NHS Digital Data Release Register - reformatted

London School Of Hygiene And Tropical Medicine

Project 1 — 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

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).

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.


Project 2 — DARS-NIC-123200-J0L4T

Opt outs honoured: N

Sensitive: Non Sensitive, and Sensitive

When: 2018/03 — 2018/05.

Repeats: Ongoing

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

Categories: Identifiable

Datasets:

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

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.

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.


Project 3 — DARS-NIC-148044-RGS7W

Opt outs honoured: Y

Sensitive: Non Sensitive, and Sensitive

When: 2016/04 (or before) — 2016/11.

Repeats: Ongoing

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

Categories: Identifiable

Datasets:

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

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.


Project 4 — 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

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

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.


Project 5 — 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)

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.

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.


Project 6 — DARS-NIC-58603-S6Z1B

Opt outs honoured: Y, N

Sensitive: Sensitive

When: 2017/03 — 2018/02.

Repeats: Ongoing

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

Categories: Identifiable

Datasets:

  • MRIS - Flagging Current Status Report
  • MRIS - Cause of Death Report

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.

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?


Project 7 — 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

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.

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.


Project 8 — DARS-NIC-72064-V5V2X

Opt outs honoured: Y

Sensitive: Non Sensitive, and Sensitive

When: 2017/12 — 2018/02.

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)

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

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.

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.