NHS Digital Data Release Register - reformatted

London School of Hygiene and Tropical Medicine

🚩 London School of Hygiene and Tropical Medicine received multiple files from the same dataset, in the same month, both with optouts respected and with optouts ignored. London School of Hygiene and Tropical Medicine may not have compared the two datasets, but the identifiers are consistent between datasets for the same recipient, and NHS Digital does not know what their recipients actually do.

Project 1 — DARS-NIC-72064-V5V2X

Opt outs honoured: Yes - patient objections upheld (Section 251 NHS Act 2006)

Sensitive: Non Sensitive, and Sensitive

When: 2017/12 — 2019/11.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012, Section 42(4) of the Statistics and Registration Service Act (2007) as amended by section 287 of the Health and Social Care Act (2012), Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii)

Categories: Anonymised - ICO code compliant, Identifiable

Datasets:

  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Admitted Patient Care
  • Office for National Statistics Mortality Data
  • Civil Registration - Deaths

Objectives:

The Clinical Effectiveness Unit (CEU) based at The Royal College of Surgeons (RCS) requires linked data from four large national databases containing information on all patients in the last two decades who have had liver cancer (Hepatocellular Carcinoma (HCC) being the most common liver cancer) and of those patients who have subsequently received a liver transplantation. The CEU is a collaborative research unit formed from both the RCS and London School of Hygiene & Tropical Medicine (LSHTM) and therefore both RCS and LSHTM are joint data controllers. The linked data requested is minimised to two cohorts of liver cancer patients and liver transplantation patients. The project is funded by the NIHR as part of a Doctoral Research Fellowship (DRF) grant. The databases include the National Cancer Registration and Analysis Service (NCRAS) to identify all patients with liver cancer in England, the Hospital Episode Statistics (HES) database and Office for National Statistics (ONS) Mortality database to determine comorbidities, treatments and outcomes, and the UK Liver Transplant Audit (UKLTA) database to evaluate the outcome of transplantation. The National Cancer Registration and Analysis Service (NCRAS) is run by Public Health England and is responsible for cancer registration. UK Liver Transplant Audit (UKLTA) is run by NHS Blood and Transplant (NHSBT) who manage blood and platelet donation, and organ, stem cell and tissue donation and transplantation. The datasets to be linked from each national database are as follows: - Liver cancer specific dataset: - records of patients diagnosed with liver cancer between 1996 and 2016, including date of diagnosis, TNM stage, cancer morphology, and treatment indicators will be used, including already linked: Chemotherapy (SACT), Radiotherapy (RTDS) and Radiology Datasets (DID) supplied from NCRAS; UK Liver Transplant Audit (UKLTA): - records of all patients who received a liver transplant since 1994 and all patients on the liver transplant waiting list, including 'standard liver dataset' and 'waiting list data', supplied from NHSBT Hospital Episode Statistics (HES) datasets (Admitted Patient Care (APC), Outpatients (OP), Critical Care (CC), Accident and Emergency (A&E) supplied from NHS Digital and ONS Mortality Data supplied by the Office for National Statistics via NHS Digital. Project aim: To maximise the benefit of liver transplantation as a treatment option for patients with liver cancer. Work packages: Detailed below are five separate work packages, each with specific objectives, that have been constructed in order address the project aim. Work package 1: Identifying the rising incidence and mortality of HCC in England and worldwide Identifying the main risk factors causing the rise in HCC will encourage NHS services to better identify HCC earlier in patients and thus increase their treatment options. It will also help to educate the public in avoiding the high-risk behaviours that can lead to the development of liver disease and subsequent risk of HCC. Work package 2: Assessing the validity of the linked national databases as a data source for HCC research Large linked health databases will provide the data to answer our research questions. Prior to conducting any analysis, the validity of the national databases will be evaluated by checking the consistency of the recorded liver disease and treatment information. Work package 3: Assessing the impact of sociodemographic and clinical factors on treatment selection and survival of patients with HCC Evaluating treatment options for patients with HCC will help us identify the best treatment available for patients based on their individual disease and medical conditions. This will promote the use of effective alternative treatments for HCC whilst potentially easing the pressure on our liver transplant services. Work package 4: Analysing outcomes of liver transplantation in patients with HCC Identifying individual patient characteristics that are associated with the best and worst outcomes following liver transplantation will help us better identify HCC patients suitable for transplantation. This could lead to an improvement in post-operative survival and increase the number of patients with HCC considered suitable for liver transplantation. Work package 5: Analysing outcomes of liver transplantation in patients with HCC who receive a cardiac death donor liver? Exploring the transplantation of livers from cardiac death donors as compared with brainstem death donor livers could potentially increase the number of livers suitable for donation. This could lead to the earlier transplantation of patients with HCC and reduce the number of patients falling of the waiting list due to spread of their cancer. Background: Hepatocellular carcinoma (HCC) is the most common liver cancer. Each year, more than 4,000 patients are being diagnosed with HCC in the UK. The incidence of HCC has increased four-fold in the last 30 years. Liver diseases such as obesity and hepatitis C lead to liver cirrhosis and eventually cancer. There is often a lag time of two decades between the acquisition of liver disease and the development of HCC. Overall survival of patients diagnosed with HCC is poor. Despite small improvements in outcome, less than 30% of the patients are alive at one year after diagnosis. The available treatment options depend on the size and spread of the cancer at the time of diagnosis. Patients who are eligible to receive a liver transplantation have the best prognosis with about 75% being alive at five years. Liver transplantation is increasingly being used as a treatment for patients with HCC. As a result, HCC is now the most common indication for liver transplantation. This development has increased the gap between the number of patients waiting for liver transplantation and the availability of suitable livers. In response, the transplant centres have started to use more and more livers from donors who have sustained a cardiac death. They accept that transplant outcomes with livers from these donors might be worse than with livers from the normal donors who have sustained brainstem death. However, transplant surgeons have little choice as they need to find a donor for patients with HCC before their disease spreads to the bloodstream and they become unfit for potentially curative transplantation.

Yielded Benefits:

The overarching theme of the results is that livers donated following circulatory death (DCD) – previously thought to be sub-optimal – produce equivocal results as livers donated after brain stem death (DBD) traditionally thought to be of higher quality. The results will therefore encourage clinicians and patients alike to increase the utilisation of DCD livers and thus increase the number of patients who are receiving a potentially life-saving liver transplantation and decrease the number patients waiting to receive a liver transplantation. To date outputs for the project include: Poster Presentations 1. British Transplant Society (BTS) Annual Congress, Harrogate, March 2017 2. British Association for study of the liver (BASL) Annual Congress, Warwick, September 2017. Oral Presentations 1. BASL Annual HCC-UK Research Meeting, Newcastle, April 2017 2. British Transplant Society (BTS) Annual Congress, Brighton, March 2018 (x2 presentations) 3. BASL Annual HCC-UK Research Meeting, London, April 2018 4. European Society of Transplantation Annual Conference: July 2018

Expected Benefits:

The incidence of HCC in the UK is increasing. Given the observed time trends in etiological and contributing factors and the considerable lag time between first onset of liver disease and the development of HCC, this increase is likely to continue over the next decade. It is imperative that we are equipped with the necessary information to combat this devastating disease and to determine the role of liver transplantation. This thesis aims to make a significant contribution in this area. CEU expect this research can make three fundamental contributions. First, it is now recognised that using linked national health based datasets will expand the scope of clinical questions that can be addressed (10). CEU will demonstrate how linked data can be used to study an entire disease pathway from recognising the first presence of aetiological agents and contributing factors to the development of cirrhosis and HCC. A better understanding of the entire disease pathway will guide NHS services in developing a comprehensive response to the increasing burden of HCC that may include developing measures to prevent viral hepatitis and cirrhosis, screening patients at risk of developing HCC, and improving the capacity of liver transplantation as a potentially curative treatment option for HCC. Second, evaluating liver transplantation as a curative treatment and exposing the liver diseases and treatments options associated with the best and worst outcome has an immediate benefit as it will help to improve the information that is available for the selection of potential recipients of a liver transplant and the allocation of donor organs. The potential of liver transplantation as a treatment option for HCC is determined by the limited availability of suitable donor organs. Using our linked dataset, we hope to determine whether transplanting organs from DCD donor’s produces improved survival outcomes. Furthermore, identifying risk factors of post-transplant survival in HCC patients, including the use of organs from DCD and other marginal donors, can improve patient selection and organ allocation policy which will further improve the potential of liver transplantation as a treatment option for HCC patients. Third, the work using the linked national databases will also demonstrate how this resource can contribute to the investigation of potential inequity of access and variation in treatment and outcomes across NHS providers. A better understanding of the determinants of treatment and outcomes has the potential to inform how HCC services, including liver transplantation, can be further improved, ultimately leading to an overall improvement of the quality of care for patients with HCC.

Outputs:

Publications: During the project, CEU would look to publish a minimum of four to five high quality research papers in high impact transplant and cancer specific journals (Target:- January 2018-2020). Selected journals include; Transplantation; Liver Transplantation; American Journal of Transplantation and The British Journal of Cancer. Significant research findings will also be put forward to the external relations departments at the London School of Hygiene and Tropical Medicine and The Royal College of Surgeons, London for further distribution. It will be mandatory to recognise all contributory organisations in all publications. Presentations: Research outputs will be presented at national and international meetings. CEU aim for yearly presentations at the British Transplant Society (BTS) Conference with international presentations focused on conferences hosted by the European Society of Transplantation (ESOT). CEU will also aim for an oral presentation at the two-yearly World Transplant Conference (WTC). Cancer specific workshops hosted by the National Cancer Intelligence Network (NCIN) will provide the platform for oral presentations on the main determinants of HCC. These meetings will provide the opportunity for CEU's results to positively affect the wider public through influencing policy on prevention strategies of the risk factors identified as causing the greatest burden to the hepatocellular carcinoma (HCC) epidemic. Intended Presentation Dates and Venue British Transplant Society Annual Conference: March, 2018, 2019 European Society of Transplantation Annual Conference: July 2018 World Transplant Conference: 2018 – venue to de determined Patient Groups: An update of progress will be made to local patient groups. This will be part of the process of informing NHS patients of CEU's findings and allowing them to help further influence their research by working with the HCC advisory group to formulate the best platforms to disseminate the research findings to the public. Local NHS Trust Feedback: CEU will use select local meetings within the Institute of Liver Sciences at Kings College Hospital to feedback the results of this thesis. In attendance, will be consultant hepatobiliary and transplant surgeons, hepatologists, junior doctors, clinical nurse specialists, transplant coordinators and NHS service managers. This forum presents an efficient way of translating the output of this research into active clinical practice. It is therefore imperative that these meetings, are conducted on a regular basis throughout the duration of the thesis. The major theme of the project is identifying the extent to which we can increase the capacity of liver transplantation to meet the increasing demand driven by HCC. It is hoped that highlighting this information will help regulate and in turn drive improvements in treatment selection and outcomes for individual HCC patients. NHSBT: The research outputs indicating the influence of the HCC epidemic and its impact on liver transplantation will be discussed with NHSBT’s Liver Selection and Allocation Working Party and Liver Advisory Group. Results from this thesis can be potentially used by these national committees to determine allocation policy by contributing to the construction of further complex statistical models that NHSBT can use to determine the allocation policy of donor organs. This will result in rapid improvements in patient outcome through maximising the survival benefit of deceased donor livers in HCC patients. All outputs will be aggregated with small numbers supressed in line with the HES analysis guide.

Processing:

PHE (NCRAS) will submit the following identifiers for a cohort of liver cancer patients to NHS Digital: NHS number, gender, date of birth, and postcode plus unique Liver Cancer ID. NHSBT will also submit the following identifiers for a cohort of liver transplant patients to NHS Digital: NHS number, gender, date of birth, and postcode plus unique Liver Transplant ID. PHE (NCRAS) and NHSBT will send additional data about these individuals from their respective databases to CEU. These datasets will contain no identifiers other than unique Liver Cancer ID and Liver Transplant ID respectively. NHS Digital will then add both cohorts together to make one cohort and will link the combined cohort to HES and ONS mortality data. The data will be pseudonymised containing no identifiers other than encrypted HESID, Liver Cancer or Liver Transplant person ID and, where applicable, Date of Death. The encrypted HESID will be the common identifier across all datasets. NHS Digital will supply the linked HES and ONS mortality data for each matched patient within the cohort of liver cancer and liver transplant patients to a secure data handling facility at the Clinical Effectiveness Unit (CEU) based at The Royal College of Surgeons of England (RCS). The CEU is a collaborative research unit formed from both the RCS and London School of Hygiene & Tropical Medicine (LSHTM). NHS Digital will also supply to the CEU the unique Liver Cancer ID or Liver Transplant ID for any patients from the respective cohorts whose data could not be matched to HES and/or ONS data. In any deterministic linkage of data, there will be a small percentage of patients whose records did not match (i.e. none of the identifiers such as NHS number, D.O.B, postcode correlated). The Liver Cancer and Liver Transplant IDs of unmatched patients will be used by CEU to link back to additional data supplied by NHSBT and NCRAS. These will be used to compare the characteristics of patients who were not matched to HES with those that were in order to assess potential bias arising from the exclusion of their HES and/or ONS data from the analyses. Bias is dangerous to any epidemiological study as it affects the strength of causality that any analysis may display it then also affects the interpretation of the results and credibility of the research. In order to test (and hopefully disprove bias) in this study CEU need to make sure the patient characteristics are not different between matched and unmatched patients. CEU will compare patients with HCC who underwent liver transplant against patients with HCC who received other forms of treatment (i.e. liver resection, radiotherapy, chemotherapy etc). In addition, CEU also need to compare patients who had a liver transplant for HCC against patients who had a liver transplant for other indications (i.e. alcohol, hepatitis etc). The CEU requires the HES and mortality data for all matched patients whether they were included in the PHE (NCRAS) cohort, the NHSBT cohort or both. There will be quite a few patients who are in one cohort but not the other as only a small proportion of patients unfortunately receive a liver transplant. CEU require all the records to compare the outcomes for patients who do receive a liver transplant against those who do not receive a liver transplant. CEU need the records to identify the characteristics (age, sex, sociodemographic status, co-morbidities) that influence patients with HCC who receive a liver transplant against those who do not. Additionally, the CEU requires all HES records of patients with an ICD10 code of ‘C22’ (liver cancer) and / or an OPCS4 code of ‘J01’ (liver transplantation) who are not linked to either the NHSBT or NCRAS data set. This will provide an even better opportunity to explore if there is a case ascertainment issue (i.e. that NHSBT or NCRAS have not identified 100% of instances of liver transplantation or liver cancer). The characteristics of omitted individuals’ hospital episodes will be considered to explore the possible bias that this will produce. Data supplied by NHS Digital will only be accessed by the clinical researcher and statistical supervisor who are substantive employees of LSHTM and the data manager who is a substantive employee of RCS. No data will be shared with a third party in any form. All outputs will be aggregated with small numbers supressed in line with the HES analysis guide. All data will be processed and accessed at the CEU. Justification of years requested in each dataset: Much of CEU's intended analysis is determining trends over time in the incidence and outcomes of patients with HCC hence the request of historical data across all 5 datasets. Important in identifying any potential improvements (or even decline) in outcomes is assessing the changing patient characteristics of patients with HCC in addition to identifying any significant changes in the services (and or treatment options) that these patients receive i.e. better post-op critical care, reduced post-op emergency department attendances, increase outpatient surveillance etc. Fundamentally important to the initial analysis (work package 1) is also mapping the pathway to the development of HCC. CEU know the development of HCC is often part of a 20-year process from the development of a primary liver disease to cirrhosis and then to cancer. Hence, in order to identify what clinical and sociodemographic factors (in addition to cirrhosis) are important in the development of HCC, CEU need the historical data. This is especially relevant of the inpatient (APC) dataset which contain the diagnosis and procedural codes necessary to perform this analysis. The linked dataset will be validated by checking the consistency of cancer diagnoses and treatment across all three databases. The level of agreement will be detailed using statistics. CEU will perform statistical analysis on their linked dataset to address five work packages (research questions). Processing of data will be done so in accordance with ONS terms and conditions. There will be no linkage with other record level data, nor will there be any attempt to re-identify an individual through the use of the data.


Project 2 — DARS-NIC-63345-L7D3D

Opt outs honoured: N

Sensitive: Non Sensitive

When: 2017/06 — 2017/11.

Repeats: Ongoing

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

Categories: Identifiable

Datasets:

  • MRIS - List Cleaning Report

Objectives:

The objective of the request is to receive information about fact of death and current postcode for members of the cohort prior to writing out therefore preventing the writing out to any people in the cohort who may have passed away and not writing to people who have moved address. The output is to create a 'live' consented database and the benefit is not to cause distress PhD Research Study on the Use of PROMs in Emergency Admissions, a feasibility study conducted to explore the use of Patient reported outcome measures in emergency admissions patient cohorts. The aim of the work is to assess the feasibility of retrospective PROMs in emergency admissions and follow-up PROMs to determine change in Health Related Quality of Life (HRQL) of patients following emergency hospital care. This is the last phase of a three year study and links directly with the National Emergency Laparotomy Audit (NELA), who if the study proves to be a success, will be looking at the feasibility of including PROMs in National Clinical Audit. In England, emergency admissions accounted for nearly 38% of all hospital admissions in 2012-13, with an increase of 47% over the last 15 years. Two thirds of hospital beds are occupied by people admitted as emergencies and the cost is approximately £12.5 billion. Of these, emergency general surgery represents approximately half of the general surgical workload and accounts for over 600,000 hospital admissions at a cost of £88 million a year. Furthermore, emergency admissions is an area whereby variation in clinical outcome is greater than for elective care, and an area where there is no information on patient-reported outcomes. Capturing PROMs for unexpected emergency admissions is primarily to measure the quality of health services. The aim of healthcare is to restore patients’ health to their full potential and health related quality of life (HRQL). Patients’ recovery can be compared with their pre-event baseline quality of life to determine the effectiveness of the health service. This, however, is impossible to obtain prior to an acute event and therefore collection of a retrospective PROM by patient recall to replace the baseline HRQL is an option. Patient Reported Outcomes Measures (PROMs) have the potential to transform healthcare delivery through enhancing patient-centred care, assessing relative clinical quality, comparing providers’ performance and evaluating the effectiveness of treatments. The development of routinely collected PROMs data in four elective surgical procedures in England has been heralded as one of the missing components of quality in the jigsaw in the evaluation of our health service. (DoH Guide to PROMs Methodology 2009, Black 2013). With growing acceptance of the importance of patients' views of their outcome, as well as clinicians' measures such as mortality and impairment, when evaluating interventions and assessing the quality of services, it is necessary to devise ways in which accurate PROMs can be obtained, since these provide information on the effectiveness of treatment, an important component in determining the quality of healthcare. Development to widen use of PROMs helps to focus the health service towards patient-centred care (Greenhalgh and Long 2004). There is sustained clinical and political interest in the systematic development of PROMS (Morris et al 2007, DoH NHS Outcomes Framework 2015-16, DoH The Mandate to the NHS 2015-16). This is a new study, a new phase as part of a 3 year doctoral programme of research on the topic of Patient Reported Outcomes Measures. This study applied for HRA approval in Nov 2016, and received approval in Dec 2016. Planned data collection to begin in March 2017. Study participant's (patient) death status (fact of death) from MRIS/ PDS is required to ensure that the researchers do not send follow-up PROMs questionnaires to patients who have passed away prior to follow-up. Emergency conditions account for 40% of NHS hospital admissions and have been an area of increasing resource use and political importance (DoH NHS Outcomes Framework 2015-16). There is mounting interest to extend the use of PROMs to emergency admissions. Participating trusts, national clinical audit group (NELA) will be informed of the research findings through dissemination through partnering providers and Collaborations for Leadership in Applied Health Research and Care (CLARHC) research network, at conferences and workshops- HSR symposium 2018, National PROMS conference 2018 and also though reports to national clinical audit collaborators as well as traditional forms of research dissemination pathways including academic conferences, publications in peer reviewed journals- e.g. BMJ journal for quality and safety, and a PhD thesis.

Expected Benefits:

Request of data for FACT OF DEATH requirement only. The purpose is to enable the researcher not to cause distress. So the objective is not to write to any dead people, the output is to create a 'live' consented database and the benefit is not to cause distress. Study findings will be disseminated to participating providers and National Emergency Laparotomy Audit and at conferences such as HSR symposium 2018, National PROMS conference 2018 involving provider trusts and clinicians, reports to National clinical audit collaborators .They will be able to use patient reported outcomes for service improvement decisions and on-going benchmarking of services. There is prior engagement with the National Clinical Audit groups who are interested in adopting the use of Patient Reported Outcomes to clinical audit. There is significant interest from policy makers in extending the use of PROMs in emergency admissions. PROMs helps providers, commissioners to measure effectiveness and quality of care, extending the use of PROMs in emergency admissions allows for increased patient-centred care. Benefiting care users through understanding quality of care and quality of life post-treatment/care from the patients' perspective. Emergency Admissions make up nearly 40% of all hospital admissions in England and is increasing each year.

Outputs:

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. The following outputs will be produced : The main findings will be included in PhD thesis due in May 2018. The final report of results will be submitted to NELA in Dec 2017. This will cover all findings of the study including: factors influencing planning and implementation and key findings. Once finalised, this will be submitted for publication in the open access, peer-reviewed journals with an estimated submission date of January 2018. Further academic paper(s) will be published in open-access and peer-reviewed journal such as BMJ quality and safety on [methodology; cost and effectiveness of the feasilibty of using PROMs in emergency admissions]; impact on policy and clinical care. A simplified version of the findings will be disseminated to patient groups of interest (e.g. CLAHRC network, participating hospitals patient forums). Findings will be presented at conferences and events with CLARHC patient groups.

Processing:

London School of Hygiene and Tropical Medicine (LSHTM) will securely transfer patient identifiers (NHS number, DOB, postcode) and unique study ID to NHS digital from consented patients of the study (patient recruitment is over 3 months from hospitals), the information will be requested monthly over 3 months before follow-up questionnaires are sent directly to patients. NHS Digital data for patients who do not respond to follow-up questionnaire will be deleted. NHS Digital will send any known fact of death with Unique study ID (and no other identifiers) from study participants to LSHTM. LSTHM stores the data on a secure server in LSHTM which can be only accessed by applicant and the study team at LSHTM. Data will only be accessed by individuals within the study team who have authorisation from the applicant (chief investigator of the study) to access the data for the purpose(s) described. Economic and Social Research Council PhD funding awards are provided through doctoral training centres for which LSHTM belong to the Bloomsbury Doctoral Training Centre partnerships which is managed by the University College London Institute Of Education, therefore the grant for the study is managed by Bloomsbury doctoral training Centre partnerships and this organisation also issues the funding letter. The PhD student conducting this study is a full time PhD student at the LSHTM and this study solely belongs to LSHTM's clinical governance; this includes the sponsorship and indemnity, quality and responsibility of the overall study. University College London Institute Of Education have no further involvement in this study. Knowledge of the fact of death of any study participants within this cohort study allows researchers to minimize any potential distress caused by sending a follow-up questionnaire to a participant who have passed away. Due to the nature of emergency admissions, there could be a 2-5% mortality within the first 2-3 months of hospital discharge in the study patient cohort.


Project 3 — DARS-NIC-58603-S6Z1B

Opt outs honoured: Y, N, Yes - patient objections upheld (Section 251 NHS Act 2006)

Sensitive: Sensitive

When: 2017/03 — 2020/05.

Repeats: Ongoing, 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 , National Health Service Act 2006 - s251 - 'Control of patient information'.

Categories: Identifiable

Datasets:

  • MRIS - Flagging Current Status Report
  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report

Objectives:

The objective for the Manchester Cohort is to study the long term risk of cervical cancer and cervical pre-cancer following Human papilloma virus (HPV) infection. The aims are to obtain the data required to evaluate the long-term benefits and costs of alternative screening strategies using primary HPV testing and to investigate; 1. The long-term protection of a negative HPV test and hence the safe screening interval at different ages 2. Optimal ages at start and stopping screening 3. The role of HPV typing and test sensitivity 4. Triage of HPV positive women, particularly the interval to retesting for HPV positive women The team will follow-up this unique cohort in order to determine long-term risks associated with HPV infection. HPV is the most common sexually transmitted disease but unfortunately most people do not know they are infected with the virus since the initial symptoms can be minor. The cohort was recruited between 1987-1993 in collaboration with over 100 general practitioners and screening clinics in the Greater Manchester area who used the Christie Hospital cytology laboratory (now the Manchester Cytology Centre sited at Manchester Royal Infirmary). 78,062 cervical cell samples were collected from 61,564 women attending for routine screening. There was no age restriction. Participating practices and clinics covered a wide area in and around the city of Manchester, and offered screening either in the context of well-woman clinics or in association with family planning services. The study was approved by the local ethics committee. Verbal informed consent obtained when the smear was taken was deemed appropriate at the time, as the clinical significance of HPV infection was not then known. However, verbal consent is not being presented as the legal basis for this application and is merely for background information. HPV assays were performed after recruitment had ended, and no HPV results were reported either to the cytology laboratory or to the women. Samples taken before Jan 1989 were centrifuged and only the pellet was stored. This procedure (in the pre-PCR era) entailed some loss of DNA and the possibility of contamination. The proposed study will therefore be restricted to the 49,549 women recruited 1989-93. The Manchester Study was an observational study and now LSHTM wish to 'flag' the cohort for cancer incidence and mortality and relate these outcomes back to their previous HPV results. At the time the Manchester Cohort was set up, HPV testing was not routine or cheap and so the study team tested only a minority of samples. The untested samples were stored until such a time as funding could cover the testing costs. Once the Manchester cohort is flagged the study team will be able to see who has developed cervical cancer or cervical pre-cancer from the cancer registration data. LSTHM will then test the stored samples from these women and also a randomly selected control group to compare them. In summary, the routine screening records collected on these women and the additional linked data will help inform policy makers about how best HPV testing should be done. Questions this research aims to influence are: (1) Is it safe to leave a longer interval between screening tests when a woman has a negative HPV test? (2) What follow-up tests should be done in women who test positive for HPV? We can evaluate cytology, genotyping (identifying the strain of HPV) or new testing methods. (3) What age is it safe to stop screening? Can a woman stop screening if she has tested negative for HPV when aged 50 years?

Yielded Benefits:

A report describing the 15 year follow-up of the ARTISTIC trial is currently in press (HTA journal). Additional papers centred on triage strategies and screening intervals are currently being prepared. The LSHTM is currently analysing data from the Manchester Study. The following publications and resources have been created to date regarding data from these cohorts: Long-term follow-up of ARTISTIC cervical screening trial cohort Gilham C, Sargent A, Kitchener H, Peto J 2018 Health Technol Assess Longer screening intervals are recommended following a negative HPV test in primary cervical screening Peto J, Gilham C 2017 Evid Based Med. Jul 22; 22(5) The PapilloCheck® Assay for the Detection of High Grade Cervical Intraepithelial Neoplasia Crosbie EJ, Bailey A, Sargent A, Gilham C, Peto J, Kitchener HC 2015 J Clin Microbiol. Nov;53(11):3553-9 The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds Kitchener H, Canfell K, Gilham C, Sargent A, Roberts C, Desai M, Peto J 2014 Health Technol Assess. Apr;18(23):1-196 Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, Berkhof J, Peto J, Meijer CJ; the International HPV screening working group 2014 Lancet. Feb 8;383(9916):524-32 A comparison of HPV DNA testing and liquid based cytology over three rounds of primary cervical screening: Extended follow up in the ARTISTIC trial Kitchener HC;Gilham C;Sargent A;Bailey A;Albrow R;Roberts C;Desai M;Mather J;Turner A;Moss S;Peto J 2011 Eur J Cancer. 2011. 47(6 ):864-871 Sexual Behavior and HPV Infection in British Women, by Postal Questionnaires and Telephone Interviews Almonte M;dos Santos Silva I;Asare A;Gilham C;Sargent A;Bailey A;Turner A;Desai M;Kitchener HC;Peto J 2011 J Med Virol. 83(7 ):1238-1246 Optimal threshold for a positive hybrid capture 2 test for detection of human papillomavirus: data from the ARTISTIC trial Sargent A, Bailey A, Turner A, Almonte M, Gilham C, Baysson H, Peto J, Roberts C, Thomson C, Desai M, Mather J, Kitchener H 2010 J Clin Microbiol. Feb;48(2):554-8 ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening Kitchener HC, Almonte M, Gilham C, Dowie R, Stoykova B, Sargent A, Roberts C, Desai M, Peto J; ARTISTIC Trial Study Group 2009 Health Technol Assess. Nov;13(51):1-150, iii-iv HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial Kitchener HC, Almonte M, Thomson C, Wheeler P, Sargent A, Stoykova B, Gilham C, Baysson H, Roberts C, Dowie R, Desai M, Mather J, Bailey A, Turner A, Moss S, Peto J 2009 Lancet Oncol. Jul;10(7):672-82 Prevalence of type-specific HPV infection by age and grade of cervical cytology: data from the ARTISTIC trial Sargent A, Bailey A, Almonte M, Turner A, Thomson C, Peto J, Desai M, Mather J, Moss S, Roberts C, Kitchener HC; ARTISTIC Study Group 2008 Br J Cancer. May 20;98(10):1704-9 HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial H C Kitchener, M Almonte, P Wheeler, M Desai, C Gilham, A Bailey, A Sargent, J Peto 2006 Br J Cancer Jul 3; 95(1): 56-61 Cervical HPV infection and neoplasia in a large population-based cohort: the Manchester study Peto J, Gilham C, Deacon J, Taylor C, Evans C, Binns W, Haywood M, Elanko N, Coleman D, Yule R, Desai M 2004 Br J Cancer Aug 31; 91(5): 942-53 Sexual behaviour and smoking as determinants of cervical HPV infection and of CIN3 among those infected: a case-control study nested within the Manchester cohort Deacon JM, Evans CD, Yule R, Desai M, Binns W, Taylor C, Peto J 2000 Br J Cancer 2000 Dec;83(11):1565-72 The National Screening Committee (NSC) makes recommendations for policy changes to the NHS Cervical Screening Programme (NHSCSP) based on published epidemiological and trial data. ARTISTIC is particularly informative to the NSC as it is the only cohort of women in the UK with long follow-up. The aims of the screening programme are to identify and treat women at greatest risk of cancer and pre-cancer, but also minimise anxiety and over-treatment in women who have transient infections, which are likely to disappear on their own without treatment. Policy changes informed by the research are made to improve the efficiency of the programme in these respects. The greatest change to the NHSCSP is currently happening this year with the introduction of primary HPV screening. The decision that led to this change was based on a pooled analysis of the 4 major European clinical trials, one of which was ARTISTIC. Despite rollout of the new programme, due to be complete by December 2019, there are still decisions to be made regarding the screening protocol. For this reason, the results from current work on the ARTISTIC and the MANCHESTER cohort will continue to influence policy and yield patient benefit.

Expected Benefits:

The demonstration that a high proportion of women who subsequently developed cervical cancer had detectable HPV by age 40, and often earlier, would be of major importance and may show for example, that a single HPV test in middle age may be the most effective practicable form of screening. The London School of Hygiene and Tropical Medicine and the lead researcher in this area have been proactive in ensuring the health system and patients benefit from the results of this research. Indeed they have already influenced policy changes in this area, with the results from a similar study (ARTISTIC TRIAL). The results have influence the piloting of primary HPV screening. The LSHTM expect evidence from this cohort to influence further screening policy changes regarding screening interval and triage strategies. This research will be disseminated officially in peer-reviewed papers. These will be used by the National Screening Committee to decide whether changes should be made to the screening programme. The lead in this research is also the chair of an advisory group specifically put together to advise the National Screening Committee on the scientific evidence that exists regarding cervical cancer and HPV screening and therefore this research could directly influence screening policy. The London School of Hygiene and Tropical Medicine findings will add to the body of evidence to allow policy-makers to improve the cervical screening programme in the UK (and around the world)

Outputs:

Human papillomavirus (HPV) infection is known to cause cervical cancer, but it is a relatively common infection, especially in young women, which usually clears without any symptoms or long-lasting effects. There are different strains (known as genotypes) of HPV, and some are more likely to cause pre-cancer or cancer than others. Until recently, cervical cancer screening has been done using a smear test (known as cytology), but the latest scientific evidence points towards screening first for HPV infection (known as “HPV primary screening”). This method is currently being tested in six areas in England, and in January 2016, the UK National Screening Committee announced that primary HPV testing should be introduced countrywide. It is not sensible or cost-effective to refer a large number of women for treatment when their infection is likely to clear on its own, so women who are positive for HPV will be only referred if they also have some abnormal cells (from their cytology test). Cytology is not always the most efficient second test and screening studies such as the Manchester Cohort study can help policy makers decide what the best options are to save women being referred unnecessarily and to save money. The long-term cervical cancer risk following HPV infection will be estimated from the following: 1. Long-term follow-up of women in The Manchester Study for whom HPV status was known at baseline, 2. a case-control analysis comparing baseline HPV status in those developing cervical cancer during follow-up in The Manchester Study. The results (target 2017) will be presented at international HPV conferences including the International Papillomavirus Conference and the Eurogin conference on HPV held every 18 months respectively. The results will also be published in peer-reviewed journals such as the European Journal of Cancer and the British Journal of Cancer. All outputs will be aggregate with small numbers supressed in line with HES analysis Guidance.

Processing:

The request is for notification of and date of cancer incidence, mortality and current status (i.e. NHS, cancelled, emigration, armed forces etc.). In order to conduct a valid statistical analysis, it is essential to know the number of individuals at risk from developing the disease of interest at any point in time. This includes being aware of which members of the cohort are being actively followed at any point in time. Once an individual leaves the notification system, due to being cancelled or emigration for example, they must be excluded from the analysis. For example, any woman who emigrated would leave the study at this point and would not be able to re-enter the study because cervical cancer may occur while a women is living abroad. LSHTM will send NHS Digital the following identifiers - NHS Number where known, Names (including former), DOB, Address, Postcode. This data will be from when the cohort was recruited. NHS Digital will provide latest demographic data (NHS number and DOB only) , cancer, NHS exits/status and cause of death data. LSHTM will quality check and merged it with the current data held on the cohort. Before merging, fields containing names and addresses will be removed. LSHTM data files being returned will not contain names or addresses, but will contain dates of birth and NHS numbers for linkage purposes to onward screening. LSHTM also hold cervical screening histories which include dates and results of cervical smears and associated histology results, and HPV results. LSHTM then analyse the data in terms of estimating risks of cervical cancer and CIN3 (cervical cancer-in-situ) associated with previous HPV results. In addition to these “cohort analyses”, the team would like to retrieve stored, yet untested, samples from the Manchester Study from women who have subsequently developed cervical cancer or CIN3. A set of controls will be analysed as a nested case-control study within the cohort. The team can directly compare the screening histories and HPV results among those women who do and do not develop cervical cancer or CIN3. Processing will include the following steps: 1. The Manchester cohort will be matched PDS (MIDAS) 2. NHS Digital will provide LSHTM with Cause of death and cancer registration data, NHS Number,DOB and NHS Exits. The data will be processed at the LSHTM and will not be shared with any third parties. All outputs will be aggregate with small numbers supressed in line with HES analysis Guidance.


Project 4 — DARS-NIC-382718-N1T4C

Opt outs honoured: Y, N

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2017/02.

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: Anonymised - ICO code compliant, Identifiable

Datasets:

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

Objectives:

To support a research study that aims to determine the association between different services aimed at identification and management of patients at risk of deterioration and ward-based cardiac arrest rates and outcomes. The London School of Hygiene & Tropical Medicine (LSHTM) will carry out a survey to map interventions across all hospitals participating in the National Cardiac Arrest Audit (NCAA) (managed by the Intensive Care National Audit and Research Centre (ICNARC)) and using a cross-sectional approach, will determine which combinations of services are associated with the lowest cardiac arrest rates and best outcomes derived from the NCAA database. The LSHTM will also look at how arrest rates and outcomes have changed over time in hospitals as new services have been. NCAA data will be linked to other ICNARC datasets: the Case Mix Programme (CMP) to determine patient's condition on admission to ICU. Linking this ICNARC dataset to Hospital Episode Statistics (HES) will provide data on co-morbidity and hospital treatments enabling case mix adjustment at Trust level and assessment of dates when interventions were received by patients (the pattern of interventions before cardiac arrest will support the cross sectional and time series analyses). Linkage to ONS death data will provide 30 day and 90 day mortality for those patients in the NCAA who were discharged from hospital alive. HES and ONS data will be requested for all patients who have been admitted to hospitals taking part in the NCAA audit since it began in 2010 and will only be used for the purposes specified above.

Expected Benefits:

By December 2016, the LSHTM aims to have identified key intervention features that improve outcomes, and will be able to disseminate the findings and recommendations across the NHS to enable hospital managers, clinicians and policy makers to raise standards of care for all patients at risk of deterioration and reduce avoidable mortality. As well as the review of the evidence associated with different interventions, the LSHTM will also be able to provide a map of the range of interventions targeting acutely ill patients in place across the NHS which will support health service managers in determining the design of their own service improvements. In addition, this study will provide preliminary information on the feasibility of using in hospital cardiac arrest rates as a routine measure of quality of care within the NHS.

Outputs:

1. A literature review and qualitative paper published describing the evidence base behind current interventions and how they are being implemented in practice (by Dec 14-Feb 16) and publication of a paper on the findings from the survey of Trusts taking part in the NCAA Trust Survey (by May 2016) 2. Publication of a paper and final report for NIHR describing the findings from analysis of the association between different intervention types and IHCA incidence and outcomes (by November 2016). 3. To inform NHS acute Trusts, NHS England and DH of intervention features associated with the lowest IHCA incidence and best outcomes and the feasibility of using in-hospital cardiac arrests as an indicator of hospital quality and safety through published reports and presentations by December 2016. This study will provide key information to guide service redesign for clinicians, hospital managers and policy makers. Evidence-based standardisation of practice across the NHS will not only result in reducing avoidable mortality and better quality care for all patients at risk of deterioration but also result in more efficient investment of NHS funds. A summary of the evidence about the effectiveness of interventions for identifying and responding to the deteriorating patient and how these were originally implemented will be produced as a guide. The service evaluation (based on in-depth work in 20 hospitals and the descriptive survey) will provide information on the variety of current service provision enabling identification of where improvements might need to be targeted. The survey will provide information on the types of interventions and will be linked with HES/ONS/ICNARC data by trust/hospital. Findings from the quantitative analyses will provide an evidence base as to which interventions should be implemented and how. It will also identify further research priorities for exploration in future studies. In addition, the LSHTM will be able to assess the feasibility of using in-hospital cardiac arrest (IHCA) rates and outcomes as indicators of hospital quality of care for acutely ill patients which will feed into the NHS Outcomes Framework Technical Advisory Group (one member of the team is a member). In addition findings will be disseminated via the following routes: • The research will produce a detailed report for NIHR Health Services & Delivery Research (HS&DR) programme detailing research methods, findings and conclusions. In addition, short summaries of the research will be produced. Summaries of the methodological approach will be made available. (By October 2016) • For national policy through links with the NHS Commissioning Board and the Care Quality Commission (and its Chief Inspector of Hospitals). • Regionally through north London, Essex and Hertfordshire via the UCL Partners Academic Health Science Network (including 15 associated NHS hospital Trusts), the Clinical Senates and the Collaboration for Leadership in Applied Healthcare Research and Care (CLAHRC) • Presentations will be made at national meetings of professional organisations including ICNARC, Resuscitation Council and Royal Colleges with study investigators drawing on their extensive contacts to ensure the widest audience possible. • Presentations to relevant patient and voluntary groups, e.g., through UCL Partners. • Production of papers for peer reviewed academic journals (such as British Medical Journal, BMJ Quality and Safety, Resuscitation, Heart, or Journal of Health Services Research and Policy) and conference presentations (International Forum on Quality and Safety, Patient Safety Congress etc.).

Processing:

The LSHTM will request HSCIC to undertake a bespoke data linkage between HES/ONS data sets and the ICNARC NCAA/CMP datasets. The primary identifier would be the NHS Number, but it may improve linkage to also include other available identifiers, i.e. date of birth and post code (ICNARC does not hold the name or full address of patients in the NCAA audit), so permission is also requested to include these (in line with the s251 support). Once linkage has been achieved, the LSHTM will request HSCIC to provide the pseudonymised linked ONS/HES data set. The process will involve: 1. ICNARC uploading a dataset of identifiers to HSCIC 2. HSCIC perform 'bespoke data linkage' to HES/ONS 3. HSCIC returns a list of matched Study_IDs to ICNARC 4. HSCIC provides pseudonymised HES/ONS data with Study_IDs to LSHTM 5. ICNARC provides pseudonymised CMP+NCAA data with Study_IDs to LSHTM 6. LSHTM link the datasets (CMP+NCAA data and HES/ONS using Study_ID). A description of the ICNARC databases is as follows: The National Cardiac Arrest Audit (NCAA) is the national clinical audit of in-hospital cardiac arrests. Data are collected on all individuals (excluding neonates) receiving chest compression(s) and/or defibrillation and attended by the hospital-based resuscitation team (or equivalent) in response to a 2222 call (2222 is the standardised number for a crash/cardiac arrest call). The dataset includes patient demographics (NHS number, date of birth, sex and ethnicity, but not full name or address), information regarding the hospital admission (date, reason), details of the arrest (time of call, status at team arrival, location, presenting rhythm) and outcomes (return of spontaneous circulation and survival to hospital discharge). The Case Mix Programme (CMP) is the national clinical audit of adult critical care units. Data are collected on all patients admitted to a participating critical care unit. The dataset includes patient demographics (NHS number, date of birth, sex, ethnicity and post code, but not full name or address), severe conditions in the past medical history, information regarding the hospital and critical care unit admission (dates/times, prior location), physiological data from the first 24 hours following admission, organ support received in the critical care unit and outcomes up to ultimate discharge from acute hospital. CMP data will only be included for patients experiencing an in-hospital cardiac arrest (identified from the NCAA dataset). No identifiers will be received, stored, or processed by LSHTM (other than the identifiable ONS Mortality fields, used for calculating 30 and 90-day mortality). Only the following HES/ONS data items will be retained at LSHTM: From HES: Patient Information:Age in years, Sex, Ethnicity, Index of Multiple Deprivation (IMD by decile),rural urban indicator Episode information: From one year before to one year after the index admission: Diagnosis and operative codes, Date of admission, Source of admissions, Method of admission, Date of interventions, Date of discharge, Start and end date of spells, Destination after discharge Organisation: SUS system codes, Hospital and Trust code, Purchaser (CCG) From ONS: Date of death, Primary and additional causes of death. Please note that the date of death will only be retained for a maximum of 3 months to carry out checks/data cleansing, in line with the s251 support. The data analysis will be completed at LSHTM by a statistician from ICNARC at LSHTM and under the supervision of co-applicants employed by LSHTM and ICRNARC on this NIHR-funded study. These are the only people who will have access to the data, and are all employed substantively by either LSHTM or ICNARC. After undertaking statistical analysis, outputs will be in the form of tables containing aggregated data with small numbers suppressed in line with the HES Analysis Guide.


Project 5 — DARS-NIC-185179-V0B0T

Opt outs honoured: No - data flow is not identifiable (Does not include the flow of confidential data)

Sensitive: Non Sensitive

When: 2018/10 — 2019/02.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii)

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care

Objectives:

Patients with acute conditions who present as emergency hospital admissions may receive emergency surgery (operative) or non-operative care. Within the emergency general surgery specialty, some patients with acute conditions have improved health following emergency surgery and others from non-operative care. However, for many patients the relative benefits, risks and costs of emergency surgery versus non-operative care are unknown. The Getting it Right First Time (GIRFT) report for emergency general surgery, found wide variation across NHS trusts in care quality and outcomes after emergency surgery, which reflect local logistical and resource constraints, but also clinical uncertainty. For common acute conditions, such as diverticular disease, there are well-developed non-operative strategies and little evidence that emergency surgery leads to better outcomes. This observational study will provide a rigorous evaluation of the relative effectiveness and costs of emergency surgery versus non-operative care for common acute conditions, and inform change to emergency general surgery provision across the NHS. London School of Hygiene & Tropical Medicine (LSHTM) requires HES and Civil Registration (Deaths) data for use in the “Emergency Surgery Or noT (ESORT)” study activities. The LSHTM instigated the work in order to estimate the effectiveness and cost-effectiveness of emergency surgery versus non-operative care for patients with common acute conditions presenting as emergency admissions to NHS trust hospitals. No other organisations are involved. Only LSHTM will have access to the pseudonymised data requested and supplied by NHS Digital. The LSHTM has applied for and secured funding from the NIHR to undertake this work. The aim of this work is to estimate the effectiveness and cost-effectiveness of emergency surgery versus non-operative care for patients with common acute conditions presenting as emergency admissions to NHS trust hospitals. The acute conditions being considered are appendicitis, gallstones, diverticulitis, hernia, intestinal obstruction, acute intestinal ischaemia, and peptic ulcer’. This observational study will provide a rigorous evaluation of the relative effectiveness and costs of emergency surgery versus non-operative care for common acute conditions, and inform change to emergency general surgery provision across the NHS. The specific objectives are to evaluate using HES and Civil Registration (Deaths) data: 1. The effectiveness of emergency surgery versus non-operative care for common acute conditions presenting as emergency admissions across broad ICD-10 categories. 2. The relative cost-effectiveness of emergency surgery versus non-operative care across broad ICD-10 categories. 3. The clinical and cost-effectiveness of operative versus non-operative care for specific patient subgroups, including diagnostic subcategories and patient characteristics. HES Admitted Patient Care (APC) and Civil Registration (Deaths) data are required from NHS Digital in order to undertake this study. Overall justification of the data requested: HES APC data are required to determine the exposure (emergency surgery or non-operative care), to identify patient characteristics (age, sex, ethnicity, index of multiple deprivation) and comorbidities, to identify subsequent admissions (emergency or elective), to derive the surgical volume (a measure of quality) for each acute condition, and to derive and the proportion of emergency admissions for each acute condition where emergency surgery is undertaken (the tendency to operate, subsequently used as an instrumental variable). Civil Registration (Deaths) data are required so that 30-day, 90-day and 1-year mortality can be considered as outcomes. The number of years of data requested (2009-2016) will provide sufficient events for analysis without being an unduly long period. National data are required to ensure sufficient events for analysis and provide nationally representative findings. The HES APC data being requested relate to: i) a specific cohort of patients (relating to the above 7 acute conditions only) and ii) a broader extract (relating to the above 7 acute conditions only) which will allow the LSHTM to assess the quality of care experienced by the patients in the cohort. i) Cohort The cohort of patients is defined as all patients with an emergency admission which includes a diagnosis (via ICD-10 code) of one of 7 acute conditions (appendicitis, gallstones, diverticulitis, hernia, intestinal obstruction, acute intestinal ischaemia, peptic ulcer) in any diagnosis field of any episode of the admission, with an admission date between 1 April 2009 and 31 March 2016. This is the index admission. LSHTM are requesting data relating to their cohort of patients for all episodes of all admissions (emergency and elective) from 1 year prior to their index admission to 1 year after their index admission (i.e. covering the period 1 April 2008 – 31 March 2017 overall). Data at the index admission will be used to determine the exposure (emergency surgery or non-operative care); data from 1 year prior to the index admission up to and including the index admission will be used to identify patient characteristics (age, sex, ethnicity, index of multiple deprivation) and comorbidities; data from the 1 year following the index admission will be used to identify subsequent admissions (emergency or elective). The sample size of this data request has been minimised by requesting only data relating to the cohort patients (i.e. for the above acute conditions only); the number of years of data requested has been minimised by requesting only data relating to the period within 1 year of the index admission for each cohort patient; the number of variables requested has been minimised by only requesting those which are necessary for the proposed analysis. ii) Broader extract LSHTM are also requesting data on a very limited number of variables relating to all episodes of all admissions (emergency and elective) which include a diagnosis (via ICD-10 code) of one of 7 acute conditions (appendicitis, gallstones, diverticulitis, hernia, intestinal obstruction, acute intestinal ischaemia, peptic ulcer) in any diagnosis field of any episode of the admission, with an admission date between 1 April 2008 and 31 March 2016 (i.e. not just the cohort patients). These data will be used to derive the surgical volume (a measure of quality) for each acute condition and the proportion of emergency admissions for each acute condition where emergency surgery is undertaken (the tendency to operate, subsequently used as an instrumental variable). The sample size of this data request has been minimised by requesting only data relating to the diagnoses of interest; the number of years of data requested has been minimised by requesting only data relating to the period of interest (1 year prior to their first index admission until their final index admission); the number of variables requested has been minimised by only requesting those which are necessary for the proposed analysis. Civil Registration (Deaths) Rather than applying to access death dates from the Civil Registration (Deaths) dataset, LSHTM are requesting derived variables indicating, for each patient in their cohort, whether or not they had died by 30-days, 90-days and 1-year after their index admission. This removes the need for them to directly access this sensitive data from the Civil Registration (Deaths) dataset.

Expected Benefits:

The aim is to complete the study by April 2021, with all the below measurable benefits scheduled between April 2019 and April 2021 (exact dates TBC). To help ensure that evidence will be generated that can improve emergency general surgery provision, the study design has been informed by service providers, commissioners and patient representatives. As well as a health economist, statisticians and an econometrician, the wider project team includes clinicians (senior perioperative researcher; consultant vascular surgeon; medical director) and a senior member of the Clinical Effectiveness Unit, Royal College of Surgeons, who will bring a national surgical perspective. The study will inform service change via a translation workshop which will draw on the views of patient representatives, surgeons, national policy makers (e.g. NICE, NHS England), commissioners and managers of surgical services and those setting future research priorities. The actual expected benefits of the project are increased effectiveness and cost-effectiveness of emergency general surgery within the NHS. Increased effectiveness will lead to improved quality of care, survival rates and quality of life. Increased cost-effectiveness will enable commissioners/care providers to reallocate funding to other areas of care, benefitting care users. It is not possible to state the expected magnitude of the impact since this will depend on the findings of the project. However, if the project identifies commonly used surgical services where disinvestment is warranted and/or potentially commonly used surgical services where additional investment is required then the impact in terms of both effectiveness and cost-effectiveness could be substantial.

Outputs:

The aim is to complete the study by April 2021, with all the below outputs scheduled between April 2019 and April 2021 (exact dates TBC). Findings will be presented at national and international conferences including clinical (surgical, perioperative) and academic (Health Services and Health Economist) meetings. A translation workshop will draw on the views of patient representatives, surgeons, national policy makers (e.g. NICE, NHS England), commissioners and managers of surgical services and those setting future research priorities, to ensure the study can inform service change. Direct communication of knowledge to key clinical organisations and, if appropriate, input into clinical guideline development will be ensured by team members. This will include contributing to future Royal College of Surgeons initiatives, and working with NHS Rightcare to modify decision aids aimed at supporting shared decision making. The LSHTM will work with its media department and its lay representatives to ensure the findings are accessible to the broader public. A full and complete account of the research will be made available by open access as a publication in the NIHR Health Services and Delivery Research Journal. Research papers will be published in peer-reviewed journals. The research will provide recommendations to commissioners and providers of surgical services on those services where disinvestment is warranted, those where additional investment is required, and those where additional evidence, for example from new randomised controlled trials, would be of greatest value. Outputs will contain only aggregate level data with small numbers suppressed in line with HES analysis guide.

Processing:

The process will involve: 1. NHS Digital provide the LSHTM a bespoke data extract of HES Admitted Patient Care episodes and mortality data including the Unique Study ID and no other identifiers. 2. Extract will be received by the LSHTM by file transfer and stored on the LSHTM secure server. 3. The historic HES records of patients will be used to calculate surgical volume (by financial year and surgeon, hospital and Trust), tendency to operate (by financial year and surgeon, hospital and Trust), and patient comorbidities. 4. Subsequent HES episodes will be used to identify patient outcomes in addition to those provided via linkage to Civil Registration (Deaths) data. 5. A single patient-level dataset will be created including the above derived variables. The main analysis will be on this patient-level dataset. No other data will be used or linked to the data provided by NHS Digital. LSHTM will store the data on a secure server in London which can be only be accessed at LSHTM. 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 i.e.: employees, agents and contractors of the Data Recipient who may have access to that data). The data will not be linked with any record level data. There will be no requirement nor attempt to reidentify individuals from the data. The data will not be made available to any third parties except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. Only specific conditions will be considered. Data relating to other conditions are not being requested. No identifiers are requested.


Project 6 — DARS-NIC-170564-P9F0D

Opt outs honoured: Yes - patient objections upheld (Section 251 NHS Act 2006)

Sensitive: Sensitive, and Non Sensitive

When: 2019/11 — 2019/11.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii)

Categories: Anonymised - ICO code compliant

Datasets:

  • Civil Registration - Deaths
  • HES:Civil Registration (Deaths) bridge
  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Critical Care
  • Hospital Episode Statistics Admitted Patient Care

Objectives:

Chronic kidney disease (CKD) is estimated to affect 1 in 10 people of the adult population in the UK. Although it is known that the bulk of patients with CKD are managed by primary care, it is not known who has progressive kidney disease, whether better management could improve outcomes other than developing kidney failure and how care (including the interphase between primary and secondary specialist care) could be improved further. London School of Hygiene and Tropical Medicine (LSHTM) and University College London (UCL) seeks to link data from the National CKD Audit to Hospital Episodes Statistics and Mortality data from the Civil Registrations dataset to create the National CKD Audit Research database. For both organisations, the legal basis for processing the NHS Digital data under GDPR is Article 6 (1)(e) - "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" and Article 9 (2)(j) - "processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes". History of the National CKD Audit giving rise to the current research data application to NHS Digital: The National Chronic Kidney Disease Audit (NCKDA) took place in England and Wales in 2014-2016. It was tendered by the Health Quality Improvement Partnership (HQIP) to a commercial provider (Informatica systems). Informatica systems extracted the primary care data from consenting GP practices and provided pseudonymised data to LSHTM for analysis. The NCKDA aimed to provide a comprehensive picture of management and outcomes for people with chronic kidney disease (CKD) stages 3-5 managed in primary care in the region. The following key questions were addressed based on the NICE CKD guidance: 1. Are patients with risk factors tested for CKD? 2. Are people who have repeated abnormal kidney function values appropriately coded? 3. Measure the number of patients assessed for cardiovascular risk and the numbers receiving cholesterol lowering treatment 4. What percentage of people with CKD received other NICE-recommended key aspects of CKD management applicable in primary care? 5. For people with CKD, what are the rates of acute complications (hospitalisation with acute kidney injury, hospitalisation with cardiovascular events/interventions, and death)? Audit data were collected from primary care up to June 2016, and subsequently linked to HES/PEDW/ONS data in September 2016 for audit reporting purposes. Data analyses using the linked Audit data were carried out at LSHTM. The most recent Audit report (published in Dec 2017) reported on short term outcomes. This showed that people who have CKD based on their biochemical data but who have no corresponding diagnosis in their GP record die more often than those who are coded for their disease, and very high burden of hospitalisations in this this population, again more often if they were not formally identified by a diagnostic GP code in the health record. However, there is a substantive proportion of patients who were only diagnosed with CKD in 2016 for whom there are no meaningful data on outcomes (i.e. in whom audit question 5 in particular was not addressed, this includes hospitalisation with acute kidney injury, [short term outcomes] hospitalisation with cardiovascular events/interventions, and death [long term outcomes] ). Therefore, there are a number of patients for whom there is not sufficient follow-up time to assess their outcomes, and some outcomes, such as cardiovascular outcomes, kidney failure and death require longer periods of follow-up to assess impact of care. In addition, understanding interfaces between primary and secondary care, i.e. supply/care pathways requires further data validation by linkage to the data held at the UK Renal Registry. Such validation is necessary for understanding features of renal service delivery; originally this was planned for years 4 and 5 of the audit, but NHS England had decided in 2016 to not continue funding the Audit. The linked Audit outcome (hospitalisation and death) data for which HQIP was not the data controller were deleted at the contract end in December 2017. After securing HRA approval for the establishment of this NCKDA research database, and section 251 approval for linking NCKDA data for research purposes without consent, prior to the end of the Audit in December 2017, HQIP signed a data-sharing agreement with UCL and LSHTM, for UCL and LSHTM to retain a copy of the historical Audit data for future research, and for set up of the National CKD Audit research database. This new agreement with NHS Digital is led by LSHTM, who was the data processor for the Audit database, in collaboration with UCL, and wishes to address the short falls of the terminated Audit that were listed above by establishing the National CKD Audit Research database. The team at UCL agreed to house the identifiers required for future data linkage, whilst LSHTM holds the pseudonymised clinical data. The audit website contains information on how to opt out from the audit, and there has been no individual contact to the study team asking for individual opt out from the study. After the data sharing agreement with HQIP was signed, a copy of the identifiable data held at Informatica systems (NHS number, study pseudo-identifier) was moved to the secure server at UCL and the original data at Informatica systems were deleted. In brief, the plan is to establish a research database by retaining the existing NCKDA data (the entire database derived from primary care records), and to augment these data by carrying out linkages with other databases (HES, Civil Registrations (deaths) data, PEDW, UK Renal Registry, and datasets held at NICOR) under the research approvals that were obtained. Research questions that the research data base will address are as follows: 1. What are the long-term outcomes of patients at risk of and with CKD and which aspects of primary care management influences outcomes? This study question relates to the original question posed by the audit data collection which HQIP could not answer with the previous Audit-linkage as at the time of the first linkage there was too short follow-up at the time for a considerable subset of study participants. Outcomes include hospitalisations, cause-specific hospitalisations (e.g. angina, stroke, heart failure, infection, acute kidney injury etc), progressive renal disease, requirement of acute and chronic dialysis (both planned and unplanned), and deaths. All of these outcomes (apart from acute kidney injury) are long-term outcomes of care. As outlined above, the preliminary audit analyses are suggestive that death rates may be higher in those people with kidney disease (based on their kidney function test results) who are not formally recognised to have kidney disease based on the coded disease list in the GP health record. Similar observations were made for hospitalisation rates, though there may be competing risk by mortality. In order to better understand how GP care of people with kidney disease impacts on their health outcomes, the research team therefore require information on mortality to deal with competing risk of death, and also cause-specific mortality to capture renal and cardiovascular deaths. It is here that data from cardiac registries held at NICOR will be very useful as some of these outcomes are only partially captured by HES. 2. How and where are patients with CKD managed? - Investigating the patient journey from primary care to dialysis. This question is crucial to address as currently there is little knowledge on where the best (i.e. most complete) clinical data on patients with more advanced kidney disease are held as these patients are often seen by specialists in secondary care, thus primary care data may be incomplete. To understand which out-patient specialist sees the patient, HES outpatient records are required for those with kidney disease. The ethics permissions for this particular study question do not cover those at risk of kidney disease and hence outpatient data are only requested for the subset of people with known kidney problems. 3. What is the burden of progressive kidney disease and what are its consequences? The audit has shown that testing of kidney disease varies by underlying risk profile, therefore to date there is no official estimate on the numbers affected by progressive kidney disease. The audit database can be used to derive an estimate of the burden of progressive kidney disease, and if linked to long-term outcome data (cardiovascular hospitalisations, death, dialysis) would inform on cardiac and renal outcomes of patients with progressive kidney disease, and also mortality (most patients with CKD die before they ever reach dialysis) 4. To which extent does acute kidney injury contribute to progressive kidney disease and incidence of acute and chronic dialysis? This question cannot be simply addressed with linking hospital admission data to the UK Renal Registry as there is significant concern that the awareness for acute kidney injury (AKI) amongst hospital doctors may depend on the patient's underlying CKD status, thus introducing differential misclassification. The data from the AKI Think Kidneys programme (held at the UK Renal Registry) may address this question with gold standard data. In addition, mortality data are needed as patients with severe AKI may have died before having been identified as a chronic dialysis patient. 5. What are the disability adjusted life years, years of life lost, healthy life expectancy and cost associated with CKD, AKI and progressive renal disease? There are no precise UK estimates for any of these important figures. The data from the above research studies can contribute to a more precise estimation of the impact of CKD on health, and when combined with estimates from existing relevant randomised trials simulations could be run to investigate which known evidence based interventions would be most cost-effective to reduce the impact on patients' lives due to CKD, as well as costs to the community. Mortality data are needed to calculate life expectancies. 6. Data validation to enable analyses of single existing datasets (e.g. primary care, or HES data) so that these do not require future linkages Questions include: How good are primary care codes of transplantation and dialysis?, How well is dialysis/transplantation captured in HES compared to the UK renal registry?, Can data from HES inform on acute dialysis?, Is there differential misclassification of AKI coding in hospital records by CKD status (see above)? The referral date held in the UK Renal Registry database could be used to validate primary care referral entries. How much extra information on renal disease progression is held in renal clinics for those with CKD stages 4 & 5? For this type of analysis HES outpatient data are needed, as well as data on admitted care and mortality data (as other data sources may only collect reliable information on survivors and this bias is important to detect) In summary, hospital data from NHS digital are key to addressing the questions listed above, informing on specialist and critical care and outcomes of people at risk of and with CKD in primary care. In addition there is the need of accurate death data to understand what people with CKD die of, whether there is a difference due to coding of kidney disease, and the role of competing mortality, duration of follow-up and causes of death. The data will not be used for commercial purposes and not used for direct marketing. Any data access for people wanting to use the research database is reviewed by the steering committee. Any research outside of the currently 6 specified research questions listed above will have to undergo new ethics and new data-sharing approvals by all data controllers who provided original data. Funding source: The current linkage has been funded by HQIP/National CKD Audit. Additional funding has been secured for pilot analyses of these linked data when these become available from Kidney Research UK. However, none of these organisations will have any influence on the research findings, and they play no role in defining the means or purpose for which the data will be used.

Expected Benefits:

The early stages of CKD are usually asymptomatic. Hence it is important that those who are at risk are tested at appropriate intervals so that CKD is identified early, with the opportunity to institute appropriate management to prevent kidney disease progression and cardiovascular disease (CVD) complications. Most patients with CKD will be identified and managed by their GP and there a number of Read codes used by practice computer systems which identify these patients and enable a practice register to support regular monitoring and treatment decisions. The specific benefit that relates to Question 1 of the Research Questions; "What are the long-term outcomes of patients at risk of and with CKD and which aspects of primary care management influences outcomes?" is as follows: Currently it is unknown how primary care activities affect long-term outcomes of people at risk of or living with kidney disease. For example, the December 2017 Audit report of the NCKDA data showed that those who have chronic kidney disease (CKD) stages 3-5 based on biochemical test results but who do not have a corresponding read code in their primary care record have worse outcomes than those who do (i.e. they die faster, have more hospital admissions). This raises the question what the outcomes are of patients at risk of CKD or with CKD in practices who are less good in identifying those with CKD have worse outcomes than those who do. The answer to this question has considerable implications for continued incentivisation of testing for and identification of CKD, including whether earlier stages of CKD (1-2) should be identified to improve cardiovascular outcomes and prevent premature deaths. The mortality data will be important to better understand the distribution of cause of deaths. Note that most patients with CKD die before they require dialysis. The specific benefit that relates to Question 3 of the Research Questions; "What is the burden of progressive kidney disease and what are its consequences?" is as follows: The statistician who carried out the NCKDA analyses has obtained a MRC PhD fellowship to investigate within the next 3 years the burden of progressive kidney disease and its consequences (Question 3). The answer to this question is currently unknown and of clear importance to the planning of health care delivery. The specific benefit that relates to Question 2 of the Research Questions; "How and where are patients with CKD managed? - Investigating the patient journey from primary care to dialysis" is as follows: HES and Mortality data will be used to examine the association between variation in coding/ management of CKD with outcomes to better understand if and how these are related. Linked data from outpatient records will identify those CKD patients who were not just managed in primary care and provide a more holistic picture of the burden of health needs of the CKD population. This will also contribute to answering Question 1. In summary: Patient information will be used to improve patient care by improving the diagnosis of chronic kidney disease (CKD) in primary care and to improve diagnosis and care using electronic patient systems. Patient information will be used to serve the wider public interest by identifying gaps or shortfalls in commissioning services and providing a more comprehensive picture of care and outcomes of people with CKD within primary care in England and Wales. The research data base will for the first time give a comprehensive picture of renal and cardiovascular care in those at risk of and with CKD. This is also contributing to answering Question 2 of the research questions. The linked data will for the first time be able to address the question whether short-term outcomes of CKD management such as acute kidney injury (AKI) contribute to later outcomes such as progressive kidney disease, and dialysis start (Question 4: To which extent does acute kidney injury contribute to progressive kidney disease and incidence of acute and chronic dialysis?) Overall, these linked data will be incredibly useful for health economic analyses which to date have only focused on subsets of patients with CKD (Question 5. What are the disability adjusted life years, years of life lost, healthy life expectancy and cost associated with CKD, AKI and progressive renal disease?) The multiple linkages will be extremely useful to understand key data items that are available in other datasets for kidney patients (Question 6. Data validation to enable analyses of single existing datasets (e.g. primary care, or HES data) so that these do not require future linkages. The National Institute for Clinical Excellence (NICE) issued guidance on the early identification and management of CKD in adults in primary and secondary care in 2008 (National Institute for Health and Care Excellence, 2008) with a recent update in 2014 (National Institute for Health and Care Excellence, 2014). These guidelines are currently reviewed. Findings from the research database will reflect how adherence to these guidelines at the time was associated with outcomes and address open research questions as listed in the respective guidelines. Engagement with all stakeholders and dissemination of findings (see section 5c) will enable further quality improvement efforts and more joint up care, and updates to any relevant further guidelines. Currently LSHTM are working on obtaining additional funding from the Wellcome trust, BHF, NIHR and Kidney Research UK for analyses of the database, and LSHTM would anticipate that within the next 3-5 years, LSHTM have analysed and published the data with regards to the 6 broad research questions covered by the audit research ethics approval.

Outputs:

What will be produced as a result of the data processing? LSHTM will process the data and proceed with analyses as outlined above for the research questions. Analyses will take place between 2019-2021. As each result becomes available, there will be submissions to peer reviewed journals (BMJ, JASN, AJKD, PLOS, BMC, JAMA, Heart, etc), presentations and conference contributions (UK Kidney week, European Renal Association, American Society of Nephrology, British cardiovascular Society, British Society for Heart Failure). Currently, ethics approvals are only until 2022, with the plan to make the most of the data until then. What level of data will be contained in the output? All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide Dissemination and communication approach The findings of the research will be shared within the renal and cardiovascular community. Preliminary findings from the National CKD Audit are currently informing discussions with regards to the NICE CKD guideline update. Researchers at LSHTM and UCL are presenting Audit findings to relevant national conferences and training days both for academics as well as clinical practitioners. Researchers from LSHTM have engaged with the public at the Pint of Science event in 2018. The planned analyses will be discussed with patients attending the Patient Council at the UK Renal Registry. There is an Audit website which informs about the audit and its findings to date. UCL plan to continue with this dissemination as more data accrue after linkage of records. The Audit steering group anticipate engaging with the renal, cardiovascular, diabetes and hypertension societies as well as the RCGP to publicise the findings of research and to inform future quality improvement projects. Exploitation of results Findings from the research will inform on the need of future linkages in cardiovascular and renal research. This information will be shared in research papers and algorithms used within the HDR UK for linked primary and secondary care data. This information will be made publicly available.

Processing:

The audit was tendered by HQIP and the commercial Audit supplier was at the time Informatica systems. Data were extracted by Informatica systems for the Audit purposes and any patients having a Read code for opt out were removed from the database at extraction. The last extraction took place in 2016. After securing ethics permissions for holding identifiable data elsewhere, and signing the relevant data sharing agreements, Informatica has now transferred NHS numbers and a corresponding pseudo-identifier code to UCL, and deleted any information related to the audit on their systems. An explanation of the role of each organisation involved in the set-up of the NCKDA is as follows: 1. UCL provides list of NHS numbers with NCKDA pseudo-id (study ID) to NHS Digital. These are the only identifiers that will flow to NHS Digital. 2. NHS digital links data for HES & Civil Registration Mortality data, and returns clinical and mortality data to LSHTM with NCKDA pseudo-id (study ID), with the NHS numbers removed. 3. UCL provides list of NHS numbers with NCKDA pseudo-id to NWIS 4. NWIS links data for PEDW and returns clinical data to LSHTM with NCKDA pseudo-id, with the NHS numbers removed 5. UCL provides list of NHS numbers with NCKDA pseudo-id to NICOR 6. UK Renal Registry provides list of NHS numbers with Renal registry pseudo-id to NICOR 7. NICOR generate Master-patient index of NHS number matches with NICOR, the UK Renal Registry, and the NCKDA. 8. NICOR return Renal registry pseudo-id and NCKDA pseudo-id to the UK renal registry 9. UK Renal Registry sends clinical data with NCKDA pseudo-id to LSHTM. 10. NICOR sends clinical data with NCKDA pseudo-id to LSHTM - University College London (UCL) - UCL is seeking to link data from the National Chronic Kidney Disease (CKD) Audit to Hospital Episodes Statistics and Mortality data to create the National CKD Audit Research database. They are working with the London School of Hygiene and Tropical Medicine to determine the nature and processing of the NHS Digital data, and will process the data. They will also provide to NHS Digital a list of NHS numbers to enable linkage with third parties (The National Institute for Cardiovascular Outcomes Research/NICOR and the UK Renal Registry). They are, therefore, a data controller who will process data. In relation to the identifiers, (NHS numbers, NCKDA pseudo-id) have already flowed from Informatica systems to UCL secure data haven - London School of Hygiene and Tropical Medicine (LSHTM) - the LSHTM is the other organisation working with UCL to link data from the National Chronic Kidney Disease (CKD) Audit to Hospital Episodes Statistics and Mortality data to create the National CKD Audit Research database. They are working with UCL to determining the nature and processing of the NHS Digital data, and will process the data. They are, therefore, a data controller who will process data. - Healthcare Quality Improvement Partnership (HQIP): HQIP were the data controller for the original primary care data extraction of the NCKDA, and tendered the Audit on behalf of NHS England and Wales. They have given permission for the data to be used by UCL and LSHTM (see SD11, SD11.1), but play no role in defining the means or purpose for which the data will be used, and therefore play no role in this application. - NICOR - the NCKDA research database will also contain data from NICOR, allowing the individual validation of key data items in HES for the population in the Audit (which will require linkage to the HES data). This is one of the stated aims of the establishment of the data base. However, NICOR play no role in determining the nature of the research or processing, and will not have access to the NHS Digital data. - UK Renal Registry (UKRR)- the NCKDA research database will eventually contain data from the UKRR, allowing the individual validation of key data items in HES for the population in the Audit (which will require linkage to the HES data). This is one of the stated aims of the establishment of the data base. However, NICOR play no role in determining the nature of the research or processing, and will not have access to the NHS Digital data. - Informatica Systems: they were original Audit provider for the NCKDA under the tender agreement with HQIP. Prior to the termination of the Audit, they transferred a copy of the identifiable data to UCL and subsequently deleted all Audit data on their systems. Since then they have had no further involvement, and have no role in defining the means or purpose for which the data will be used for this application. - Queen Mary, University of London (QMUL) - researchers at QMUL previously contributed to the writing of two national Audit reports from the NCKDA, but have had no further involvement, and have no role in defining the means or purpose for which the data will be used in this application. Data flows for this current agreement for linkages carried out by NHS digital: All data flows have been reviewed by ethics and CAG and have section 251 approval for linkage without individual consent. 1. Any identifiable data flows only involve transfer of the NHS number and a pseudo-identifier (study ID) to allow data linkage. 2. Data flows to LSHTM involve pseudonymised linked data. 1. The Patient Identifiable data: Data flows to NHS Digital include the identifiable data held at UCL (NHS number) with the pseudo-id for the clinical data held at LSHTM. UCL will supply data from the entire Audit dataset irrespective of GP location in order to track patients who have moved across national boundaries. Cohort details will be transferred as a password-protected and encrypted CSV file to NHS digital. Details of patients who have chosen to opt out during 2014-16 will not be sent to NHS digital as these were never extracted. Data extraction stopped in 2016, and no new data were extracted since then. There has been no contact asking for individual opt outs from 2014 up to now. NHS digital will check whether there are any national opt-outs that UCL were not made aware of and quantify the total number for the study. LSHTM anticipate that this number will be very small, as all research opt-outs were removed from the outset prior to Audit data extraction. Data requested from NHS digital include hospitalisation, outpatient and critical care and death data. In order to supplement the data from primary care in terms of comorbidities (allowing the control for confounding for the objectives outlined above) LSHTM require data on past hospital admissions and care received in the patient population. LSHTM require data from Audit participants who are located either in England or Wales, as some patients from Wales may have had acute care in England (and vice versa). 2. The Pseudonymised data: NHS digital will supply HES in and outpatient records, critical care records (for England) and mortality data from the Civil Registration dataset (for England and Wales) for the cohort provided for the agreed period to LSHTM with the pseudo-id to be incorporated in the existing database held at LSHTM which only uses pseudonymised data. NHS digital will not supply records for those who have opted out from research. Further linkages: A similar process will take place to obtain hospitalisation and outpatient data for people seen by health services in Wales, with identifiable data flowing from UCL to NWIS, and NWIS supplying pseudonymised hospital outpatient and admission data to LSHTM. Therefore, the NCKDA research database will have hospital data and death data for England and Wales. Data will also be linked to data held at the UK Renal Registry and data held at the National Institute for Cardiovascular Outcomes Research (NICOR) to gather further information on kidney and cardiovascular outcomes. The data for NICOR and the UK Renal Registry will be using NICOR as trusted third party for linkage, and therefore are not shown on this simplified diagram. The full data flow diagram can be found in the data management protocol. In brief, audit identifiable data (NHS number) and pseudo-identifier will be sent to NICOR. NICOR will then send linked pseudonymised data to LSHTM for analysis. A similar process applies to UK renal registry data where NICOR will act as trusted third party. Legal/ethical basis: The entire set-up of the NCKDA research database has been ethically approved for research purposes as outlined above, and with approval by CAG for linking data without individual consent. The NCKDA was originally set up and funded by NHS England and Wales to audit care and to determine how care impacts on long-term health outcomes, and so there is in addition a need to capture these data for historical research/statistical purposes. Identifiable primary care data will only be handled by UCL as outlined above for linkage purposes. Data will only be accessed by individuals within UCL who have authorisation as per the data-sharing agreement with HQIP and ethics/CAG to process the data for the purposes described above, all of whom are substantive employees of UCL. The core clinical pseudonymised data will only be accessed by 2 individuals within LSHTM who have authorisation as per the data-sharing agreements with HQIP and ethics/CAG to process the data to produce subsets of the data that will be accessed by researchers using the data. These subsets of data will only be extracted after the project has been reviewed and approved by the NCKDA steering group. The NCKDA steering group consists of former representatives of the Audit steering group when the Audit was live (before 2017), representatives from UCL, LSHTM, NICOR, Wales, and the UK Renal Registry. Research project-specific data would be analysed on a project by project basis. Analysts who used the project specific data are trained in analysing routine electronic health record data under appropriate supervision by LSHTM and UCL at LSHTM and UCL (other locations are not suitable based on the existing data sharing agreements). Results from analyses of the pseudonymised clinical data will be published in peer reviewed clinical and epidemiological journals. All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide. 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 i.e.: employees, agents, and contractors of the Data Recipient who may have access to that data). There will be no data linkage undertaken with NHS Digital data provided under this agreement other than that which is already stated. Data will only be accessed and processed by substantive employees of UCL, or LSHTM and will not be accessed or processed by any other third parties not mentioned in this agreement.


Project 7 — DARS-NIC-148101-R7RSL

Opt outs honoured: Y

Sensitive: Sensitive

When: 2016/09 — 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
  • MRIS - Scottish NHS / Registration

Objectives:

The data supplied by the NHS IC to London School of Hygiene & Tropical Medicine will be used only for the approved Medical Research Project MR104A.

Expected Benefits:

To be completed by the customer on re-submission

Outputs:

To be completed by the customer on re-submission

Processing:

To be completed by the customer on re-submission


Project 8 — DARS-NIC-148044-RGS7W

Opt outs honoured: Yes - patient objections upheld (Section 251 NHS Act 2006)

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2020/07.

Repeats: Ongoing, One-Off

Legal basis: Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , National Health Service Act 2006 - s251 - 'Control of patient information'.

Categories: Identifiable, Anonymised - ICO code compliant

Datasets:

  • MRIS - Cause of Death Report
  • MRIS - Cohort Event Notification Report
  • MRIS - Bespoke
  • Civil Registration - Deaths
  • Demographics

Objectives:

The objectives of the Whitehall resurvey are to quantify reliably the relevance of blood lipids, markers of inflammation and nutrition and genetic markers, for cardiovascular and non-cardiovascular mortality in older people. This resurvey in 1997 of over 5500 older men (mean age 77 years) with questionnaires and blood samples who participated in the 1970 Whitehall study, involves over 3300 deaths over a 14-15 year follow-up period in the subset with complete data. The study has already contributed reports on vascular and non-vascular mortality in relation to blood lipids, biomarkers of inflammation, phospholipid fatty acids and cystatin C. Work is ongoing on reports mortality in relation to 25-hydroxy-vitamin D, smoking and alcohol consumption.

Yielded Benefits:

The study already made a major contribution to the identification of cardiovascular risk factors in middle aged men in the UK. The study confirmed the importance of smoking, elevated blood cholesterol, elevated blood pressure and diabetes for heart disease death rates in lower compared with upper employment grades which were not fully explained by established risk factors. The access to lifestyle and medical information in both middle and old age allowed assessment of prolonged differences in such risk factors for life expectancy and causes of death in old age. The study has provided unique data on causes of death in old age in relation to very prolonged differences in cardiovascular risk factors and socioeconomic circumstances in middle and old age. These reports will guide public health policy on the provision of health services to reduce the risks of death and disability in older people in the UK and elsewhere. The study will highlight the importance of modifiable risk factors for avoidable disability in old age using information collected in both middle and old age. Influence on guidelines for the management of hypertension and blood lipids: The 2002 report of the Prospective Studies Collaboration report on blood pressure and stroke and heart disease (Lewington et al, Lancet 2002), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies (Clarke et al, Am J Epidemiol 1999). Likewise, the 2007 report of the Prospective Studies Collaboration report on blood cholesterol and stroke and heart disease (Lewington et al, Lancet 2007), included the Whitehall data and was also based on the methodology to correct for regression dilution bias developed in the Whitehall and Framingham studies. These reports influenced JNC7 Guidelines on the Detection and Treatment of Hypertension in the USA and NICE guidelines for the management of hypertension and blood lipids in the UK in addition to the European Society of Cardiology reports on prevention of heart disease (Piepolo 2016) and detection and management of blood lipids (Capetano, 2016) and American Heart Association reports for prevention of heart disease over the last 15 years. References for benefits of study Lewington S, Clarke R, Quizilbash N, Peto R, Collins R for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: One million adults in 61 prospective studies. Lancet. 2002;360:1903-1913. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R on behalf of the Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual participant data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829-1839. Piepolo MF, Hoes AW, Agewal S, Albus C, Brotons C, Catapano AL, Cooney MT. 2016 guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2016; 37 (29): 2315-81. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37: 2999-3058.

Expected Benefits:

The study will conduct medical research into the causes of death in this sample of the UK population. It is anticipated that the results of the planned analysis will be published in peer review medical journals. The results from this study have helped to inform UK response to the epidemic of deaths from heart disease and stroke in 1970’s and 1980’s and the extent to which mortality from both of these diseases have declined thereafter. Anonymised data from this study were incorporated in the Prospective Studies Collaboration meta-analysis which guided public health policy on detection and treatment of elevated blood pressure and of elevated cholesterol levels in the UK and worldwide. Data from the resurvey on blood lipids and CHD mortality have helped to clarify the relevance of lipids for prediction of death from vascular disease in old age. Lastly, data on blood levels of vitamin D (25(OH)D) in this study have guided policy on the relevance of vitamin D and specifically for testing for vitamin D for prediction of vascular and non-vascular causes of death in the UK. The study will generate a series of scientific publications on the causes of mortality, particularly focusing on determinants of cardiovascular disease in old age in relation to cardiovascular risk factors measured in middle and old age. It will also generate reports on cardiovascular and non-vascular causes of death in relation to socioeconomic circumstances measured in both middle and old age. As well as peer-reviewed scientific publications, the University of Oxford will also communicate with NHS and other organisations (Food Standards Agency) or Public Health England where outputs from the study will provide information needed for health strategies using up-to-date evidence on effects of cardiovascular risk factors on risk of death. This will improve provision of health care delivery and health services in response to demands on health and social care in the present and the future.

Outputs:

The chief aim of the study is to assess mortality risks in old age in relation to cardiovascular risk factors measured in middle and old age, and assess life expectancy and lifetime risks of cardiovascular risk factors measured in middle and old age. All outputs and publications contain only aggregated data with small numbers suppressed in line with HES Analysis Guide. The results of analyses of the Whitehall study have been presented at national and international meetings, including the Society of Social Medicine and the European Society of Cardiology and American Heart Association annual scientific sessions. The results of planned analyses will be submitted for publication and some may also be presented at national and international meetings. Likewise, results of some analyses will be posted on the Nuffield Department of Population Health (a department within the University of Oxford) website. The target time frame for publication of the results of the planned analyses is during 2018-2020. Examples of publications are: Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Clarke R, Shipley M, Collins R, Marmot M, Peto R. Am J Epidemiol. 1999;150:341-353. Re-survey of the Whitehall study of London civil servants: changes in risk factors for cardiovascular disease during 29 years of follow-up. Clarke R, Breeze E, Youngman L, Sherliker P, Bell P, Shah S, Shipley M, Collins R, Leon D, Marmot M, Fletcher A. J Cardiovasc Risk. 2000;7:251-257. Socioeconomic disadvantage persists into old age: self-reported morbidity in a 29 year follow-up of the Whitehall Study. Breeze E, Fletcher AE, Leon DA, Marmot MG, Clarke R, Shipley MJ. Am J Publ Health. 2001;91:277-283. Cause-specific mortality in relation to body mass index in middle age in old age. Breeze E, Clarke R, Shipley MJ, Marmot MG, Fletcher AE. Int J Epidemiol. 2006;35:169-178. Cholesterol fractions and apolipoproteins as risk factors for heart disease mortality in older men. Clarke R, Emberson J, Armitage J, Shipley M, Clark S, Linksted P , Fletcher A, Collins R. Arch Intern Med. 2007;167:1373-1378. Survival in relation to angina symptoms and diagnosis among men aged 70-90 years: the Whitehall Study. Clarke R, Shipley M, Breeze E, Collins R, Marmot M, Halsey J, Fletcher A, Hemingway H. Eur J Cardiovasc Prev Rehabil. 2007;14:280-286. Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19000 men in the Whitehall Study. Clarke R, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley M J. BMJ. 2009;339:b3513. doi: 104136/bmj.63513 Risk factors for pancreatic cancer mortality: extended follow-up of the original Whitehall Study. Batty GB, Kivimaki M, Morrison D, Huxley R, Smith GD, Clarke R, Marmot M, Shipley MJ. Cancer Epidemiol Biomarkers Prev. 2009;18:673-675. Plasma phospholipid fatty acids and CHD in older men: Whitehall study of London civil servants. Clarke R, Shipley M, Armitage J, Collins R, Harris W. Br J Nutr. 2009; 102:279-284. Whitehall Study Authors’ reply. Clarke R, Shipley MJ. BMJ. 2009;339:b5097. Height loss and future coronary heart disease in London: the Whitehall II study. Batty GD, Shipley MJ, Gunnell D, Smith GD, Ferrie JE, Clarke R, Marmot MG, Kivimaki M. J Epidemiol Comm Health. 2011;65:461-464. Modifiable risk factors for prostate cancer mortality in London: forty years of follow-up in the Whitehall study. Batty GD, Kivimäki M, Clarke R, Davey Smith G, Shipley MJ. Cancer Causes Control. 2011;22:311-318. Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Eur Heart J. 2013;34:1365-74

Processing:

The cohorts were flagged by NHS Digital under an earlier data sharing agreement (DARS-NIC-148044-RGS7W-v0.0). NHS Digital will provide updates on participant events, including removals and re-entries to NHS Registration, cancer registrations and deaths including cause of death details. Participants in the Whitehall study were flagged for mortality and cancer registration at the Office for National Statistics (England), which provided the date (mm/yyyy) and cause (including International Classification of Disease (ICD) codes) of all deaths. Cause-specific mortality is coded using ICD-9 up to August 2002 and ICD-10 subsequently. In the past, mortality data and cancer registration data were provided electronically at 3-monthly intervals to the London School of Hygiene and Tropical Medicine. The data were sent to University of Oxford by encrypted email. The University of Oxford incorporated these data into the Whitehall database but in summer 2018 the data provided by NHS Digital was securely destroyed. The participants in this study have agreed to prolonged follow-up via central registries via patient consent, with the patient information sheet and consent form making reference to the fact that information about health and lifestyle and causes of death could be collected for medical research purposes. Due to the age of the consent involved, Section 251 support was also obtained to cover the continued use of identifiable data. All data on the study will be stored in secure electronic files at University of Oxford. Pseudonymised copies of the linked study data will be sent at periodic intervals by secure email using password encrypted files to named researchers at LSHTM and UCL to maintain the 3-way collaboration for supervision of the study. The Whitehall study database held by the University of Oxford contains identifiable data for the study participants, including date of birth and name if this was provided by participants in response to questionnaires. The data disseminated by NHS Digital will be in a pseudonymised format using a Study ID, but once received by the University of Oxford the data will be combined with the identifiable study data already held. For the purposes of this agreement the data disseminated by NHS Digital is therefore considered to be identifiable. A senior statistician at the Clinical Trial Service Unit (CTSU) links the data, using study ID, with the study participants questionnaire records. All subsequent analyses use only subsets of the pseudonymised data. All such subsets are customised for specific analyses intended for specific purposes. 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, i.e. employees, agents and contractors of the Data Recipient who may have access to that data). The study will not share any data supplied by NHS Digital with any other institution or individual outside the study of the University of Oxford, London School of Hygiene, or UCL.


Project 9 — DARS-NIC-145260-G4Y0G

Opt outs honoured: No - data flow is not identifiable (Does not include the flow of confidential data)

Sensitive: Non Sensitive

When: 2019/02 — 2019/02.

Repeats: One-Off

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii)

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care

Objectives:

Plain language summary: Respiratory viruses (like colds and flu) trigger asthma attacks, chronic obstructive pulmonary disease (COPD) exacerbations, and heart attacks. Other factors like air pollution can trigger these attacks too. Virus surveillance data on its own is not good enough to work out what proportion of these attacks are from viral infections or are caused by other factors. The research team at the London School of Hygiene and Tropical Medicine (LSHTM) need to know which factor is most important so that they can try to do something to prevent these attacks. The pattern of viral circulation in populations is affected by how people mix together and pass viruses to each other. Children have a lot of contacts each day and pass a lot of viruses to each other, to their parents, and to other people they meet. School holidays are especially important, because children pass viruses less when they are not in school, because they meet fewer people. By combining what is known about how viruses transmit and how people mix together, it is possible to better understand the circulation of viruses. This can then be used with the viral surveillance data (which is not good enough on its own) to understand the effect of each factor on the number of attacks of asthma, COPD, and heart disease each day. This kind of analysis is scientifically really hard to do, because it depends on the small differences in school holidays from place-to-place, and different amounts of pollution in one place compared to another. These small differences in lots of places over many years add up, and so scientists can calculate the effect of each factor. This is the benefit of “big data”, which lets scientists do studies that would not work otherwise, and is how NHS data can be used to help other patients. It should be noted that the entire population is of interest for this study, not just children. Further details: This study examines the timing of hospitalisations for three major chronic diseases to detect associations between known viral and environmental triggers for these conditions. The health impacts of asthma, chronic obstructive pulmonary disease (COPD), and coronary heart disease (CHD) are greatly increased by acute episodes of worsening symptoms (exacerbations). Exacerbations are triggered by environmental factors e.g. poor air quality and temperature, and by acute respiratory infections. The large (and growing costs) of exacerbations provide considerable motivation to improve understanding the triggers of exacerbations. Current methods do not include the dynamic risk of exacerbation caused by respiratory virus transmission, which means that estimates of risk from other variables may be unreliable. This project will begin to tackle the need to understand how viral triggers affect population-level timing of exacerbations. The project will use interdisciplinary methods to develop a novel quantitative framework to assess the population-level drivers of chronic disease exacerbations. The outcome under study is the daily timing of inpatient chronic disease exacerbations for three chronic diseases under study. Therefore, this study is requesting these data from NHS digital for this analysis. The study is also requesting information from NHS digital on infectious respiratory inpatient hospitalisations to aid in the analysis of the chronic disease exacerbations. Specific information: The London School of Hygiene & Tropical Medicine (LSHTM) requires Hospital Episodes Statistics data for use in project: “Novel methods in data science to quantify viral and environmental triggers of chronic disease exacerbations”. There are two organisations involved in this work: the London School of Hygiene & Tropical Medicine, and Public Health England (PHE). LSHTM is the lead for the study, and instigated it as part of the research project being carried out by the Principal Investigator of this project, who is substantially employed by the LSHTM. Members of staff at PHE are also involved in an advisory capacity to the Principal Investigator, due to their expertise in respiratory infections and respiratory virus surveillance. They have no further role in the study, and will not have access to the data provided by NHS Digital. The LSHTM is, therefore, the sole data controller who will also process data. The raw data will only be viewed, accessed and analysed by direct substantive employees of the London School of Hygiene & Tropical Medicine (LSHTM). PhD students may use aggregated time series containing small numbers but will not access the record-level data. This must be aggregated with small numbers suppressed in line with the HES Analysis Guide. Only substantive employees at LSHTM will have access to the record-level data requested from NHS Digital. LSHTM established the Electronic Health Records Research Group to undertake health research using electronic health records. This project was proposed as part of a request for projects using UK health data, funded by Health Data Research UK (HDR-UK). LSHTM responded to a call for research in this area, and the project proposed by the lead researcher for the project was successful. LSHTM/lead researcher applied for and secured funding from Health Data Research UK (HDR-UK) to undertake this work. HDR UK is a joint investment led by the Medical Research Council, together with the National Institute for Health Research (England), the Chief Scientist Office (Scotland), Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the British Heart Foundation and Wellcome. It supports world-leading research to develop cutting-edge analytical tools and methodologies to address the most pressing health research challenges. This work is a study on inpatient hospitalisations resulting from exacerbations of 3 chronic diseases. Inpatient hospitalisation from respiratory infections will be an input to the study. Inpatient data are requested from NHS digital. The aim is to better understand the triggers of chronic disease exacerbations, and to do this LSHTM need to link the circulation of respiratory viruses to the patterns of exacerbations. Inpatient hospitalisation data are needed to achieve this aim and deliver the study results and benefits. This study will develop new methods that allow estimation of both the parameters of dynamic transmission models for viruses, and the contribution of environmental factors, at the same time. This is a new study, and no data have been supplied for this study before.

Expected Benefits:

Decreasing the cost of chronic disease exacerbations is a public health priority, because those costs are rising in the UK and worldwide. To do this, LSHTM need better scientific understanding of the factors that can trigger exacerbations. There is a lot of research from studies of individuals with chronic conditions that viral infections can trigger exacerbations of their conditions. However, public health policy is made at the level of populations, not individuals. There is a real need to determine if the effects we see in individuals are true at the population level. Previous research has shown that environmental variables affect the population-level patterns of exacerbations, but no study has included both environmental triggers and infectious triggers in the UK. The benefits of this study will therefore be in bringing scientific understanding to the interactions between environmental and infectious triggers. The study is generating new knowledge that will not only benefit researchers but will benefit the wider community and society as a whole. Analyses of the patterns of these serious conditions will help to better understand the risks and causes of ill health, especially in these populations that already have serious chronic conditions. Rigorous epidemiology like this study will allow design of better preventive strategies, to help patients and populations decrease the burden of chronic disease exacerbations. Studies of long time series of cases from around England and Wales will allow understanding of whether the exacerbations from one factor, for example, air pollution, have gotten more or less likely over time. It also allows estimation of whether the baseline rate of exacerbations has improved or gotten worse. Short studies cannot detect these kind of changes. Studies of long time periods allow evaluation of interventions that have been made, such as vaccination programs, but to properly estimate their impact, the analysis must have enough data before the intervention before estimating the impact of the new intervention. Results will be shared in open-access scientific articles, in reports, and in talks, and promoted as widely as possible. They will be shared with scientists, and through links with PHE, with public health officials. The results will also be shared publicly and written so that non-specialists can understand and interpret the results. Findings on environmental triggers, especially air quality, will feed into evidence of the role of air pollution on health. These benefits are achieved through the full use of hospital data on exacerbations, public air quality sources, and surveillance data on the viruses involved. These can then be used in population modelling and quantifying public health outcomes

Outputs:

A final report of results will be submitted to HDR-UK in February 2021. This will cover key findings of the study including: methodological developments, scientific findings, policy implications. Academic paper(s) will be published in open-access, peer-reviewed journals, and on the organisation’s website on the following topics: • impact of air quality, viral circulation and other covariates on daily exacerbation rate for each condition; • methodology in using “big data”; • cost and effectiveness of potential vaccination strategies. Target dates for submission will be minimum 2 per year, starting mid 2019. Where possible, the project will target general public health and/or epidemiology journals with a broad audience (e.g. Lancet Respiratory Medicine, Lancet Global Health, Lancet Public Health. PLOS Medicine, PLOS Computational Biology. BMJ, BMJ Open. International Journal of Epidemiology, American Journal of Epidemiology, Epidemiology.). Because analyses are likely to be of interest not just in public health but in methodological advance, the project will also consider specialist journals in statistical methods for large datasets. Dissemination at national and international conferences will adopt a similar strategy of aiming for as broad as possible a reach. They will include disease-focused meetings such as Chest, COPD, and Asthma, and modelling meetings such as Epidemics. The project will also seek presentations at specialty conferences where results have relevance to those audiences, as well as meetings where public health decisionmakers are likely to be represented. For each paper published, a presentation will be developed to summarise the findings for a range of stakeholders, e.g. scientists, patient groups, public engagement events, outreach, policymakers. Findings will be presented at appropriate events. A simplified version of the findings will be generated for sharing with charities/patient groups of interest, and publishing on the organisation’s website. Findings from the study like this will also be shared in posters, presentations, and online. They will be promoted through Twitter and the University website. Where appropriate they will be included in the public engagement work the PI already does (e.g. New Scientist Live, TEDx talks, other events). The LSHTM website provides links to LSHTM open access papers. All publications and conference presentations are promoted on twitter, via the @ehr_lshtm account (Electronic Health Records Research Group, >200 followers), @cmmid_lshtm account (Centre for Mathematical Modelling of Infectious disease, >600 followers) and sometimes the @LSHTM account (main University account, >19,000 followers). They may be promoted through the @HDR_UK account (the funder, >1300 followers), or my personal account (>200 followers). All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Processing:

Processing information: There will be no flows of data to NHS Digital. There will be a flow of requested data from NHS Digital to LSHTM. The pseudonymised HES data will be transferred from NHS Digital using the secure data transfer portal. This data will be stored on the secure server at LSHTM which can be accessed only by the LSHTM study team using a unique network password. No-one else outside of the LSHTM study team will have access to any of the NHS Digital data from this application. There are no subsequent flows of data. 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 i.e.: employees, agents and contractors of the Data Recipient who may have access to that data). The data will not be linked with any record level data. There will be no requirement nor attempt to reidentify individuals from the data. The data will not be made available to any third parties other than those specified except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. Data requested: This project requests Hospital Episode Statistics Admitted Patient Care data. The project minimises data requested by limiting to specific health conditions and diagnosis codes. This is a large study, and needs to be, because the differences from city-to-city in viral circulation and pollution are expected to be quite small. Therefore “big data” are needed to give the statistical power to estimate these effects. The project requests 13 years of data. This number of years is needed for 4 major reasons: 1) School holidays affect transmission of viruses and hence risk of exacerbations. There are small changes to school calendars each year, and so as many years as are possible are needed to be able to detect the effect of these small changes in holiday timing. 2) Over long time periods we expect demographic change in the populations (e.g. increase or decrease in number of children, or fraction of older adults). These changes can alter viral circulation, i.e. a higher proportion of children in the population increases the circulation of respiratory viruses, because children have higher contact rates. This is a slow process, and therefore a fairly long time period is needed over which to estimate these effects. If the time period is too short, the estimation procedures will not have the power to detect the effect of demographic changes on viral circulation. Therefore the public health benefit may not be met. 3) The fraction of older adults with chronic conditions has been increasing through time in the UK. These changes are quite slow and therefore a fairly long time period is needed over which to estimate these effects. If the time period is too short, the estimation procedures will not have the power to detect the effect of demographic changes on number of individuals at risk. Therefore the public health benefit might not be met. 4) Affecting all 4 previous reasons, the study period contains two major events in influenza circulation: the 2009 pandemic, and the phased introduction of the paediatric influenza vaccination program (2013 onwards). Influenza is known to be a trigger for chronic disease exacerbations, so data from before and after these events is needed in order to properly assess the baseline and the effect of these events on viral circulation. Without this, the effect of viral circulation may be confounded by these events/changes and the study will not achieve the aims and therefore the public health benefit. Data is requested nationally because there is variation in school calendar timing and air quality in different regions, and this is what is being studied. Using national-level data will maximise the number of hospitalisation events in each school calendar year which will increase power to detect the effect of each factor on exacerbation risk. Data are minimised by filtering to limited specific conditions of relevance. There are 4 categories: 1) Asthma and similar, 2) COPD and similar, 3) CHD and similar, 4) respiratory infections and similar. Categories 1, 2 & 3 are the target conditions, and Category 4 is an input to the model to understand the exacerbations of 1, 2 & 3. Daily resolution is required to detect effects of air quality on exacerbation risk, because air quality changes every day. Age of patients (month-year) is required for assigning to correct year of school. Location is required for assigning to geographic areas covered by particular school calendars, but only first part of postcode is needed.


Project 10 — DARS-NIC-123200-J0L4T

Opt outs honoured: No - consent provided by participants of research study

Sensitive: Non Sensitive, and Sensitive

When: 2018/03 — 2018/12.

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 – s261(2)(c), Informed Patient consent to permit the receipt, processing and release of data by NHS Digital

Categories: Identifiable

Datasets:

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

Objectives:

The Chief Investigator for this feasibility study is from the London School of Hygiene & Tropical Medicine, and instigated this with support from interested collaborators in Queen Mary University of London and University College London. This is a feasibility study for a larger trial. The question the main trial will address is whether vitamin D supplementation reduces morbidity and increases lifespan in men and women aged 65 to 84 in response to a growing literature base suggesting that such trials are required. The International Agency for Research on Cancer (IARC) Working Group on vitamin D and cancer, of which the chief investigator was a member, reviewed the epidemiological evidence on vitamin D and cancer and concluded that the evidence was strong for colorectal cancer but inconclusive for other individual cancers (IARC Working Group on Vitamin D, 2008). Their report concluded: “The only way to further address the cause-effect issue is to organise new randomized trials to evaluate the impact of vitamin D on all-cause mortality and on the incidence and mortality from common conditions including cancer. These trials should make sure that key parameters of vitamin D status (e.g., serum 25-hydroxyvitamin D levels before and in trial) can be assessed.” Many people in the UK do not receive enough sun exposure to achieve a satisfactory vitamin D blood level. Epidemiological evidence suggests that people with low vitamin D levels are at increased risk for several diseases, including heart disease, various infections and some types of cancer. However, similar epidemiological evidence of benefit for various other vitamins was disproved when randomized trials were conducted. LSHTM is therefore planning a large (n=20,000) trial to evaluate the effect of vitamin D supplementation on mortality and morbidity among older members of the general population. For the primary endpoint of overall mortality in the main trial the necessity of placebo control is not clear. This feasibility study, which is funded by the Government’s Health Technology Assessment agency, will compare a placebo controlled trial in 10 GP practices against an open randomised trial in 10 practices, randomising 800 people aged 65-84 double blind to monthly placebo versus monthly vitamin D for 2 years, and 800 to no treatment versus 2 years of monthly vitamin D. One of the research objectives is to establish the feasibility of flagging for lifelong follow-up through national registers for death and cancer registration, and tracing through the Hospital Episodes Statistics database (HES) for hospital admissions and diagnoses. Comparing hospital admissions, cancer registrations and deaths between participants who have and have not taken vitamin D will answer the question of whether high-dose vitamin D supplementation might help to prolong life and reduce various diseases. The other primary objectives of the trial are to determine the recruitment rate and the compliance rate (the proportion adhering to allocated treatment over 2 years) in practices with placebo control, and in practices with open control. The institution shall also determine contamination rates in those allocated to placebo and those allocated to open control (ie self-administration of >400 IU vitamin D per day or equivalent). IMP adherence and use of additional vitamin D supplements were studied both by self-report and from blood levels of 25(OH) vitamin D at entry and at 2 years. The outcomes of this feasability study will assist with a decision as to the study design of the main trial by providing unbiased data on adverse events in each treatment arm. This will be compared to the (potentially) biased real-time collection of adverse events during the trial to see whether an open allocation trial (where people know which treatment they’ve been allocated to) is more biased in this regard than a blinded design (where patients either receive treatment or placebo). This in turn will help us to present a reasoned argument for the study design that should be adopted in the main trial.

Expected Benefits:

There is a growing consensus that most people in the UK do not receive enough sun exposure to achieve a satisfactory vitamin D blood level, and that current recommendations on the optimal daily dose of vitamin D should be increased. Eighty percent of men and 87% of women aged over 65 years living independently in the UK have blood levels of 25hydroxyvitamin D (25(OH)D the measure of vitamin D status) below the recommended concentration for optimal health (75 nmol/l or 30 ng/ml). Epidemiological evidence suggests that people with low blood levels may be at increased risk for several diseases, including heart disease, various infections and some cancers. However, similar epidemiological evidence of overall benefit for various other vitamins was disproved when randomized trials were conducted, and no adequately powered trial has tested vitamin D in doses that are high enough to achieve blood 25 (OH)D concentration > 75 nmol/l. Although the majority of observational studies report associations between vitamin D deficiency and susceptibility to a range of pathologies, some studies are null, and a few report opposite associations. A large randomized trial is therefore required to assess whether vitamin D supplementation can decrease the risk of various diseases and increase longevity. The importance of a clinical trial of oral supplementation of vitamin D is emphasized by the finding that in practice it is difficult for the majority of UK residents to obtain optimal vitamin D from sunlight or diet. If self administered vitamin D supplementation were shown to confer substantial health benefits it would be routinely recommended and widely adopted. This would also provide a rationale for a national policy of vitamin D supplementation for the general population, a review of the relative risks and benefits of sun exposure, and a revision of existing policy on vitamin D fortification of foods. If no benefit or unforeseen disadvantages are shown this will also be a valuable contribution to knowledge. The target audience for such findings would be the Department of Health and National Institute for Health Research. An important public health priority is therefore to demonstrate the feasibility of a large randomized trial of prolonged vitamin D supplementation in older people, and to show that this will increase serum 25(OH)D to >=75 nmol/l in the majority of subjects. The main trial for which this is the feasibility study will be a randomized trial with 20,000 participants followed for 10 years. A trial of that size is needed to detect the 7% reduction that vitamin D supplementation might plausibly achieve in total mortality in healthy adults aged over 65. As well as demonstrating an expected increase in circulating 25hydroxyvitamin D levels, the feasibility study will provide estimates of cost and establish the study design and procedures required for the main trial. Feedback from patients and GP practice nurses was encouraging for the feasibility study. A number of sites reported that there was a strong interest among the study population and indeed, overall trial response rates were nearly double the protocol target. The final number of patients randomised was 1615 (vs protocol target of 1600) and the overall response rate was 17.2% (9,406 invited, 1615 randomised) compared with the protocol target of 9%. The final study analyses are currently underway, but interim estimates of participant compliance demonstrated excellent compliance at 3, 6 and 9 months, with 97.3%, 96.7% and 95.9% respectively taking all 3 monthly doses of trial medication. The draft report containing all study results is scheduled for Spring 2018.

Outputs:

The results of this feasibility study will be reported in peer reviewed scientific journals with accompanying conference presentations and submissions to regulatory authorities. The first NIHR draft report was submitted in Autumn 2017 to the peer-reviewed Health Technology Assessment journal. It will be several months before this draft version of the NIHR report is finalised, pending referees' comments. During this period, the institution will also target the scientific medical community by submitting a report to the peer-reviewed British Medical Journal. In addition, further funding will be sought for a larger “main” trial (for which this is a feasibility study), involving up to 20,000 participants across 200+ GP practices in the United Kingdom. NIHR have indicated that they would like to see the results of several similar large scale international vitamin D trials, due in the next few years, before they will consider funding a similar large scale study in the UK.

Processing:

Data from all 1615 patients randomised to the trial will be included for the statistical analysis. LSHTM will supply each participant's unique Study ID, NHS number, date of birth and post code to NHS Digital for the purpose of following each participant's health status (mortality, cancer registration data and hospital admissions) on the basis of informed patient consent to permit the receipt, processing and release of data by NHS Digital. The participant's Study ID, NHS number, date of birth and postcode will be linked to medical records held by NHS Digital on cancer registrations (provided by NHS Digital on behalf of Public Health England), deaths (sourced from civil registration data and provided by NHS Digital on behalf of the Office for National Statistics) and the Hospital Episodes Statistics database on hospital admissions. This linked data will then flow to LSHTM, and the trial statistician will analyse the mortality, cancer registration and hospital admissions data by treatment allocation & baseline blood serum vitamin D level to assess how vitamin D deficiency and treatment with vitamin D might affect these outcomes. The main analyses will be the matched pair comparison of recruitment and overall compliance rates between placebo control and open control designs. Details of additional vitamin D supplement use will be recorded at entry, and retrospectively at the 2 year final visit. Failure to report taking at least 19 doses of allocated IMP or to attend the 2 year final visit are included in the definition of noncompliance, so there will be no missing data for the main analyses. Change in blood level of 25(OH) vitamin D from entry to exit will be analysed in relation to self reported compliance. The effect of treatment on serum 25(OH)D both overall by allocated treatment, and in compliant participants, will also be analysed in relation to the pre treatment 25(OH)D level. Other principal outcome data from this trial will include deaths, cancer cases and hospital admissions from major causes during and after the trial. This is the reason for requesting the mortality, cancer registration and HES data from NHS Digital. The data from a year preceding the beginning of the trial are required to provide baseline rates for deaths, cancer cases and hospital admissions. Deaths, cancer registration rates and hospital admission rates for major disease categories will be estimated by treatment allocation group (vitamin D versus no treatment) and baseline serum vitamin D level (blood samples were taken at entry to the trial). The data will be used to assist the LSHTM making a decision as to the study design of the main trial by providing unbiased data on adverse events in each treatment arm. This can then be compared to the (potentially) biased real-time collection of adverse events during the trial to see whether an open allocation trial (where people know which treatment they’ve been allocated to) is more biased in this regard than a blinded design (where patients either receive treatment or placebo). This in turn will help the LSHTM to present a reasoned argument for the study design that should be adopted in the main trial. Data containing personal identifiers will be transferred to and from NHS Digital using the secure data transfer portal. This data will be stored on the secure server at LSHTM which can be accessed only by the LSHTM study team using a unique network password. No-one else outside of the LSHTM study team will have access to any of the NHS Digital data from this application. The data will only be viewed, accessed and analysed by direct substantive employees of the London School of Hygiene & Tropical Medicine (LSHTM). There are two collaborators in this study – University College London and Queen Mary University of London, they do not have access to the data. All processing of ONS data will be in line with ONS standard conditions. The data will not be made available to any third parties except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide apart from the date of death which is converted from age at death down to the granularity of weeks to ensure sufficient anonymisation as described.


Project 11 — DARS-NIC-104802-G2J0P

Opt outs honoured: Y

Sensitive: Non Sensitive

When: 2017/09 — 2017/11.

Repeats: Ongoing

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

Categories: Identifiable

Datasets:

  • MRIS - Flagging Current Status Report

Objectives:

The need to research for potential genetic damage amongst British nuclear test veterans and the possibility of transmitted genetic alterations in their children has been a cornerstone requirement identified by members of the nuclear community for many years. A recent award from the Aged Veteran Fund (AVF) is now enabling such investigations to take place in a study led by Brunel University London in collaboration with the London School of Hygiene & Tropical Medicine. The project is part of a larger portfolio coordinated by the Nuclear Community Charity Fund (NCCF) on behalf of British Nuclear Test Veteran Association. This project will carry out chromosomal analysis of cells from nuclear test veterans and their children. The study will recruit 50 veteran family trios (father, mother, child) to provide samples for fluorescence in situ hybridisation (FISH)-based analyses to ask if there is any evidence of altered frequencies of chromosomal aberrations in veterans and/or their children when compared to 50 control family groups. Participants will be selected from a defined group of veterans known to have been present at nuclear tests and inclusion will not be related to ill-health (case veterans). The control group of veterans will be matched on age, service, rank and will have served at the same time in tropical regions but will be verified as not being present at test sites. All veterans will be interviewed for their medical and service history. Knowledge gained from this project will make significant in-roads into clarifying ongoing uncertainties about the possible impact on health by providing cytogenetic evidence to address identified issues and/or to dispel unfounded concerns. Outputs from this work will benefit the broader nuclear community by providing a scientific rationale that will improve understanding and, if genetic effects are observed, to inform health and social care providers to better support this community’s needs. The applicant has received approval for a “Consent for Consent” application from the Confidentiality Advisory Group (CAG) for the London School of Hygiene & Tropical Medicine (LSHTM) to receive NHS number, date of birth (for validation) and GP details of armed services veterans identified from Public Health England’s (PHE’s) nuclear test veteran’s cohort study via NHS Digital. LSHTM has gained Section 251 Approval to cover NHS Digital receiving and processing NHS Number and date of birth from PHE, and the receipt from NHS Digital of NHS number, date of birth and GP name and address code for the purpose of patient identification and recruitment via the GP practice. The applicant is applying to NHS Digital with S251 support for the contact data. PHE will supply NHS number and date of birth for selected cases (those who have been exposed to nuclear testing) and control veterans (those who have not been exposed) to NHS Digital for linkage to GP practice details. NHS Digital will remove deceased veterans and those with a diagnosis of cancer (other than non-melanoma skin cancer) from the list prior to sending on NHS number, date of birth, GP practice details and case/control status to the London School of Hygiene & Tropical Medicine for the purpose of patient identification and recruitment via GP practices. At this stage, only the above linkage (NHS number, date of birth, GP details and case/control status) from NHS Digital for the purpose of patient identification and recruitment via GP practices is being requested. However, the Section 251 application includes approval for all participants to be flagged for lifelong followup through national registers for death and cancer registration and hospital admissions via HES, subject to further funding for this aspect of the study. It is therefore anticipated that a subsequent amendment to NHS Digital for this additional work will be made in the future.

Expected Benefits:

The benefit of this application is patient identification and recruitment via GP practices to gain consent from individuals to participate in the study and not contacting deceased patients and causing distress to their families. Outcomes from this project will bring benefit to families in the nuclear community by providing them with the first ever comprehensive cytogenetic exploration to examine for possible genetic differences between members of their community and control family groups. The findings will underpin evidence-based information and education that will seek to reduce the reported confusion, anxiety and uncertainties voiced by members of the nuclear community. The findings, which will be translated for the benefit of the nuclear community, may also lead to further research with the aim of informing care & wellbeing programmes. Participating families will also benefit from a sense of contributing and being part of a research study, designed in partnership with the BNTVA that has the sole aim of seeking answers to outstanding questions within their community.

Outputs:

There will be no outputs produced directly from the data requested under this application. The wider project, which will be subject to a further application for data will produce a number of outputs and on completion of the study report, the main findings will be summarised and sent in a letter to those who participated in the study. The study results will also be published in peer-reviewed scientific journals and presented at conferences. Examples of conferences that this work may be presented at include the International Congress of Radiation Research 2019 in Manchester (the largest Congress for radiation research, held every 4 years); the Association for Radiation Research; the European Association for Radiation Research; the Radiation Protection Week (large EU supported conference); the Annual General Meetings of British Nuclear Test Veterans Association). The study is being conducted on behalf of the Nuclear Community Charity Fund, so there will also be presentations at nuclear community events and articles pertaining to the study results will be published in nuclear community publications. All outputs and publications contain only aggregated data with small numbers suppressed in line with the HES Analysis Guide.

Processing:

PHE will provide to LSHTM a completely pseudonymised data set containing the exposure data held on the Nuclear Test Veterans in the cohort. This will not include any NHS Digital data. These data will be used to select the most heavily exposed test veterans (using stratified random sampling based on number and location of tests attended, measured or estimated exposures, job role at test site) including personnel who flew through the dust cloud after each test. Unexposed controls will be matched on age, rank, service (RAF, Royal Navy, Army) and period of service in tropical regions. PHE will submit lists of identified patients to NHS Digital who hold the flagging data on these individuals. Participants who have died or have cancer registrations (other than non-melanoma skin cancer) will be excluded by NHS Digital. NHS Digital will also match the list against the national register to exclude the most recently deceased or cancer registered participants prior to linking with GP data and sending the finalised list [containing NHS number (for identification), DOB (for validation) and GP name and address] to LSHTM. This is the minimum identifiable data required in order to seek consent. Access to the data will only be by substantive employees of LSHTM. The LSHTM study team, who are substantive employees of LSHTM, will invite potential subjects to participate in the study via their GP practice. The LSHTM study team will write to each potential participant's GP, supplying the subject's NHS number and date of birth for identification, and explaining the purpose of the study. If the GP does not feel it is inappropriate for any reason, the GP practice is requested to pass on a letter, patient information sheet & consent form and reply slip with pre-paid addressed envelopes outlining the study and asking the couple to let the LSHTM study team know whether or not they might be willing to take part. Those replying and supplying a contact telephone number will be telephoned by the LSHTM study team to discuss the study, answering any questions the respondents may have. Fully informed written consent to participate in the study will then be obtained from willing eligible participants. Identifiable data is required in order to identify, contact, and gain consent from individuals to participate in the study (via their GP practice). This by definition would not be possible with anonymised or pseudonymised data. Sampling from the PHE nuclear test veteran’s cohort is a non-biased method of identifying potential participants. This is also an unbiased source of exposure data which will be used to identify those veterans who are likely to be at the highest risk of radiation exposure. The cohort also contains an unexposed set of veterans from which controls for this study will be selected. If the applicant were not able to utilise this cohort as the sampling frame, the study would have to rely on a biased set of volunteers. The response rate for veteran trios recruited is anticipated to be quite low due to the multi-step nature of the recruitment process. Initially, case veterans will be anonymously selected from the PHE cohort based on exposure history, with control veterans being selected to match on various variables (age, rank, service type and period of service). Once veterans are selected, NHS Digital will remove members who are deceased or registered with cancer (other than non-melanoma skin cancer) prior to sending to the study team. GP practices will then be contacted to confirm eligibility, at which point ineligible veterans will be excluded. Subsequently, eligible veterans and their wives or partners will both have to agree to take part in the study and they need to have had a biological child together, who is still alive and resident in the UK. Thus potentially eligible veterans will be lost at this stage of the recruitment process. Eligible and willing veteran couples will then forward a letter on behalf of the study team to their child, who must also be confirmed as eligible (via their GP) and agree to take part in the study before the veteran trio can be counted as one unit towards the overall response rate. Further to this, control veterans must be frequency matched on four different variables to case veterans (age, rank, service type and period of service), without knowing a priori which case veterans will respond and take part in the study. This will require four times as many controls to be selected a priori. Previous studies in this age-range have achieved a response rate of approximately 10% for individual respondents. It may therefore be prudent to assume that approximately 3-4% of case veterans will eventually participate as a complete veteran trio in this study, with approximately 1% of control veterans participating as a family trio once matching has been done. To avoid time-consuming and costly multiple applications to NHS Digital for recruitment purposes, the applicant is therefore seeking to receive NHS number, date of birth and GP practice details from 1500 case veterans (to allow for an eventual response rate of 3-4% for case trios), plus 6000 controls (to allow for a priori frequency matching on four variables). Appropriate controls will be in place to ensure that access to confidential research information is restricted only to those who need it. The study data will be electronically stored inside a secure network at LSHTM, apart from the percentage which are paper copies of study materials (reply slips, consent forms and telephone interview data). These will be stored in locked filing cabinets at LSHTM, accessible only to the direct study team. Data containing personal identifiers will be transferred to and from NHS Digital using their secure data transfer portal. This data will be stored on the secure server at LSHTM which can be accessed only by the LSHTM study team using their unique network password. Brunel University London staff will not have access to any NHS Digital (or otherwise) patient identifiable data as part of this application. Once consent has been gained and that data collected, the two organisations will liaise over patients using study ID (though again Brunel will not be accessing any NHS Digital data).