Pharmacovigilance 1

Question 1

What is HSA’s role in risk management of therapeutic products?

Answer 1

• HSA approves a drug when it assesses that benefits outweigh the risks for the intended population and use
• tolerance for risk is higher for drugs that treat serious and life threatening diseases eg cancer or diseases that have no or few treatment options
• balance of risk vs benefit continued to be monitored post marketing -> regulatory action taken when B/R ratio changes

Question 2

Is any product risk free?

Answer 2

No, no product is risk-free.

Question 3

What is the basis for licensing medicines?

Answer 3

Efficacy, safety and quality.

Question 4

How is efficacy usually shown?

Answer 4

Randomised trials

Question 5

How is safety shown?

Answer 5

• animal testing
• human volunteer studies
• early clinical trials in patients
• large scale trials
• post marketing surveillance/pharmacovigilance

Question 6

What is an adverse drug reaction?

Answer 6

A reaction that is noxious and unintended and occurs at doses normally used in man for prophylaxis, diagnosis or treatment of disease or modification of physiological function.

Question 7

What is the required sample size for detecting a rare ADR?

Answer 7

Rule of 3 (95% CI)
Incidence of 1 in 100 -> need sample of 300
Incidence of 1 in 1000 -> need sample of 3000

Question 8

In a clinical trial with 1800 patients where white blood cell counts were performed and no agranulocytosis was found, what can we conclude?

Answer 8

There is only 95% confidence that the true frequency of this ADR is less than 1 in 600.

Question 9

What are the limitations of clinical trials?

Answer 9

• test efficacy
• detect common ADRs (1 in 100 to 1 in 1000)
• short duration: 1-3 years only
• by the time a drug is marketed, usually 1500-3000 pts are exposed

Question 10

What is pharmacovigilance?

Answer 10

The science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medicines, biological products, herbals and traditional medicines, with a view to:

• identify new information about hazards
• prevent harm to patients

Question 11

What is the relevance of pharmacovigilance?

Answer 11

• biomedical sciences is our 4th pillar of economic engine -> need to pick up adverse reactions fast to give ppl confidence to set up BMS sector here
• clinical trials mainly powered for efficacy
• genetic/environmental influences
• ageing population (polypharmacy and reduced organ handling of medications)
• increasing use of complementary medicines

Question 12

What is the pharmacovigilance framework?

Answer 12

1. Signal/risk detection:
   Monitoring ADRs to detect risks and change in risk/benefit ratio
2. Risk assessment:
   Assessing risk-benefit ratio
3. Risk minimization:
   Minimize risk by appropriate regulatory actions
4. Risk communication:
   Communicate information to optimize safe and effective use of drug

Question 13

What are signals?

Answer 13

An early indicator or warning of a potential new problem with a drug W

Question 14

What are the sources of signal detection?

Answer 14

International data:

• WHO international drug monitoring program
• environmental scanning
• international regulatory exchanges

Local data:

• healthcare professionals
• autopsy reports, toxicology lab
• active surveillance initiatives eg CMIS (critical medical information system)
• mandatory reporting of ADR by drug companies

Question 15

What are the advantages of ADR reporting?

Answer 15

• operates for all drugs given to pts
• operates throughout whole of drug’s life
• relatively inexpensive
• accessible to all doctors/dentists/pharmacists
• can provide rapid identification of newly identified ADRs

Question 16

What are the disadvantages of ADR reporting?

Answer 16

• low level of reporting
• scheme requires HCPs to recognize ADRs; recognition complicated by ADRs mimicking naturally occurring illnesses
• data collected only suspected associations
• unable to provide incidence rates bc lack of denominator data

Question 17

What are some channels of reporting ADRs?

Answer 17

• mail
• telephone
• email
• online reporting
• e reporting linked to medical records (CMIS - critical medical information store)

Question 18

How do we follow up on signal detection?

Answer 18

• need to confirm signals via hypothesis testing and epidemiological study

Question 19

How do we do step 2 - risk assessment?

Answer 19

• review safety signals received and further confirmatory studies/data
• determine benefit vs risk profile of drug through collection and review of relevant data

Consider:

• efficacy data
• safety data
• therapeutic alternatives
• type of disease
• impact on population
• ability to mitigate risks

Question 20

How do we do step 3 - risk minimization?

Answer 20

If there is a favourable risk benefit analysis -> retain product in the market, but:

• enhance warnings in package inserts
• change of indications eg second line to third line
• new contraindications
• post market studies by company, registries
• restriction to use by certain disciplines only
• restriction of access to certain patients only

Question 21

What do we do if there is unfavourable risk benefit analysis?

Answer 21

• suspension of sales
• recall product
• withdrawal of product

Question 22

How do we do step 4 - risk communication?

Answer 22

• update and inform intended audience of safety issues in a timely, transparent and unbiased manner
• eg Dear healthcare professional letters, public advisories, public campaigns, bulletin inserts to TCMPs, poster advertisements,