Disease Causation

Question 1

Importance of cause

Answer 1

-so that we can intervene and prevent disease
-Cause is any factor that produces a change in severity or frequency of outcome

**do not need all causal factors

Question 2

Inductive reasoning

Answer 2

-the process of making generalized inferences about causation based on repeated observations

Question 3

Inductivism and logical fallacies

Answer 3

-After this, therefore because of this

Question 4

Koch’s postulates

Answer 4

Causal if:
-present in all cases of disease
-it does not occur in another disease as a fortuitous and non pathogenic parasite
-it is isolated in pure culture and induces the same disease in other animals

Question 5

Issues with Koch’s postulates

Answer 5

-ignores environmental factors
-not applicable to non infectious diseases

Question 6

Epidemiology vs lab

Answer 6

-hard to recreate in lab (ethical, don’t know how, cost)

-complex issues occurring in natural world

-discussions of causation are usually limited to observational research rather than experimental research

Question 7

Experimental studies

Answer 7

-traditionally, the Gold standard
-randomize individuals to receive a factor and some to receive nothing
*factor precedes disease and other variables accounted for by randomization
-compare outcomes of tx and control groups
-Assume if groups had been switched we would have got the answer

Question 8

Observational studies

Answer 8

-Estimate the outcome differences between individuals that happen to vary in their exposure status

-use matching and restriction to minimize differences between groups

-Measure association between changes in exposure and outcome

Question 9

Limits to experimental studies

Answer 9

-often difficult to duplicate realistic dose, exposure pathway, complete set of typical cofactors

-difficult to carry out experiments that resemble real world conditions

Question 10

Observational studies

Answer 10

-Have environmental exposure AND disease or outcome
-must have complete and careful description of the referent group

But need to be able to determine if this is a cause-effect relationship

Question 11

Trials of treatedd vs untreated

Answer 11

Not really allowed now. Usually have to give one medication to one and the second best treatment to the other

Question 12

Cohort studies

Answer 12

-Classify groups based one exposure
-follow these groups forward in time

Question 13

What is cohort studies reported as?

Answer 13

Report as relative risk
*compare attack rates and then get relative risk

*can be used to look at more than one disease resulting from a specific exposure

*Closest observational study to randomized control trial

Question 14

Case-control studies

Answer 14

-define groups of diseased and healthy animals
-assess whether the animals in the two groups have differences in past exposure to different risk factors

**hard because looking back in time= RECALL BIAS
**had to determine whether the exposure came before the disease actually began (eg. cancer)

Question 15

How are Case-control studies reported?

Answer 15

Calculate the odds ratio
-estimates the relative risk provided that the incidence of disease is low and cases/controls are random

**good for rare disease
*can assess more than one exposure in same study

Question 16

Statistical significance and causation

Answer 16

Statisitical significance does not equal cause

**to prove causal association we need to describe a chain of events from cause to effect at the molecular level

Question 17

Confounding

Answer 17

The effect of an extraneous variable that can wholly or partly account for an apparent association between variables in an investigation
*confounding can mask a real association

eg. large herd size and aprons= leptospirosis

Question 18

Confounder components

Answer 18

1. be associated with response variable
2. Be associated with the risk factor of interest
3. Not be an intervening or intermediate step between the risk factor and response

Question 19

Component model of causation

Answer 19

-all disease is multifactorial
-cause is sufficient if it produces effect
-a cause almost always comprises a number of component causes

**A particular disease may be produced by different sufficient causes

Question 20

Necessary cause

Answer 20

-A risk factor that is a component of every sufficient cause

Question 21

Components of a sufficient cause

Answer 21

-Factors may be present concomitantly or may follow one another in a chain of events

Question 22

Causal web

Answer 22

A number of chains with one or more factors in common
*includes indirect causes activating direct causes

Question 23

Indirect vs direct causes

Answer 23

Indirect= the effects of exposure are mediated through one or more intervening variables

direct= often the proximal causes emphasized in therapy

Question 24

Causal mechanism and strength of an association

Answer 24

Mechanism remains constant

Strength between an exposure of interest and the outcome will vary
*depends on distribution of risk factors

Question 25

Interaction among causes

Answer 25

Two or more component causes acting in the same sufficient causes interact causally to produce disease

Question 26

Hills criteria for causality

Answer 26

-Temporality
-strength of association
-biological gradient or dose response
-coherence or plausibility

Others:
-consistency
-specificity
-analogy
-experimental evidence

Question 27

Temporality

Answer 27

-cause must always precede effect in time
-but the same factor could occur again after disease in some individuals
-often difficult to establish time sequence especially with surrogate measutes

Question 28

Strength of Association

Answer 28

-a strong statistically significant association between a factor and disease increases the likelihood that the factor is causal
-assumes less likely for residual confounding to explain results

Question 29

Issue with strength of association

Answer 29

Depends on distribution of other components of sufficient cause

eg. weak associations (tobacco smoke and lung canceR) can be considered causal

Question 30

Biological gradient

Answer 30

-a dose response relationship between a factor and disease increases the plausibility of a factor being causal

Question 31

Consistency

Answer 31

-repeated observations of an association in different populations under different circumstances

**role of systemic reviews and meta analysis

Question 32

Coherence/plausibility

Answer 32

-compatibility with existing knowledge
-it is more reasonable to infer that a factor causes a disease if a plausible biological mechanism has been identified than if mechanism is unknown

Question 33

Specificity

Answer 33

-A cause leads to a single effect or an effect has one cause

**not necessary but can support when logical deduction from causal hypothesis

Question 34

Analogy

Answer 34

-too subjective and open
-possible source of new hypothesis

Question 35

Experimental evidence

Answer 35

-clinical trials, animal lab experiments or both

-uncertainty in extrapolating across species and outside tested dose ranges

Question 36

Does using hills criteria balance out interpretations?

Answer 36

No, there are lots of different perspectives and even using criteria, epidemiologists only agreed 68% of the time

Question 37

Causal inference

Answer 37

-Need a mathematical association between the exposure and the hypothesized effect or outcome
**the outcome have a monotonic association with the increasing exposure

-besides temporality, there is no criteria that is needed or sufficient

Question 38

Potential errors that can lead to observed association

Answer 38

1. Chance
   -assessed through correct application of statistical analysis
2. Systemic error in the design of the study or data
   -sampling bias
   -misclassification of exposure or disease status
3. Confounding or mixing of effects
   -results from a 3rd unaccounted risk factor associated with both exposure and disease

Question 39

What does consistency across different study populations mean?

Answer 39

Means that information is supportive