe L, McPherson K, Mann J, British Medical Journal 1990;300:1297-1301. (h:\docs\ovs\dietary_intake_and_plasma_lipid_levels.pdf) Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores. Key TJA, Roe L, Thorogood M, Moore JW, Clark GG, Wang DY. British Journal of Nutrition 1990;64:111-119. Asymptomatic hypothyroidism and hypercholesterolaemia. Ball MJ, Griffiths D, Thorogood M. Journal of the Royal Society of Medicine 1991;84:527-529. Risk of death from cancer and ischaemic heart disease in meat and non-meat eaters. Thorogood M, Mann J, Appleby P, McPherson K. British Medical Journal 1994;308:1667-1671. (h:\docs\ovs\risk_of_death_BMJ1994.html) Emergency appendicectomy and meat consumption in the UK. Appleby P, Thorogood M, McPherson K, Mann J. Journal of Epidemiology and Community Health 1995;49:594-596. Results are disseminated in peer-reviewed open-access papers in research journals, and related presentations to national and international colleagues, including clinicians. This study currently has funding to follow up patients until 2020. The data is processed only by one named researcher within the Cancer Epidemiology Unit (CEU). For all of these outputs, data is aggregated with small numbers suppressed in line with the HES analysis guidance. Future anticipated work using ONS mortality and cancer registry data: The Medical Research Council Grant MR/M012190/1 "Health of vegetarians" specifies a programme of research on the associations of vegetarian diets and related nutritional factors with the incidence of common diseases. In 2017 and 2018 the study will analyse: • the relationships of vegetarian diets with the risk for death from ischaemic heart disease, extending previous published research on this topic with larger numbers of cases and examining the extent to which the effects of a vegetarian diet may be explained by the consumption of saturated and polyunsaturated fatty acids, fruit and vegetables and dietary fibre; the intent is to complete this manuscript in late 2017 and to submit it to the BMJ. • In parallel, analyses commencing later in 2017 will examine the associations of vegetarian diets with risk of death from stroke, it was suggested that vegetarians had a somewhat higher risk of stroke than meat-eaters, but the number of cases was too small for robust analyses; with the new current linkage combined with data from EPIC – Oxford, it is expected that approximately 2000 cases of stroke which will provide sufficient power to conduct reliable analyses, and to explore the possible roles of protein and vitamin B12 in determining stroke risk in vegetarians. The intent is to submit this manuscript in 2018 to the journal Circulation. • In analyses of prostate cancer, the study will report on the risk in relation to vegetarian diets and submit to the British Journal of Cancer, and present the results at the conference of Urologists stated below. Conferences University of Oxford plan to present research findings at the following conferences: • 2017 – Nutritional Society UK Symposium • 2017 – European Association of Urologists • 2018 – 7th International Congress on Vegetarian Nutrition, Loma Linda, California • 2018 – NCIN Conference • 2019 – NCIN Conference

Processing:

The participants in the study are already flagged on the NHS Digital system, therefore the customer does not need to send in the cohort again. NHS Digital provides quarterly updates on participant events including removals and re-entries to NHS registration, cancer registrations and deaths, including cause of death details. The future extracts provided will be pseudonymised and will not be linked to the Identifiable data held in any way. NHS Digital will provide University of Oxford with month and year and causes of deaths and month and year and diagnosis of cancer and a unique study id. The Senior Statistician within the Cancer Epidemiology Unit (CEU) at the University of Oxford links the data, using Study ID, with study participants’ pseudonymised questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. All such subsets are customised according to the characteristics relevant to the specific analysis containing only the minimum data required for the specific purpose. Various types of analyses are undertaken on an on-going basis for the overarching purpose of assessing cancer incidence and overall mortality. The data will be held only at the Cancer Epidemiology Unit at the University of Oxford. The datasets will be pseudonymised as described above before statistical analyses are undertaken. The study will not share any data supplied by NHS Digital with any other institution or individual outside of the study team at Oxford University (i.e. the named users within this agreement). All users of the data are substantive employees of the University of Oxford. All processing of ONS data will be in line with ONS standard terms and conditions. Data supplied by NHS Digital and existing data will be kept in separate electronic files linked by a numerical, anonymous subject identifier. Lifestyle/dietary data required for analysis will be extracted from the relevant data files (which do not contain subject names, NHS numbers or full dates of birth) and merged with the data supplied by NHS Digital using the subject identifier, without having recourse to any identifiable data.

Objectives:

The study aims to compare mortality from cancer and other causes in vegtarians with the general population and to relate their occurrence where possible to diet.


Project 17 — DARS-NIC-148322-TMFVQ

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2017/05.

Repeats: Ongoing, One-Off

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Other-Data was previously disseminated on the basis of: National Health Service Act 2006 - s251 - 'Control of patient information' , and Health and Social Care Act 2012 – s261(7). Data will be retained and new data will be disseminated on the basis of

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Flagging Current Status Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration
  • Hospital Episode Statistics Admitted Patient Care

Benefits:

Diet has been identified as the number one cause for the burden of disease worldwide, and by providing new evidence on the impact of diet on health EPIC-Oxford will contribute to reducing the work and cost to the NHS of diet-related ill-health. The aim of EPIC-Oxford is to improve information on diet in relation to the risk of cancer and other chronic diseases, which offers huge potential for improvements in public health in the UK. The results are published in peer-reviewed publications and presented at conferences, and are also reported through national media. Over 500 peer-reviewed publications, mostly on diet and cancer, have included data from EPIC-Oxford: see http://www.epic-oxford.org/publications/. EPIC-Oxford’s research relates directly to the health of 1.2 million people in the UK who follow vegetarian diets (NHS 2014). The long-term effects on health of a vegetarian diet are not well understood, and little is known about the health effects of a vegan diet. Previous research has demonstrated lower risks of ischaemic heart disease, stomach cancer and perhaps haematological cancers in vegetarians compared with non-vegetarians (Crowe et al 2013, Key et al 2009, 2014), but understanding of these relationships is incomplete. Further research is needed to assess both the potential beneficial effects of a vegetarian diet and also possible hazards associated with low intakes of some nutrients, such as protein, long-chain n-3 fatty acids, vitamin B12, vitamin D and calcium (particularly in vegans). As well as peer-reviewed scientific publications, the EPIC-Oxford website (www.epic-oxford.org) will be used to describe all findings, with lay summaries of findings when appropriate, copies of abstracts, and links to pdfs of full papers. The website provides information both for study participants and for a wider audience in the UK and worldwide and where appropriate we will also communicate with the NHS because the research will provide information to underpin their advice, e.g. as on their website: http://www.nhs.uk/Livewell/Vegetarianhealth/Pages/Goingvegetarian.aspx EPIC-Oxford will directly benefit health care through the NHS by providing clinicians and other NHS health care professionals with up-to-date evidence-based guidance on the effects of diet on long term health and the risk of death. This will improve clinical health care and inform planners and policy makers to address demands on health and social care in the present and the future. Target dates are ongoing.

Outputs:

Publications are produced on an ongoing basis. These do not identify individuals and contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide. Results are disseminated in peer-reviewed open-access papers in research journals, and related presentations to national and international colleagues, including clinicians. EPIC currently has funding to follow up patients until 2020. The data is processed only by those named researchers and students within the Cancer Epidemiology Unit. For all of these outputs data is released only de-identified data in aggregate form (tabulations and figures showing analysis results at the minimum level of detail required, using small number suppression). Publications and a summary of the research outputs are available to the public, to participants and to health researchers and clinicians through the study website (www.epic-oxford.org). EPIC–Oxford results are reported in the media such as the BBC and national newspapers e.g. (http://www.bbc.co.uk/news/health-21258509 and http://www.telegraph.co.uk/news/health/news/9837285/Vegetarians-a-third-less-likely-to-develop-heart-disease.html) and its outputs reach a worldwide audience. Future anticipated work using HES, ONS mortality and Cancer Registry Data: The EPIC-Oxford’s Medical Research Council Grant MR/M012190/1 "Health of vegetarians" specifies a programme of research on the associations of vegetarian diets and related nutritional factors with the incidence of common diseases. In 2017 and 2018 the study will analyse: • the relationships of vegetarian diets with the risk for ischaemic heart disease, extending previous published research on this topic with larger numbers of incident cases identified through HES and examining the extent to which the effects of a vegetarian diet may be explained by the consumption of saturated and polyunsaturated fatty acids, fruit and vegetables and dietary fibre. The intention is to complete this manuscript early in 2018 and to submit it to the British Medical Journal. • In parallel analyses commencing in 2017, the study will examine the associations of vegetarian diets with risk for stroke, using the HES linkage to identify incident cases and to categorise then as ischaemic, haemorrhagic, or other types of stroke. Preliminary analyses based on a previous linkage to the HES data suggested that vegetarians had a somewhat higher risk of stroke than meat-eaters, but the number of cases was too small for robust analyses. With the new linkage to HES about 2000 cases of stroke are expected which will provide sufficient power to conduct reliable analyses, and to explore the possible roles of protein and vitamin B12 in determining stroke risk in vegetarians. The intention is to submit this manuscript in 2018 to the journal Circulation. • Following these analyses of cardiovascular disease, at the beginning of 2017, the study will commence analyses of the relationships of vegetarian diets with the risk for musculoskeletal disorders: fractures of the forearm, wrist and hip, hip and knee replacement, and carpal tunnel syndrome. The study will examine whether associations of vegetarian diets with the risk for these disorders may be due to differences in intake of calcium and protein, and will aim to submit the papers to the American Journal of Clinical Nutrition in late 2018/early 2019. • In 2019-2020 the intention is to examine vegetarian diet and gastrointestinal diseases including Crohn’s disease, ulcerative colitis and gallstones. • The study’s Cancer Research UK grants on the Epidemiology and Aetiology of High Risk Prostate Cancer and the core grant of the Cancer Epidemiology Unit(CEU) specify a program of research on the risk for prostate cancer and the cancers in relation to and related factors and other diseases. Conferences The intention is to present the research findings at the following conferences: • 2017 – Nutritional Society UK Symposium • 2017 European Association of Urologists • 2018 7th International Congress on vegetarian Nutrition., Loma Linda California. • 2018 The National Cancer Research Institute (NCRI) • 2019 The National Cancer Research Institute (NCRI)

Processing:

The majority of the EPIC-Oxford cohort are flagged on NHS Digital’s MIDAS system. NHS Digital provide monthly updates on participant events including removals and re-entries to NHS registration, cancer registrations and deaths including cause of death details. The EPIC-Oxford team will supply a file of identifying details for additional participants of the EPIC-Oxford study that are not currently flagged within this cohort on the NHS Digital system. NHS Digital will then flag these members. NHS Digital will link the full cohort to Hospital Episode Statistics records and supply pseudonymised linked data to EPIC-Oxford. Using the study ID, the EPIC-Oxford team link the data with study participants’ records collected over time directly from the participants and from NHS Digital and ONS plus linked data from Scotland (via the Public Benefit and Privacy Panel for Health and Social Care) and from Northern Ireland (via the Central Services Agency). The linked data is stored separately from the patient identifiers. Participant identifiers linked to the study ID numbers are stored separately to the dataset for use in analysis and are held only for administrative purposes and for use in facilitating ongoing data linkage. The analysis dataset (containing the study participant’s linked records from the sources specified above) will not be re-linked with the identifiers. The analysis dataset contains full date of death for individuals whose deaths were reported prior to December 2016. This is the only identifiable field held within the analysis dataset. All subsequent data supplied by NHS Digital will be pseudonymised. It will contain month and year of death rather than full date of death. The analysis dataset also contains month and year of birth. Only month and year of birth and/or death will be used in future analyses. All subsequent analyses use only subsets of the pseudonymised data. All such subsets are customised according to the characteristics relevant to the specific analysis containing only the minimum data required for the specific purpose. Various types of analyses are undertaken on an ongoing basis for the overarching purpose of assessing cancer incidence, health risks and overall mortality. The data will be held only at the Cancer Epidemiology Unit at the University of Oxford. The datasets will be pseudonymised as described above before statistical analyses are undertaken. The data will only be accessed by authorised members of the EPIC-Oxford study team, all of whom are substantive employees of the University of Oxford, or non-contractual DPhil,MSc students who complete University Research Services form agreeing to terms and conditions of the project, grant and latest Data Sharing Agreement. These are filed in Research Co-ordinators office with signed copies sent to Director of Research Services at University of Oxford. Access to ONS mortality data is restricted to individuals with Approved Researcher accreditation named within the Data Sharing Agreement. The data will only be used for the objectives of the study as described within the Data Sharing Agreement. The EPIC-Oxford study will not share any data supplied by NHS Digital with any other institution or individual outside of the study team at Oxford University.

Objectives:

To Examine the relationship of nutrition with the risk for developing cancer.


Project 18 — DARS-NIC-148341-TC6TD

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Members and Postings Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

The data supplied will be used only for the approved medical research project MR706 - SEARCH: STUDY OF THE EFFECTIVENESS OF ADDITIONAL REDUCTIONS IN CHOLESTEROL AND HOMOCYSTEINE


Project 19 — DARS-NIC-148369-8PPWK

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

The aims of the Oxford Vascular Study (OXVASC) are: 1. To document the incidence, burden and cost of all acute vascular events in the same population during the same period. 2. To compare risk factors for different types of acute vascular event. 3. To compare short and long-term outcome and prognosis after different types of acute vascular events, including different clinical and aetiological subtypes of TIA and stroke. 4. To determine how best to improve the provision of secondary prevention in patients with TIA and stroke.


Project 20 — DARS-NIC-148435-2T54S

Opt outs honoured: N

Sensitive: Sensitive

When: 2016/04 (or before) — 2017/02.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Members and Postings Report
  • MRIS - Personal Demographics Service

Benefits:

To be completed by applicant

Outputs:

To be completed by applicant

Processing:

To be completed by applicant

Objectives:

Data supplied will be used by Clinical Trials Service Unit (CTSU) for the approved Medical research Project, ASCEND - ( Study Of Cardiovascular Events In Diabetes).


Project 21 — DARS-NIC-148436-W4NL6

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2017/02.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration

Objectives:

A randomised controlled trial of iodine supplementation in preterm infants (I2S2) Primary research question: Does iodide supplementation of extreme preterm infants change neurodevelopmental outcome at 2 years corrected age? Secondary research question: What is the relationship between supplementation, blood levels of thyroid hormones, illness, drug usage, other events of postnatal period and neurodevelopment? Specifically includes -Collection of blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age will confirm the efficacy of iodide supplementation; and will distinguish between transient hypothyroxinaemia, transient hypothyroidism and transient hyperthyrotropinaemia. If this work shows benefit to the supplemented neonates there will be worldwide clinical support for iodide supplementation for preterm infants. The study hopes to achieve iodide sufficiency in parentally fed infants, ensuring that the nutrition is adequate for development. In addition, the current iodide recommendation of 1mcg/kg/day extends to term infants and children up to 15 kg and they are also likely to benefit.


Project 22 — DARS-NIC-148456-2YZGZ

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

A randomised controlled trial to assess the cost-effectiveness of intensive versus no scheduled follow-up in patients who have undergone resection for colorectal cancer with curative intent.


Project 23 — DARS-NIC-183082-K3CPB

Opt outs honoured: Y, N

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2016/08.

Repeats: Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report

Objectives:

SIFT is a multi-centre randomised controlled trial to assess whether the speed of increasing milk feed volumes in very preterm (<32 weeks) or very low birth weight (<1,500 g) infants has any effect on survival without moderate or severe disability at 24 months of age corrected for prematurity. The primary objective is to assess and compare the effects of a fast (30 ml/kg/day) and a slow (18 ml/kg/day) increase in milk feed volumes on survival of very preterm (<32 weeks) or VLBW (<1,500 g) infants without moderate or severe disability at 24 months of age corrected for prematurity. The secondary objective is to assess and compare the effects of a fast (30 ml/kg/day) and a slow (18 ml/kg/day) increase in milk feed volumes on survival of very preterm (<32 weeks) or VLBW (<1,500 g) infants with respect to: • Incidence of microbiologically-confirmed or clinically suspected lateonset invasive infection from trial entry until hospital discharge • Incidence of necrotising enterocolitis (NEC) [Bell stage 2 or 3] from trial entry until hospital discharge • Time taken to reach full milk feeds (tolerating 150 ml/kg/day for 3 consecutive days) • Growth (weight and head circumference) at hospital discharge • Duration of parenteral feeding before hospital discharge • Length of time in intensive care • Length of hospital stay In addition to this, the data will be used to ensure that the questionnaire sent to parents at 24 months of age will not go to parents who have lost their child or no longer live in the UK. Given the potential emotional impact of being contacted by SIFT in error on parents who have lost their child, this is very important information for SIFT to acquire.


Project 24 — DARS-NIC-29827-Q8Z7Q

Opt outs honoured: Y

Sensitive: Sensitive, and Non Sensitive

When: 2017/12 — 2018/02.

Repeats: One-Off

Legal basis: Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Health and Social Care Act 2012

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • Office for National Statistics Mortality Data
  • Hospital Episode Statistics Admitted Patient Care
  • Bridge file: Hospital Episode Statistics to Mortality Data from the Office of National Statistics

Benefits:

BENEFIT The study will inform patients, NHS managers, commissioners and health professionals of the NHS costs and patient outcomes and cost-effectiveness associated with the treatment of upper limb conditions, and the key elements that are most clinically and cost effective. It will provide patients with information on variation in outcomes of surgery to inform patient choice and decision-making. NDORMS will work alongside charities and learned societies to disseminate the findings of this study using established platforms that include social media such as Twitter and a study website, as more patients are now turning to these resources for information about planned surgery. NDORMS will provide evidence of modifiable hospital organisational factors that can explain unwarranted geographical variation in patient outcomes of surgery. This can be used to inform healthcare organisations of factors identified as improving patient outcome and both local and national level, and can be used by clinicians and policy makers to inform healthcare policy . IMPACT The exploration of current trends in procedures undertaken, in temporal and geographical variation in operation numbers and type, mismatch of prevalence and surgery rates, and of outcomes will enable NDORMS to understand more about the current management of upper limb conditions and how to improve NHS services nationwide. NDORMS will explore variations found to identify whether differences in the way hospitals or regions organise their services, such as specialist surgeons, use of new surgical techniques, or centralising care into specialist hospitals, can explain any observed variations. Similarly, understanding the variation in outcomes following a range of procedures enables greater knowledge of which interventions should continue to be funded. Knowledge of these factors would inform changes that can be made to the way services are organized and provided, leading to better access for patients and helping to standardise evidenced based care and patient pathways across the UK. The target date for output and dissemination to produce measurable benefit is 24 months from receipt of data.

Outputs:

DISSEMINATION PLANS Throughout all stages of this project, NDORMS will engage with key stakeholders including NHS managers, healthcare professionals, patients and the public for interpretation, dissemination and direct communication of the main findings. This will be facilitated through collaboration with the James Lind Alliance, support of specialist societies, and Patient and Public Involvement (PPI) representation. A Professor of Orthopaedic Surgery at the University of Oxford and a Professor of Plastic Surgery at Oxford University Hospitals NHS trust are named co-applicants on this study and will assist in interpreting and the national dissemination of findings. This project has also been informed by results from the recent James Lind Alliance (JLA) Priority Setting Partnership (PSP) for surgery for common shoulder conditions, carried out within the Oxford NIHR Musculoskeletal BRU and supported by the British Shoulder and Elbow Society (BESS) and the British Orthopaedic Association (BOA). NDORMS shoulder and elbow, and hand and wrist applicants both have national roles and collaborations that provide excellent access and influence to disseminate the study findings nationally and internationally through the following societies and funded research centres: 1. British Elbow and Shoulder Society (BESS) – Dissemination to all British shoulder surgeons and shoulder physiotherapists. Presentation at the National Congress. 2. British Society for Surgery of the Hand (BSSH)- Dissemination to all British hand surgeons and hand therapists. Presentation at the biannual National Congress. 3. NIHR Oxford Biomedical Research Unit/Centre – Dissemination to all linked patient and local GP networks 4. ARUK Centre of Excellence (CoE) for Sports and Exercise Medicine – Dissemination to all patients and professional sporting bodies linked to this CoE. 5. Internationally NDORMS will disseminate through peer review publications and via presentations at the European Shoulder and Elbow Society (SECEC) and the Federation of European Societies for Surgery of the Hand (FESSH) One of the NDORMS professors using this data has written national guidelines for NICE and the specialist societies on managing many shoulder conditions including authoring national commissioning guidelines. This study will allow evidence-based updating of these guidelines will be able to influence these as an Executive Council member of BESS and the BESS Quality Outcomes Lead. Dominic Furness, a senior researcher on the application, is a member of the British Society for Surgery of the Hand (BSSH) Research Committee, and will use the aggregated, anonymised results generated from this study to influence practice nationwide. BSSH is in the process of gaining accreditation from NICE for guideline development and NDORMS anticipate this to be in place by the time the results of this work are published. Working with and informing all stakeholders will remain an important part of NDORMS dissemination plans. NDORMS recognize the importance of meaningful PPI involvement and have worked collaboratively with the PPI Officer at NIHR Research Design Service (RDS) to identify individuals to become involved, and NDORMS Director of Patient Involvement at the Oxford NIHR BRC. NDORMS have identified three lay people who understand the needs and problems of upper limb conditions. Through their involvement and recommendations regarding the dissemination of findings, NDORMS will ensure results are readily available and interpretable to the wider patient and public community. NDORMS shall disseminate findings in peer-reviewed journals, at national and international conferences, and inform learned societies that include the British Orthopaedic Association, The British Shoulder and Elbow Society (BESS), British Society for Surgery of the Hand (BSSH), Arthritis Research UK, rheumatology (British Society for Rheumatology), care of the elderly (British Society of Geriatrics). NDORMS will work alongside charities and learned societies to disseminate the findings of this study using established platforms that include social media such as Twitter and a study website, as more patients are now turning to these resources for information about planned surgery. Based on the findings NDORMS will write scientific papers for submission to high quality peer-reviewed journals. NDORMS will also present findings to professionals at conferences and meetings, will develop Plain English summaries of findings for communication to patients and members of the public . All outputs will adhere to HES analysis guide so that data is only shown in aggregate form with small numbers supressed. NDORMS will publish a full and complete account of that research in the NIHR HS&DR Journal, ensuring the research is reported fully, and publicly available via the NIHR Journals Library website and Europe PubMed Central. A webpage will be developed within the NDORMS website specifically for this study in order to further transmit the results to the public. This study aims to capture the attention of patients and the public by presenting the long term results of surgery for upper limb conditions in the UK not previously undertaken, and to also present the potential reasons why there may be variation in outcomes following surgery. Previous PPI work has shown that variation in disease progression, and outcome following intervention is of particular interest to patients and the public. The target date is 24-months following receipt of the data.

Processing:

Upon receiving the data from NHS Digital, a senior data manager with experience in managing HES datasets will process the raw data into smaller extracts. Smaller extracts will be made available for analysis based upon disease pathology and surgical intervention undertaken. This will enable the separate research questions defined by the aims of the study to be answered. NDORMS will provide data at the small area level presented as maps to describe variation in outcomes, before and after accounting for these organisational and surgical factors. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. All processing of ONS data will be in line with ONS standard conditions. NDORMS will also focus on variation in outcomes of specific patient groups (old and frail with co-morbidities and obese) and present evidence as to whether the introduction of new surgical innovations (e.g. minimally invasive surgery), and centralisation of services, has led to improved patient outcomes. ONS mortality data for the patients selected will enable analysis of associations between surgery and death rates. Investigation of spatial and longitudinal trends in mortality will also be studied . Multilevel regression modeling of HES data will assess the association of surgical factors on patient outcomes of surgery, adjusting for patient case-mix. Random intercept models will explore geographical variation in outcomes across hospital trusts and Clinical Commissioning Groups. Geographical Information Systems will be used to produce maps depicting variation in outcomes, and graphically display the influence these factors have on explaining such variation. NDORMS will then use a natural experimental study design to specifically examine the impact that the new treatments have had on NHS resource use, NHS costs and patient outcomes (based upon length of stay, complications, readmission, further surgical intervention including revision surgery). Interrupted time series analysis will examine changes in secular trends in outcomes and NHS costs before and after the introduction of the new treatments. There will be a focus on the benefit of the new treatments to specific patient groups such as frail older people with complex co-morbid conditions. An economic evaluation will describe the hospital NHS costs, patient health related quality of life and cost effectiveness that reflect the new treatments for upper limb conditions. The predominant method of limiting the data requested is through the study of selected upper limb conditions only, and through only selecting certain procedures. Due to the lack of existing evidence surrounding the role of comorbidities in this research area, it is not advantageous or appropriate to further select a subgroup of patients with certain co-morbidities . A cost-effectiveness analysis will be performed to estimate the economic burden of conservative and surgical care in relation to trends in outcome, adjusting for socioeconomic status and case-mix. This is largely unexplored to date and essential for further studies potentially exploring the cost-effectiveness of the surgical intervention. Once data has been disseminated to the study; - The HES datasets will be held on a password protected University Computer on an encrypted drive at the Botnar Research Centre, Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS). - Only authorised users where they hold Approved researcher status for the ONS data will have access to the data, these users will change their password every 90 days, according to the IG guidelines of the Big Health Data Group (BHDG). - The data will be managed by a statistician based at the Botnar Research Centre Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS) University of Oxford. - The data will be used exclusively for the purpose of this project - At the end of the study, the data will be safely held in a password protected University Computer at the Botnar Research Centre, for further 36 months, and assessed only to answer questions arising from the publication and other publicity. All processing of ONS data is in accordance with standard ONS terms and conditions. All data will be processed only by substantive employees of University of Oxford. Data will not be linked to any other record level data, no attempts will be made to identify any individual from the data being supplied, and there will be no onward disclosure of record level data.

Objectives:

Musculoskeletal conditions of the upper limb (arm) are a significant disease burden, affecting all age groups including the working population. Prevalence of conditions affecting the hand such as osteoarthritis and carpal tunnel syndrome are estimated at between 15-36% of the population, causing pain, numbness and loss of function. Shoulder osteoarthritis prevalence is estimated to be as high as 32% in those over 60 years, which stands to increase as the UK population ages. Research also has shown that approximately 20% of the population present to their GP to discuss a musculoskeletal condition each year, with NHS spending totalling over £5 billion annually on musculoskeletal conditions. There has been little research exploring national trends in treatment, outcome or access to care in upper limb musculoskeletal conditions in the UK, and Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS), at University of Oxford believe that research in this field is vital for patients, clinicians and the NHS alike in order to improve patient care, patient information and patient pathways. Around 5300 shoulder replacement operations now take place each year in the UK and this number is expected to increase, including revision (re-do) surgery. Elbow replacement surgery is rarer with only a few hundred cases per year, but revision rates are thought to be potentially very high and the costs even higher. It is currently difficult to estimate the considerable number of surgeries undertaken for hand and wrist arthritis, as this data is not yet collected into any national database. Some forms of upper limb arthritis can develop following joint dislocation or injury to the soft tissues. Shoulder rotator cuff tendon tears and joint instability following shoulder joint dislocation are common injuries that may contribute to the development of osteoarthritis. Surgery to repair rotator cuff muscles and to stabilize the shoulder following dislocation seems to be rapidly increasing in recent years. Investigation of the use of these new procedures, and whether they have an impact upon the development of arthritis in later life is not yet known. In the hand, dupuytrens disease is disorder of the connective tissue (soft tissue) of the hand causing a progressive significant deformity and reduced ability to use the hand. There are a variety of treatment options, ranging from splinting the affected finger, to local injections to break down the abnormal tissue, to surgery to remove it. It is thought that availability of treatment options available varies across the UK. There is an increasing trend in patients being diagnosed with the condition. Compression of nerves in the arm is very common, and this is called nerve entrapment conditions. Carpal tunnel syndrome and cubital tunnel syndrome being the most common and treatment remains varied, with some patients undergoing local steroid injection and splinting of the affected area, and others proceeding to surgery to stop compression of the nerve. Previous evidence has suggested some nerve entrapment conditions may be related to obesity and diabetes, and therefore the number of patients suffering with the condition is expected to increase. There are some links suggesting development of nerve compression during pregnancy. The interaction between surgery to treat arthritis, and the development of a nerve entrapment condition is not yet understood. This study aims to investigate the impact of treatment for the most prevalent upper limb conditions and will include investigation of surgical treatment trends, revision surgery trends (in particular upper limb joint replacement surgery) and current resource demands in treating these common conditions. These conditions include osteo- and rheumatoid arthritis of the upper limb joints, shoulder rotator cuff (muscle) tendinopathies and tears, Frozen shoulder, shoulder joint instability (joint dislocation), Dupuytren’s contracture of the hand, and nerve entrapment (nerve compression) syndromes. AIMS The main aims of this study are: 1. Investigation of the variation in surgical treatments, revision rates and mortality rates in upper limb conditions A large variety of new surgical techniques coupled with a rapid expansion of surgical implants mean that many different options exist in the surgical treatment of upper limb conditions. Newer innovative surgical options might enable patients to undergo less invasive surgery with reduced recovery time and improved return of function. Some new techniques aim to prevent disease recurrence or progression. NDORMS wish to investigate these surgical techniques, and the impact upon the need for further interventions following these procedures. 2. Geographical and temporal trends in management and outcome Having identified the types of surgical intervention undertaken, NDORMS will investigate whether there are temporal or geographical trends associated with intervention type, compared to geographical and temporal trends in disease prevalence. NDORMS will investigate this comparing patient demographics within regions and over time, and produce maps highlighting these trends. NDORMS will also produce maps highlighting variation in length of stay, readmission complication and revision rates across the country as proxy measurements for patient outcome. 3. Assessment of access to care & care costs Statistical analysis of national data from the HES admissions database will allow identification of hospital organisation and surgical factors that may explain geographical variations in patient outcomes of surgery, after adjustment for patient level case-mix. In this study we aim to identify whether the different ways that hospitals organise services for patients presenting with upper limb conditions can lead to improved patient outcomes, and postulate reasons why outcomes may vary between hospitals or regions. NDORMS will investigate whether these differences cause a variation in access to care, due to disease prevalence, or due to variation in management and how these factors influence the cost of patient care. Greater understanding of trends in how these interventions are being used and the outcomes following them will enable NDORMS to propose changes that will influence health service provision and workforce planning. This dataset has the unique and exciting opportunity of exploring the changes that have occurred in disease presentation, development, treatment and outcome over an extensive time period. Studies that have follow up of this duration have not been previously undertaken in this country, and undertaking research using routinely collected NHS data will enable us to better understand how to care for patients with upper limb conditions . Long term follow up of surgical interventions allows evaluation of the impact of new techniques and devices, and especially the effect of new implants upon implants failure rates. Analysis of long term outcomes are vital in order to determine which implants and interventions should continue to be used; evidence that is not available elsewhere. Patient focused priorities for research NDORMS have recently run a successful James Lind Alliance Priority Setting Partnership (non-profit making initiative to identify and prioritise uncertainties and questions about the effects of treatments) for “Surgery for Common Shoulder Conditions” which brought together patients, carers and clinicians to set the ongoing treatment uncertainties with regards to surgery for common shoulder conditions. These results are now published and highlight research questions that are important for UK patients. This application will help address some of these questions Including; Which shoulder replacement type operation should be undertaken in different patient groups. Due to the short term NJR data this is currently not answerable but HES data over a longer period of time will allow for a separate and much more detailed data interrogation, potentially answering this question and negating the need for an expensive national surgical trial. Appreciating that the James Lind Alliance Priority Setting Partnership for “Common Hand conditions” is currently underway in the UK but has not yet reported, NDORMS have lead a regional patient and public engagement project in hand surgery. This study has emphasized that improving patient selection for surgery, timing of surgery and type of surgical management undertaken is seen as a priority. NDORMS study will help answer or contribute further important information to those trying to answer these treatment uncertainties. Alignment with NHS agenda In the NHS, patients can choose which hospital they want to have their surgery in. Information on access to treatments and the outcomes of surgery between different hospitals would help patients in making their decision. Outcomes of surgery may vary across different regions and hospitals. Any such differences might be explained by a hospital treating more complex and sicker patients, but could also be explained by the surgical techniques employed in different centres, or centralization of care into specialist high volume hospitals. Knowledge of this would inform dashboards and aid NHS managers and clinicians in changing and optimising service organisation to reduce any variations in outcomes. The national audit into the orthopaedic surgical procedures called Getting It Right First Time (GIRFT) was launched in 2013. Initial results released in March 2015 found large variations in practice, and have called for better research into the timing and types of procedures undertaken. Better understanding of regional and temporal variations in procedures, and which surgical procedures have the best outcomes would improve the quality of patient care in the UK, reduce costs for the NHS and more importantly provide better patient information to inform shared treatment decision making. This dataset has the unique and exciting opportunity of exploring the changes that have occurred in disease presentation, development, treatment and outcome over an extensive time period. Studies that have follow up of this duration have not been previously undertaken in this country, and undertaking research using routinely collected NHS data will enable the study to better understand how to care for patients with upper limb conditions . Long term follow up of surgical interventions allows evaluation of the impact of new techniques and devices, and especially the effect of new implants upon implants failure rates. Analysis of long term outcomes are vital in order to determine which implants and interventions should continue to be used; evidence that is not available elsewhere. The predominant method of limiting the data requested is through the study of selected upper limb conditions only, and through only selecting certain procedures. Due to the lack of existing evidence surrounding the role of comorbidities in this research area, it is not advantageous or appropriate to further select a subgroup of patients with certain co-morbidities . The NJR data for shoulder replacement only began in 2012, and the elbow data began this year. There is no other source available to evaluate implants and procedures used for hand and wrist conditions. Over the time that HES data has been collected, there has been a rapid evolution of the implants available for these procedures, which have yet to be evaluated. The importance of long term data has been shown in other areas of orthopaedics, especially in hip surgical research where metal on metal hip replacements have since been shown to have higher long term failure rate than other implants. A lack of long term data surrounding complications associated with these new implants to treat hip osteoarthritis led to patients undergoing procedures that have since been withdrawn due to excess morbidity associated with their use. This work aims to identify implants and procedures with higher rates of complications using the long term data available in HES APC, to optimise future patient care and prevent harm. This data will not be available in other sources for many years, and therefore this emphasises the real value of the long term data available through using HES to prevent future harm, and why we have specifically chosen to use this dataset for this work. The hand, wrist and elbow procedures that this study wish to look at have been in use for well over 20 years, and as such the study would like to look specifically at the changes over time in their usage, for example in response to key papers, guidelines, changes in policy. Releasing less data than this would limit the usefulness of the study and the results that we would be able to make to inform future patient care.


Project 25 — DARS-NIC-302994-C2Q2Y

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/12 — 2018/05.

Repeats: One-Off, Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Critical Care
  • MRIS - Members and Postings Report
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Benefits:

ASCEND is a high profile trial (already widely referred to in international journals) whose results have the possibility of influencing national and international guidelines for the use of anti-platelet therapy in this very large patient group (currently at least 3M in the UK and over 300M worldwide). Access to the data requested will allow a complete and unbiased analysis of the benefits and hazards of allocation to aspirin and to omega-3 fish oils in the ASCEND study, thus enhancing the reliability of the study findings. The study results are expected in 2018 but any changes to treatment guidelines as a result of the ASCEND trial may take several years to emerge.

Outputs:

The main outputs from the research will be in the form of scientific reports of the results of the trial. If ASCEND can reliably demonstrate that aspirin and/or omega-3 FA safely reduce the risk of cardiovascular events, cancers and deaths in diabetic patients, without pre-existing occlusive arterial disease, this would be relevant to some hundreds of millions of people world-wide currently not receiving such therapy, and could save tens of thousands of lives each year. On the other hand, if the risks of serious bleeding outweigh or are similar in magnitude to the cardiovascular benefits in this group, then these risks could be avoided by the very large number of diabetic patients who are currently being treated with aspirin. The results will be presented during 2018 at international scientific meetings and published in a prominent peer-reviewed medical journal within about a year. The arrangements are not yet finalised but the international meeting is likely to be one of: American Diabetes Association, European Society of Cardiology or the American Heart Association. The journal is likely to be The Lancet but again not finalised at this stage. In addition the BHF will play a role in the advertising and promotion of the results. The results are likely to be incorporated into an individual participant data meta-analysis of similar trials run by the Anti-thrombotic Trialists Collaboration. All outputs will consist of aggregate data only with small numbers suppressed in line with HES analysis guide. In addition to this the two pharmaceutical companies providing the medication and matching placebo for the study and some funds to cover the costs of packaging the treatment have an interest in seeing these treatments (aspirin and fish oils) properly evaluated in a large well run randomised trial. They will receive the same publically available results. If the study results show benefits for diabetic patients, the pharmaceutical companies may wish to use tabular data from the study to seek approval from the regulatory agencies for the marketing of these treatments to this group. The data provided would be aggregated with small numbers suppressed in line with the HES Analysis Guide. If a submission is made to a regulatory agency, the Clinical Trial Service Unit at Oxford University would provide relevant information in the form of tabulations of numbers (for example: number of participants randomized, experiencing serious or other adverse events) with no individuals being identifiable in any submission. There would be considerable overlap between any tabulations provided to the companies and the published results, however the companies might ask for specific detail that were not considered necessary to publish. No participants will be identifiable in any information provided and the pharmaceutical companies do not have any influence in the research or the results. All data provided to the companies would be aggregate with small numbers suppressed in line with the HES Analysis Guide.

Processing:

Information is collected routinely of the ~15,480 participants who were randomised between June 2005 and July 2011 by postal questionnaire however, over time, some participants stop returning questionnaires and this is more likely among people who have also stopped their study treatments. To minimise bias all participants need to be followed-up irrespective of whether they have been taking their study treatments and all events included in intention-to-treat analyses. In order to comply with the EU Clinical trials directive, the data received will be transferred into the trial database by the person registered to receive data. The ASCEND trial database is study specific and is stored on an ASCEND specific server. The identifiable HSCIC data is stored in an encrypted TrueCrypt container to which access is granted on a "need to know" basis i.e. the level of access will depend on the staff role. All such access will be granted on the instruction of the Information Asset Owner for ASCEND. Access is routinely reviewed and revoked when the team member leaves ASCEND. The complete supplied HES data will need to be retained for 15 years (as per the ASCEND Protocol, section 2.4.6) as the team need to be able to trace all study medical events (some of which may be identified from HES data) back to source data to comply with the European Medicines Agency guidelines for good clinical practice and have this readily available during any Medicines and Healthcare Products Regulatory Agency (MHRA) inspection. The ASCEND study team shall not, except as may be strictly necessary for carrying out the project, provide or otherwise make available the HES or ONS data to any third party or allow use of it or them by or on behalf of any third party, in whole or in part, whether by way of sale, resale, loan, transfer, hire or any other form of exploitation. This statement is intended to cover the situation where there may be a need to write to an individual participant’s GP for further clarification about a medical event or death to support the adjudication coding process undertaken by the study medical team. The event/death may have been supplied by ONS/HSICIC although the source of the event would not be supplied to the GP. Clinical trials involving Investigational Medicinal Products (IMPs) are legally required to comply with GCP which is regulated by the MHRA so this phrase also covers MHRA Good Clinical Practice inspections, during which an inspector may see an individual record with a medical event or death recorded which may have been supplied by ONS/HSCIC. Cause of death data from the Office for National Statistics has been processed by NHS Digital through a separate Data Sharing Agreement and will be assessed separately when the agreement is due for review in March 2017.

Objectives:

The aim of the British Heart Foundation (BHF)-funded ‘A Study of Cardiovascular Events iN Diabetes’ (ASCEND) randomised trial is to determine reliably whether aspirin (100mg daily or matching placebo) and/or supplementation with omega-3 fatty acids (1g capsule or matching placebo) safely prevents cardiovascular events and deaths in patients with diabetes, who do not already have clinically manifest arterial disease. Although aspirin is recommended for people with arterial disease, since it also causes bleeding, the balance of benefits and possible harms are not clear in this group with diabetes. The study is funded by the British Heart Foundation and the packaged study treatment is provided free of charge by Bayer Pharma AG [100mg aspirin/matching placebo] and Abbott Products Operations AG [1g omega-3 capsule/matching placebo]. 15,480 participants were randomized between June 2005 and July 2011 and median follow-up is currently ~4 years with a planned duration of at least 7 years. All serious adverse events (SAEs) are to be recorded among the randomised participants to allow detailed analyses of both the safety and efficacy of trial treatments. In order to reliably record and code reported SAEs during follow-up, as outlined within the study protocol, the team require clinical information about diagnoses and operations, including dates of occurrence. Access to electronic central records of hospital episodes will allow this complete and unbiased follow-up and appropriate intention-to-treat analyses. The sensitive identifiable fields are required to ensure robust linkage to ensure that the records pertain to the correct participant, which is vital for the accuracy of the study data. The HES data will also provide additional confirmation of some participant reported events. The HES data relevant to the trial outcomes (heart attacks, strokes etc.) will be further followed up via GPs for additional information, and will be reviewed by study clinicians (who remain blind to treatment allocation) with the aim of confirming or refuting events.


Project 26 — DARS-NIC-315419-F3W7K

Opt outs honoured: N

Sensitive: Non Sensitive, and Sensitive

When: 2017/09 — 2017/11.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Office for National Statistics Mortality Data (linkable to HES)

Benefits:

UHCE’s database and research is unique. Nowhere else can research use hospital data from 1963 to present day to provide such a complete picture of the progress of secondary care and cover such a large percentage of the history of the NHS. With 50 years’ worth of hospital data, research into areas such as hospital trends, mortality rates, disease history and maternal disease links, that could take years to complete, can be achieved extremely efficiently. This means UHCE can react extremely swiftly to issues arising for the health care system or from patients. For example, in the questions over the ‘week-end effect’, UHCE was able to publish on mortality rates for meningococcal meningitis. There are few other diseases which can act as such a good marker to show the difference between expert treatment or no or suboptimal treatment. The study showed no evidence of an adverse day of the week effect. This database and the research which uses it significantly contributes to the body of evidence and knowledge available which leads to changes in treatment, care and policies which are of benefit to the patient and the health care system. There are many examples of benefits; the following provides just a small sample; 1.Hospital Trends: One of the overall aims is to undertake a comprehensive study of trends in hospitals from the 1960s to now. This will provide policy makers with an understanding of the factors that have led to the seemingly inexorable rise in hospital admissions over the decades, the trends in which diseases are being treated and the changes in mortality rates from these diseases. This programme of research will form a body of publications which will be of benefit to clinicians and policy makers who want to understand impacts such as the use of prevention versus treatment in particular conditions. There are hundreds of publications using this data for this aim; the following are just a few some examples; I. Publications on hospital admissions for children Using this unique database research was able to look at the long term trends in hospital admissions for children with various conditions. In particular to document the beneficial impact of the MMR vaccination when uptake was high, and the negative impacts when MMR coverage dropped. This research was reported into NICE as well as the Department of Health’s Joint Committee on Vaccination and Immunisation in order to add to the information used in polices to reduce disease rates. II. Public health finding for the Department of Transport This research looked at the hospital admission rates over time compared with falling police reported incidents. UHCE were able to report back to the Department that the hospital data showed no such fall and advised the department and the Chief Medical Officers that there was a need for closer collaboration with official statistics in order to fully understand the numbers of injuries and fatalities on the roads and so improve road safety. III. Public health finding on Rickets UHCE was able to show that admission rates in 2011 were higher than at any time since the 1960s. This publication adds to the evidence and knowledge used by public health policy makers in advising the general public in how to avoid this preventable disease. 2. Geographical Variation: Another aim is to study geographical variation in hospital rates, some cases to study of the epidemiology of a particular disease or to investigate potential clinical variations in treatment and care. Again, these outputs cover a large amount of time and so are of benefit in adding robust research to the evidence base in these areas for the improvement of patient outcomes. An example of a past publication, which was aimed at ENT surgeons, was about the huge variation in tonsillectomy rates. As this was unlikely to be warranted by epidemiology it was more likely to be variation between clinicians. NIHR went on to use this research as an example of variation which could be used by commissioners and clinicians to identify cost savings. 3. Mortality rates: There have been many publications on mortality rates with many aimed at clinicians. For example, a study showing the elevated mortality rate following admission for anorexia nervosa adding to the evidence that this can be a life threatening disorder and this was published in journals specifically aimed at clinicians who treat these disorders. Being able to provide accurate knowledge mortality risk provides benefits in terms of (i) its value in informing clinicians, public health and the public about success (or lack of it) in health-care performance, and (ii) its value in informing clinicians about the likely course of illness and risk in their individual patients. 4. Disease: It is crucial that clinicians, researchers, patients and public-health policymakers are made aware of important associations between diseases in order to prevent multi-morbidity and to reduce "years of life lost" and "years lost due to disability" through identification of at-risk groups of the population. This crucial database and associated research provides this opportunity. The following are examples of recent UHCE studies in this area; - Significantly increased risk of primary malignancies in people with non-melanoma skin cancers, particularly the young - Severe under-diagnosis and under-treatment of cataract and other sight disorders in people with dementia - Significantly increased risk of dementia in people with obesity - Significantly increased risk of autoimmune disease in people with vitamin D deficiency, and vice versa - Significantly increased risk of biliary tract and liver complications in people with polycystic kidney disease By way of further illustration, the following provides a small sample of publications and the impact they have had. 1. Seagroatt V, Goldacre MJ. Crohn's disease, ulcerative colitis, and measles vaccine in an English population, 1979-1998. J Epidemiol Community Health. 2003 Nov;57(11):883-7 Key point: This study directly influenced official NHS public engagement policy in relation to the measles vaccine. Detail: Publication of this study was followed immediately by a NHS Immunisation Information press release (11 Dec 2003), which stated: “A new study has confirmed that the introduction of measles vaccine in this country played no part in causing Crohn’s Disease and Ulcerative Colitis. The theory that measles vaccine was linked to bowel disease and then autism depended on a belief that measles virus damaged the bowel. This study adds to the available evidence that says that this is not the case.” 2. Seminog OO, Goldacre MJ. Risk of pneumonia and pneumococcal disease in people hospitalized with diabetes mellitus: English record-linkage studies. Diabet Med. 2013 Dec;30(12):1412-9. doi: 10.1111/dme.12260. Epub 2013 Jul 24 Key point: This study directly informs the position statements of high-profile diabetes charities in the UK. Detail: Following publication of this study, position statement from Diabetes UK: “All people with diabetes over the age of two years should be offered the pneumococcal vaccine.” 3. Goldacre MJ, Maisonneuve JJ. Mortality from meningococcal disease by day of the week: English national linked database study. J Public Health (Oxf). 2013 Sep;35(3):413-21. doi: 10.1093/pubmed/fdt004. Epub 2013 Feb 1 Key point: This study directly informed the legal debate about the 7-day NHS and the "weekend effect". Detail: This study featured in various mainstream news outlets at the time and was referenced in the High Court judicial review case between NHS junior doctors, the British Medical Association and the Secretary of State for Health in relation to the new NHS contract for junior doctors. The study was described by Mr Justice Green as a "trenchant" piece of evidence. 4. Mukhtar TK, Yeates DR, Goldacre MJ. Breast cancer mortality trends in England and the assessment of the effectiveness of mammography screening: population-based study. J R Soc Med. 2013 Jun;106(6):234-42 Key point: This study directly informed the public debate about breast cancer screening. Detail: Publication of this study was immediately followed by an NHS news release, which stated: “There is a great deal of information on both the pros and cons of screening…This study provides additional valuable population data to inform the breast cancer screening debate.”

Outputs:

All outputs will be aggregated analysis, with suppression in accordance with the HES analysis guide. Such data will appear within research papers, academic journals and conference presentations. The presentation format of that data may vary – from individual tabulation, through to geographical presentation through the Atlases mentioned previously. Such analysis is derived from data provided by UHCE, who receive requests for aggregated, non-sensitive, non-identifiable tabulated data in fulfilment of its research work programme (as detailed above). These tabulations require statistical analysis prior to being provided to researchers, whilst equivalent in format to those provided by NHS Digital (hence could not be provided directly). UHCE does not solicit requests for tabulations through any web advertising or promotional activity. It does welcome collaborative research work with academic researchers on topics that can be covered by its existing research themes already described in this document. For researchers outside the UHCE but working with the UHCE, the UHCE will only provide aggregated tabulations, not individual-level records. It does not and will not provide UHCE tabulations on request to people outside the UHCE for any purpose other than research. UHCE have a long track record in published work in the programme of work described in this document. More information can be found here https://www.uhce.ox.ac.uk/uhce/publications.php The Unit was, historically, very closely associated with the Regional tier of the NHS and with the Department of Health. Although the UHCE is part of Oxford University, it was based on the Oxford RHA’s site from 1963 until the reorganisation of Regional Health Authorities in the mid-1990s. In particular, the UHCE worked closely with the Oxford RHA on medical statistics, record linkage (including the Oxford Record Linkage Study (ORLS), and health services research. From 1998-2005, the Unit had strong service links with the Department of Health’s National Centre for Health Outcomes Development (NCHOD) - the Unit Director, directed the work programme of the Oxford site of NCHOD. As part of the NCHOD work, the DH commissioned the UHCE to construct and analyse English national record-liked HES files, with HES-to-HES linkage and HES-to-mortality linkage, along the lines of the Oxford Record Linkage Study. The Unit Director was also Co-founder and Scientific Director of the South East England Public Health Observatory from its inception in 2000 until 2005. The UHCE has run a continuous work programme of rolling research, notably using hospital statistics, mortality data, and record linkage, from 1963 to the present. It is part of the University of Oxford’s Department of Public Health (now, as from 2013, the Nuffield Department of Population Health).

Processing:

Only substantive employees of the University of Oxford will have access to the data and only for the purposes described in this document. The University of Oxford will amend this agreement if the requested data is needed for research which does not fall under the themes described here. Background of the datasets used in these projects: UHCE undertakes research on hospital statistics, and on mortality, using four different datasets. These are the :- a. Oxford Record Linkage Study, phase 1 (1963-1998) (ORLS1); b. the Oxford Record Linkage Study, phase 2 (1989/90-2013/14) (ORLS2); c. the Hospital In-patient Enquiry for England (1968-1985) (HIPE); d. Hospital Episode Statistics (HES) for England, 1989/90-2013/14 (provided by NHS Digital) These four datasets are not linked to one another as individual-level records. These four datasets constitutes the longest run of hospital data in England. The UHCE dataset for the ORLS spanning 1963-2013/14 is the longest run of hospital data in England at regional level and is the only long-running dataset in England with record linkage going back decades (to 1963). UHCE holds ONS data which was provided directly by ONS. This will be the first time that UHCE are requesting ONS data from NHS Digital. In the development and use of large datasets of routine health data, UHCE undertakes original research; it collaborates with others on research projects; and it provides support as required to the NHS, DH and their information functions. Processing: NHS Digital will supply pseudonymised HES and the ONS (including month and year of death) data to UHCE via a secure file transfer system. The data are held in individual SQL databases, subject to individual user control. The HES and ONS national data are processed on receipt so as to have the same database configuration, in order to ‘look like’ the hospital and mortality data in the ORLS. This is done to facilitate the running of the same software across all the databases. The datasets are all de-identified and are held securely within the UHCE and no individual-level records are ever provided to anyone outside the UHCE. The datasets are not linked to one another as individual-level records. When there is a need to construct studies based on data that span the time frame of the years covered by the different datasets – typically in, for example, studies of hospital admissions across five decades – the UHCE software packages are invoked to run the analyses within each dataset to produce aggregated statistical results. At the stage of the aggregated statistics, UHCE software templates are used to bring together the tabular results that span individual results from within each dataset – e.g. electronic tables for admission rates in the years 1968-1985, 1989-1998, 1989/90-2013/14 are brought together – into combined tables for the whole period 1968-2013/14. UHCE have suites of software, developed over many years in the UHCE, which can be used to run the trend analyses in a highly automated way. Researchers do not need to ‘see’ individual level records in order to ‘queue and run’ the software. The UHCE has developed a ‘front end’ to the analytical software such that, for each new run, the member of staff uses a menu. The menu gives the operator a choice of selecting the ICD code and diagnostic code (or equivalent for operations), the required age groups, selection of gender, selection of people, the calendar or financial years required, whether to select the primary diagnosis or all diagnostic fields, whether to select all cases or just electives or just emergencies, and so on. A suite of templates and data manipulation tools then analyses the data in the four files separately (ORLS1, ORLS2, HIPE, HES 1989/90-2013/14) automatically. When the results in each separate dataset have run, another suite of templates and data manipulation tools automatically ‘pulls together’ the results from each set of electronic tables and combines them into tables and graphs giving (seemingly) continuous runs of trends Similarly, in studies that require data for the full length of the ORLS (1963-2013/14), UHCE software packages are invoked to run the analyses within ORLS1 and, separately, within ORLS2 to produce aggregated statistical results based on the data within each of the two datasets separately. At the stage of the production of the aggregated statistics, UHCE software templates are used to bring together the tabular results that span individual results e.g. electronic tables for admission rates in the years 1963-1998 and for 1999-2013/14 – into a combined table for the whole period 1963-2013/14. Outputs are therefore all aggregated data, suppressed in line with the HES analysis guide. No record level data may be extracted from the server. Access to the data is controlled through specific user access controls. Each user has to complete a staff declaration form which ensures that the user is aware of their obligations in relation to the data (eg: to not attempt any re-identification, to use the data solely for the purposes of the individual project). The information systems used by the Unit of Health-Care Epidemiology are secure and comply with the principles outlined in BS7799 (The Code of Practice for Information Security Management). All the datasets proposed for use in these studies are pseudonymised. They include no direct identifiers, no NHS number, and the smallest geographical unit associated with each record is that of the person’s Local Authority area of residence (of which there are currently 354 in England). UHCE have no requirement to re-identify the individuals within the datasets and will make no attempt to re-identify. UHCE will not share any record level data and all outputs will be aggregated with small numbers suppressed in line with the HES analysis guide. UHCE will not link the data provided with the dataset described, or any other datasets. The processing of ONS data is in accordance with standard ONS terms and conditions.

Objectives:

The Unit of Health-Care Epidemiology (UHCE) was founded in 1963 as a research Unit that, among other activities, undertook research using routinely collected hospital admissions data and mortality data. The Unit’s overall aims, currently, are to undertake epidemiological and health services research, in particular by using routine NHS statistical data and by undertaking studies that use cohort methodologies. Pseudonymised data is required to support the following work projects :- 1. Trends in admission rates in hospital specialties; trends in admission rates for individual diseases and operations UHCE is undertaking research into trends in most hospital specialities, and for many individual diseases, distinguishing the extent to which increases or decreases have occurred; distinguishing between episode-based rates, multiple episodes per person, and person-based rates; assessing the extent to which changes represent or go beyond demographic changes in the resident population; profiling changes in the clinical content of specialties’ work and in lengths of stay (including the use of day case care); and, involving clinicians, attempting to explain the trends. UHCE is also undertaking studies of trends in the use of hospital care by particular demographic groups including children, adolescents, and the elderly. In addition to the study of individual diseases, UHCE will also include studies of medical problems defined by behaviour and aetiology (e.g. self-poisoning in teenagers and young adults; accidental injury), where appropriate studying age and cohort effects as well as period effects. The overall aim is to undertake a comprehensive study of trends in hospital admission rates in England from the 1960s to the present. The study will serve two main purposes. First, it will provide a detailed understanding of factors underpinning the long-term growth in hospital admission rates in the NHS: hospital admission rates in England have risen seemingly inexorably for decades. Second, it will provide epidemiological insights into trends in incidence and prevalence of diseases that warrant hospital care. 2. Geographical variation in hospital admission rates across England UHCE have used the data to analyse the distribution of hospital admission rates across England. Where admission rates for a condition vary – particularly for chronic conditions like asthma and diabetes – linked data are invaluable in distinguishing whether the variation is attributable to differences in the number of individuals admitted or in the scale of multiple admissions per person. The geographical units would vary according to the topic (and in particular according to the incidence/prevalence of the condition). For example, local authority level would be appropriate for common conditions such as myocardial infarction, asthma and diabetes; county or regional level would be appropriate for less common conditions such as multiple sclerosis, motor neurone disease or haemophilia. UHCE intend to update the ‘atlases’ of disease across England. 3. Mortality rates for each diagnosis and operation This data can be used to develop ‘a science of prognosis’. The aim is to study mortality rates following admission for each diagnosis and operation. UHCE will focus on diseases and operations for which there is likely to be interest in long-term trends, using the benefit of the five-decade runs of data. For example, in studies in the former Oxford region UHCE have shown substantial declines in 30-day and 90-day mortality after emergency admission for myocardial infarction and stroke. 4. Natural history of disease: disease associations The aim is to use patient pathways within the data to investigate associations between diseases and, where relevant, between operations and diseases, to determine the likelihood that, given one clinical condition, other conditions may follow. The work programme will quantify known disease associations accurately; will test hypotheses about suspected associations; and will generate hypotheses about possible hitherto unrecognised relationships between diseases. Associations between diseases may indicate shared genetic susceptibility, e.g. leukaemia and other cancers in people with Down’s syndrome. Clinical conditions may be associated because one may predispose to the other, e.g. ulcerative colitis and large bowel cancer, benign and malignant breast disease. 5. Maternal, obstetric and perinatal factors and subsequent disease One area of work currently proposed is a study of maternal and perinatal factors and subsequent asthma in the child; others include the study of perinatal factors and cerebral palsy and congenital malformations. The maternal and perinatal factors include, for example, mother’s history of disease, mother’s smoking in pregnancy, child’s birth weight, gestational age, and number of siblings. Similar studies have been done by UHCE on diabetes mellitus and on congenital conditions in the past. Work is underway to analyse characteristics of the pregnancy and its ‘child’ outcomes for women with a range of diseases (e.g.mothers with diabetes); and to analyse the maternal and pregnancy characteristics of children with a range of diseases (e.g. maternal and pregnancy characteristics of children who develop diabetes, bronchiolitis, cancer, and other child outcomes).


Project 27 — DARS-NIC-358191-T5P4G

Opt outs honoured: N

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Patient Reported Outcome Measures

Benefits:

Patient reported outcome measures (PROMs) have increasingly gained prominence in the NHS for routine care and research in recent years particularly in areas, such as hip or knee replacement, hernia repair, to assess the effects of surgery and other interventions on health and quality of life. They form an important addition to long term clinical outcomes, which are not able to capture patients’ perceptions of their individual experiences outcomes with regards, to the results of an intervention or disease burden. However, as the use of PROMs within the NHS is still relatively new, more research is needed in this area to better understand and interpret results used for clinical decision making. A particularly important area for research is the occurrence of missing data within PROMs, as they rely on participants to be able and willing to complete the relevant questionnaires, and are therefore often subject missing data. It is unclear what the impact of missing data may be, which means that the available PROMs data may not be representative of the general population, and conclusions based on this data may not be appropriate for the wider population – for example, if more patients with poor outcomes were much more likely to not provide feedback. The proposed work focusses on identifying factors that influence non-compliance with PROMs to create a better understanding of the available data and improve the results drawn from it to avoid reducing the likelihood of routine analysis and studies producing biased and misleading results. In line with the interest expressed by the NHS and other health care providers, regulators and funding bodies (as stated in the section labelled ‘purpose’), this work will help the NHS to choose effective and cost-effective treatments, and target available resources on the most appropriate treatments backed by the most robust research methodology. By contributing to the implementation of the most robust methodology and health research used, amongst others in clinical trials, this research aids the decision making with regards to which treatments are most effective for certain disease areas and patient populations. Thereby, this research will contribute to policy changes (changes in medication or interventions supported and financed by the NHS). This means that by having better evidence to choose the most effective and cost-effective treatments, the NHS will save money otherwise spent on less effective interventions. This will result in better treatment for participants, because as a result of this work, patients will be more likely to receive the best interventions available, which will maximise their health and wellbeing though more robust research and evidence. They can also be more certain of the decision-making process underlying their treatment choices. Through less uncertainty around the results of clinical studies, new treatments will also be implemented more quickly into routine care, which means that patients can receive novel interventions and medication sooner. Outputs are to be published in peer reviewed, open-access journals by April 2017. Thereby, results and conclusions will be freely accessible to researchers, NHS staff and decision makers and the public alike. The researcher will liaise with NHS England and the NHS Outcomes Framework for additional opportunities to present and discuss their work. Through the open-access publications and targeted presentations as described above, outputs are expected to impact on the current practice of handling, analysis and reporting clinical research in the presence of missing data thereafter. Past presentations of this work have been described above.

Outputs:

The outputs from this research will provide relevant information in their own right, and also contribute to simulation models of the PhD project statistical modelling of data. Clear plans to communicate the potential and athe outcomes of the work: Results from this research project in the field of missing data methodology will be published in relevant peer-reviewed, open-access journals reaching a wide audience including health care professionals, NHS staff and decision maker, statisticians and methodologists working in clinical trials and health research more generally. Findings will also be presented at relevant local, national and international conferences aimed at a wide range of audiences, as described above. In particular, NHS and health care conferences will be targeted, such as the National PROMs Summit, and a short summary of the research aimed specifically at NHS staff will be submitted to the Health Services Journal. Also, the researcher will liaise with NHS England and the NHS Outcomes Framework for additional opportunities to present and discuss their work. In addition, the researcher has established close links with local clinical trial teams, researchers and health professionals (including consultants, chief investigators and research nurses within the NHS) to whom the initial research aims have been described and findings will be presented on a regular basis. By contributing to and co-designing research with these groups and patient representatives, research outputs can be implemented into future and ongoing clinical trials and research projects where appropriate. To date, presentations on the topic of missing data arising from the broader research have been delivered at various meetings including the following: Oxford Research Network Conference, Musculoskeletal Study days held at the Oxford University NHS trust and the Thames Valley Clinical Research Network Meetings (Oxford University Hospital Trust). Any published information will be restricted to summary statistics (i.e. means, medians, standard deviations/ 95% Confidence intervals or ranges), as well as to the reporting of the results from statistical models (logistic regression and similar). Under no circumstances will individual patient level data or any patient information that could be used to identify individual patients be published. Outputs are expected to be published within the next two years, i.e. before April 2017.

Processing:

All processing is secured in line with the system level security policy. The project is being supervised by HERC which is a research group with the University of Oxford so the data is controlled by HERC. The University Data Protection policy applies to the project http://www.admin.ox.ac.uk/councilsec/compliance/dataprotection/policy/ . This policy equally applies to staff, students and visitors and states: “A failure to comply with the provisions of the Act may render the University, or in certain circumstances the individuals involved, liable to prosecution as well as giving rise to civil liabilities. Individuals are encouraged to familiarise themselves with the general aspects of Data Protection contained in the University's guidelines to the Act, referred to above and with any specific measurements recommended by the University or their Department relevant to the particular nature of their work.” More precisely, failure comply with the University Data Protection policy can lead to students being expelled http://www.admin.ox.ac.uk/statutes/352-051b.shtml#_Toc28142348 and staff being dismissed from office http://www.admin.ox.ac.uk/statutes/353-051a.shtml#_Toc28073905 as part of the disciplinary measures. The merged dataset will be used to explore in detail the rates of missing questionnaires and the rates of missing items within the different questionnaires. It aims to investigate the characteristics of patients with missing data, compared to those without any missing data in their questionnaires. Statistical models will be used to model the relationship between patient characteristics and the completeness of their PROMs data. Furthermore, the project will look at a number of simulation models based on the dataset to assess the performance of different models dealing with missing data in PROMs, and to compare them to each other. The simulation models will also assess the impact of different missing data assumptions (data is missing completely at random, missing at random or missing not at random) on the results and interpretation of statistical models. The customer has requested a copy of the National PROMs dataset. As the project is specifically looking at missing data, it is important that the data the customer receives will be the original data, in which none of the items for the Oxford Knee Scores (OKS), Oxford Hip Scores (OHS) and EQ-5D (PROMS data field) have been imputed. The customer requests the HES data for all patients having undergone any hip and knee replacements or operations (i.e. not just for those that can be linked with the PROMs data) starting from 2009. From these patients, only HES data for episodes relating to hip and knee operations/ replacements is requested.

Objectives:

Sponsorship: The National PROMs data is requested as part of a DPhil research project with the title ‘Missing data in Patient Reported Outcome Measures’. The DPhil project is funded by the Medical Research Council (MRC) and the Nuffield Department of Population Health at the University of Oxford. The MRC’s mission statement (http://www.mrc.ac.uk/about/mission/?nav=sidebar) is described as follows: “The heart of our mission is to improve human health through world-class medical research. To achieve this, we support research across the biomedical spectrum, from fundamental lab-based science to clinical trials, and in all major disease areas. We work closely with the NHS and the UK Health Departments to deliver our mission, and give a high priority to research that is likely to make a real difference to clinical practice and the health of the population.” By receiving this prestigious funding, the proposed project is recognised by the funders to have a beneficial impact on clinical practices and the health outcomes of the population. Support from relevant groups in health and social care: Through the receipt of funding by the MRC and Department of Population Health, University of Oxford, the project is directly supported by those groups. More precisely, senior academics from the Health Economics Research Centre, the Health Services Research Unit and the National Perinatal Epidemiology Unit are directly supervising the project. The proposed project is a methodological study looking at the handling, analyses and reporting of missing data in PROMs. The issue of missing data in clinical research has been recognised as important, and is attracting continued interest from researchers, as well as funding and regulatory bodies including the UK NHS National Co-ordinating Centre for Research on Methodology, the Food and Drug Administration (FDA) and European Medicines Agency (EMA). Indeed, the FDA specifically stipulates that the treatment of missing data in clinical trials is a crucial issue and should be given a higher priority by the sponsors of statistical research. The NHS has also signalled explicit interest in research regarding missing data, by commissioning a report on the subject (Carpenter JR and Kenward MG (2008). Missing data in clinical trials – a practical guide. National Health Service Coordinating Centre for Research Methodology: Birmingham. Downloadable from http://www.haps.bham.ac.uk/publichealth/methodology/docs/invitations/Final_Report_RM04_JH17_mk.pdf.) Similarly, the www.networks.nhs.uk/ webpage provides a wealth of information on missing data methodology and current research and best practice, demonstrating the NHS’s recognition of the relevance of this research and an interest of developing it further. The pharmaceutical industry and health care providers (including health insurers) have been involved in research on missing data, including the funding of research and provision of data. Inadequate analyses of data with missing observations can lead to biased and insufficiently powered results from clinical studies. This can prevent clinicians and health authorities, including those in the UK health and social care system, from making appropriate health care decisions, and may even lead to inferior interventions being accepted or recommended. The research aims to create a better understanding of missing data within clinical research and aims to provide guidelines on how to deal with, and report, studies which contain missing data. To do this the researcher will specifically consider a single case study – that of PROMS data. By focussing specifically on missing data in PROMs, this work will expand the current research in an area that has not received as much attention as broader missing data research. How does this work fit into a broader research project: The DPhil project in the remit of which this data is requested is looking at the handling, analysis and reporting of missing PROMs outcome data. By means of a systematic review of the currently literature (in the process of being published in a peer reviewed journal, this research has also been presented on numerous occasions as stated elsewhere in this application), the project has confirmed deficits in the current practice of handling, analysing and reporting missing outcome data. The requested data will contribute to the second objective of the DPhil, i.e. using real data sets to better understand pattern in missing PROMs. Furthermore, the data will be used in simulation studies to address the third objective of the DPhil, i.e. to investigate the best way to analyse studies with missing data. Results from those two objectives will then be used to investigate different sensitivity analysis scenarios, and to consolidate guidance and methodology around the handling, analysis and reporting of missing PROMs outcome data. In conclusion, this research project will contribute to the more robust and reliable analysis of studies with missing data, and will therefore contribute to improving health care within the UK and other countries.


Project 28 — DARS-NIC-359651-H3R1P

Opt outs honoured: Y

Sensitive: Non Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data

Categories: Identifiable

Datasets:

  • Birth Notification Data

Benefits:

cted measurable benefits to health and/or social care including target date: Target date: 2020 There are two overarching goals of the MBRRACE-UK programme: (1) To improve care provided to women during pregnancy and the care provided to their babies following birth; and (2) To reduce the rate of late fetal losses, stillbirths and infant deaths. The MNI-CORP programme is commissioned by HQIP on behalf of NHS England. MBRRACE-UK delivers the programme and is responsible for conducting national surveillance of late fetal losses, stillbirths and infant deaths to contribute to national learning to reduce these rates. The MBRRACE-UK team does not have direct responsibility for directly carrying out any actions which follow from this national learning. The surveillance is conducted in the context that the UK has one of the highest rates of perinatal death (deaths around the time of births which include late fetal losses, stillbirths and neonatal deaths) and infant deaths (deaths from birth to one year of age) in Europe. Recent figures published in the Lancet places the UK 20th out of 28 for highest stillbirth rates in Europe and it has been estimated that had the UK had a similar neonatal mortality rate to the rate in Sweden, in 2013 1,000 fewer babies would have died. In March 2015 Bill Kirkup published his report of the investigation of perinatal and maternal deaths in the Universities Hospitals of Morecambe Bay – the ‘Morecambe Bay Enquiry’ Report. As part of the recommendations of that report it was noted that good information on pregnancy outcomes (including deaths) is a key driver for improvements in the quality of care provided for pregnant women and newborn babies. This is the role of the MBRRACE-UK programme. The first report of national perinatal mortality surveillance by MBRRACE-UK for deaths in 2013, reported for the first time ‘stabilised and adjusted’ perinatal mortality rates for individuals Trusts which enabled appropriate comparison of mortality rates across health care organisations, taking into account the fact that some hospitals provide care for high risk women and hospitals care of vastly different numbers of pregnant women each year. This analysis has enabled MBRRACE -UK to not only report the national perinatal mortality rate but also to identify variation in death rates between Trusts. Using comparisons by level of care provided, MBRRACE-UK has identified those Trusts with higher than average mortality rates and published the findings using a traffic light system. For those Trusts with ‘red’ and ‘amber’ mortality rates it has been recommended that they review all their perinatal deaths individually to identify potentially preventable causes of death to enable them to put actions in place to prevent such deaths in the future. Evidence of action in individual units has come from the submission of abstracts to the MBRRACE-UK up-coming conference where the second national MBRRACE-UK report will be launched. For example, on the back of their review, one small district general hospital has introduced a new referral form for antenatal booking to enable risk factors for stillbirths to be clearly identified, so that timely consultant review can be arranged if required and any women meeting the NICE criteria for risk of gestational diabetes have an appropriately timed glucose tolerance test arranged at their dating scan appointment (which ensures that the test is not missed). As a consequence of these and other actions this hospital has seen a reduction in the number of stillbirths in the past 12 months. There has also been action at national level; this year NHS England launched the ‘Saving Babies’ Lives Care Bundle which is aimed specially at ensuring Trusts put in place a series of key actions to prevent stillbirths which will also have an impact on neonatal and infant morbidity. It is against this background that on the 13th November 2015 the Secretary of State for Health announced additional funding for maternity services and the national ambition to reduce the perinatal mortality rate by half by 2030 with a 20% reduction by 2020. It is the role of MBRRACE-UK to monitor progress towards this ambition and to identify Trusts which are failing to achieve progress. For MBRRACE-UK’s second national report (to be published May 2017), Ben Gummer, Parliamentary Under-Secretary of State for Care Quality wrote in his Foreword to the report: “I want to pay tribute to the remarkable academic achievement that is MBRRACE-UK and underline the influence it is now having on the formulation of policy and impact on services. By providing a consistent and robust evidence base on which to take decisions, MBRRACE-UK is already saving lives.” Kirkup B. The Report of the Morecambe Bay Investigation. March 2015. The Stationery Office, London. 2015. [https://www.gov.uk/government/publications/morecambe-bay-investigation-report]

Outputs:

Purpose 1: MBRRACE-UK outputs A. Data processing by MBRRACE-UK of the 2013 birth notification data has resulted in findings which have been included in Trust level reports which has been issued to Trusts/Health Boards in autumn 2015; and also included in peer-reviewed scientific outputs reporting the methods and results from the analyses and findings which were published in the 'Perinatal Mortality Surveillance Report - UK Perinatal Deaths for births from January to December 2013' issued on 10th June 2014: [https://www.npeu.ox.ac.uk/downloads/files/mbrrace-uk/reports/MBRRACE-UK%20Perinatal%20Surveillance%20Report%202013.pdf]. B. Data processing by MBRRACE-UK of the 2014 birth notification data has resulted in findings which have been included in the 'Perinatal Mortality Surveillance Report - UK Perinatal Deaths for births from January to December 2014' which has been issued on 17th May 2016.; this was accompanied by further relevant scientific reports of methodological developments and further in-depth analyses. The data will also be used to generate Trust/Health Board Level reports for issue to Trusts/Health Boards in summer/autumn 2016. C. Data processing by MBRRACE-UK of the 2015 birth notification data will result in findings which will be included in the 'Perinatal Mortality Surveillance Report - UK Perinatal Deaths for births from January to December 2015' which will be issued by the target date of March 2017 (end of current contract); this will be accompanied by scientific reports of relevant methodological developments and further in-depth analyses. The data will also be used to generate Trust/Health Board Level reports for issue to Trusts/Health Boards in March 2017 (end of current contract). D. Data processing by MBRRACE-UK of the 2016 birth notification data will be used in the collection and process of 2016 data in anticipation of the contract extension for MBRRACE-UK and the issuing of a report etc. as above, in 2018 OR for transfer to newly appointed suppliers of the National MNI-CORP Programme commissioned by HQIP. E. Data processing by MBRRACE-UK of the 2013 and 2014 birth notification data to generate aggregated tables of live births by gestational age by hospital by year will be used to further analyse the audit measure published in the NNAP report for 2014 which has been issued by NNAP in the autumn of 2015.F. Data processing by MBRRACE-UK of the 2015 birth notification data to generate aggregated tables of live births by gestational age by hospital by year will be used in the production of audit measures for the NNAP report for 2015 which will be issued by NNAP in October 2016. Purpose 2: Outputs G. Data processing by MBRRACE-UK of the 2016 birth notification data to generate aggregated tables of live births by gestational age by hospital by year will be used in the production of audit measure for the NNAP report for 2016 which will be issued by NNAP in October 2017 following a contract extension OR by the newly appointed supplier of the NNAP programme by the commissioners HQIP. All outputs (for Purposes 1 and 2) are aggregated with small numbers suppressed adhering to the HES analysis guide.

Processing:

Purpose 1: Processing for MBRRACE-UK purposes The birth notification data are stored on the National Perinatal Epidemiology Unit (NPEU) secure high compliance servers which are used solely for MBRRACE-UK data processing activities. The servers are accessed only at the National Perinatal Epidemiology Unit (NPEU), University of Oxford. Processing of ONS and birth notification identifiable data occurs in the high compliance area. The birth notification data are linked to the ONS births and stillbirths data in order to add the key variables gestational age and ethnicity to the ONS births/stillbirths information. Once a combined ONS/birth notification dataset has been generated and cleaned the clinical data on late fetal losses (in utero deaths 22-23 completed weeks' gestation), stillbirths (in utero deaths 24+ weeks' gestation) and neonatal deaths (0-27 days after birth) collected by MBRRACE-UK are linked to the combined ONS/birth notification dataset. The identifiable dataset is stored only on the secure NPEU servers. The analyses take place in two locations. The MBRRACE team based at University of Oxford analyse the data in relation to the maternal aspects of the programme on the secure NPEU servers. A partially de-identified dataset is also extracted into a whole disk encrypted laptop on which it is analysed by the MBRRACE-UK analysts at the University of Leicester. The de-identified dataset extracted into the whole disk encrypted laptop has all identifiers other than dates of birth and dates of death removed. These identifiable data items remain as they are required to generate clean date dependent variables at the University of Leicester. All other Identifiable data items are removed before transfer on to the laptop (e.g. name and NHS number). Dates (e.g. baby date of birth, date of death, estimated date of delivery) are required to generate date dependent variables for the analysis together with the woman’s postcode (required to identify both area based scores of social deprivation and geographical location for regional and local analysis) therefore both are retained in the copy of the dataset which is transferred onto the laptop. The laptop is physically transferred to the University of Leicester by a member of the Oxford-based MBRRACE team when the data analysis is to be performed by analysts at the University of Leicester. The laptop is whole disk encrypted and complies with the MBRRACE-UK security protocols (256 bit AES) which have been approved as part of the NPEU NHS IG Toolkit submission. Purpose 2: Processing for NNAP purposes MBRRACE-UK will produce aggregated data with small number suppression, in line with HES analysis guide, and supply it to the National Neonatal Audit Programme (NNAP).

Objectives:

Purpose 1: Processing for MBRRACE-UK purposes The Maternal, Newborn and Infant Clinical Outcome Review Programme (MNI-CORP) is a national programme, delivered by the MBRRACE-UK collaboration, which aims to systematically assess quality and stimulate improvement in safety and effectiveness in maternal, newborn and infant healthcare by enabling clinicians, commissioners and policy makers to learn from adverse events and good practice. The purpose of the programme is to monitor, through population surveillance, the frequency of deaths and review clinical practice in relation to maternal, perinatal and infant mortality and morbidity, and identify factors that can be attributed to suboptimal clinical care, and also examples of good practice. MBRRACE-UK received from the HSCIC a data extract from the NHS Numbers for Babies (NN4B) dataset and requires a further extract of equivalent data. MBRRACE-UK will link this data with statutory birth, stillbirth and infant death notification data supplied under a separate Data Access Agreement to University of Oxford from Office for National Statistics in order that essential additional data items are available on an individual level, most importantly gestational age at birth and ethnicity. This linkage process generates the denominator data for the calculation of 'crude' and 'stabilised & adjusted' perinatal mortality rates; individual level data are required for these calculations. The numerator data come from clinical data about perinatal deaths collected directly by MBRRACE-UK from NHS Trusts and Health Boards. These two additional variables are essential to enable 'adjusted' perinatal mortality rates to be calculated for commissioning organisations and individual hospitals which take into account the risk profile of the population served by that commissioner and hospital; the risk profile includes high risk pregnancies which are defined by gestational age at birth and the ethnicity of the population served, as well as other risk factors for example maternal age. This enables 'fairer' comparisons of mortality rates between hospitals and commissioning organisations which deal with 'high risk' cases, for example tertiary referral centres which have a higher proportion of preterm births compared with smaller 'district general hospital' type hospitals which would refer high risk pregnancies (for example those at risk of preterm birth) to tertiary hospitals. 'Crude' comparisons which fail to take the risk profile of the different patient populations into account lead to spurious conclusions concerning relative mortality rates and variations in outcomes. Data are required at an individual identifiable level to enable both the linkage and adjusted analyses to be performed. The linkage also allows MBRRACE-UK to identify deaths and missing information which have not been notified directly to MBRRACE-UK and using this information MBRRACE-UK is able to chase up missing cases to collect the relevant clinical information. Purpose 2: Processing for NNAP purposes MBRRACE-UK will produce aggregated data with small number suppression, in line with HES analysis guide, and supply it to the National Neonatal Audit Programme (NNAP). This activity is separate to the primary purpose for MBRRACE-UK receiving and processing the data. However, as a consequence of the processing activities involved in MBRRACE-UK’s primary purpose, MBRRACE-UK will produce a dataset that, with minimal additional processing, would meet NNAP’s requirements and thus negate the need for NNAP to duplicate this data processing. Further details relating to the use of the aggregated data in support of the aims of NNAP can be found in the latest NNAP Annual Report published on the HQIP website. http://www.hqip.org.uk/public/cms/253/625/19/310/NNAP%202015%20Annual%20Report.pdf?realName=KbrdD3.pdf


Project 29 — DARS-NIC-366845-Q1F0Q

Opt outs honoured: N

Sensitive: Non Sensitive

When: 2017/03 — 2017/05.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Patient Reported Outcome Measures (Linkable to HES)

Benefits:

STUDY 1: STAR POST SURGICAL PREDICTORS OF CHRONIC PAIN AFTER PRIMARY TOTAL KNEE REPLACEMENT SURGERY The dissemination of the findings of this study is intended to benefit health care by improving understanding of the reasons why patients suffer long-term pain after knee replacement and therefore how best to prevent or manage it. The study aims to provide crucial pieces of information to aid this understanding, as identification of post-operative factors associated with long-term pain is expected to pave the way for the development of interventions to prevent and manage this kind of pain. First, by providing evidence about how to proactively identify patients who are most likely to go on to experience long-term pain following surgery, the study is a building block in the development and evaluation of interventions targeted to these patients. Such interventions may help to prevent the development of long-term pain and therefore reduce incidence in the population as a whole. Second, as the study will identify post-operative factors contributing to the development of long-term pain, interventions that address pain could be put in place earlier in the pain trajectory, as pain emerges rather than once it starts to become persistent. When interventions for pain take place earlier, then they are more likely to be successful than interventions that take place once pain has become persistent with more impact on general and psychological wellbeing. BENEFITS AS PART OF THE WIDER MAIN PROGRAMME GRANT Findings from this work will be communicated in the context of the wider main programme of research of which this forms a part. The programme as a whole aims to provide guidance about better care for people with long-term pain after total knee replacement, and this guidance will be developed in the final phase of the programme, which is due for completion in August 2020. The Programme has been designed to deliver improvements to services and patient well-being within one to three years of its completion. In addition to activities described above, the Programme contains activities designed to have impact. Total knee replacement is a common elective procedure in the NHS. Although usually conducted to relieve pain associated with osteoarthritis, it is now known that 20% of people who have this surgery will have moderate to severe pain afterwards. It is also known that people with chronic pain after knee replacement are not provided with adequate care, that they may find it hard to cope and that services are not well-placed to help them. While it would be ideal to identify who is at risk before they have surgery,-it is known that an operation is itself a risk factor for chronic pain. It is a priority for the Programme to find out how to look at the period after surgery to see if this can help in future identification and intervention for people at risk of chronic pain. Alongside this an aim is to address the pressing needs of patients who are unfortunate enough to have pain after surgery, and this will be done by evaluating an intervention. Many people with chronic pain do not seek help, and that this is particularly evident among older people. However, it is not known why this is the case in relation to chronic pain after knee replacement, or what is needed to ensure better engagement with services. The Programme therefore includes research about why people do not use services. This will enable development of recommendations to encourage better engagement between health services and these individuals. An understanding of individuals’ decisions about use of healthcare will be contextualised in their previous experiences of service use. This will mean that recommendations will be developed for healthcare professionals and providers as well as individuals with pain and their families, carers or friends. STUDY 2: ATLAS - THE ROLE OF HOSPITAL ORGANISATION, SURGICAL FACTORS AND THE ENHANCED RECOVERY PATHWAY ON PATIENT OUTCOMES AND NHS COSTS FOLLOWING PRIMARY HIP AND KNEE REPLACEMENT SURGERY The study outputs will inform patients, NHS managers, commissioners and health professionals of the NHS costs about patient outcomes and cost-effectiveness associated with the enhanced recovery treatment pathway and the key elements that are most clinically and cost effective. It will provide patients with information on variation in outcomes of surgery to inform patient choice and decision-making. The study outputs will provide commissioners with evidence of modifiable hospital organisational factors that can explain unwarranted geographical variation in patient outcomes of surgery. The maps highlighting how patient outcomes of hip/knee replacement vary across different hospitals and clinical commissioning groups would be informative to patients in making a choice of where to have surgery. The study will identify whether differences in the way hospitals organise their services, such as bed availability, numbers of operating theatres and specialist surgeons, using new surgical techniques, or centralising care into specialist hospitals, can explain why such variation exists. Knowledge of this would inform NHS managers of changes that can be made to the way services are organised, that lead to improved patient outcomes, and reduce unwarranted variation in outcomes between hospitals. The study will provide evidence of the clinical and cost-effectiveness of the new enhanced recovery pathway for hip/knee replacement surgery. The study will identify which elements and ways of organising these services are best in terms of NHS cost and improved patient outcomes. The future benefit to patients will be through improving and standardising their care before, during and after surgery, helping reduce the risk of complications and speeding up their recovery time. NHS managers will benefit through knowledge of the best ways to organise enhanced recovery services that lead to improved patient outcomes. The target date is 24-months following receipt of the data.

Outputs:

STUDY 1: STAR POST SURGICAL PREDICTORS OF CHRONIC PAIN AFTER PRIMARY TOTAL KNEE REPLACEMENT SURGERY The STAR study sits within work package 1. The main output of this study will be a summary of post-operative predictors of long-term post-surgical pain from the results of the regression model. Based on the findings, the BHDG will write a scientific paper for submission to high quality peer-reviewed journals. Currently the plan is to submit this paper to the Journal of Rheumatology to the BHDG also aims to present findings to professionals at conferences and meetings. The specific conferences to submit findings of this research to are: the British Pain Society and the British Orthopaedic Association. The BHDG will develop Plain English summaries of findings for communication to patients and members of the public. These will be developed working with patients and Arthritis Care who are members of the research programme team of which this study forms part. All outputs will adhere to the HES analysis guide so that data is only shown in aggregate form with small numbers supressed. The target date for just the publications is 12-months following receipt of the data. This study will additionally contribute to the broader outputs of the main programme. Work Package 6 includes dissemination activities to maximise impact of the Programme on care for patients with chronic pain after total knee replacement. Outputs will include robust evidence about best assessment, referral and management options. The study will host a workshop, present at conferences, publish articles and disseminate to professionals, patients and the public. The study team will host a dissemination workshop with invited delegates to share findings of the Programme. The workshop will engage with healthcare professionals to disseminate and discuss findings and ensure maximum diffusion into practice. At the workshop it is aimed to introduce a web-based information resource to professionals, which will be refined on the basis of their feedback. The study team will disseminate at two international conferences, engaging audiences interested in pain and in orthopaedics: the International Association for the Study of Pain (World Pain Congress) and the European Federation of National Associations of Orthopaedics and Traumatology. National conferences will be chosen to ensure that findings reach clinicians specialising in pain and orthopaedics as well as methodologists. It is aimed to maximise exposure of findings and efficiency of the budget by submitting more than one presentation to each conference. Conferences will include: British Pain Society; the British Orthopaedic Association; the Society for Social Medicine; MRC Network of Hubs for Trials Methodology Research Clinical Trials Methodology Conference. The study team has developed a list of proposed publications from each Work Package. The study will work in partnership with patients and Arthritis Care to develop accessible, evidence-based information. These resources will be disseminated through press releases, a web-based resource, written information, and other appropriate outlets. The study will ensure that communication is clear, and that there is the chance for a two-way flow of information between the research team, patients and members of the public. Engagement with the public and patients will also take place through web-material and social media hosted at the University of Bristol, including podcasts and Twitter. All participants in WPs 2-6 will receive feedback on study findings, developed in partnership with patients. Other avenues (e.g. YouTube, provision of downloadable summaries of findings) will be discussed with patients in the PPI group to ensure that results and recommendation reach audiences who may benefit most: for instance those people living with long-term pain who have yet to receive support. STUDY 2: ATLAS THE ROLE OF HOSPITAL ORGANISATION, SURGICAL FACTORS AND THE ENHANCED RECOVERY PATHWAY ON PATIENT OUTCOMES AND NHS COSTS FOLLOWING PRIMARY HIP AND KNEE REPLACEMENT SURGERY The study team will produce maps highlighting how patient outcomes of hip/knee replacement vary across different hospitals and clinical commissioning groups. Throughout all stages of this project,-the study group will engage with key stakeholders including NHS managers, healthcare professionals, patients and the public for interpretation, dissemination and direct communication of findings. This will be facilitated through involvement of NHS management, collaboration with the James Lind Alliance, support of learned societies, and PPI representation. Based on the findings, an aim is to write scientific papers for submission to high quality peer-reviewed journals. The three key papers will be: 1. Determinants of geographical variation in patient outcomes of hip and knee replacement surgery 2. A Natural experimental study to evaluate the impact of enhanced recovery on trends in patient outcomes of hip and knee replacement surgery 3. Cost effectiveness of the enhanced recovery pathway for hip and knee replacement The journals the studies aim to publish in are: Lancet, British Medical Journal, Arthritis and Rheumatology, Osteoarthritis and Cartilage. So either general medical journals, or a more specific rheumatology or Orthopaedic journal depending on where they ultimately get accepted. Other aims are to present findings to professionals at conferences and meetings and to develop Plain English summaries of findings for communication to patients and members of the public. The health professionals will broadly be Rheumatologists, Orthopaedic surgeons. GPs, physiotherapist, nurses. Specific conferences are: British Society for Rheumatology (BSR), British Orthopaedic Association (BOA), Osteoarthritis Research Society International (OARSI). All outputs will adhere to HES analysis guide so that data is only shown in aggregate form with small numbers supressed. It is planned to publish a full and complete account of that research in the NIHR HS&DR Journal, ensuring the research is reported fully, and publicly available via the NIHR Journals Library website and Europe PubMed Central. The target date is 24-months following receipt of the data. This project is informed by results from the recent James Lind Alliance (JLA) Priority Setting Partnership (PSP) for Hip/Knee Replacement, carried out within the Oxford NIHR Musculoskeletal BRU and supported by the Oxford NIHR Biomedical Research Centre (BRC). Two of the co-applicants on this study were members of the partnership, which is also supported by the BRC Director of patient involvement and who has been working with the JLA since it began in 2004. University of Oxford recognize the importance of meaningful Patient and Public Involvement (PPI) and have worked collaboratively with the PPI Officer at NIHR Research Design Service (RDS) to identify individuals to become involved, and the Director of Patient Involvement at the Oxford NIHR BRC. The study team identified two lay people who understand the needs and problems of hip and knee replacement patients. Through their involvement, the study has listened to their ideas regarding the dissemination of findings so they are readily available and interpretable to the wider patient and public community. It is planned to disseminate findings in peer-reviewed journals, at national and international conferences, and inform learned societies that include the British Orthopaedic Association, The British Association for Surgery of the Knee (BASK), Arthritis Research UK, rheumatology (British Society for Rheumatology), geriatrics (British Society of Geriatrics). University of Oxford will work alongside charities and learned societies to disseminate the findings of this study using established platforms that include social media such as Twitter and a study website, as more patients are now turning to these resources for information about planned surgery.

Processing:

Northgate Information Solutions will provide patient identifiers (NHS number, date of birth, gender and postcode) plus a unique NJR patient identifier (pseudonymised) for individuals whose records are held in the National Joint Registry (NJR). NHS Digital will link the data to HES admitted patient care and PROMS data. NHS Digital will perform this linkage by first matching NJR identifiers (and associated unique NJR pseudonymised patient identifier), to HES/PROMS identifiers. A file containing NJR identifiable fields, unique NJR pseudonymised patient identifier, identifiable HES/PROMS fields with associated pseudonymised records will be created. The BHDG requires details of all hospital episodes for the patients who have had hip or knee replacement surgery (identified from the NJR data) as both studies will explore potential links between surgery and subsequent health issues that are not necessarily specific to the knee or hip (e.g. hospital acquired infection). All identifiers will then be removed to produce a pseudonmyised linked extract of HES/PROMS records, with each record having the associated unique NJR pseudonmyised patient identifier. The BHDG will receive from NHS Digital patient level pseudonymised data only, i.e. the linked HES/PROMS data with the unique NJR patient identifier. The unique pseudonymised NJR patient identifier will allow the BHDG to further link patient level pseudonymised NHS Digital data to pseudonymised NJR records which the BHDG will receive separately from Northgate Information Solutions. The linked NJR, HES and PROMS datasets will be held on a password protected University Computer on an encrypted drive at the Botnar Research Centre, Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS). Access to the data will be restricted to two statisticians, both of whom are substantive employees of the University of Oxford and based at the Botnar Research Centre, who will work collaboratively on both studies. The same fields of data are required for both studies and the knee replacement data will be used in both but the hip replacement data will only be used for ATLAS. The data will be used exclusively for the purposes of the specified studies. The data will not be made accessible to any third parties. At the end of the studies, the data will be safely held in a password protected University Computer at the Botnar Research Centre, for further 5 years, and accessed only to answer questions arising from the publication and other publicity if required. STUDY 1: STAR - POST SURGICAL PREDICTORS OF CHRONIC PAIN AFTER PRIMARY TOTAL KNEE REPLACEMENT SURGERY The analysis of the linked datasets aims to identify post-operative predictors of long-term pain. Outcome will be assessed using the Oxford Knee Score (OKS) collected pre- and six months post-operatively in the PROMs database. The ‘OKS pain component’ provides a measure of chronic pain following surgery. Information on post-operative predictors within the NJR dataset includes intraoperative events (fracture, tendon avulsion, ligament injury) and revision surgery. Linkage to HES provides additional post-operative predictors, including readmission, reoperation, length of hospital stay, and medical complications. Regression modelling will be used to identify post-operative predictors of chronic pain. Linearity of continuous predictors will be assessed using fractional polynomial regression modelling and linear splines. Missing data will be handled using multiple imputation methods. STUDY 2: ATLAS - THE ROLE OF HOSPITAL ORGANISATION, SURGICAL FACTORS AND THE ENHANCED RECOVERY PATHWAY ON PATIENT OUTCOMES AND NHS COSTS FOLLOWING PRIMARY HIP AND KNEE REPLACEMENT SURGERY VARIATION IN OUTCOMES: Multilevel regression modelling of HES/NJR/PROM linked data will describe the association of hospital organisation, surgical factors and the enhanced recovery pathway on patient outcomes of surgery, adjusting for patient case-mix. Random intercept models will explore geographical variation in outcomes across hospital trusts and Clinical Commissioning Groups. Geographical Information Systems will be used to produce maps depicting variation in outcomes, and graphically display the influence these factors have on explaining such variation. ENHANCED RECOVERY: A disease specific Markov model will simulate the costs and health-related quality of life of hip/knee replacement patients before and after introduction of the pathway. A cost-effectiveness analysis will be performed using outcome measures such as Quality-Adjusted Life Years gained. Interrupted time series analysis will be used to evaluate the impact of change in service delivery on trends in rates of outcomes, adjusting for socioeconomic status and case-mix.

Objectives:

The University of Oxford’s Big Health Data Group (BHDG) is undertaking two distinct research studies that require data from the National Joint Registry (NJR) linked with Hospital Episode Statistics (HES) and Patient Reported Outcome Measures (PROMs) data from NHS Digital. The same individuals, all of whom are substantive employees of the University of Oxford, will undertake both studies at the Botnar Research Centre at the Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS). STUDY 1: STAR - POST SURGICAL PREDICTORS OF CHRONIC PAIN AFTER TKR The main reason that people undergo knee replacement is to alleviate pain. However it is recognised that around 20% of patients experience long-term post-surgical pain. The potential value of identifying patients at risk of long-term pain and targeting interventions is clear, but existing models have low predictive power, particularly for pain related outcomes. Given the difficulties around pre-operative prediction of long-term pain, it is important to consider post-operative factors. An operation itself is an important risk factor for long-term pain, and factors relating to the operation and early recovery may be of greater importance than pre-surgical factors. In the context of major orthopaedic surgery, interventions targeting post-operative determinants of outcomes are likely to be more beneficial than pre-surgical interventions. Research is required into the post-operative determinants of long-term outcomes after total knee replacement. Achieving a better understanding of post-operative factors associated with the development and persistence of pain after surgery will inform future development of interventions that can either reduce the incidence of this kind of pain or that will provide more effective management for pain. Analysis will take place from HES-PROMS data linked to data from the National Joint Registry (NJR), data to see if any of these issues after surgery predict who will experience long-term pain. WIDER PROGRAMME OF RESEARCH This study is part of a NHS National Institute for Health Research (NIHR) Programme Grant for Applied Research (PGfAR) (RP-PG-0613-20001 Chronic pain after total knee replacement: better post-operative prevention and management). The NIHR provide the framework through which the Department of Health position, maintain and manage the research, research staff and research infrastructure of the NHS in England as a national research facility. Within this five year programme of research there are six work packages: 1. Synthesise evidence about the effectiveness of interventions for chronic pain after knee replacement and other surgeries and identify post-surgical predictors of chronic pain after knee replacement. 2. Characterise the long-term trajectory of chronic pain including pain characteristics, disability and resource use up to five years after knee replacement. 3. Finalise an assessment process and a care pathway for patients with chronic pain after knee replacement. 4. Evaluate the clinical and cost-effectiveness of a new care pathway for patients with chronic pain after knee replacement. 5. Identify reasons for non-use of services and provide recommendations. 6. Make recommendations about best-practice care for patients with chronic pain after knee replacement and evaluate implementation of these. STUDY 2: ATLAS - THE ROLE OF HOSPITAL ORGANISATION, SURGICAL FACTORS AND THE ENHANCED RECOVERY PATHWAY ON PATIENT OUTCOMES AND NHS COSTS FOLLOWING PRIMARY HIP AND KNEE REPLACEMENT SURGERY Osteoarthritis is a leading cause of pain and disability. Many people with severe hip or knee pain caused by osteoarthritis have an operation called total joint replacement. This involves replacing the painful hip or knee joint with an artificial joint. Over 150,000 hip and knee replacement operations take place each year in the NHS and this number is expected to increase. In the NHS patients can choose which hospital they want to have their surgery in. Information on the outcomes of surgery between different hospitals would help patients in making their decision. Outcomes of surgery will vary across different hospitals and areas of the country. This may be explained by a hospital treating more complex and sicker patients, and this must be accounted for. However, differences in patient outcomes could also be explained by how hospitals organised their services, such as bed availability, numbers of operating theatres and specialist surgeons, using new surgical techniques, or centralising care into specialist high volume hospitals. Knowledge of this would help NHS managers to change the way services are organised and reduce variation in outcomes between hospitals. A new patient pathway for hip and knee replacement called enhanced recovery has been introduced in NHS and private hospitals. It is hoped this will benefit patients, through patient education before and after surgery, that includes making changes around the home, exercises to strengthen the joint and changes to diet, to help reduce the risk of complications and speed up a patient’s recovery time. For patients in whom it is suitable, they will further benefit by being able to return home earlier to continue their recuperation at home with appropriate support. This in turn will benefit the hospital by freeing up space for other patients on the waiting list. However, hospitals organise enhanced recovery services in different ways and it is unclear which way is best. In this study University of Oxford will identify whether the different ways that hospitals organise services for hip and knee replacement patients can lead to improved patient outcomes, and explain why outcomes vary between hospitals. University of Oxford will produce maps highlighting how outcomes of surgery vary across the country and exploring organisational processes in the way enhanced recovery has been implemented across different hospital settings. The department will look at whether the introduction of enhanced recovery has improved patient outcomes and the potential cost saving to the NHS. Statistical analysis of national linked data from the NJR/HES/PROMs databases will allow identification of hospital organisation and surgical factors that explain geographical variations in patient outcomes of surgery, after adjustment for patient level case-mix. University of Oxford will provide data at the small area level presented as maps to describe variation in outcomes, before and after accounting for these organisational and surgical factors. Focus will be on variation in outcomes of specific patient groups (old and frail with co-morbidities and obese) and provide evidence as to whether the introduction of new surgical innovations (e.g. minimally invasive surgery), and centralisation of services, has led to improved patient outcomes. The project will then use a natural experimental study design to specifically examine the impact that the new enhanced recovery treatment pathway has had on NHS resource use, NHS costs and patient outcomes (PROMs, length of stay, complications, readmission). Interrupted time series analysis will examine changes in secular trends in outcomes and NHS costs before and after the introduction of the new treatment pathway. There will be a focus on the benefit of the new enhanced recovery pathway to specific patient groups such as frail older people with complex co-morbid conditions. An economic evaluation will describe the hospital NHS costs, patient health related quality of life and cost effectiveness that reflect the new treatment pathway for hip/knee replacement surgery.


Project 30 — DARS-NIC-388486-D9M5N

Opt outs honoured: N

Sensitive: Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: One-Off, Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Outpatients
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Members and Postings Report

Benefits:

The results of analyses based on the data received from HSCIC would be considered by guidelines writers and agencies such as NICE when updating recommendations for the care of transplant recipients. They would be unique in the field of kidney transplantation in that they would provide unbiased, randomised assessment of the long-term effects of different immunosuppression strategies. They are highly likely to affect the management of future patients receiving kidney transplants.

Outputs:

The 3C Study has already had one publication in the Lancet (http://dx.doi.org/10.1016/S0140-6736(14)61095-3). The data requested here would be used first in a submission to an international transplantation conference in 2016 with publication in a high-impact medical journal at around the same time. The long-term follow-up is also likely to be of substantial interest and would be presented and published in the future. For example, the protocol-specified 5 year follow-up will be conducted in 2017/18, but later analyses will also be of substantial interest. The results of the 3C Study will be published in general and renal/transplant journals. The early results were published in The Lancet and the first results using these data will also be published there. In addition, they will be presented at national and international meetings such as the British Transplantation Society, the Renal Association, the European Society of Transplantation, the American Transplant Congress and the Transplantation Society. The outputs will also be shared with all appropriate bodies such as NICE and the Cochrane Centre.

Processing:

The 3C study includes 800 patients aged over 18 years who were listed for kidney transplantation. Participants were recruited around the time of transplantation when informed consent was sought and they were randomised into the study prior to receiving their transplant. They have then been followed-up alongside their routine clinical care for one year with case report forms being completed at 1, 3, 6, 9 and 12 months after transplantation. Data will be collected on adverse events they have experienced, current medication, laboratory results, quality of life and healthcare usage. After this time, the coordinating centre (at CTSU, University of Oxford) will write to surviving participants annually to collect relevant information about relevant adverse events, quality of life and healthcare usage. The approved study protocol also specifies that all participants will be “flagged” with NHS registries such as the Medical Research Information Service, Hospital Episode Statistics and UK Renal Registry. CTSU would seek information on cause-specific mortality, cancer diagnoses and hospital admissions on a regular basis. Any relevant information supplied may be verified with the participant’s managing doctors and then used in the study analyses. In addition, information on mortality would be used to prevent the coordinating centre from contacting any participant known to be dead.

Objectives:

Despite improvements in short-term outcomes in kidney transplantation (e.g. acute rejection rates) there has been no improvement in long-term outcomes (e.g. transplant survival at 5 – 20 years after transplantation). One reason for this is that drugs (in particular, calcineurin inhibitors or “CNIs”) used to prevent rejection in fact damage the transplant in the long-term and are major reasons for its ultimate failure. The 3C Study is investigating two strategies that may allow the use of CNIs to be minimised or removed completely. Nearly all kidney transplant trials to date have been both too small and in particular too short-term to detect any clinically meaningful treatment effects in outcomes that matter to patients i.e. long-term function and survival of the transplant. The 3C study therefore aims to study a large enough group of patients for long enough to detect such treatment effects. The 3C Study is investigating two possible strategies that could improve the lifespan of kidney transplants: firstly, is Campath-based induction treatment superior to standard basiliximab-based treatment; secondly, is sirolimus-based maintenance treatment superior to standard tacrolimusbased treatment. Although the primary outcomes of the study are relatively short-term, there is considerable scientific interest in the long-term (i.e. 5 – 20 year) outcomes from this study. In particular, there is uncertainty about the safety of such treatments with malignancy being one complication of transplantation that often occurs late.


Project 31 — DARS-NIC-389134-S8L1C

Opt outs honoured: N

Sensitive: Sensitive, and Non Sensitive

When: 2016/04 (or before) — 2018/05.

Repeats: Ongoing, One-Off

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • MRIS - Cohort Event Notification Report
  • MRIS - Cause of Death Report
  • MRIS - Scottish NHS / Registration
  • MRIS - Bespoke
  • Hospital Episode Statistics Admitted Patient Care
  • MRIS - Members and Postings Report

Benefits:

The Million Women Study research using linked health data has directly influenced health care. Results showed, for example, that women using hormone replacement therapy are at increased risk of breast cancer; this work helped inform changes in prescribing, and it is estimated that tens of thousands of cases of cancer worldwide have been avoided as a result of the subsequent fall in use of hormone therapy. Another example where HSCIC data contributed to an influential paper was in showing that risk of blood clots after surgery was far higher, and lasted for much longer, than had been previously thought. This work is helping to inform European surgical care guidelines. Other influential MWS work with direct health care benefits is looking at how to best implement a screening programme for bowel cancer following a study into how characteristics of individuals affect participation and outcomes of screening.

Outputs:

The data set (HES data) will be used to examine relationships between lifestyle and reproductive factors (collected via questionnaire data) and a wide range of outcomes. These outcomes would mainly consist of a variety of cancer diagnoses, hip fractures and joint replacements and cardiovascular disease. CEU plan to publish their anonymised findings in peer reviewed scientific journals so that they can contribute to knowledge of common diseases and causes of hospital admissions. CEU have successfully published papers using data from their previous HES extract (ET2535) and wish to continue using similar data together with extra information, to increase the understanding of patterns of disease groups including cancer diagnoses, joint replacements, fractures and cardiovascular disease. Further information can be found on the website at www.millionwomenstudy.org

Processing:

The cohort participants are already flagged with the HSCIC, and this will be used to link to the HES data. Data will be used by teams of researchers/statisticians in the Cancer Epidemiology Unit (CEU) at the University of Oxford. The data will be used solely within the CEU and will not be shared with any other organisation.

Objectives:

The Million Women Study (MWS) is a national study of women’s health funded by Cancer Research UK and the Medical Research Council. The study involves 1.3 million UK women, recruited in 1996-2001, who have given written consent for follow up of their health through their medical records, to examine how reproductive and lifestyle factors affect their future health.


Project 32 — DARS-NIC-392669-T1F8B

Opt outs honoured: N

Sensitive: Non Sensitive, and Sensitive

When: 2017/12 — 2018/02.

Repeats: One-Off, Ongoing

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC

Categories: Identifiable

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Office for National Statistics Mortality Data
  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Outpatients
  • Bridge file: Hospital Episode Statistics to Mortality Data from the Office of National Statistics
  • MRIS - List Cleaning Report

Benefits:

In summary, this data will be used to characterize the predictors of clinical outcome post cardiac surgery. This will allow for the identification of patients at risk and take measures to improve clinical outcome (survival and hospitalization rates) in this population. The outputs of this research will be published in high impact peer review journals and will be presented in scientific congresses. Due to the unique baseline phenotyping of these patients, the tested set of predictors for clinical outcome post cardiac surgery will provide a unique opportunity to understand the mechanisms affecting morbidity and mortality of these patients, and will lead to the development of novel therapeutic strategies to improve health care in this population. Benefits: 1. The potential design of risk stratification models in primary and secondary prevention to improve clinical outcome at population level in cardiovascular disease 2. Identify high risk features that enable aggressive therapeutic strategies in high risk populations that can be implemented in to clinical practice. 3. Identify potential novel therapeutic targets involved in cardiovascular disease progression which will lead to future drug discovery.

Outputs:

The initial output will be a list of surviving cohort members which will be used to write out to participants with fair processing information and the opportunity to withdraw from the study. The list cleaning will help to ensure material is sent to only cohort members who are alive thus reducing the risk of causing emotional distress to family members of deceased participants. The study will then supply NHS Digital with a 'cleaned' version of the cohort for linkage. The research outputs will include peer reviewed publications in leading international journals, presentations in scientific meetings and possible media reports. Access to the data provided will be given only to the study investigators, within the University of Oxford, and no third parties will have access to this information. The study outputs will include publications in peer reviewed journals, presentations in international and national congresses. The data will be used for research only and not be used to create indicators showing the performance of any organization. All outputs will only contain aggregated data with small numbers suppressed in adherence to the HES analysis guide. Outputs are expected 6-12 months after the data is received. In summary: Journals being targeted to submit to/publish in: • The New England Journal of Medicine, • The Journal of the American Medical Association, • The Lancet, • Circulation, • Journal of the American College of Cardiology or The British Medical Journal. Congresses targeted to submit to: • Scientific sessions of the American Heart Association • Scientific sessions of the European Society of Cardiology • Scientific sessions of the American College of Cardiology • Scientific sessions of the British Cardiac Society

Processing:

The data needed from NHS Digital are: a) Fact of death data via list cleaning - this will be used to send an update to participants describing how data will be linked and providing withdrawal instructions. b) The mortality data (including cause of death) from the day of surgery (provided) until today. Oxford will provide a list of NHS numbers so the mortality data returned should include the cause of death and the date of death for each individual patient c) Similarly, hospitalization/admissions (that should include reason for hospital admission and the date, for each individual patient in the cohort). Collection of this data is vital to obtaining the primary endpoint statistics linking the existing study data with post-surgery clinical outcome. Only the named study investigators will have access to the record-level data, which will be stored securely in swipe-card-secured premises in the University of Oxford, in a password protected computer. No record-level data is being provided to a 3rd party and only aggregated data will be publicised/provided to 3rd parties. The University will directly send NHS Digital a list of NHS numbers on the NHS Digital transferring system. An internal study number will identify subjects, and study details will not contain personal data such as names, NHS numbers or date of birth. The personal data that applies to a particular number would be kept locked separately away in the Division of Cardiovascular Medicine at the John Radcliffe Hospital. The linking database will be kept on a high security password protected computer (to which only the study investigators will have access). Furthermore, the database computer will be kept in a swipe card-secured area of the Department (only authorized individuals have access to this area, and it is carefully controlled). If applicable, information stored on laptop computers of the study investigators will contain additional password protection pertaining to relevant documents; this will be in addition to all computers being password protected. All data will not contain subject-identifiable material, and will be stored in a linked de-identified form. The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. No third parties will have access to the information as all analyses will be carried out within the University of Oxford, and no third organization will be involved. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data). The applicant agrees to adhere to the Office for National Statistics terms and conditions as described in this agreement. The data will only be used for the purposes described in this agreement. No data will shared with 3rd parties. No data will be used for commercial purposes.

Objectives:

The University of Oxford require a list cleaning to take place first following approval. Then there would be a period of time to allow for any participant withdrawals before Oxford supplied the cohort to NHSD for linkage. The purpose of the list clean is to notify the study of any cohort members that have died. Confirmation of deceased cohort members will allow the study not to cause further distress by sending newsletters to the families of the deceased. Coronary artery bypass graft surgery (CABG) continues to be the optimum revascularisation strategy for most patients with multi-vessel coronary artery disease. Although the biological variability between patients should be crucial for the prediction of long-term outcome of patients undergoing cardiac surgery, the exact mechanism linking the biology of the heart, the vascular grafts used and the myocardium with clinical outcome are unclear. To address this shortfall in literature evidence, this study is aimed at assessing the venous and arterial redox states of patients undergoing CABG and valve repair/replacement surgery, in addition to data related to myocardial redox state, general biochemistry and imaging. The cohort includes patients from 3 studies 1) the Arterial Revascularisation Trial (ART) (November 2004 to current; REC: MREC04/03/006) aimed at comparing survival following bilateral versus single internal mammary grafting in coronary revascularisation 2) the Bypass Vascular study (January 2005 to current; REC: 04/Q1605/95 ) aiming among others to compare in vivo measures of vascular function with post-operative clinical outcome after cardiac surgery 3) the AdipoRedOx study (15/09/2011 to current; REC: 11/SC/140), aiming to investigate the role of the interactions between adipose tissue and cardiovascular oxidative stress, in the prediction of post-operative outcome of patients undergoing cardiac surgery. Each study has gained informed consent from participants to access their medical records to collect post-operative information that may have a predictive value after cardiac surgery. Importantly, these studies aim to link the collected data (i.e. risk factors, data on vascular function etc.) with patient clinical outcome data, producing the world’s most comprehensive resource comparing vascular biology with clinical outcome post-cardiac surgery. The primary objectives of the study are to - Investigate the mechanisms by which adiponectin affects vascular/myocardial redox state, endothelial function and clinical outcome of patients undergoing coronary artery bypass grafting operation (CABG). Secondary objectives are to- 1) Search for a possible signal from the myocardium/vascular wall to epicardial/perivascular adipose tissue, that regulates the synthesis of adipokines and other signalling molecules 2) Search for novel biomarkers/signalling molecules identified in peripheral blood or expressed in adipose tissue, that regulate vascular/myocardial redox state and/or predict vein graft patency In summary these objective will then potentially results in the creation of patient risk models with which to improve health outcomes. The first step in achieving these objectives will be to provide further fair processing information to the participants via a newsletter. This will be followed by linkage to HES and ONS mortality data.


Project 33 — DARS-NIC-61090-T9Y0G

Opt outs honoured: Y

Sensitive: Non Sensitive, and Sensitive

When: 2017/12 — 2018/02.

Repeats: One-Off

Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Health and Social Care Act 2012

Categories: Identifiable

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Office for National Statistics Mortality Data
  • Bridge file: Hospital Episode Statistics to Mortality Data from the Office of National Statistics

Benefits:

The University anticipate the findings of the study informing the next iterations of NICE Clinical Guideline [CG124] "Hip fracture: management", the British Orthopaedic Association (BOA) Standards for Trauma 1, and the BOA/British Geriatric Society Blue Book: "Care of patients with a fragility fractures”. These are all due for revision in, or shortly after, 2017. The findings of the study should therefore begin having an impact on the health status of patients (by ensuring they are offered the most appropriate operation) within two years. This is clearly important to ensure that patients are being offered the most effective choice of operation after a broken hip. Importantly, once the NHFD-HES data linkage has been established, this resource could be used to address other important clinical questions aimed at improving outcomes for older adults with hip fractures. Any further use of the resource would result in amendment requests to NHS Digital

Outputs:

The University anticipate presenting the results at the British Orthopaedic Association Annual Congress 2018 and publishing in a journal that is most likely to reach the broadest possible audience of UK orthopaedic surgeons, e.g. the Bone & Joint Journal. The findings will also be communicated directly to the guideline teams at the National Institute for Health and Clinical Excellence (NICE), British Geriatric Society (BGS), and British Orthopaedic Association. If it is found that compliance with this NICE guideline benefits patients, the study will advocate for greater compliance among orthopaedic surgeons and wider access to THA among hip fracture patients. If the findings suggest that THA makes little difference to patient outcomes, the study will suggest that this guideline be reconsidered by NICE. The study ultimately hopes to influence the advice provided to clinicians as part of NICE Clinical Guideline [CG124] "Hip fracture: management", the British Orthopaedic Association (BOA) Standards for Trauma 1, and the BOA/British Geriatric Society Blue Book: "Care of patients with a fragility fractures”. All outputs will be aggregated with small numbers suppressed in line with the HES Analysis guide.

Processing:

In this study, the University will use linked NHS datasets, the National Hip Fracture Database from the Healthcare Quality Improvement Programme and Hospital Episode Statistics from NHS Digital. Individual NHS trusts send patient-identifiable information to the Falls and Fragility Fracture Audit Programme (FFFAP, which is run by the Royal College of Physicians [RCP] on behalf of the Healthcare Quality Improvement Programme [HQIP]) to populate the National Hip Fracture Database (NHFD). The NHFD data is processed by Crown Informatics Ltd on behalf of the FFFAP. Crown Informatics will provide NHS Digital with a list of NHS numbers along with date of birth, postcode, gender (injury date) and a unique ID number from patients that are included within the National Hip Fracture Database (NHFD). These patients will all have been aged >60 and treated for a hip fracture at a hospital in England from 2011 onwards. Although the NHFD has existed since 2007, data quality improved with the introduction of the Hip Fracture Best Practice Tariff in 2012. The University have therefore opted to restrict their data request to the period from 2011 onwards. NHS Digital will link these records stored within the Hospital Episode Statistics (HES) admissions file and return pseudonymised HES data and the date of death and the study ID to Crown Informatics. This will include admissions before the hip fracture (as patient co-morbidities will be used for risk adjustment) and afterwards (as re-admission, re-operation, and health service utilisation) will be used as outcome measures. All data analyses will be undertaken using the linked NHFD-HES-ONS dataset. Crown Informatics will add relevant non identifiable data from the National Hip Fracture Database to the linked database and remove the unique ID. This data (linked pseudo HES+Date of death+NHFD) is then supplied to the University of Oxford for analysis. Data from the NHFD and NHS Digital will only be stored and accessed by the researchers at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford. It will not be linked to any other datasets. It will not be shared with any 3rd parties. The data will only be used for the purposes stated in this agreement. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data). All ONS terms and conditions described in the special conditions section of this agreement will be adhered to .

Objectives:

This study aims to examine a guideline published by the National Institute for Health and Clinical Excellence (NICE) with regards treatment of patients with hip fractures. There are 70,000 hip fractures every year in the United Kingdom at a total cost exceeding £2 billion. Mortality is high, with 8.5% of patients dying within 30 days of admission and 30% within a year. Many surviving patients are unable to continue living independently and 4.5 million patients are disabled worldwide as a consequence of hip fracture every year. Two thirds of hip fractures are displaced, i.e. there is separation of the bony fragments, and these are usually treated with arthroplasty (joint replacement). There are broadly two arthroplasty options: total hip arthroplasty (THA) in which both the femoral head and acetabulum are replaced and hemiarthroplasty (HA) in which only the femoral head is replaced. There have been a number of small, randomised controlled trials that compared THA to HA. When taken together, they suggest that THA is associated with better functional outcomes, fewer wound infections, and reduced need for secondary procedures. However, THA is a longer operation, more complex, and has a significantly higher risk of subsequent dislocation (9% versus 3%). THA is also a more specialised operation that might not be within the skillset of every orthopaedic surgeon treating patients with hip fractures. Despite the existing evidence base, one recent survey found that 73% of orthopaedic surgeons prefer HA to THA. The National Institute for Health and Clinical Excellence (NICE) has elected to reserve THA for the fittest patients as they are more likely to survive a prolonged operation and gain the most from its enhanced functional properties. NICE recommend that patients with displaced hip fractures should be treated with arthroplasty and THA offered to patients who: • Could walk independently before the fracture; • Are not cognitively impaired and; • Are medically fit for anaesthesia and the procedure. Despite this guidance, the NICE criteria are not universally applied throughout the NHS. In particular, there is evidence that surgeons incorporate other considerations (including patient age and admission at the weekend) into their decision-making. The University of Oxford have previously shown that this leads to considerable variation across the country in terms of which treatment is offered to patients with hip fracture. In this study, the University will use linked NHS datasets (the National Hip Fracture Database and Hospital Episode Statistics) to test two related hypotheses: 1. THA is associated with better outcomes than HA for independently mobile older adults with hip fractures, i.e. patients satisfying the criteria proposed by NICE. 2. Patients that receive an operation that is non-compliant with NICE guidance (i.e. HA despite being eligible for THA or THA despite being ineligible) will have worse outcomes than those receiving NICE-compliant treatment. The data requested from NHS Digital are necessary to (a) aid risk adjustment by enriching the NHFD with details of patients' co-morbidities and (b) provide data about re-admission to hospital and re-operation for patients in the NHFD cohort.


Project 34 — DARS-NIC-68703-R4Y6C

Opt outs honoured: N, Y

Sensitive: Non Sensitive, and Sensitive

When: 2017/06 — 2017/08.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Anonymised - ICO code compliant, Identifiable

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Office for National Statistics Mortality Data (linkable to HES)

Benefits:

The dissemination of the findings of this study is intended to benefit health care by rigorously reporting the rate complications and outcome of knee arthroscopy. It is highly likely that for many patients currently undergoing knee arthroscopy, the procedure may not be beneficial – for example, when performed on a background of advanced osteoarthritis. It is important to investigate the association of knee arthroscopy procedures with a diagnosis of osteoarthritis and knee replacement surgery, complications and outcome of any subsequent knee replacement. The study aims to improve health practice, reducing rates of unnecessary surgery by disseminating findings on the rate of complications of the procedure in different populations of patients. We will determine predictors of outcome through multiple variable regression analysis. Trends in the rate of surgery in groups of patients categorised by age and diagnosis of osteoarthritis will be determined and highlighted. Geographic variation will also be determined and publicised. The study will provide evidence on identifying patients who are highly likely to progress to require a joint replacement at an early stage and determine if the outcome of their knee replacement may be compromised by the prior knee arthroscopy. The information will inform patients and surgeons and the aim is to improve health practice and reduce rates of knee arthroscopy when this is unlikely to be beneficial. The study outputs will also inform NHS managers, commissioners and other health professionals of the outcomes and predictors of outcome of knee arthroscopy. This will encourage a change in practice where necessary, for example due to geographic variation or inappropriately high rates of surgery for patients with osteoarthritis. The study outputs may provide commissioners with evidence of any factors that can explain unwarranted geographical variation in knee arthroscopy surgery. The target date is 18-24 months following receipt of the data.

Outputs:

The main output of this study will be a summary of post-operative complications of knee arthroscopy in the short and long term. Independent predictors of complications and repeat surgery such as knee replacement will be identified from the results of the regression model. Outcomes of knee replacement after knee arthroscopy will be compared to those without prior knee arthroscopy. Association of knee arthroscopy with a ICD-10 diagnosis of osteoarthritis will be investigated and analysed in context of any subsequent knee replacement. Based on the findings of the study, we will write a scientific paper for submission to high quality peer-reviewed journals (for example, previous work from the group has been published in the BMJ, The Lancet). The study also aims to present findings to professionals at conferences and meetings. The specific UK conferences to submit findings of this research to are: the British Orthopaedic Association (BOA) and the British Association for Surgery of Knee (BASK). International dissemination will also be sought, through journal publication and conferences such as the American Academy of Orthopaedic Surgeons (AAOS) and European Federation of National Associations of Orthopaedics and Traumatology (EFORT). The study will develop Plain English summaries of findings for communication to patients and members of the public - these will be freely available and published on the NDORMS website (ndorms.ox.ac.uk). The findings may also be presented at established patient and public engagement events. The proposed analysis plan and outputs has been reviewed and approved by an established patient and public involvement (PPI) group. All outputs will adhere to the HES analysis guide so that data is only shown in aggregate form with small numbers suppressed. The target date for just the publications is 18-months following receipt of the data. Key project outputs: 1. The rate of serious complications following knee arthroscopy (including comparison of groups by diagnosis and the arthroscopic procedure performed). 2. The rate of knee arthroscopy in patients with osteoarthritis / ligament rupture / meniscal tears. 3. The rate of progression to osteoarthritis in patients without osteoarthritis (after arthroscopy; after diagnosis of ligament rupture; after diagnosis of meniscal tear). 4. The rate of knee replacement surgery after knee arthroscopy (and time points). 5. The complications of total knee replacement and predictors including comparison of those previously undergoing arthroscopy to matched controls. 6. Trends in the rates of arthroscopic procedures (historical trends and factors underlying this) 7. Geographic variation in the rates of arthroscopic procedures and associated knee replacement procedures. All outputs will be controlled for factors such as patient demographic, co-morbidity, and other surgical procedures with regression analysis.

Processing:

The University of Oxford requires details of all hospital episodes for the patients who have had knee arthroscopy as the study will explore potential links between surgery and subsequent health issues that are not necessarily specific to the knee (e.g. venous thromboembolism, stroke, heart attack, hospital acquired infection). In addition, the same data is required for all total or uni-compartment knee replacement patients – to investigate outcomes in this group, comparing those having undergone a prior knee arthroscopy to all others. Finally, data on patients with a diagnosis (ICD-10) of osteoarthritis, meniscal tear or knee ligament rupture is required to analyse the overall rate of surgery in these groups and rate of complications in matched groups undergoing or not undergoing surgery. The only identifier being disseminated to University of Oxford will be Date of Death. The datasets will be held on a password protected and encrypted drive at the Botnar Research Centre, Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS). Access to the data will be restricted to members of the research team employed by the University of Oxford and based at the Botnar Research Centre. The data will be used exclusively for the purposes of the specified study. The data will not be made accessible to any third parties. At the end of the study, the data will be safely held on a password protected and encrypted drive at the Botnar Research Centre, for further 5 years, and accessed only to answer questions arising from the publication and other publicity if required. Simple descriptive statistics will be used to report trends in the rate of surgery and overall rates of complications. Regression analysis will be used to identify predictors of complications (e.g. venous thromboembolism) or further surgery (e.g. knee replacement). The data on all knee replacements will be used to compare the outcome of patients previously undergoing knee arthroscopy to those not having undergone knee arthroscopy. These groups will be carefully matched for any potentially confounding factors. Missing data will be handled using multiple imputation methods. Geographical Information Systems will be used to produce maps depicting variation in the rates of knee arthroscopy in different sub-populations (e.g. patients with osteoarthritis) and to depict any variation in the rate of complications and further surgery.

Objectives:

The purpose of this application is to support a University of Oxford’s Big Health Data Group (BHDG) study of knee arthroscopy surgery. The study will require HES Inpatient and ONS mortality data. The study will be performed by employees of the University of Oxford at the Botnar Research Centre, Nuffield Department of Orthopaedic, Rheumatology & Musculoskeletal Science (NDORMS). Knee arthroscopy is a very commonly performed procedure and around 150,000 knee arthroscopies are performed in England every year. Despite the frequency with which the procedure is performed, data on the risks and complications associated with the procedure is limited. In relatively small cohort studies, arthroscopic surgical procedures such as meniscectomy and anterior cruciate ligament (ACL) reconstruction have been shown to be associated with the subsequent development of osteoarthritis. There is also high-level evidence to suggest that many arthroscopic procedures (such as knee washout and meniscectomy) are ineffective if performed on patients with osteoarthritis. These patients may be more appropriately managed with other interventions such as physiotherapy or knee replacement. Data demonstrates the number of knee arthroscopies performed each year is rising, especially in older age groups and a key objective of the proposal is to investigate the historical trends in arthroscopy practice and the factors underlying this. It is highly likely that knee arthroscopy is being over-performed. This study proposes to determine the rate of complications (such a venous thromboembolism, stroke, heart attack, death) that occurs following knee arthroscopy. The study also propose to investigate the association of the procedure with a diagnosis of osteoarthritis and with further procedures such as repeat arthroscopy or knee replacement. For patients subsequently undergoing knee replacement the study wishes to determine if previous knee arthroscopy is associated with any subsequent complications. The study will compare patients undergoing early joint replacement after arthroscopy (e.g. within 90 days) to those undergoing later joint replacement (e.g. after 2 years). The study will compare the outcomes of all knee replacement patients previously undergoing knee arthroscopy to those not previously undergoing knee arthroscopy. For this the study the University of Oxford require all inpatient and ONS data for all knee replacement (total or uni-compartment) patients. The role of arthroscopic treatment in the management of early osteoarthritis has been highlighted as a Top 10 research priority in the recently published James Lind Alliance (JLA) Priority Setting Partnership on Early Osteoarthritis. The James Lind Alliance (JLA) is a non-profit making NIHR supported initiative which brings patients, carers and clinicians together in Priority Setting Partnerships (PSPs) to identify and prioritise the Top 10 uncertainties, or 'unanswered questions', about the effects of treatments that they agree are most important. This study aims to inform on the complications, short and long term outcome of knee arthroscopy surgery. The study will also investigate the number of cases being performed in patients with osteoarthritis – a group that evidence suggests are less likely to benefit from arthroscopy. The association with total knee replacement will be investigated and any impact on complications of total knee replacement determined. Finally, the study will report in detail on the trends in rates of knee arthroscopic procedures and how these have varied over time along with geographic variation. The data years requested are required for the analysis of the following: trends in the rates of certain procedures (e.g. with publication of evidence) and coding of index procedures, trends in the rates of complications (and changes with changing practice), and trends in associations between procedures – such as knee arthroscopy followed by total knee replacement and any complications or compromised outcome that may be associated with this. This information will be of value to patients, the public and to health care professionals: informing on the pictures of changing surgical practice, the risks of current practice with comparison to previous practice and a review of how practice has changed in response to the publication of guidelines (for example, from the National Institute for Health and Care Excellence, NICE). The study has minimised the data requested during the time-period as much as possible by limiting to defined OPCS index procedure codes and specific ICD-10 codes (osteoarthritis, meniscal tears, ligament rupture). It is not possible to reduce the data further without compromising the ability to analyse trends in complications and associations between knee arthroscopy and knee replacement which is a key output of the project. Surgical practice has changed considerably over the time-period requested – for example, reduced rates of knee ‘washout’ (e.g. OPCS W852, often performed to treat osteoarthritis in the 1990s) but increased rates of ‘meniscectomy’ (e.g. W822) beyond 2002. It is important to explore the demographics and population rates of these procedures and to investigate factors underlying these changes. There is the possibility that patients with osteoarthritis previously underwent washout but may now be undergoing a meniscal procedure – and therefore subsequently being at high risk of requiring a total knee replacement soon afterwards. The association between changing practice such as this and complications and repeat surgery rates is currently unknown and would benefit health care practice. Much of the evidence against knee washout was published around 1999-2002 and therefore this data period is required to investigate treatment practice before publication of this evidence, the transition period include the rate of change in practice, and the subsequent period which seems to include some increase in the rate of alternative surgical procedures for the degenerative knee with osteoarthritis. Other past trends of interest include the rate of cruciate ligament reconstruction and developing osteoarthritis or requiring total knee replacement. The delay between ligament injury, reconstructive surgery, and development of symptomatic osteoarthritis could easily be 15-20+ years and this period of data follow up is therefore required to investigate time to a diagnosis of osteoarthritis and time to total knee replacement. The association of meniscal surgery with a diagnosis of osteoarthritis and requiring total knee replacement later in life will also be explored.


Project 35 — DARS-NIC-78397-Z1F1Q

Opt outs honoured: Y, N

Sensitive: Non Sensitive, and Sensitive

When: 2017/09 — 2018/05.

Repeats: One-Off, Ongoing

Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • Mental Health and Learning Disabilities Data Set
  • Hospital Episode Statistics Accident and Emergency
  • Bridge file: Hospital Episode Statistics to Mental Health Minimum Data Set
  • Hospital Episode Statistics Outpatients
  • Mental Health Minimum Data Set
  • Hospital Episode Statistics Admitted Patient Care
  • MRIS - Flagging Current Status Report
  • MRIS - Cause of Death Report

Benefits:

The ACST-1 trial showed that early carotid surgery prevents future fatal and disabling strokes for at least 10 years. This finding changed clinical practice worldwide, with rates of asymptomatic carotid intervention rising sharply in the UK and Europe. However, due to improvements in medical therapy (chiefly better lipid-lowering drugs) there is renewed uncertainty about the benefits of preventative carotid surgery and rates of intervention are falling (particularly in the UK). If this study shows an additional benefit of carotid surgery on dementia risk (NB: Statins do not protect against dementia in several very large randomised trials), then rates of carotid intervention may rise again, thereby preventing large numbers of strokes and also helping to prevent dementia. Rates may rise once advisory boards have been notified. This is common practice in any change of medical practice. E.g. NICE, and the Royal College of Surgeons will need to be involved to advise on the best treatment dependent on results. CTSU know that at 5 and 10 years, carotid endarterectomy reduces stroke (Lancet 2004, 2010). However CTSU do not know whether it still reduces stroke rates in the longer-term (e.g. median 22 years). In addition, no other large randomized controlled trial has investigated whether this type of surgery reduces the rate of dementia with results within the next year. No other surgical study has looked at dementia. This is the first and CTSU have a large cohort. There are other surgical studies looking at dementia but their results will not be available for a number of years. The ACST-1 trial 5, and 10 year results (Lancet 2004, 2010) showed that surgery reduced the risk of stroke at 5 and 10 years after the operation substantially and changed medical practice worldwide. CTSU anticipate that the results of this long-term study will have a similar impact. Dementia develops over many years, and intervention may take a long time to have an effect so long-term follow-up is vital. The ACST-1 trial has >15 years of follow up and is therefore uniquely placed to help answer the question of whether increased rates of carotid intervention prevent large numbers of strokes and help prevent dementia. It may be able to detect an effect of carotid intervention on dementia more reliably than any previous study. The study is funded by a grant from the Alzheimer’s Society who supports this research question as part of their emphasis on dementia prevention and also by the University of Oxford as sponsor*, the Clinical Trials Service Unit and the Nuffield Dept. of Population Health. *'Sponsor' in this context means the legal establishment which: • takes legal responsibility for initiation and management of the study; • provides insurance for the study; • is required for all clinical research not just trials • is not necessarily the funder. Many funding bodies are unable to provide Sponsorship.

Outputs:

All outputs will consist of aggregate data only with small numbers suppressed in line with the HES analysis guide. Results of the analyses will be presented at relevant international scientific meetings 2018-2019. The results of this analysis will be posted on the ACST-1 section of website www.acst-2.org in a similar manner to multiple previous ACST-1-related publications and will also be available through the ISRCTN registry. The target time frame for publication of the results of analyses is 2018-2020. If ACST-1 can reliably demonstrate that carotid intervention (carotid endarterectomy or carotid stenting) in middle age leads to a reduction in the risk of dementia, stroke or death in the longer term this may increase the number of carotid interventions performed and help patients make better decisions about their treatment. The outcome of the research will inform clinicians and patients about potential preventative treatment pathways. Any change in medical practice will need to be discussed with advisory boards (eg, NICE) but patients will be informed of the outcome in discussions with their doctor. Alzheimer’s Society have provided CTSU a lay network monitors and CTSU will be taking on their advice with regard to disseminating this information into the public forum. The results will be presented during 2018 at international scientific meetings and published in a prominent peer-reviewed medical journal by 2019. The results of the research will be disseminated in leading peer-reviewed, high impact-factor journals and conferences including the American Heart Association, UK Stroke Forum, European Society of Cardiology, European Society for Vascular Surgery and the European Stroke Organisation Conference.

Processing:

The data supplied to NHS Digital by CTSU for each participant will be: unique ACST-1 trial Identifier (ID); first and last name; date of birth, and NHS number. The data will be in an encrypted format via the Oxford secure data transfer system. The data received back from NHS Digital will include the ACST-1 trial ID, date of birth (as provided by CTSU), gender, and outcomes of potential relevance (e.g. strokes and dementia) from the following datasets: HES Admitted Patient Care, HES Outpatients, and A&E, Mental Health, and Date of Death (obtained from demographics). The data will be securely transferred to the secure database at Clinical Trial Service Unit (CTSU), Richard Doll Building, University of Oxford. Upon receipt, these data will be entered into the existing ACST-1 trial database, and hence will remain identifiable. However, access to this database is tightly restricted, and any outputs are aggregated and entirely non-identifiable. Date of birth is required back from NHS Digital in order apply a two-fold validation of the individual records by linking participants in the original trial dataset with their health recorded in the hospital episode statistics. This is due to policy at CTSU to employ rigorous data-checking procedures for all imported data. By doing this, CTSU can have higher confidence that matching of data is accurate. The ACST-1 trial has a study specific database that is password protected and held securely on one University drive only. The ACST-1 database contains detail from the original ASCT-1 study where members are archived according to the original paper consent forms and records. These records include full name and date of birth but these are the only identifiable data contained within the ACST-1 database. The identifiable HES data will be stored in an encrypted TrueCrypt container where all such access will be granted on the instruction of the Information Asset Owner for ACST-1. The database with imported NHS Digital information will be modified and only Trial ID and age will be used in the database for analysis. Pseudonymised data (with exception to date of death) will only be available for analysis. Access is routinely reviewed and revoked when the team member leaves ACST-1. Only personnel substantively employed by the University of Oxford and are involved in this long-term follow-up study for ACST-1 study (processing and analysing data) will have access to this data. The data received will be combined with existing information on rates of stroke, other vascular disease and death (obtained previously up to 2008) and used to compare rates of dementia (and also stroke) amongst participants originally allocated to undergo carotid surgery versus those managed with medical therapy alone (i.e. intention-to-treat analyses). The ACST-1 study team shall not make the data provided by NHS Digital available to any third party or allow use of the data by or on behalf of any third party or for any purpose other than those described, in whole or in part or as linked data within the ACST-1 database.

Objectives:

Stroke is the third leading cause of disability and premature death worldwide, Around 20% of all strokes are caused by narrowing of carotid arteries, when fatty deposits break off from such lesions and lodge in the brain, thereby causing a stroke and over 80% of these carotid related strokes occur without warning. ACST-1 showed that preventative surgery to remove carotid narrowing (carotid endarterectomy) halves the risk of stroke up to 10-years following a successful procedure and these operations are performed widely worldwide (around 200,000 per year in US and Europe). There is a strong association between carotid stenosis and dementia, but (unlike the link between carotid disease and stroke) it is not clear if this association is causal, and whether carotid surgery could also prevent cognitive decline. Determination of causality requires randomised evidence, and this is the purpose of this study. ACST-1 (ISRCTN26156392), randomly allocated 3120 participants with asymptomatic narrowing of the carotid artery to carotid surgery (endarterectomy) plus best medical therapy or to best medical therapy alone. Procedural complications (i.e. those occurring within 1 month) were recorded by surgeons collaborating in the trial, and thereafter participants informed the trial coordinators of any late strokes by means of an annual postal questionnaire, the last of which was mailed in 2008. Cause specific mortality was also provided by ONS for the 1069 UK participants. The relationship between carotid disease and dementia was not well recognised when ACST-1 was designed in the early 1990s, nor was dementia the major public health priority that it now is. Accordingly, ACST-1 did not routinely collect information on cognitive decline. However, this trial provides a unique opportunity to reliably assess the effect of carotid surgery on dementia. This question is also being assessed (at considerable expense) by a similar trial currently underway in North America (CREST-2), but meaningful results may only emerge in around 10 years’ time. This work will be conducted by the MRC Population Health Research Unit, Clinical Trial Service Unit (CTSU), Nuffield Department of Population Health, which is based at the University of Oxford. The aim of the Unit is to generate and disseminate reliable evidence from observational epidemiology and from randomised trials that leads to practicable methods of avoiding premature death and disability. Prevention of premature vascular death and morbidity is a major focus of CTSU’s work, and the effects of drugs such as statins and aspirin on dementia are currently being investigated (led by members of CTSU). Consequently, the proposed study fits within an established research program, and the required specialist skills and knowledge exist at CTSU. Whilst CTSU have data on stroke rates at up to 10-years post-surgery, CTSU did not collect information on incident dementia during ACST-1 follow-up which ended in 2008, and CTSU have no information on any health outcomes after 2008. Indirect follow-up via routinely collected health records is necessary to assess rates of dementia in this cohort of participants thereby allowing a complete and unbiased follow-up of the UK ACST-1 participants. The data held prior to 2008 does not contain information on incident dementia. The CTSU seeks data on dementia from before this date as well as after to answer an additional question on whether patients who had carotid surgery (endarterectomy) in the original cohort also had a lower risk of contracting dementia. Dementia is an insidious process which takes a number of years (usually decades) to develop which is why if only a short time was requested CTSU would miss potential dementia and stroke diagnoses. The risk of stroke and dementia increases with age which is why this is such an important study in a high-risk elderly cohort. CTSU know that the 5 and 10 year results of ACST-1 trial highlighted the benefit of carotid endarterectomy however CTSU do not know the longer term and potentially enhanced benefits seen at >20 years post-intervention. Data on incident dementia is required going back to as early as possible for this reason. ACST-1 Long-term follow-up study is funded by an Alzheimer’s Society project grant and also by core funding from the Clinical Trial Service Unit (CTSU), University of Oxford.