NHS Digital Data Release Register - reformatted

University Of Southampton projects

218 data files in total were disseminated unsafely (information about files used safely is missing for TRE/"system access" projects).

MR250 - Chemical Workers Exposed to Phenoxy Acids — DARS-NIC-148413-JDKYG

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable, Anonymised - ICO Code Compliant

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

Purposes: No (Academic)

Sensitive: Sensitive, and Non-Sensitive

When:DSA runs 2011-09-29 — 2026-09-28

Access method: One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Flagging Current Status Report
  4. MRIS - Members and Postings Report
  5. MRIS - Personal Demographics Service
  6. MRIS - Scottish NHS / Registration

Objectives:

Our aim is to describe and interpret patterns of mortality and cancer incidence in extended follow up of historical cohorts of workers exposed to styrene, phenoxy herbicides and formaldehyde. The information obtained will be used to inform regulatory risk assessment and management for the chemicals, both in the UK and internationally. Optimal risk management is important since workers must be adequately protected, but at the same time, unwarranted restrictions on exposure could have adverse impacts on people's quality of life.

MR278 - Study of Birth Cohort from Hertfordshire — DARS-NIC-148284-T2GPT

Type of data: information not disclosed for TRE projects

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

Legal basis: Section 251 approval is in place for the flow of identifiable data, Health and Social Care Act 2012 – s261(7), National Health Service Act 2006 - s251 - 'Control of patient information'. , Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'.

Purposes: No (Academic)

Sensitive: Sensitive, and Non Sensitive, and Non-Sensitive

When:DSA runs 2019-03-02 — 2022-03-01 2016.04 — 2024.03.

Access method: Ongoing, One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Scottish NHS / Registration
  4. MRIS - Members and Postings Report
  5. Civil Registration - Deaths
  6. Demographics
  7. Hospital Episode Statistics Admitted Patient Care
  8. MRIS - Flagging Current Status Report
  9. Hospital Episode Statistics Admitted Patient Care (HES APC)
  10. Civil Registrations of Death

Objectives:

The University of Southampton are the Data Controller for The Hertfordshire Cohort Study (HCS), which has been active since the late 1980's during which time it has contributed to the understanding of lifecourse influences on health in later life. It was during the 1980's that the wider cohort was established by the MRC Environmental Epidemiology Unit (a forerunner of the MRC Lifecourse Epidemiology Unit (LEU)) to test the hypothesis that chronic, non-communicable diseases of ageing had their roots in fetal and infant life. 37,000 men and women born in Hertfordshire between 1911 and 1939, whose early health had been documented by health visitors, were flagged for continuous notification of death. Given the accrual of deaths over time and the increasing age of the cohort, a re-examination of early life influences on mortality is due, hence the request for further MRIS data.

A subset of 2997 cohort members born between 1931 and 1939 and still resident in Hertfordshire were genotyped and underwent a comprehensive characterisation of their health in the clinic phase of the project during 1998-2004. They have since been followed-up in repeat clinics, by postal questionnaires and through data of two types from NHS Digital.

The first of these is an extract of HES data, used to create an admission history for each participant from the date of clinic attendance to 31/03/2010. These histories, underpinned by prospectively measured data, are being used to investigate lifecourse influences on hospital admission. It is crucial to understand and prevent admissions among older people in the context of current pressures on the NHS: those aged 65+ occupy 2/3 of hospital beds though they represent only 1/6 of the population.

In addition, the civil registration data that are available for the wider cohort are also applicable to clinic participants. To date they have mainly been used to ascertain loss to follow-up (data obtained from NHS Digital). However, the rich data collected in clinic (DNA extracted from blood samples), combined with increasing numbers of deaths among clinic participants (700 approx. to date), provides the potential to examine the impact of genotype as well as health and lifestyle in early old age on subsequent longevity and cause of death. This allows the researcher to investigate whether people who survive to very old ages do so because they have 'good genes' or because they have lived 'healthy lives'.

The work is being undertaken to provide a publicly funded resource for research. By comparing observed health outcomes from the NHS Digital data with prospectively measured risk factors from the cohort data, the research aims to elucidate pathways to ill-health and mortality in old age, and the concomitant need for hospital care. Such research is an iterative process, and whilst specific outputs planned are outlined below, it is important that The Hertfordshire Cohort Study (HCS) remains reactive to changing research priorities. Any changes to the purpose would however require an amendment to this agreement.

Yielded Benefits:

Early findings from Hertfordshire provided the catalyst for a new field of research: the Developmental Origins of Adult Disease. An international learned society (https://dohadsoc.org/) has developed to support it, and the earliest paper based on Hertfordshire data (Barker DJP, Osmond C, Winter PD, Margetts BM, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989;2:577-80) has nearly 2000 citations to date. Over 260 papers have been published in peer-reviewed journals. Since 2004 HCS has focused on musculoskeletal disease. Key findings are summarised below: Growth in utero and in infancy are determinants of adult bone mass, bone geometry, microarchitecture, strength and fracture risk Adult bone mass is related to circulating GH and cortisol concentration; SNPs within candidate genes; ischaemic heart disease and risk of diabetes Fracture risk is predicted by measures of bone density and architecture other than dual-energy X-ray absorptiometry Markers of bone turnover, but not volumetric bone density, are associated with knee osteoarthritis Genetic factors and vitamin D status influence the incidence and progression of knee osteoarthritis Functional limitation associated with hand OA is driven by pain rather than by comorbidity Adult bone mass and grip strength are related to quality of life Bone health is directly influenced by muscle function Early life factors are related to body composition in late adulthood Muscle size and strength are related to growth in early life Sarcopenia and frailty are prevalent conditions in older men and women, newly recognised in clinical practice Sarcopenia in later life is associated with altered muscle morphology HCS data have contributed to the development of normative guidelines on grip strength Early environment influences development of autoantibodies Inflammaging is a powerful predictor of future frailty Adult anthropometry is associated with several candidate genes Birth weight and adult fat consumption interact to determine serum cholesterol levels Unhealthy lifestyles (obesity, smoking, poor diet, physical inactivity) are strongly linked to poor physical function and increased risk of hospital admission in older men and women. The data remain as relevant today as when the work begun, and the growing percentage of deaths among the wider cohort only add to their value. In addition, notification of death is crucial for individuals with whom the study is in contact: given their age, death rates are high, but having received no mortality data for over two years sometimes unknowingly the team approach a cohort member who has died. This is distressing to the bereaved relatives and to the team and could be avoided by reinstating the flow of mortality data.

Expected Benefits:

The research described is focused on accruing evidence on risk factors for disease, thus it sits at the head of a research discovery process. In time, and with consistent evidence generated from other studies on the same theme, this body of evidence may lead to the design of an intervention. For example, if the work on risk factors for hospital admission (described above) identifies a characteristic pattern of morbidity and behaviour that is associated with increased rates of admission among older people, an intervention (perhaps a combination of treatment and behaviour change) might target individuals in whom the pattern exists with the aim of reducing the need for hospitalisation which is to the detriment of the individual and places demand on the NHS. Only after an intervention study provides evidence for the effectiveness of an intervention will implementation science be used to embed the intervention within clinical practice with the involvement of all necessary care-giving stakeholders.

Mortality: The wider study aims to inform a body of evidence about how intrauterine (occurring within the uterus) and early life conditions affect health, longevity and eventual cause of death. As such, it represents the first stage in a process which may eventually impact on health and social care. The process is long: early evidence of a link between birth weight and mortality was produced by this study in the 1990s. Investigation of the mechanisms underlying the link followed, using animal and then human models, and it is only now that Randomised Controlled Trials are being carried out with the aim of modifying intrauterine conditions. With sufficient evidence, an intervention in routine obstetric care could follow in the future.

HES: Research using HES data has thus far addressed risk factors for hospitalisation generally, although the research is not principally service based. The aim is not to identify specific procedures, interventions and policies that will have immediate benefit for the health of older people and the care that they receive from the NHS but rather, to inform a body of evidence about likely risk factors for hospitalisation. In time, this could lead to interventions as described above.

Nutrition programme: There is a very compelling case for knowing more about nutrition and health in older age. One third of older patients are categorised as being at risk of malnutrition on admission to hospital, and malnutrition is associated with poorer health outcomes and longer hospital stay. HCS is the only UK cohort that has collected dietary data in later life and offers the opportunity to define the role of nutrition as a determinant of health in later life. The MRC LEU are developing a programme that will run till 2020, using both HES and mortality data to chart the development of disease in relation to diet.

Outputs:

Over 250 publications in peer-reviewed scientific journals have resulted from the Hertfordshire Cohort Study to date; civil registration data have constituted a specific outcome in 3 of these and HES data in 4. Over the next 1-2 years the analyses proposed below will consider mortality or HES data as a specific outcome and, as explained in the processing activities, continuous notification of death will underlie many more outputs.

HES data: An exploration of the risk factors for hospital admission in later life has produced 3 papers, all of which are drafted and ready for immediate submission:
• Predictive factors for 30-day readmission among older people
• Predictive factors for emergency admission among older people
• Predictive factors for elective admission among older people

Three further papers using HES data will be written:
• The contribution of co-morbidity to risk of hospital admission
• The contribution of obesity to risk of hospital admission
• The contribution of socio-economic status to risk of hospital admission

In addition to the outputs listed, which are aimed at the scientific community, material is produced for cohort members. This includes
• An annual newsletter, the latest edition of which will be mailed in February 2019
• A website https://www.mrc.soton.ac.uk/herts/
• Occasional public meetings, most recently on 23/06/18 in Harpenden

Processing:

Tracing and flagging of the wider cohort (n=C37,000) was carried out by NHS Digital during the 1980s and 1990s on receipt, from the MRC unit, of patient identifiers from cohort members’ birth records (name, sex, DoB and address at birth). In return, current names, HA ciphers of residence and NHS numbers of flagged individuals were notified to the MRC, together with details of deaths that had already occurred. Incident mortality has subsequently been reported monthly by NHS Digital under this data sharing agreement.
Mortality data are used for two purposes:
i) To investigate the associations between conditions in early life, ageing, longevity and cause of death.
ii) To avoid unnecessary contact with bereaved relatives of those who are deceased

In 2011, the NHS numbers of 2997 clinic participants originally provided to the LEU by the NHS Central Register (NHSCR) were supplied to NHS Digital and an extract of HES data covering the period between the earliest baseline clinic and 31/03/2010 was received in return. HES data were cleaned and episode records collapsed to produce an admissions history for each HCS member from the date of their baseline assessment (which varied from person to person) to the universal end date in 2010. Admission histories (which could potentially be identified by date of birth in association with sex) were created through linkage to the HCS database and have been subjected to ongoing analyses using survival models in STATA (data analysis and statistical software). The HES data can be linked by the LEU with fact and date of death derived from civil registration data as well as with other study data, as explained in the following paragraph

Data derived from multiple sources (birth records, home interviews, clinics, postal questionnaires, health authorities, GPs, NHS Digital and ONS) are stored in a series of databases in a dedicated secure area of the MRC LEU computer server. A unique serial number acts as the primary key and is the only common field between databases. This allows the data to be linked as necessary to investigate emerging research questions. Any emerging research questions are not permitted to go beyond any significant extension of the purpose without an amendment being submitted and agreed by NHS Digital.

All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data).

Data will only be processed and stored at MRC LEU and will not be available to any other individual for any other purpose. All outputs will contain only aggregate level data with small numbers suppressed in line with the HES analysis guide.

Processing of NHS Digital data occurs only within the MRC LEU. The LEU is a part of the University of Southampton's Faculty of Medicine. All staff accessing the data disseminated under this agreement are substantively employed by University of Southampton but are limited to those staff based in the LEU.

The LEU is located on the campus of the University Hospitals Southampton NHS Trust but is otherwise unrelated to the NHS.

The applicant will not link the data further and the only data linkages are those permitted under this application.

MR1175 - PROSPECTIVE STUDY OF OUTCOMES IN SPORAIC VERSUS HEREDITARY BREAST CANCER (POSH) — DARS-NIC-148334-51PXR

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable, Yes (Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'.

Purposes: No (NHS Trust, Academic)

Sensitive: Sensitive

When:DSA runs 2019-03-01 — 2020-11-01 2023.08 — 2023.08.

Access method: Ongoing, One-Off

Data-controller type: UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST, UNIVERSITY OF SOUTHAMPTON, UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Flagging Current Status Report
  4. MRIS - Members and Postings Report
  5. Cancer Registration Data
  6. Civil Registrations of Death
  7. Demographics

Objectives:

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The University of Southampton and The University Hospital Southampton NHS Trust to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

The following provides background information on the purpose of the original study:

The Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH) study focuses on younger patients, who have a significantly reduced chance of survival. Breast cancer is the most common type of cancer in the UK, but thanks to international research efforts, over 80 per cent of women are alive five years after diagnosis and at least two-thirds survive for 20 years or more. However, it is known that women diagnosed under the age of 40 often have more aggressive cancers, with a significantly lower chance of survival, and some carry genetic factors predisposing them to the disease.

The study is a multicentre prospective observational cohort study of 3000 young women diagnosed with breast cancer in the UK between 2000 and 2008. It completed recruitment of just over 3000 cases by 31st December 2008. The study continues to follow up annually as funding allows. Oncologists at hospitals throughout the UK recruited patients.

The primary aims of the POSH study are to determine whether:
• The prognosis of patients with breast cancer who harbour BRCA1 or BRCA2 gene mutations differs from non carrier patients matched for age and other major prognostic indicators.
• Breast cancers occurring in patients with different predisposing inherited gene mutations have a consistent and distinct tumour phenotype?
• There are differences in the pattern of distant breast cancer recurrence between patients with BRCA1 or BRCA2 gene mutations and matched non carrier patients?

This study is funded by Breast Cancer Campaign and Cancer Research UK. The study began in 2001 and is a purely non-commercial study. The recruitment period ended at the end of December 2008 and since then follow up data has been collected from hospitals, and when not known by the original recruiting hospital, by requesting data from NHS Digital. NHS Digital has previously provided cohort data.

The sponsor of the study is University Hospital Southampton NHS Foundation Trust and it is being managed on their behalf by University of Southampton's Southampton Clinical Trials Unit (SCTU).
N.B. A Sponsor is an individual, company, institution, organisation or group of organisations that takes on responsibility for initiation, management and financing (or arranging the financing) of the research. A sponsor can delegate specific responsibilities to any other individual or organisation that is willing and able to accept them. All research falling under the remit of the Secretary of State for Health must have a formal sponsor. This includes all research in health and social care that involve NHS patients, their tissue or information.

More than 3,000 women diagnosed with breast cancer under the age of 40 took part in the study. Only about five per cent of all breast cancers are diagnosed in women under 40 years of age, so over the eight years that patients joined the study, this makes up around a quarter of all women with breast cancer in this age group in the UK. Participants contributed a blood sample and tumour tissue for genetic research. The progress of study participants is followed annually, including using data received from NHS Digital for women who are no longer in contact with their treating hospital centre.

Data supplied by NHS Digital is being used for long-term follow up of patients to assess their primary and secondary endpoints. SCTU Statistics Team analyse the data and alongside the chief investigator (Professor of Genetics) write a number of papers which will be published in medical journals. All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.
N.B. An endpoint in clinical trials, is an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

The research team are examining inherited high-risk genes for breast cancer, such as BRCA1 and BRCA2, in this group, with a view to developing treatments for genetic breast cancer. They are looking at the DNA from younger breast cancer patients to find out whether clues in the BRCA genes could help predict their response to treatment and the risk of cancer coming back. There is some evidence that BRCA1 gene carriers may be more sensitive to certain types of chemotherapy.

Yielded Benefits:

To date the team have published data (Copson et al JNCI 2013) showing that two different types of breast cancer have very different patterns of relapse potentially relating to how they are treated and long term outcome data (to median of 15 years) is needed to really understand the pattern of recurrence. The study has already found that women diagnosed with breast cancer with a family history of the disease face a similar prognosis after treatment to other women with breast cancer.

Expected Benefits:

This Agreement permits the secure retention of the data only and no other processing.

The study team want to empower women who carry this faulty gene to make informed decisions about their treatment options. The research could also lead to targeted ways to treat young women with breast cancer and improve their chances of beating the disease.

This study is a unique opportunity to chart the long term outcome for patients who have a specific genetic reason for the development of breast cancer. Patient advocates have been extremely supportive of continuing follow up of the cohort study in this way.
The latest data is beginning to suggest a survival advantage across the cohort for patients with a genetic predisposition who are offered more extensive surgery after their initial cancer treatment – again the data must have longer follow up to be certain of how beneficial this might be over time.

These longer term analyses are essential to provide accurate information for patient care in the current era where early genetic testing in young onset breast cancer is becoming routine – no other study will be able to provide this detailed evidence.

The study is looking at the prognosis for breast cancer patients with BRCA1 or BRCA2 gene mutations, at differences in patterns of recurrence and whether cancers in these patients have a distinct tumour phenotype or host tissue response.
If the outlook for BRCA carrier patients is more optimistic than previously thought, preventive surgical options could be more confidently planned at the same time as breast cancer treatment. Ultimately the team want to empower women who carry this faulty gene to make informed decisions about their treatment options. The research could also lead to targeted ways to treat young women with breast cancer and improve their chances of beating the disease.

Results published January 2018 show that young onset breast cancer patients have a high mortality and those who carry a BRCA gene mutation have similar survival to non-carriers. BRCA carriers presenting with triple negative breast cancer may have a survival advantage during the first few years after diagnosis compared to non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary cancer risks should take into account prognosis associated with the first malignancy and patient preference.

A final outcome analysis is planned when the study follow up reaches a minimum duration of 15 years (2023).

Outputs:

This Agreement permits the secure retention of the data only and no other processing.

No new outputs will be produced under this Data Sharing Agreement.

Processing:

Under this Agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement.

The study data, including data provided by NHS Digital under previous agreements, are currently held by University Hospital Southampton NHS Foundation Trust.

The following provides background on the processing activities undertaken prior to this Agreement:

Identifiable data was shared with ONS to carry out the linkage between the study data and civil registration data. Participants records were ‘flagged’ with the Office for National Statistics (ONS). ONS notified the study team at University Hospital Southampton NHS Foundation Trust of participants’ deaths (date and cause) and cancer events when they occurred. The ‘flagging for long-term follow up’ service transferred from ONS to the HSCIC in 2008. Data was last supplied in March 2016.

MR168 - FORMALDEHYDE WORKERS IN CHEMICAL INDUSTRY (PART 2 ) — DARS-NIC-148196-4WQRP

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable, Yes

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

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2011-09-29 — 2026-09-28 2018.11 — 2018.11.

Access method: One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Flagging Current Status Report
  4. MRIS - Members and Postings Report
  5. MRIS - Personal Demographics Service
  6. MRIS - Scottish NHS / Registration

Objectives:

Our aim is to describe and interpret patterns of mortality and cancer incidence in extended follow-up of historical cohorts of workers exposed to styrene, phenoxy herbicides and formaldehyde. The information obtained will be used to inform regulatory risk assessment and management for the chemicals, both in the UK and internationally. Optimal risk management is important since workers must be adequately protected, but at the same time, unwarranted restrictions on exposure could have adverse impacts on people's quality of life.

MR132 - EFFECTS OF EXPOSURE TO STYRENE — DARS-NIC-148382-7KTF1

Type of data: information not disclosed for TRE projects

Opt outs honoured: Y, Identifiable, Yes

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'., 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'.

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2011-09-29 — 2026-09-28 2016.12 — 2018.09.

Access method: Ongoing, One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Scottish NHS / Registration
  2. MRIS - Cause of Death Report
  3. MRIS - Cohort Event Notification Report
  4. MRIS - Flagging Current Status Report
  5. MRIS - Members and Postings Report
  6. MRIS - Personal Demographics Service

Objectives:

Our aim is to describe and interpret patterns of mortality and cancer incidence in extended follow-up of historical cohorts of workers exposed to styrene, phenoxy herbicides and formaldehyde. The information obtained will be used to inform regulatory risk assessment and management for the chemicals, both in the UK and internationally. Optimal risk management is important since workers must be adequately protected, but at the same time, unwarranted restrictions on exposure could have adverse impacts on people's quality of life.

MR129 - Formaldehyde Workers in the Chemical Industry — DARS-NIC-148417-FT2KY

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable, Yes

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

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2011-09-29 — 2026-09-28 2018.01 — 2018.01.

Access method: One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Flagging Current Status Report
  4. MRIS - Members and Postings Report
  5. MRIS - Personal Demographics Service
  6. MRIS - Scottish NHS / Registration

Objectives:

Our aim is to describe and interpret patterns of mortality and cancer incidence in extended follow-up of historical cohorts of workers exposed to styrene, phenoxy herbicides and formaldehyde. The information obtained will be used to inform regulatory risk assessment and management for the chemicals, both in the UK and internationally. Optimal risk management is important since workers must be adequately protected, but at the same time, unwarranted restrictions on exposure could have adverse impacts on people's quality of life.

MR187 - STUDY OF HERBICIDE MANUFACTURERS AND SPRAYERS — DARS-NIC-148386-78PDC

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable, Yes

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

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2011-09-29 — 2026-09-28 2017.04 — 2017.04.

Access method: One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Flagging Current Status Report
  4. MRIS - Members and Postings Report
  5. MRIS - Personal Demographics Service
  6. MRIS - Scottish NHS / Registration

Objectives:

Our aim is to describe and interpret patterns of mortality and cancer incidence in extended follow-up of historical cohorts of workers exposed to styrene, phenoxy herbicides and formaldehyde. The information obtained will be used to inform regulatory risk assessment and management for the chemicals, both in the UK and internationally. Optimal risk management is important since workers must be adequately protected, but at the same time, unwarranted restrictions on exposure could have adverse impacts on people's quality of life.

MR1245:Patient Tracking Service - New EPOC — DARS-NIC-189166-R0Y9Y

Type of data: information not disclosed for TRE projects

Opt outs honoured: N, Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(2)(b)(ii)

Purposes: No (Academic)

Sensitive: Non Sensitive, and Sensitive

When:DSA runs 2017-12-01 — 2022-11-30 2016.12 — 2017.02.

Access method: Ongoing, One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. MRIS - Members and Postings Report
  2. MRIS - Cause of Death Report

Objectives:

New EPOC is a prospective randomised open label trial where all patients are given the chemotherapy drugs oxaliplatin or irinotecan with fluorouracil, and then randomised to also have/not have cetuximab - the drug under investigation. These drugs are given pre and post-surgery to patients with resectable colorectal liver metastases requiring chemotherapy.

Firstly patients were consented to provide a sample for KRAS gene testing. KRAS genes play an important role in instructing colorectal cancer cells to grow and divide as part of the epidermal growth factor receptor (EGFR) process. If the biomarker test indicates there is a KRAS mutation, drugs that target EGFR (like cetuximab, which is used in this trial) may not benefit the patient. Anyone who has a KRAS mutation is therefore excluded from the trial.

Once these results were known, patients were consented to join the trial and then randomly allocated at the start of chemotherapy to receive either:
Arm A: Oxaliplatin / irinotecan plus fluorouracil chemotherapy
Arm B: Oxaliplatin / irinotecan plus fluorouracil chemotherapy plus cetuximab

Patients then received 12 weeks of the randomly allocated chemotherapy, underwent surgery and then received a further 12 weeks of chemotherapy. They are/were then followed up for 5 years at the treating hospital.

The trial is looking to see the effect of the drugs on progression free survival, this is the primary endpoint. i.e. whether the introduction of cetuximab makes a difference to the occurrence or rate of the patient’s disease progression. Other endpoints include pre-operative response rate, survival rates, quality of life and cost effectiveness.

This trial was funded by Cancer Research UK with the drug under investigation, cetuximab, being supplied for free by Merck, the Pharmaceutical company who manufacture the drug. It is a purely non-commercial trial. Interim results showed that this treatment made patients’ disease progress sooner i.e. the patient’s condition worsened sooner in the cetuximab arm and so further follow up data is required to assess whether this is also true with long term survival data. See publications section for further details – Lancet 2014.

The trial is sponsored by the University Hospital Southampton NHS Foundation Trust and is being delivered by the University of Southampton’s Southampton Clinical Trials Unit (SCTU). The trial began recruitment on 15 October 2008 and ceased recruitment and treatment in November 2012. Oncologists at hospitals throughout the UK recruited patients. Patients were informed by letter, approved by REC, that trial recruitment and treatment ceased in November 2012.

Data supplied by NHS Digital (formerly known as Health and Social Care Information Centre) has been used for long-term follow up of patients to assess their primary and secondary endpoints. SCTU Statistics Team analyse the data and alongside the chief investigators (a liver surgeon and liver oncologist) write a number of papers which will be published in medical journals. All publications will use any data collected, either directly from the hospital or from NHS Digital, in anonymised form so no patient can be identified.

The independent Data Monitoring and Ethics Committee (DMEC) met on the 18th of October 2016 to assess the maturity of the dataset and has recommended that the trial closes and final analysis is completed as soon as possible so the results can be published because there is an urgent need for the clinical community to see these results. However, closure of the trial SCTU felt was dependent upon the acquisition of the most up to date patient flagging data. A final Cause of Death report will still be required shortly thereafter to ensure that details of any participants passing away before this end date are captured.

Yielded Benefits:

In September 2009, National Institute of Clinical Excellence (NICE) approved the use of cetuximab for patients with k-RAS wild type tumours who have inoperable liver-only metastases. It is a further requirement that a hepatic surgeon reviews the patients’ images and so formally determine inoperability. The NICE decision is appropriate as there is some evidence of cetuximab benefit for this group of patients. The New EPOC trial is studying patients with operable colorectal liver metastases. These patients were specifically excluded from the NICE approval at the time and consequently, funding of cetuximab from Primary Care Trusts was unlikely to be approved. This was because there was no data on the benefit of cetuximab in patients with operable disease and therefore the question being addressed by the New EPOC trial was critically important. The interim result (as determined in Nov 2012) pointed towards a conclusion that was not expected and there have been a number of publications refuting it. Therefore gaining the current patient status data is critical to inform whether cetuximab affects overall survival and not just time to progression. In the UK, Cetuximab is used in the palliative setting which can and does often include liver metastasis. It is currently off NICE for use as downsizing strategy in borderline operable patients but is still used in other countries. Reliable Overall Survival data is crucial to understanding the degree of detriment that occurred. If cetuximab has utility for downsizing but results in earlier progression that does not result in more deaths that is one thing. This is possible if it simply brings forward the point at which progression would have occurred or of progressive disease is still treatable with curative intent The interim result has been widely published and circulated amongst oncologists at both European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meetings. However until the primary end point has been reached the trial cannot be closed. The Clinical Trials Unit at the University of Southampton believe that they are now at that point. In order to undertake this analysis, the data pertaining to patient survival is key. Therefore the SCTU are requesting the data in order to complete the final analysis and so hope to alter practice in the NHS, and worldwide. Now the final cause of death report has been processed and the Data Monitoring and Ethics Committee (DMEC) has been reviewed, the trial has finally come to an end. Within the next 12 months, the Clinical Study Report will be written and Publications generated. The details of the publication strategy will be available soon.

Expected Benefits:

In September 2009, National Institute of Clinical Excellence (NICE) approved the use of cetuximab for patients with k-RAS wild type tumours who have inoperable liver-only metastases. It is a further requirement that a hepatic surgeon reviews the patients’ images and so formally determine inoperability. The NICE decision is appropriate as there is some evidence of cetuximab benefit for this group of patients. The New EPOC trial is studying patients with operable colorectal liver metastases. These patients were specifically excluded from the NICE approval at the time and consequently, funding of cetuximab from Primary Care Trusts was unlikely to be approved. This was because there was no data on the benefit of cetuximab in patients with operable disease and therefore the question being addressed by the New EPOC trial was critically important.

The interim result (as determined in Nov 2012) pointed towards a conclusion that was not expected and there have been a number of publications refuting it. Therefore gaining the current patient status data is critical to inform whether cetuximab affects overall survival and not just time to progression. In the UK, Cetuximab is used in the palliative setting which can and does often include liver metastasis. It is currently off NICE for use as downsizing strategy in borderline operable patients but is still used in other countries.

Reliable Overall Survival data is crucial to understanding the degree of detriment that occurred. If cetuximab has utility for downsizing but results in earlier progression that does not result in more deaths that is one thing. This is possible if it simply brings forward the point at which progression would have occurred or of progressive disease is still treatable with curative intent

The interim result has been widely published and circulated amongst oncologists at both European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meetings. However until the primary end point has been reached the trial cannot be closed. The Clinical Trials Unit at the University of Southampton believe that they are now at that point. In order to undertake this analysis, the data pertaining to patient survival is key. Therefore the SCTU are requesting the data in order to complete the final analysis and so hope to alter practice in the NHS, and worldwide.

Following the independent Data Monitoring and Ethics Committee (DMEC) review in October 2016, the trial will come to a close following receipt and processing of 1 final cause of death report. Upon closure, the Clinical Study Report will therefore be written before within 12 months. Publications will also be generated from this final data. The details of the publication strategy will be further developed following the end of the trial.

Outputs:

Publications will be written following analysis and agreement from DMEC/TMG. The Trial Management Group would be aiming for high impact journals such as the New England Journal of Medicine, The Lancet or similar. Poster presentations would be expected at the American Society of Clinical Oncology (ASCO) meeting in early 2017 and the European equivalent meeting later in the year.

The Clinical Study Report will be written within 12 months of the End of Trial.

Upload of aggregated dataset with small numbers suppressed to EudraCT would follow the clinical study report publication since, from 21 July 2014, it has become mandatory for sponsors to post summary clinical trial results in the European Clinical trials Database (EudraCT), managed by the European Medicines Agency (EMA). This is mandated under the UK and EU legislation which underpins clinical trial work and as a requirement will become publically available to being greater transparency for the public who are involved in clinical research or who may to be in the future. This date corresponds to the finalisation of the programming of the database as referred to in a European Commission guideline, in application of the current clinical trials Directive 2001/20/EC.

For any publications, outputs will contain only aggregate level data with small numbers suppressed in line with Hospital Episode Statistics (HES) Analysis Guide.



The following publications or oral presentations have already been delivered:
American Society of Clinical Oncology (ASCO) meeting 2013, oral presentation. Conclusions: Although the data are immature, the accumulation of more events is unlikely to change this result. In patients with resectable liver metastases and K-RAS wild type tumours the addition of cetuximab to chemotherapy is not beneficial. http://meetinglibrary.asco.org/content/112298-132

National Cancer Research Institute conference 2013, oral presentation – Conclusion: The addition of cetuximab to chemotherapy in patients with operable or borderline operable CRLM increases the pre-operative response rate in line with prior studies. Despite this the PFS is significantly worse in the cetuximab treated patients. In this setting the presence of KRAS wild-type is insufficient to predict benefit. Further translational work is needed to determine the nature of the interaction leading to this unexpected outcome and also to determine whether there may be circumstances in which cetuximab may be of benefit
http://conference.ncri.org.uk/abstracts/2013/abstracts/ClinicalShowcase1.html

European Society of Medical Oncology 2013, poster -
http://eccamsterdam2013.ecco-org.eu/Scientific-Programme/Abstract-search.aspx#

American Society of Clinical Oncology (ASCO) meeting 2014, posters:
http://meetinglibrary.asco.org/content/128283-144 - Conclusions: Both the distribution of progressive disease and further treatment are as expected for such a cohort and are evenly balanced between the arms. Despite this there is a trend towards an inferior survival post progression in those receiving cetuximab for whom revisional surgery is not appropriate.

http://meetinglibrary.asco.org/content/129363-144 - Conclusions: The addition of cetuximab to chemotherapy and surgery for operable CRLM in KRAS wild-type patients results in an inferior PFS. More stringent selection of an all WT cohort does not significantly alter the detriment observed in the KRAS WT population.
http://meetinglibrary.asco.org/content/129221-144 - Conclusions: The trial demonstrated for the first time that miR31-3p expression is predictive of cetuximab effects and replicated association of its expression with PFS in patients receiving cetuximab. Furthermore miR31-3p allowed identification of a subgroup of patients in which cetuximab with chemotherapy had a detrimental effect on PFS. Eventually the correlation of miR31-3p expression in metastases and primary tumors in the control arm, but not in the cetuximab arm, suggests cetuximab has an effect on miR31-3p expression, supporting its involvement in the EGFR pathway.

European Society of Medical Oncology 2014, posters:
http://annonc.oxfordjournals.org/content/25/suppl_4/iv185.1.full.pdf+html?sid=3f34ecbf-150b-4078-af28-a3232efa426e Conclusions: In this study the addition of cetuximab to chemotherapy and surgery for operable CRLM in KRAS wild-type patients resulted in an inferior PFS. More stringent selection of an all RAS WT cohort did not alter the detriment observed. BRAF mutation is uncommon and likely reflects the selection of a relatively good prognosis cohort. Differences in mutational status between primary and metastasis were infrequent and could reflect either a treatment effect or clonal outgrowth. Initial pyrosequencing failed to detect <1% of mutations subsequently detected and most new mutations were discovered in previously un-interrogated sequences.

http://annonc.oxfordjournals.org/content/25/suppl_4/iv185.2.full.pdf+html?sid=967c6813-1c2d-4048-98ba-327cfc53589f Conclusions: The trial demonstrated that miR-31-3p expression is predictive of cetuximab effects. Furthermore, the trial identified a subgroup of patients with high miR-31-3p expression in which cetuximab with chemotherapy had a detrimental effect on PFS. The correlation of miR-31-3p expression in metastases and primary tumors in the chemotherapy arm, but not in the chemotherapy plus cetuximab arm, suggests that cetuximab affects on miR-31-3p expression, supporting its involvement in the EGFR pathway.

Lancet oncology 2014, publication - http://www.ncbi.nlm.nih.gov/pubmed/24717919 - Conclusions: Addition of cetuximab to chemotherapy and surgery for operable colorectal liver metastases in KRAS exon 2 wild-type patients results in shorter progression-free survival. Translational investigations to explore the molecular basis for this unexpected interaction are needed but at present the use of cetuximab in this setting cannot be recommended.


American Society of Clinical Oncology (ASCO) meeting 2015, poster: http://meetinglibrary.asco.org/content/145968-156 Conclusions: In a trial that showed substantial detriment with EGFR inhibition a subgroup has been identified who derived significant benefit from cetuximab. The loss of correlation between primary tumors and CRLM suggests that cetuximab may modulate miR-31-3p and c-Met expression and that these may be implicated in the mechanism by which earlier progression occurred in these patients.

Processing:

Participating patients consented to the University of Southampton Clinical Trials Unit (SCTU) obtaining ‘information about [their] health status’ from ‘information held by the NHS and maintained by The NHS Information Centre’ (now NHS Digital) ‘and the NHS Central Register’ – then the provider of the Medical Research Information Service (MRIS) and now part of NHS Digital – ‘to enable long-term follow-up’.

The identifying details of the study cohort were supplied to NHS Digital (then NHS IC) and the patients’ entries were ‘flagged’ on the MRIS computer system in April 2013. NHS Digital has provided adhoc reports (typically annually) on the patients' health status including details of removals from or re-entries to NHS registration, details of cancer registrations and details of deaths including cause of death details from ONS mortality data.

For patients who have died, the date of death and cause of death will be added into the analysis dataset (patient initials, month/year of birth and patient ID are included in the dataset already). The full date of death is needed so the SCTU statistics team can work out time from randomisation to progression/death for all patients for the trial’s final analysis. Any publication would just show this data in aggregated form by arm (as a graph). Month/year of birth or Age at time of adverse event is required by the Medicines and Healthcare products Regulatory Agency to report Serious Adverse Reactions therefore this data is collected for this trial.

For any patient for whom there is no known date of death, the statisticians undertaking the analysis will assume that they are still living in data analyses.

Data from NHS Digital is password controlled, stored electronically in a controlled area on the file server with restricted access. Data will only be accessed by authorised individuals who are substantively employed by the University of Southampton. Once no longer required. the data will be destroyed in line with the UK legislation for Clinical trials, DPA and the terms of the DSA. In line with EU Clinical trials - Directive 2001/20/EC and UK law, Clinical Trials of Investigational Medicinal Products (CTIMPs) SI 2004:1031, data from clinical trials must be kept for a minimum of 5 years following end of trial notification.

Any publications (aiming for high impact journals such as New England Journal of Medicine, The Lancet or similar) will contain anonymised tables derived from the data supplied by NHS Digital. No individual patient will be able to be identified. Outputs will only contain aggregated data with small numbers suppressed in line with the HES Analysis Guide.

This aggregated dataset with small numbers supressed will be uploaded to European Clinical Trials Database (EudraCT), in line with EU Clinical Trial Regulations. Again this will not identify any particular patient. Their requirements for Interventional Clinical Trials that ended on or after 21 July 2014 (i.e. the date of finalisation of the programming according to Commission Guideline (2012/C 302/03)) for non-paediatric trials where regulated by Directive 2001/20/EC (this includes this trial) the composition of results includes full data set mandatory and summary attachment(s) optional. (https://eudract.ema.europa.eu/result.html).

After the final data has been collected and analysed, the Trial Management Group (TMG) will meet with SCTU to finalise the publication plan.

Evaluating the effects of Community Treatment Orders (CTO) in England — DARS-NIC-07360-K4R9R

Type of data: information not disclosed for TRE projects

Opt outs honoured: N, Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(2)(b)(ii)

Purposes: No (Academic)

Sensitive: Non Sensitive, and Sensitive, and Non-Sensitive

When:DSA runs 2019-04-01 — 2022-03-31 2016.09 — 2016.11.

Access method: One-Off

Data-controller type: UNIVERSITY OF SOUTHAMPTON

Sublicensing allowed: No

Datasets:

  1. Hospital Episode Statistics Accident and Emergency
  2. Mental Health Minimum Data Set
  3. Office for National Statistics Mortality Data (linkable to HES)
  4. Bridge file: Hospital Episode Statistics to Mental Health Minimum Data Set
  5. Civil Registration (Deaths) - Secondary Care Cut
  6. HES:Civil Registration (Deaths) bridge
  7. Civil Registrations of Death - Secondary Care Cut
  8. Hospital Episode Statistics Accident and Emergency (HES A and E)
  9. Mental Health Minimum Data Set (MHMDS)

Objectives:

Community Treatment Orders (CTOs) were introduced to the Mental Health Act in 2007 in England and 2008 in Wales allowing patients detained in hospital to continue treatment in the community under specific conditions. To be eligible for a CTO, a patient must be detained in the hospital under the Mental Health Act on a section that allows for compulsory treatment. Around 20,000 patients have been placed on CTOs since 2008. CTOs were introduced to reduce the ‘revolving door’ phenomenon (frequent re-admission to hospital by small number of people with severe and persistent mental illness) and to provide treatment in the least restrictive setting. In practice CTOs tend to be applied at the end of an admission, following complete remission, as a means of optimising treatment adherence in those likely to default or disengage from care. Patients and carers perceive CTOs as coercive and mainly concerned with medication adherence. The use of CTOs remains controversial as its applications seems to run counter to the notions of ‘preventative’ and ‘least restriction’ for which CTOs were introduced to the mental health care system.

The Oxford Community Treatment Order Evaluation Trail (OCTET) compared discharged from hospital on a CTO with discharge from the hospital under section 17 of the Mental Health Act. No significant differences between the groups were found. Swartz et al (1999) randomized 264 severe and persistent mentally ill patients to either CTO or voluntary care following discharge. The results showed that schizophrenia patients on CTO for longer than 180 days had fewer hospital admissions and spend less time in the hospital then the controls receiving voluntary care. Limitations of these trial studies include small sample size, sample selection (exclusion of specific patients, refusal of participation by specific patients). In addition, the relative brief duration of follow-up might be too short to observe beneficial outcomes. Observational studies evaluating CTOs have been undertaken in diverse settings, at different times, using different methods. Results from these studies are inconsistent. Discrepant findings about CTO outcomes highlight the importance of local context. Understanding the effects of local context may also be the key to explaining persistent ethnic inequalities in CTO use.

This lack of evidence for the effectiveness of CTOs is problematic for policy makers, service commissioners and providers and for those who receive mental health care. CTOs require stringent governance and therefore place significant demands on the already stretched NHS mental health budgets. CTOs also reduce satisfaction with care and increase stigma. The Care Quality Commission and the House of Commons Health Committee have called for research into the ‘value of CTOs in different clinical and social circumstances’. The House of Commons Health Committee has noted:’… that the evidence base for this policy remains sparse…’ and recommended ‘…,a fuller analysis of the value of a CTO in different clinical situations’.

The aims of this research project are:

1. To explore spatial and secular variation in the use of Community Treatment Orders (CTOs) in England over a four-year period (2011/12 to 2014/15), including variation between people, places and services and over time in the likelihood of patients on Sections 3 and 37 being placed on CTOs, and in the frequency and time to subsequent events including recall, revocation, readmission and discharge from CTO.

2. To describe and model associations between CTO use and outcomes, namely re-admission, time spent in hospital, time spent in intensive psychiatric care or forensic units, episodes of seclusion and restraint, community mental health service contacts, criminal justice system contacts, Accident & Emergency Department attendances and deaths, after adjusting for propensity to require compulsory treatment.

3. To test the hypotheses that outcomes associated with CTOs (including the re-admission and the adverse outcomes listed in (3) above) vary between people and places. These models will be used to explore which patients, if any, benefit from CTOs and the types of places and service context where CTOs might have the greatest impact on patient and service-level outcomes.

4.To model the additional health care costs associated with CTOs (including administrative and regulatory costs) and the impacts of increasing or decreasing their use using a range of projections.

Note: The term ‘Mental Health (MH)’ data is used to refer to the Health and Social Care Information Centre’s Mental Health Minimum Data Set (MHMDS) for the years from 2011/12 to 2014/15 and Mental Health and Learning Difficulties Minimum Data set for the years since 2014. MH data will be used to address these questions. A cohort of mental health users will be selected from MH data and these records will be linked with corresponding Hospital Episode Statistics Accident and Emergency and ONS Mortality records.

Using Lower Super Output Area (LSOA), ONS staff will link HSCIC MH data to the publicly available data, i.e. Indices of Multiple Deprivation (Department for Communities and Local Government) and aggregate LSOA Census 2011 (ONS) data. This is to further explore the spatial variation in CTO use in England. Effectiveness of CTO will be measured in relation to compulsory treatment. The exposed group will be patients discharged from the hospital on CTOs, the unexposed group will be patients discharged from hospital treatment orders but not subject to CTOs. The two groups will be matched on time of discharge, service provider, and propensity score. The HSCIC data will be used to determine the effectiveness of CTOs compared to compulsory treatment.

Primarily this project will lead to submission of academic papers describing spatial and secular variations in the use of CTOs in England, the effectiveness of CTOs, and healthcare costs associated with CTOs. Results from the project will be presented at internal and external conferences. Findings from the research will be used to engage with public/ third sector organisations or mental health care providers during meetings or conferences. The Mental Health Foundation is a key partner in this research project. With their help two expert reference groups will be recruited: one with carers/mental health care users and one with mental health care professionals. These reference groups will meet to discuss the study aims and methods as well as comment on the released non-disclosive results and support dissemination of findings.

Yielded Benefits:

The lack of evidence for the effectiveness of CTOs is problematic for policy makers, service commissioners and providers and for those who receive (and those who care for people receiving) mental health care. CTOs require stringent governance and therefore place significant (and costly) administrative demands on already stretch NHS mental health budgets. They are perceived by patients and carers as coercive and focused on ensuring medication compliance at the expense of other forms of treatment and (social) support. CTOs may reduce satisfaction with care and increase stigma without achieving any positive health or social care gains. The Care Quality Commission and the House of Common Health Committee have called for research into “the value of CTOs in different clinical and social circumstances”, for instance by evaluating whether CTOs are having an impact on ‘revolving door’ patients, something that clinical trials cannot address and whether and how CTO use is related to uses of other parts of the MHA, given accelerating detention rates. It is possible that services in which large numbers of patients are placed on CTOs are also places with high rates of compulsory admission. With NIHR approval, an advance summary of the research was provided and cited by the Wessely Independent Review of the Mental Health Act. Further detail on the study is eagerly awaited as the Review enters its discussion and implementation phases and we are keen to seize this opportunity to ensure significant impact. The extended data access will facilitate this achievement, offering, for the first time, insights into the practicalities of CTO use drawing on a large ‘real-world’ population study and providing a grounded evidence base for determining the future of CTOs.

Expected Benefits:

Date:
• Improved insight in the use of CTOs. CTOs have been used far more extensively than was anticipated. Analyses will show when, where, and for whom CTOs are being used. Understanding the large spatial and secular variation in the use of CTOs can help inform mental health policy and support commissioning decisions on productive monitoring procedures for CTOs.

• Developing evidence on the effectiveness of CTOs. Understanding patient and outcome characteristics can help identify those inpatient detained under hospital treatment orders that would benefit most from CTO upon release from the hospital.

• Understanding the cost-effectiveness of CTOs. Identifying positive outcomes and the reduced health care costs associated with the use of CTOs will help direct mental health care related funds to where they are most needed.

• Findings that can be translated into actionable conclusions for service users. Involvement of mental health care users, carers, and professionals will ensure a study focus on outcomes and associations relevant to mental health care users. The findings can then be translated into patient-approved interventions. Involvement of the Mental Health Foundations also facilitates dissemination of study findings.

• Findings with direct policy relevance. The research team will ensure that these findings are shared at the earliest opportunity with the Care Quality Commission, the Department of Health, the Chief Medical Officer, the Royal College of Psychiatrists, the NHS Confederation, and NICE.

• Guidance to the National Institute for Health Research on strategies for future policy and practice with regard to CTO use in England. Results might inform future interventions to reduce compulsory admission and variation in CTO use. The research team will work on facilitating the adoption of these patient beneficial interventions within the NHS.

The project is expected to start around March 2016 and expected to be completed in March 2018. Funding for this project has been requested for a period of 2-years.

Outputs:

The expected outputs from this study will include papers on:

• The use of CTOs in England including variations in rates of CTO use at different spatial levels

• The hypotheses that CTOs are associated with reduced (mental health) inpatient care, reduced interaction with accident and emergency services, reduced mortality, and increased community mental health service contacts and these associations vary between places after controlling for patient characteristics.

• The health care resources employed by CTOs for mental health treatment

In addition to mandatory publication in the NIHR Journals Library as required by the project’s funder, the findings will be submitted to high impact journals.

Presentations of interim results will be made to relevant national and international conferences.

The project (i.e. production and dissemination of outputs) is expected to be completed in September 2018. Funding for this project has been awarded for a period of 2-years from March 2016. The project has an absolute end date of September 2020.

The intention is to maximise the potential impact and societal benefits of the research through:
1. Presentation of findings and contributions at national and international scientific conferences
2. Workshops for key stakeholders in each of the three regions from which the clinical academic applicants are drawn: London, the Midlands, and the North East.
3. Discussion of the implications for health services with health care providers and patient support groups (Mental Health Foundation)
4. Engagement with other academics – discussing avenues for future research if the research suggests differential use of CTOs in England
5. Deposition of academic papers in accordance with open access protocol to ensure that published papers are not withheld from a wider audience via journal pay-walls.
6. Development of short plain-language summaries of findings targeted towards non-academic professional audiences (e.g. patient support groups, local authorities, health care professionals, policy makers).
7. Work with Trusts, Innovation Hub, University Partners, and AHSN to ensure dissemination of results and adoption of proposed interventions locally, regionally, and nationally.

Processing:

The HSCIC will create a cohort of Mental Health patient records based on the following criteria:

Patients that have or had a MH spell of care open within the period from April 2011 to March 2015 that includes:
a) any associated Mental Health Act Event Episode/s where the legal status is coded as one of a list of supplied codes indicating detention under specific sections of the Mental Health Act or the Criminal Procedure (Insanity) Act 1964 as amended by the Criminal Procedures (Insanity and Unfitness to Plead) Act 1991, or;
b) any associated Supervised Community Treatment Episode

The HSCIC will then generate a file of pseudonymised Mental Health patient identifiers.

Using this file, the HSCIC will determine the relevant HES ID using a bridging file. They will then extract the relevant HES and ONS Mortality records for those patients identified within the Mental Health cohort. Two bridging files will be created i.e. a HES/ONS bridging file and a Mental Health/HES bridging file. HSCIC will extract the remaining Mental Health data records for the cohort. From the ONS mortality data, the field 'Date of Death' will be replaced with the derived month and year of death only.

The Mental Health data is classed as sensitive. All of the linked data is classed as pseudonymised.

The multiple files will be transferred to the secure environment at ONS VML in Titchfield where ONS staff will use the LSOA to link the HSCIC data to publicly available data (Indices of Multiple Deprivation and aggregate LSOA Census 2011 data) as described above. All data linked to HSCIC data are non-identifiable and publicly available.

Data will be used only for the purposes indicated on the approved ADRN project application and only by ADRN accredited researchers named in this application. Researchers have to undergo ADRN training before accessing any data or intermediate outputs and will only access the data in the secure environment. ONS will ensure that any researchers accessing data have accredited researcher status. All researchers have been guaranteed by someone who can sign up to the breaches and penalties policy by their institution and have received safe data handling training.
Data will not be used for commercial purposes.

The secure environment at ONS VML Titchfield uses state-of-the-art secure information technology and procedures which provide physical, hardware and software security.

Data will be processed (i.e. linked and assembled) in a separate (virtual) secure area than the area the researchers will be accessing the data. All staff handling the data are required to have security clearance at a level appropriate for the data they are going to handle as per the ADRN Secure Environment Policy (ADRN032).

All named individuals in this agreement are employed by the ONS, University of Southampton, the University of Portsmouth, University of Warwick, Ulster University or the Northern Ireland Statistics and Research Agency (NISRA). The researchers named in the application will be granted access to the VML ONS for this specific research project as part of the ADRN services and infrastructure.

The research team will visit ONS VML Titchfield on location to access the linked de-identified dataset in a dedicated secure room. They will be able to use installed software on their allocated PC (thin client) to analyse the data and produce outputs (e.g. tables), but they cannot take anything in or out of the room with them (including mobile, phones, memory sticks or even pen and paper). They will also be watched by the secure environment staff via a CCTV and all their activity when logged in on the PC will be monitored. They will not be able to copy, download or disseminate the data in any way – if they do there will be strict penalties for any breach or misuse of data, following the ADRN breaches and penalties policy (ADRN003).

Due to geographical distance, one instance of remote access to the VML from the secure environment of the Administrative Data Research Centre of Northern Ireland (ADRC-NI) will be needed for one of the researchers (from Ulster University) working on the project, however all data will remain on the ONS VML Titchfield server as per named users accessing on location. ADRC-NI secure environment is located in the Northern Ireland Statistics and Research Agency (NISRA) and the user will undergo training in accordance with the ADRN policy, adhering to the operating procedures of both NISRA and VML safe settings, which will include site specific training and BPSS security. Statistical outputs will only be cleared and released by VML Titchfield.

ONS will act as joint data controller, as theirs will be the location where data will flow to and be stored and ONS will have full control of access of the data. As such, they have provided all the necessary security assurances (current IG toolkit and DPA registration). The listed data users' organisations will not need to separately demonstrate compliance with security assurances as they will be performing data processing activities solely in ONS' controlled environment and will not be storing or transferring data in any way. They are therefore covered by the security assurances of ONS. ONS is ultimately responsible for managing secure access.

Data will be only stored and processed within ONS VML Titchfield.

For all users, outputs will be statistical tables and output of statistical models reviewed by ONS to ensure they are non-disclosive and suitable to be made publicly available. Once cleared for release, ONS then supply the outputs to the named researchers via secure encrypted email.

All outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

After the end of the project, secure environment staff in ONS Titchfield will store the dataset for as long as required and authorised to do so and will destroy the data, as per the data retention and destruction policy when appropriate, securely and in line with HSCIC requirements.

Once analysis is completed, the research team will produce a two-page plain English summary for ADRN and publish their results.

Finally, note that non-disclosive outputs and results will be discussed among the whole research team before final results are compiled for dissemination. These results will also be used to populate the health care cost analyses. As health cost modelling is based on the non-disclosive results, these analyses can be performed outside the secure facility of the ADRN.