Post market surveillance

Question 1

1) What is the main purpose of post marketing surveillance?

Answer 1

o (most important) To monitor safety and identify real, rare adverse effects (special indication for patient subgroups)

o To evaluate long term efficacy/tolerance

Question 2

2) How is post marketing surveillance done?

Answer 2

1. Hospital/HSA websites have reporting systems for adverse effects
2. Prolonged multicentre trials (generally not feasible, require reapplication of new trial)

Question 3

3) Why are adverse effects not detected in earlier clinical trials?

Answer 3

Rare ADR at the rate of 1 in 5000 to 10000, require 15000 to 30000 trial subjects to be reasonably sure even one ADR occurs.

Question 4

4) What happens if rare ADR occurs during post marketing surveillance?

Answer 4

• the ADR/risks are added to the drug’s labeling, black box warning
• doctors are informed of the new information through letters and other education.
• rarely that the drug needs to be reassessed

Question 5

5) What is a black box warning?

Answer 5

• The strictest warning put in the labelling of prescription drugs or drug products by the FDA when there is reasonable evidence of an association of a serious hazard with the drug
• A means of communication from the FDA to highlight the potential risk in taking the drug so these risks may be taken into consideration
• Indicates a need to closely evaluate and monitor the potential risks of the medication, or an adverse reaction to the drug that may lead to death or serious injury

Question 6

6) What are the considerations when deciding whether a drug gets withdrawn?

Answer 6

1. The nature and frequency of ADR
2. How the drug compares with the ADR of treatment alternatives

Question 7

7) Why does a drug get withdrawn?

Answer 7

1. Rare, unpredictable problems
2. More toxic than expected
3. When safer options are available
4. Dangerous combinations
5. Improper use (that lead to severe ADRs)

Question 8

8) What are examples of drugs that got withdrawn and what is the cause?

Answer 8

• Rofecoxib: In the treatment for pain, voluntary withdrawal by MSD following reports of increased MIs following chronic use. COX2 inhibitors being reviewed as a class.
• Thioridazine: Old phenothiazine antipsychotic, associated with sudden CV collapse and death. Voluntary withdrawal worldwide.
• Nefazodone: possible liver dysfunction, poor sales