Question

In a famous prospective cohort investigation, the population to be studied encompassed all physicians listed in the British Medical Register and resident in England and Wales as of October 1951. Information about present and past smoking habits was obtained by questionnaire. Information about lung cancer came from death certificates and other mortality data recorded during ensuing years.

1. What makes this study prospective? List two advantages and two disadvantages of this approach.
2. What advantages and disadvantages come with selecting physicians as a cohort for follow-up?

Answer 1

Advantages of prospective study

Advantages

One of the advantages of prospective cohort studies is they can help determine risk factor for being infected with a new disease because they are a longitudinal observation over time, and the collection of results is at regular time intervals, so recall error is minimized.

Clarity of Temporal Sequence (Did the exposure precede the outcome?): Cohort studies more clearly indicate the temporal sequence between exposure and outcome, because in a cohort study, subjects are known to be disease-free at the beginning of the observation period when their exposure status is established. In case-control studies, one begins with diseased and non-diseased people and then acertains their prior exposures. This is a reasonable approach to establishing past exposures, but subjects may have difficulty remembering past exposures, and their recollection may be biased by having the outcome (recall bias).

Allow Calculation of Incidence: Cohort studies allow you to calculate the incidence of disease in exposure groups, so you can calculate:

• Absolute risk (incidence)
• Relative risk (risk ratio or rate ratio)
• Risk difference
• Attributable proportion (attributable risk %)

Facilitate Study of Rare Exposures: While a cohort design can be used to investigate common exposures (e.g., risk factors for cardiovascular disease and cancer in the Nurses' Health Study), they are particularly useful for evaluating the effects of rare or unusual exposures, because the investigators can make it a point to identify an adequate number of subjects who have an unusual exposure, e.g.,

• Exposure to toxic chemicals (Agent Orange)
• Adverse effects of drugs (e.g., thalidomide) or treatments (e.g., radiation treatments for ankylosing spondylitis)
• Unusual occupational exposures (e.g., asbestos, or solvents in tire manufacturing, )

Allow Examination of Multiple Effects of a Single Exposure

Avoid Selection Bias at Enrollment: Cohort studies, especially prospective cohort studies, reduce the possibility that the results will be biased by selecting subjects for the comparison group who may be more or less likely to have the outcome of interest, because in a cohort study the outcome is not known at baseline when exposure status is established. Nevertheless, selection bias can occur in retrospective cohort studies (since the outcomes have already occurred at the time of selection), and it can occur in prospective cohort studies as a result of differential loss to follow up.

The "Air Force Health Study" on agent orange illustrates these advantages.

• It was clear that the exposure preceded adverse outcomes among exposed subjects who developed problems.
• It was used to evaluate the effects of an unusual risk factors (agent orange).
• It allowed direct calculation of incidence rates.
• It enabled the investigators to study multiple outcomes of this single unusual exposure.
• The prospective component of the study was not biased by knowledge of outcome status, because the outcomes hadn't occurred at the time of enrollment.

Disadvantages of Prospective Cohort Studies

1. You may have to follow large numbers of subjects for a long time.
2. They can be very expensive and time consuming.
3. They are not good for rare diseases.
4. They are not good for diseases with a long latency.
5. Differential loss to follow up can introduce bias.

Advantages of selecting physicians as cohort in prospective study

They provide reliable information

They are easier to follow-up.

For further reading about this study....

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.

In October 1951, Sir Richard Doll and Sir Austin Bradford Hill sent a questionnaire on smoking habits to all registered British doctors. Of the 59600 questionnaires mailed, 41024 replies were received and 40701 (34494 males and 6207 females) were sufficiently complete to be included in the follow-up. Further questionnaires about changes in smoking habits were sent in 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 the study has focused on the males.

The 1978 questionnaire sought information from all male doctors born in the 20th century about a wider range of characteristics (including alcohol consumption and self-reported body mass index) and invited them to participate a randomised trial of prophylactic daily aspirin to prevent death from stroke, myocardial infarction, or other vascular conditions. This trial has engendered others, some much larger, and has contributed to statistically stable meta-analyses of all trials.

Follow-up of the incidence of cancer and of cause-specific mortality among the male doctors is still continuing. All study participants are registered with the Office of National Statistics (ONS) to obtain mortality data (date of and cause of death) are provided by NHS Digital on behalf of ONS and is sourced from Civil Registration Data. Study participants are also registered with the National Cancer Registration and Analysis Service (NCRAS) to obtain cancer diagnoses.

This information received from NHS Digital and NCRAS (which is patient identifiable data) will be imported to a securely accessed computer by The University of Oxford (Data Controller), and used solely for academic research purposes by the study team in Oxford. Before analysing this complete dataset (including information already provided by the study participants, patient identifiers will be removed. Importantly, whilst the information received is specific to each study participant, no individual person will be identifiable in any publication arising from this work. Furthermore, the British Doctors Study database will not be shared with organisations outside of the University of Oxford and only accredited researchers in Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), University of Oxford will have access to the data. Anonymous results of the study may be made available to collaborators and relevant bone fide researchers according to the Nuffield Department of Population Health (NDPH), data sharing policy.Mortality and cancer registrations will continue to be collated up to 2021 to complete follow up (it is estimated that approximately 10% of the original cohort might still be alive).