A long term prospective cohort study on the effects of smoking and prophylactic aspirin on all-cause mortality in male British doctors

The University of Oxford requires access to NHS England data for the purpose of the following research project:

A long-term prospective cohort study on the effects of smoking and prophylactic aspirin on all-cause mortality in male British doctors

The following is a summary of the aims of the research project provided by the University of Oxford:

1) To determine the continuing effects of smoking in old age and benefits of giving up at different ages

2) To determine the long term effects of aspirin on cancer, degenerative diseases and on cause-specific mortality

The British Doctors Study (BDS) was originally set up in 1951 in response to the striking increase in the number of deaths from lung cancer seen in the population of England and Wales between 1922 and 1947 and to investigate its possible link to tobacco consumption. It is the world’s first large prospective study of the effects of smoking to establish a convincing linkage between tobacco smoking and cause-specific mortality.

To recruit participants, a simple questionnaire on smoking habits was sent to all registered medical doctors practising in the United Kingdom in October 1951. Of the 59600 questionnaires mailed, 40701 replies (34494 males and 6207 females) were sufficiently complete to be included in follow-up. Follow up data were collected by questionnaires sent to the original cohort on smoking habits in 1951, 1957, 1966, 1971, 1978, 1991, 1998, and 2001. Because of the limited sample size and limited tobacco consumption females were excluded from most reports, and from 1971 the study has focused on males only. The 1978 questionnaire, which was limited to those born in the 20th century, sought information about a wide range of characteristics including height, weight, blood pressure, alcohol, etc.

The 1978 questionnaire also invited the cohort to participate in an embedded randomised trial of prophylactic daily aspirin - the British Doctors Aspirin Trial (BDAT). The aim of BDAT is to assess the long-term use of aspirin to prevent death from stroke, myocardial infarction, or other vascular conditions and cancers. The participants were randomised (2:1 ratio) to daily aspirin versus no aspirin. Treatment continued for 5-6 years until 1984. All participants signed and returned a recruitment form were asked to complete a questionnaire every 6 months about their health and recent use of aspirin or other antiplatelet drugs. At the end of the trial a further questionnaire was completed by 99% of all surviving participants. In total, 5139 participants were included in BDAT.

The following NHS England Data will be accessed:

• Civil Registration Mortality and Cancer Registration – necessary to determine cause of death for this long-term follow-up for the BDS male cohort, to investigate the Incidences of cancer and other disease and mortality in current and former cigarette smokers and comparable lifelong non-smokers. Also to investigate the participants who were part of BDAT and the possible role of aspirin in the prevention of heart attacks and strokes among apparently healthy people with no history of cardiac or cerebrovascular disease.

• Demographics – necessary as part of the matching process for the British Doctors Study cohort

The level of the Data will be:

• Identifiable – necessary to enable linkage of the BDS participants with NHS England central health records. Data received back from NHS England to include BDS ID and date of birth to ensure perfect match with study data previously collected e.g., participant questionnaires. Identifiers required for analysis will be

i) Date of birth modified to month and year in order to obtain age at death or cancer

ii) date of death retained in full in order to calculate age at death/cancer and other disease diagnosis.

The Data will be minimised as follows:

• Limited to a study cohort identified by the University of Oxford – consisting of approximately 1,400 doctors recruited to the British Doctors Study (BDS), whose vital status is unknown.

The University of Oxford is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

Processing sensitive personal data from the participants of the BDS by the BDS researchers at the University of Oxford is in the public interest and is necessary for scientific and research purposes.

The funding comes from Nuffield Department of Population Health, University of Oxford. The funding is specifically for the study described.

The funders will have no ability to suppress or otherwise limit the publication of findings.

A Public and Patient Involvement and Engagement group- Stroke Prevention and Research Volunteer Advisory Group (SPaRVAG) reviewed the purpose of the research. The group strongly supported the collection of the data for the purposes described above.

The group agreed it is important to conclude the study in this way and is an ‘ideal opportunity’ to do this now especially as such a study cannot be replicated. The group felt that as there has been such input from scientists, previous funders and not least the commitment of the participants themselves over time it would be ‘tragic’ if the study was not finished. The group are also very keen that the results should be provided in a lay format for everyone to understand. The researchers plan for the results to be provided as a lay summary on the study webpage and also will be available through the end of study report (in lay language) that will be published alongside the research summary record on the Research Summaries section of the HRA website.

The University of Oxford will transfer data to NHS England. The data will consist of identifying details (NHS Number, Name, Date of Birth, Postcode, Gender and a unique person ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the Cancer Registrations, Civil Registration Deaths and Demographics datasets to the Clinical Trial Service Unit (CTSU), Nuffield Department of Population Health (NDPH) at the University of Oxford. The Data will

• contain directly identifying data items including: Cause of Death lines which are required to determine the long term effects of aspirin on cause-specific mortality.

The Data will not be transferred to any other location.

The Data will be stored on servers at the CTSU/NDPH at the University of Oxford

The Data will be accessed onsite at the premises of the University of Oxford only.

The Data will not leave: England/Wales at any time.

Access is restricted to employees of the University of Oxford who have authorisation from the Chief Investigator.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will be linked at person record level with the British Doctors Study dataset. The CTSU removes identifiable information from the copy of the British Doctors Study dataset. The de-identified copy of the dataset is processed by the team of the British Doctors Study using standard statistical techniques to generate analyses of the risks of smoking and the benefits stopping smoking, and analyses of possible long-term benefits or harms of prophylactic aspirin.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from the University of Oxford will process the Data for the purposes described above.

The expected outputs of the processing will be:

• Submission to a peer reviewed journal- there will be one final 70-year follow-up paper planned for 2025/2026

• Presentation or poster of the 70-year results at an appropriate external scientific conference or internal conference in the University of Oxford

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the datasets from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Posters displayed at an appropriate external scientific conference or internal conference in the University of Oxford

• Lay report of results aimed at participants on the BDS study webpage (https://www.ctsu.ox.ac.uk/research/british-doctors-study)

The target time frame for publication of the results of analyses is 2025-2026.

The British Doctors Study, which began in 1951, was the world's first large prospective study of the effects of smoking to establish a convincing linkage between tobacco smoking and cause-specific mortality, and demonstrated prospectively the risk of death from lung cancer (1954) and myocardial infarction and chronic obstructive pulmonary disease (1956).

Its results, then and subsequently (particularly the 10-year, 20-year, 40-year and 50-year results), have substantially influenced national and personal decisions about quitting, as they assessed the lifelong effects of smoking seriously and then of stopping seriously. The ongoing follow up for the 70-year results will allow further analysis of long-term outcomes in a well characterised cohort which is unique in its length and detail of outcomes at follow up.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could:

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as cardiovascular disease and cancer.

There are no specific benefits to patients but outcome may have public benefits as detailed below.

The long-term follow-up for the BDS male cohort will investigate the incidences of cancer and other disease and mortality in current and former cigarette smokers and comparable lifelong non-smokers. Also study the aim is to investigate the possible role of aspirin in the prevention of heart attacks, strokes and cancer which may provide a public benefit in the prevention of disease.

The results will be published in an open access scientific journal and on the study webpage in lay format as detailed above.

The British Doctors Study, which began in 1951, was the world's first large prospective study of the

effects of smoking to establish a convincing linkage between tobacco smoking and cause-specific

mortality, and demonstrated prospectively the risk of death from lung cancer (1954) and myocardial

infarction and chronic obstructive pulmonary disease (1956).

Its results, then and subsequently (particularly the 10-year, 20-year, 40-year and 50-year results), have

substantially influenced national and personal decisions about quitting, as they assessed the lifelong

effects of smoking seriously and then of stopping seriously. The ongoing follow up for the 70-year results

will allow further analysis of long-term outcomes in a well characterised cohort which is unique in its

length and detail of outcomes at follow up.

The findings of this research study are expected to contribute to evidence-based decision-making for

policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the

care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could: advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as cardiovascular disease and cancer.

There are no specific benefits to patients but outcome may have public benefits as detailed below.

The long-term follow-up for the BDS male cohort will investigate the incidences of cancer and other

disease and mortality in current and former cigarette smokers and comparable lifelong non-smokers. Also

study the aim is to investigate the possible role of aspirin in the prevention of heart attacks, strokes and

cancer which may provide a public benefit in the prevention of disease.

The results will be published in an open access scientific journal and on the study webpage in lay format.