Pharmacovigilance 1 Flashcards
What is HSA’s role in risk management of therapeutic products?
- 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
Is any product risk free?
No, no product is risk-free.
What is the basis for licensing medicines?
Efficacy, safety and quality.
How is efficacy usually shown?
Randomised trials
How is safety shown?
- animal testing
- human volunteer studies
- early clinical trials in patients
- large scale trials
- post marketing surveillance/pharmacovigilance
What is an adverse drug reaction?
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.
What is the required sample size for detecting a rare ADR?
Rule of 3 (95% CI)
Incidence of 1 in 100 -> need sample of 300
Incidence of 1 in 1000 -> need sample of 3000
In a clinical trial with 1800 patients where white blood cell counts were performed and no agranulocytosis was found, what can we conclude?
There is only 95% confidence that the true frequency of this ADR is less than 1 in 600.
What are the limitations of clinical trials?
- 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
What is pharmacovigilance?
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
What is the relevance of pharmacovigilance?
- 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
What is the pharmacovigilance framework?
- Signal/risk detection:
Monitoring ADRs to detect risks and change in risk/benefit ratio - Risk assessment:
Assessing risk-benefit ratio - Risk minimization:
Minimize risk by appropriate regulatory actions - Risk communication:
Communicate information to optimize safe and effective use of drug
What are signals?
An early indicator or warning of a potential new problem with a drug W
What are the sources of signal detection?
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
What are the advantages of ADR reporting?
- 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
What are the disadvantages of ADR reporting?
- 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
What are some channels of reporting ADRs?
- telephone
- online reporting
- e reporting linked to medical records (CMIS - critical medical information store)
How do we follow up on signal detection?
- need to confirm signals via hypothesis testing and epidemiological study
How do we do step 2 - risk assessment?
- 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
How do we do step 3 - risk minimization?
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
What do we do if there is unfavourable risk benefit analysis?
- suspension of sales
- recall product
- withdrawal of product
How do we do step 4 - risk communication?
- 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,
