LEC 8 Pharmacovigilance ll Flashcards
WHO
World Health Organisation
CIOMS
Council of International Organisations of Medical Sciences
ICH
International Council for Harmonisation
Adverse Drug Event (ADE) vs Adverse Drug Reaction (ADR)
ADE
- causality not implied
ADR
- causality implied
Side effects
Any unintended effect occurring at doses normally used in humans that is related to the pharmacological properties of the drug
Spontaneous Reporting ADE/ADR
- voluntary submission
- outside of a systemically planned study
Mandatory Reporting of ADR
- legal obligation to report ADR
- srs ADR within 15 calendar days
Minimum information of an Individual Case Safety Report (ICSR) (4)
- identifiable reporter
- identifiable patient (eg age, gender, initials)
- at least 1 identifiable drug
- at least 1 identifiable suspected ADR
ICSR
Individual Case Safety Report
Serious ADR (6)
- death
- threatens one’s life
- cause or prolong hospitalisation
- persistent or significant disability or incapacity
- congenital anomaly / birth defects
- judged to be medically important
Listed / Labelled / Expected ADR
- ADR alr known
- found in package insert etc
Frequency
- includes both incidence & prevalence
Incidence
- number of new cases during a given period of time
Prevalence
- number of old & new cases during a given period of time
Frequency of ADR (5)
Very common : >=1/10
Common : 1/100 to 1/10
Uncommon : 1/1,000 to 1/100
Rare : 1/10,000 to 1/1,000
Very rare : <1/10,000
Pharmacoepidemiology
- studies like cohort studies
Predictive value
- diagnostic test to assess suitability of drug for a specific patient
- positive or negative
Causality assessment based on (5)
- Pharmacological plausability
- pharmacological properties - Chronology
- temporal relationship (side effects after taking drug)
- dechallenge & possibly rechallenge - Synergistic PK
- enzyme inhibitors & victim drug (increased victim drug conc)
- >1 factors synergistic interactions - Synergistic (broad sense)
- Alternative
eg genetics for allergy
Causality classes (5)
- Certain
- dechallenge & rechallenge - Probable
- recovery upon withdrawal - Possible
- more than 1 drug - Unlikely
- Unclassified / Unassessable
- not enough information
Local legislation on PV requirements for therapeutic products (6)
- Duty to maintain records of defects & adverse effects
- at least 2y after expiry - Duty to report adverse effects
- all serious ADR report within 15 calendar days
- non-serious ADR exempted - Duty to report defects
- report within 48h that pose serious threats
- all others report within 15 calendar days
- can be therapeutic products - Duty to notify HSA regarding recall
- at least 1 day prior to recall
- class (depends on health consequence)
- level (wholesaler, retailer or consumer) - Duty to carry out risk management
- new drugs
- biosimilars
- upon request from HSA - Submission of benefit-risk evaluation report
- only for selected therapeutic products
- 6 monthly intervals for first 2 years then annually for another 3 years
Risk management process (3)
- cyclical process
- to ensure benefits > risks of the product throughout the product life cycle
- Proactive risk assessment (pre & post marketing)
- Develop & implement tools to minimise risks
- Continual reassessment of benefit-risk balance
Risk reduction methods (2)
Prefer to retain product in market than withdrawal/suspend sales from market
- educational materials
- restrict use/access of drugs
Restrict use/access of drugs (3)
- when product still has an important role in therapy despite its serious potential risks
- restrict use for specific groups of patients where there is no other suitable alternatives
- restrict access to certain medical disciplines
- diagnostic tests / predictor values to ensure suitability
Example of drug on restriction for use (1)
Tegaserod
Drugs on pregnancy prevention program (3)
PIL
- Pomalidomide
- Lenolidomide
- Isotretinoin
Examples of when are educational materials as part of Risk Management Plan used? (4)
To communicate
- groups of patients that are at risk
- serious safety signals from clinical studies or post-market experience
- monitoring parameters for HCPs
- to increase HCPs awareness of potential signs & symptoms of the drug associated ADR (help to identify ADR vs disease
i-access program use
- pregnancy prevention program for the use of thialidomide analogues (pomalidomide & lemalidomide)
i-access program overview
One time registration with Celegene
- prescriber registration
- pharmacy/dispensing clinic registration
