L2: Classical Epidemiology II

Question 1

Name the phases of a clinical trial process

Answer 1

1. Phase O: Pre-clinical, Discovery etc.
2. Phase 1: safety + immunogenicity in a few (20-80) human volunteers.
3. Phase 2: Proof of concept; efficacy assesment in small groups (around 100) with exposure to disease,
4. Phase 3:pivotal trials, full scale clinical trials in hundreds of people.
5. Phase 4: post marketing, long term impact, rare side effects etc.

Question 2

Describe the epidemiological study cycle

Answer 2

You start with and idea. Then you run your first descriptive studies from which you formulate hypothesis and models. You test those with analytical studies such as cohort or case control studies. You ten implement a intervention. Next you run randomized controlled trials to assess the efficacy. If efficacy is good you go on to implement the programme and can then in the long run evaluate the imact. If your efficacy was not good, you need to re-run descritive studies.

Question 3

Just name the elements, no explanation.

What is a Randomized controlled trials RCT? Which elements are essential?

Answer 3

RCTs are sudies that assess the efficacy of a health interventiaon. The design is “experiment-like” and resembles that of a cohort study. In an RCT you have at least two groups, one which recieves the intervention and a control group which does not recieve the intervention.
The essential elements are min. 2 out of the following 3:
1. Contemporary controls
2. Randomization
3. Blindness

Being a control does not necessarily mean recieving nothing: it can also be that you recieve standard care while the other group recieves new drug.

Question 4

Explain what
1. Contemporary controls
2. randomization
3. blindness
are and in what context they are important.

Answer 4

All these elements are important for randomized controlled trials.
1. This is necessary bc. diseases have natural fluctuations and spontaneous cures. This is the baseline against which the intervention is measured.
2. Who recieves the intervention is based on chance to eliminate bias and confounding.
3. Blindness is needed to avoid that investigator or participants react differently due to their knowledge of the recieved intervention. It also makes it possible to control for the placebo effect. Simple blind: participant does not know. Double blind: participant and investigators do not know. Triple blind: even analysis is done blind.

Participant bias: Knowing that one is on the old drug-> less cooperation-> measurement problems.
Interviewer bias: Knows that X is using a bednet and tries less hard to find diesease.
Not always possible-> open label trials e.g. bednets.

Question 5

What is bias and how to deal with it?

Answer 5

Bias is related to a decision/assessment in the study that is made unevenly in the groups. One form is selection bias: error can arise in selecting the study groups (e.g. allocate healthier looking people to intervention group). You can avoid this by careful study design, randomization and blindness.

Question 6

How to deal with confounding?

Answer 6

1. Restrict the study population e.g. by age, gender etc.
2. Randomize a sufficient number of individuals
3. In the analysis control for confounding, multivariable analyses.