Lecture 3. Causality and Error

Question 1

In a causal diagram, what do solid arrows represent?

Answer 1

A causal relationship between two variables

Question 2

In a causal diagram, what do dashed lines represent?

Answer 2

Not a causal relationship, but a relationship driven by an unmeasured risk factor

Question 3

What can causal relationships be?

Answer 3

Necessary and/or sufficient

Question 4

What is an examples of a necessary and sufficient causal relationship?

Answer 4

e.g disease if and only if S. typhi pathogen is present

Question 5

What is an examples of a necessary but not sufficient causal relationship?

Answer 5

e.g dietary factors enable S. typhi to adhere to the intestinal wall

Question 6

What is an examples of a sufficient but not necessary causal relationship?

Answer 6

e.g. Shigellosis may also cause disease or influence severity (might have the S. typhi pathogen and not have the disease)

Question 7

What is Hill’s Criteria?

Answer 7

The seven tests for causality

Question 8

What are the seven tests for causality?

Answer 8

Strength of association
Dose-response relationship
Correct temporal relationship
Independent or recognised confounders
Consistency with other knowledge
Biologically plausible
Reversible

Question 9

What is strength of association?

Answer 9

High Relative Risk or Odds Ratio – these are measures of association and estimate the increase or decrease in exposure/disease in a cohort or case control study.

Question 10

What are examples of confident and non confident association strengths?

Answer 10

More confident: smoking increased the risk lung cancer by a factor of 22
Less confident: Oral contraceptives increased the risk of breast cancer by 1.2

Question 11

What is dose-response relationship?

Answer 11

The disease increases as the exposure increases

Question 12

What is an example of dose-response relationship?

Answer 12

The longer duration of smoking and higher daily number of cigarettes, the greater the reduction in life expectancy

Question 13

What is a correct temporal relationship?

Answer 13

The exposure occurs before the disease

Question 14

What study type are the best and worst at informing correct temporal relationships?

Answer 14

Easier to establish the sequence of events in a cohort study (prospective) than in case-control study due to potential imprecision in records
Cross-sectional studies do not inform correct temporal relationship

Question 15

What does independent of recognised confounders mean?

Answer 15

Once known ‘causes’ are accounted for there is still a significant association

Question 16

What is an example of independence of recognised factors?

Answer 16

Asbestos increases the risk of lung cancer, independent of smoking cigarettes

Question 17

What does consistency with other knowledge mean?

Answer 17

If a study is the third or fourth to report the same findings then one can be more convinced that the relationship is causal

Question 18

What are examples of consistencies with other knowledge?

Answer 18

There are many studies suggesting a link between smoking and cancer
Early studies on the risk of breast cancer following oral contraception use varied in findings

Question 19

What does biologically plausible mean?

Answer 19

Coherence with the current body of biological literature
i.e. The association makes sense with other sources of data (makes sense mechanistically within the disease)

Question 20

What does reversible mean within Hill’s criteria?

Answer 20

Remove the risk factor and there is a change in the outcome

Question 21

What is an example of reversibility within Hill’s criteria?

Answer 21

If you stop smoking, life expectancy increases again

Question 22

When might a study have insufficient power?

Answer 22

Failure to detect an association between two variables that is truly present in population

Question 23

What are measurement errors and what do they result in?

Answer 23

Random, measurement error results in the dependent and/or independent variables being misclassified, but not systematically. Result is reduced likelihood of detecting a significant effect.

Question 24

What do random errors result in?

Answer 24

Measurement error
Results in a reduced likelihood of detecting an effect

Question 25

What does bias result in?

Answer 25

Results in misclassification, but occurs in a systematic way
Bias potentially modifies the association

Question 26

What are the four types of bias?

Answer 26

Selection Bias
Recall Bias
Funding Bias
Bias due to confounding

Question 27

What is selection bias?

Answer 27

Individuals are not representative of the population from which they are drawn because they were not randomly selected to be in a study

Question 28

What study types are at risk of selection bias?

Answer 28

All of them

Question 29

When does selection bias occur?

Answer 29

The stage of recruiting or retaining participants

Question 30

What are the three types of population?

Answer 30

Target population (generalise to)
Source population (who do you invite)
Study population (who do we sample)

Question 31

What is an example of selection bias in a case-control study?

Answer 31

1929 Study of 7,500 autopsy records
Hypothesis: Tuberculosis protected against cancer
Cases & Controls = 816 cancer cases (autopsies with malignant tumours) and 816 non-cancer cases (autopsises without cancer tumours) at John Hopkins Hospital
Lower rate of TB in cancer patients: 6.6% of patients with cancer had TB; 16.3% without cancer had TB.
Concluded TB was protective against cancer

Question 32

What are the three common and important types of selection bias (ranked in descending order of how reliable they are)?

Answer 32

1) Case control studies - Selection of cases or controls on the basis of an exposure which is associated with the disease in question
2) Randomised Clinical Trails - Non-random allocation of patients to treatment groups in a clinical trial -Younger people, or sick people are offered the “new” drug
3) Cohort Studies - Loss to follow up (when one group is less likely to come back)

Question 33

What is information/recall bias?

Answer 33

Patients with a disease recall their histories differently from patients without the disease

Question 34

What are examples of information/recall bias?

Answer 34

A diagnosis of liver cancer might influence the recall of the amount of alcohol consumed in the past
Women generally report fewer sexual partners than men

Question 35

What is funding bias?

Answer 35

It is very important when doing work that the results are impartial of the sponsors
When reading papers check who are the sponsors

Question 36

What is bias due to confounders?

Answer 36

Confounding occurs when a variable is associated with a dependent and independent variable
A problem for observational studies
Well-recognised potential confounders are age, sex, social class, race
Most confounders are not measured because they are unknown (If we measured and accounted for it, then it isn’t a confounder)

Question 37

What is an appropriate study design?

Answer 37

Type of study
Quantify power and significance and estimate required sample size
Measure the confounder and include in the analysis

Question 38

What can ignoring confounders lead to?

Answer 38

Identifying associations that are false or failing to identify true associations