Principle of cohort studies Flashcards by Shahana Sengupta

What is a cohort study?

longitudinal, prospective study

following groups with different exposures forward over time, providing disease incidence

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What is the design of a cohort study?

exposed subject vs unexposed subjects

do they develop disease or not?

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What is the definition of a cohort study?

Hennekens et al, 1987

A prospective, cohort study is one in which a
group of people with different exposures is
followed over time to see if they acquire a
disease/outcome

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What are the strengths of a cohort study?

strong research design (exposure measured before disease)
provide info on several parameters (RR, incidence and attributable risk)
several expos and several disease outcomes in one study

BUT not quick or cheap option

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What are the classic cohort studies in CHD?

Global:

Framingham study (5000 people)
Seven countries study (12000 people)

UK based:

Whitehall (12000)
British Regional heart study (8000)
Scottish heart and health study (10000)

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What are the key pitfalls in cohort study design?

hypothesis, confounding factors
size and statistical power
selection bias
follow up methods
approach to analysis

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What is a confounding factor?

factor associated both with the exposure and with the outcome of interest

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What are the important considerations for study size and statistical power?

strength of association (RR)
is expo common?
incidence rate in unexposed group
what p value will be statistically significant
what are the chances of detecting an association if present (study size)?

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What is important to consider when selecting a cohort study population?

range of exposures low to high
general population would be helpful: representative

2 options:

geographically define
well-define groups *(e.g. occupation)

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How can cohort studies inform on exposures that are uncommon in general population?

e.g. occupational hazards - asbestos

highly exposed occupational group
vs
low expo comparison group"
(+ve/-ve control)
(internal comparisons in same factory w/o expo and external group of similar exposure)

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How can you define exposure as accurately as possible in a cohort study?

questionnaire, examination, blood, medical records
make OBJECTIVE measurement
repeat assessment if possible: more accurate associations

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Where does the ‘outcome data’ for cohort studies come from?

N.B multiple outcomes may be measures

routine surveillance/registers
medical records
questionnaires
physical examination

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How is risk presented from a cohort study?

usually expressed as number of outcomes per 1000 recruited in a defined period (expo vs. non-expo)

relative risk or attributable risk

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What is relative risk (RR)?

RATIO

measured as risk in exposed/ risk in unexposed

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What is attributable risk (AR)?

EXCESS risk (difference)

risk in exposed MINUS risk in unexposed

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What are the ways that cohort data may be analysed?

logistic regression

- Cox proportional hazards modelling

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What is logistic regression?

takes account of WHETHER an event has occurred during follow up ( 0 or 1)

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What is Cox proportional hazards modelling?

takes account of WHETHER and WHEN and event has occurred

Can account for graded expos and for confounding

MORE PRECISE

What criteria are used to assess whether an association is causal?

Bradford-Hill criteria

What are the Bradford Hill criteria?

Strong
Independent
Dose response
Temporal sequence (exposure precedes outcome)
Consistent
Specific
Reversible
Biological plausibility (biological mechanisms)
Analogy (similar to other studies)

What factor lead to high total and LDL-cholesterol levels in the population?

high dietary saturated fat intake
high dietary sat fat: polyunsaturated fat ratio
obesity
genetics

What is familial hypercholesterolaemia?

genetic predisposition to elevated total and LDL cholesterol

autosomal dominant

1:500 hets

What are the determinants of high HDL cholesterol levels?

high levels of exercise
higher EtOH intake
lower adiposity
non-smoker
(potentially protective factors)

What are the important causes of CHD identified in cohort studies?

high blood cholesterol
high BP
smoking
DM
adiposity

What makes the identified causes of CHD 'casual'?

- strong evidence - RR associated with exposure are high - risks are widespread in population

What happens when there are multiple causes of CHD co-existing?

Risks MULTIPLY together

What are the other contributing factors that INCREASE risk of CHD?

- DM (>2x elevated risk, F>M) | - obesity

What are the other contributing factors that REDUCE risk of

- physical activity - EtOH (light to moderate) - high HDL-chol.

What are the other potential causes of CHD?

- poor foetal growth and nutrition - factor related to inflammation - micronutrient status (low vit D or C or low folate) BUT the evidence is inconsistent

What is a disease cause?

a factor which, of itself, increases | the risk of a disease occurring

What is a risk factor?

any characteristic which IDENTIFIES a group at increased (decreased) risk of disease now or in the future

What are the non-modifiable causes of CHD?

Age Sex Ethnicity FHx

What are the modifiable causes of CHD?

- BP - blood cholesterol - smoking - obesity - T2DM

What are the main potential biases in cohort studies?

- SELECTION BIAS: marked and selective loss to follow up - INFO BIAS misclassification of outcome status (disease or not) usually influences by knowing their expo status

What can be done to ensure that bias is limited in cohort studies?

- make follow-up as complete as possible - standardised reference for assessment of outcome - blinding to exposure status

What is the validity of case-control vs cohort study?

- cohort is a stronger study design: exposure (potential cause) is studies prior to disease onset) - bias can occur in either study type but is much more likely in case-control

What can be added to cohort studies to strengthen the design?

- v. large cohorts - pooling of data (statistical power and precision) - nested case-control within cohort study - retrospective cohort studies

What is advantage of using ver large cohorts in cohort studies?

good for studying less strong associations good for studying interplay of multiple factors

What is the UK biobank prospective cohort?

500, 000 UK men and women aged 40-69 extensive baseline questions, assessment and stored samples

What is a nested case-control study design?

= prospective case-control 4 groups: exposed vs non-exposed disease vs no disease

What is a historical cohort study?

exposures have already occurred and been assessed cohort established whilst follow up is occurring or has occurred

What are the main advantages of cohort studies?

- exposure measured before disease onset (reduced bias) - temporal sequence of events - multiple outcomes/disease can be studied from one exposure - incidence can be measures (expos vs. non-expo)

What are the main pitfalls of cohort studies?

- slow, expensive and complex - need large number for long time - data collection may change participant behaviour - expo knowledge may impact outcome ascertainment - selection bias: losses in follow up