Observational studies

Question 1

What are the different types of epidemiological studies?

Answer 1

Descriptive = distribution of disease therefore help to generate a hypothesis

• ecological
• case reports/series
• cross-sectional studies

Analytic = uncover causes of disease to help analyse hypotheses

• observational = cohort and case control studies
• intervention = clinical trials

Question 2

Define bias:

Answer 2

systematic deviation of results from the truth, or the processes leading to such deviation

Question 3

What are the different types of bias?

Answer 3

Selection bias - sampling, responder and follow up bias

Information (obs) bias - recall bias / social acceptability bias, recording bias / interviewer bias

Question 4

What is sampling bias?

Answer 4

occurs if each potential member of the population doesn’t have an equal selection into the study - more of a problem in an interventional study

Question 5

What is responder bias?

Answer 5

some people are more likely to take part in these studies and therefore they may differ systematically to those who don’t and therefore they aren’t representative of the population

Question 6

What are confounding factors?

Answer 6

effects of additional variable that might be responsible for an observed association
- situation where another factor associated with the exposure of interest and independently of that relationship the outcome
They can..
- cause spurious association
- exaggerate association
- or mask association between exposure and disease

Question 7

Define incidence:

Answer 7

the total number of new cases commencing during a specified period in a defined population

Question 8

Define prevalence:

Answer 8

total number of individuals who have the disease at a particular time
= incidence x duration of disease

Question 9

What is the incidence rate?

Answer 9

number of new cases of a specific disease arising within a population over a specified time period divided by the person-time accumulated

Question 10

What is the incidence risk?

Answer 10

number of new cases of a specific disease arising within a population over a specified time period divided by the number of persons at risk at the beginning of the time period

Question 11

What is the point prevalence?

Answer 11

number of persons with disease at some point in time / total population at risk of disease at the same time point

Question 12

What is period prevalence?

Answer 12

number of persons with disease at any time during a specified period / total population seen over the period of time

Question 13

What does the ratio measure?

Answer 13

measures the strength of association

- risk ratio or odds ratio

Question 14

What does the difference measure?

Answer 14

measures the magnitude of effect

• risk difference (therapy studies - interventional studies)
• attributable risk (aetiological studies)- measures how much disease in the disease group is caused by the exposure

Question 15

What are the criteria for assessing causality?

Answer 15

1) biological plausibility - does it make biological sense
2) time - logically a cause must precede its potential effect
3) strength of association - stronger the association of an exposure with disease occurrence then the harder to conceive of likely confounders which might explain the association
4) biological gradient or dose-response relationship - causality as a plausible interpretation is strengthened if there is a strong dose-response
5) consistency - consistent with other studies in different populations, places and times add weight to a cause-effect interpretation
6) specificity - if supposed cause is associated with one disease only, or the disease is associated with one cause only, can add weight to causal interpretation
7) coherence - should not contradict what is already known about the natural history and biology of the disease
8) experiments - occasionally natural experiments offer themselves

Question 16

What factors are important to consider when thinking about a cause and effect relationship?

Answer 16

First consider- chance, bias, confounding

Second - use criteria for causality as an aid to inferring causation

Question 17

What are the functions of descriptive observational studies?

Answer 17

characterise disease in terms of time, place and person with several aims:

• alert medical community to what types of persons were most/least affected by disease
• assist in the evidence-based planning of health and medical care facilities
• to provide suggestions concerning disease aetiology for further investigation using analytic studies (hypothesis generation)

Question 18

What are case reports/series?

Answer 18

careful detailed report of individual patients or a series of patients
suggest hypotheses
no control groups
e.g. MMR and autism

Question 19

When are cross-sectional studies important?

Answer 19

if in a particular geographical region we were to determine the point prevalence of a particular disease
e.g. determining need for specific health or social services

Question 20

How is the study population acquired for a cross-sectional study?

Answer 20

drawn from the target population using a sampling frame

- critical sampling because it affects the generalizability of the findings

Question 21

What are the random and non-random methods of selecting your sample?

Answer 21

Random

• simple random sampling
• cluster sampling
• stratified sampling

Non-random - may produce a population that is atypical to your population

• systematic sampling
• snowball sampling
• street survey

Question 22

What are the advantages of cross-sectional studies?

Answer 22

inexpensive

quick

Question 23

What are the disadvantages of cross-sectional studies?

Answer 23

time sequence and causation (disease and exposure measured simultaneously and so sometimes hard to interpret results in terms of cause and effect)
Cohort effects when interpreting relationships with age
Problems with interpretation of prevalence which is a mixture of incidence and survival relating to a disease

Question 24

What analyses can be carried out for cross-sectional studies?

Answer 24

Compare means = t-test
Compare proportions= chi-square
Correlation = pearson
Strength of association = prevalence ratio, odds ratio

Question 25

What sources of potential bias are there in a cross-sectional study?

Answer 25

``` Selection bias - sampling bias - responder bias Information bias - observer bias - recording bias - subject bias ```

Question 26

What are ecological studies?

Answer 26

correlation studies - measure rate of death or disease in a population and the population rate of a risk factor - group of individuals as units of study

Question 27

How are ecological studies analysed / interpreted?

Answer 27

scatter plots- visually inspect the relationship between exposure and disease correlation (pearson's correlation coefficient) - numerically describes the association between exposure and disease, values range from +1 to -1, statistical significance of r is shown by a p value: null hypothesis is r=0

Question 28

What are the advantages of ecological studies?

Answer 28

quick inexpensive hypothesis generation

Question 29

What are the disadvantages of ecological studies?

Answer 29

subject to confounding prone to sampling bias prone to information bias group of people described by disease data are often not the same people as those described by the exposure data time relationship between the measurements for exposure and disease is often unclear

Question 30

What 2 features distinguish cohort and case-control studies from cross-sectional and ecological studies?

Answer 30

both cohort and case-control studies: - the unit of observation is at the individual level - the period at risk tends to be prolonged

Question 31

What are cohort studies?

Answer 31

studies in which a group of individuals who are defined on the basis of their exposure to a risk factor and are then followed up over time to determine who develops the disease of interest - can be defined either prospectively or retrospectively

Question 32

What are the key features of a cohort study?

Answer 32

exposure status known at start - exposed group + unexposed group prospectively follow up cohorts to see who develops disease

Question 33

What are the key features of case control study?

Answer 33

disease status is known at the start - have disease (cases) + disease-free (controls) Retrospectively determine exposure in the 2 groups

Question 34

What are the advantages and disadvantages of prospective cohort studies?

Answer 34

Adv - exposure accurately measured - confounders can be assessed Disadv - time consuming - expensive

Question 35

What are the advantages and disadvantages of retrospective cohort studies?

Answer 35

Adv - cheap - short-time scales Disadv - exposure records may be incomplete - confounders may be unknown

Question 36

How do you choose the exposed cohort?

Answer 36

- for a common exposure there is a wide choice, but for a rare exposure occupationally or therapeutically defined groups have been proved useful

Question 37

How do you choose the unexposed cohort?

Answer 37

general population (national surveys / stats) and the use of SMRs and SIRs another occupational group a sub-cohort of the original exposed cohort

Question 38

In cohort studies what sources of measurement of exposure can be used?

Answer 38

existing records, questionnaires to study subjects, clinical investigations

Question 39

In cohort studies how can the measurement of exposure be refined?

Answer 39

- Dichotomous - ever / never exposed - Categorical - no / low / medium / high - Quantitative measure exposure (continuous variable)

Question 40

What are the pros and cons of using pre-existing records?

Answer 40

cheap, collected before disease occurs (reduces bias) but level of the info may not be sufficient to answer specific questions

Question 41

What are the pros and cons of using clinical investigations?

Answer 41

time consuming and invasive prevent responder bias (could be influenced by stigma / individuals who are ill or preconceive connotations with the disease may provide answers that suit investigators)

Question 42

What factors need to be in place for efficient follow up and outcome ascertainment in a cohort study?

Answer 42

well defined end points minimise and record losses to follow up follow up should be the same for all cohorts length of follow up needed related to latency of disease outcome measurement / diagnosis should be blinded

Question 43

How are adjustments made for confounding factors in a cohort study?

Answer 43

achieved by use of standardisation, stratification or use of a suitable regression model (linear regression model, logistic regression model, cox regression model and poisson regression model)

Question 44

What analysis should be undertaken for cohort studies?

Answer 44

compare mortality in exposed group to that in the general population use SIR/SMR (standardised incidence ratios/mortality ratios) comparison adjusted for age and sex

Question 45

What are survival curves?

Answer 45

time taken for a disease related event to occur - compare survival of subjects exposed and not exposed - differences in survival may be due to chance - large difference at the end may be based on very few patients - statistical test is needed for comparing survival curves

Question 46

What is the log-rank test used for?

Answer 46

test for equality of survival in 2 or more curves

Question 47

What are the advantages of cohort studies?

Answer 47

provides estimate of absolute and cumulative risks of disease particularly useful for following up rare exposures eliminate some of the sources of bias which are unavoidable in case-control studies which rely on recall of past events exposure is measured before disease occurrence - so little doubt about the cause and effect relationship No limit to the diseases for which the risk of occurrence may be related to exposure

Question 48

What are the disadvantages of cohort studies?

Answer 48

Not useful for very rare diseases as few of the individuals exposed will develop the disease As they often involve following up large numbers of people over decades they are expensive and difficult to maintain If disease is rare and we only need relative risks associated with different levels of exposure to risk factors then unnecessarily expensive

Question 49

What are case-control studies?

Answer 49

studies in which a group of individuals with a particular disease (the cases) are retrospectively compared with an appropriately selected group of controls in relation to their previous level of exposure to the risk factor of interest

Question 50

When are prevalent and incident cases used in case control studies?

Answer 50

If interested in determining aetiological factors then incident cases are preferable Prevalent cases are influenced by risk factors for incidence and survival and use incident cases removes the latter

Question 51

How are controls selected in case- control studies?

Answer 51

controls should be selected from subjects who if they had developed the disease would have become cases in the study Should be selected from an underlying cohort from which the cases were ascertained more difficult it is to conceive of an underlying cohort from which controls are bein selected, the more difficult it is to be sure that the selection has been unbiased Biased here = sampling of controls has over or under represented individuals with respect to exposure than in the underlying cohort

Question 52

What are some sources of controls?

Answer 52

``` From the underlying cohort from which the cases were ascertained hospital controls general practitioner controls neighbourhood controls random digit dialing by telephone number ```

Question 53

What happens when the number of controls increases per case and what is the max?

Answer 53

As number of controls per case increases the power of the study increases - max number of control : cases = 4:!

Question 54

What can be a useful way of matching controls to cases?

Answer 54

can be advantageous to match controls to cases on factors which may confound the relationship between disease and exposure - this forces cases and controls to be identical in regards to the matched factors, which controls for confounding factors - important to use methods of analysis which account for such matching otherwise it will be biased

Question 55

What are the different forms of potential bias in case control?

Answer 55

``` selection bias - sampling bias - response bias info bias - recall bias -recording bias - interviewer bias ```

Question 56

What can't be measured in case control studies and what does this mean?

Answer 56

incidence can't be measured and therefore you can use relative risk you have to use odd ratio

Question 57

What regression model is used for adjusting for confounding factors for matched and unmatched studies?

Answer 57

matched - conditional logistic regression | unmatched - logistic regression

Question 58

What are the advantages of case control studies?

Answer 58

effective use of resources to study the aetiological factors for rare diseases Explore multiple exposures for a disease study of disease with long latency periods

Question 59

What are the disadvantages of case control studies?

Answer 59

it is a retrospective study - temporal relations may not be clear - which came first the cause or effect? subject to selection and information bias address single disease only can't estimate absolute risk