Pharmacovigilance Flashcards
Objective of Health Product Regulation Group
1) Safeguard public health
- ensure appropriate technical standards are met
- facilitate recalls, pdct withdrawals
2) Facilitate
- support development of high quality healthcare system
- access to safe, gd quality & efficacious health products
3) Assure
- instil trust, confidence & credibility of pdcts
Range of HPs regulated by HSA
- investigational drugs
- therapeutic pdcts
- complementary HPs
- medical devices
- cosmetics
- advanced therapy pdcts (ie CTGT products)
- tobacco pdcts
Overview of HP Regulation
1) Pre-market stage
- Clinical trials
- Pdct registration/listing
- Dealers licensing
2) Placing on-market
- storage & distribution (ie. GDP)
- advertising
- supply & sale
3) Post-market stage
- vigilance, surveillance, compliance monitoring, enforcement
HSA’s role in Risk Management
- Risk based approach titrated according to inherent risks
- > stringent controls for high risk products
- Balance of B/R
- -> reg, action taken when B/R changes
- -> HSA approves a drug when benefit > risk for intended population (professional judgement - may be given off-label)
How is safety regulated?
Animal testing, human volunteer studies, early clinical trials in pts, large scale trials, post-marketing surveillance/pharmacovigilance
What is an Adverse Drug Rxn
- Noxious/harmful, unintended, occurs at doses normally used for treatment/prophlaxis/diagnosis
What is a side effect
- Unintended effect @ normal doses
- Related to pharmacological actions of drug
Note: +ve/-ve
Required sample size for detecting rare ADR
Rule of Three
Eg. 1800 pts
- Only 95% confidence that the true frequency of this ADR is less than 1/600
Limitations of Clinical Trials
- Clinical trials are designed to test for efficacy & detect common ADRs
- by the time drug is marketed only small no. of pts are exposed
- short duration: 1-3yrs
Impact on ADRs
Economic social & health impact!
- ADRs 2x the mean length of stay, $ & risk of mortality for pts vs controls
What is Pharmacovigilance
- Science of collecting, monitoring, assessing, evaluating info from healthcare providers & pts about the ADVERSE EFFECTS of meds/biological pdcts/herbal & traditional meds…
- Identify new info about hazards
- Prevent harm to pts
Relevance of Pharmacovigilance
- biomedical sciences: 4th pillar of economic engine
- limitations of clinical trials
- genetic/envt influences
- ageing population
- Increase use of complementary medicines
Pharmacovigilance framework process
1) Signal/Risk detection
2) Risk assessment
3) Risk minimisation
4) Risk communication
Signal/Risk detection
Signals: Indicators/warning of a potential new problem with a drug, or class of drug
- Repeated info on possible casual r/s btwn an adverse effect & a drug
- Signal is a hypothesis with data & arguments that support it
Sources: *ADR reports, literature report, new epidemiological study, randomised trial
Qualitative method - case by case evaluation
Quantitative method -
i) frequentist methods (ability to detect disproportionate no. on databases)
ii) bayesian approaches
Follow up by:
- Hypothesis testing
- Epidemiological study
Advantages of ADR Reporting
- Operates for all drugs given to pts
- Operates throughout whole of drug’s life
- relatively inexpensive to operate
- accessible to all physicians. dentists/ pharmacists
- rapid identification of newly identified ADR
Disadvantages of ADR Reporting
- low level of reporting
- scheme requires HCPs to recognise ADRs (complicated by many ADRs mimicking naturally-occurring illnesses)
- data collected relate to suspected associations only
- unable to provide incidence rates bc of lack of denominator
Risk/Benefit Assessment
- Review safety signals & further confirmatory studies/data
- Determine B/R profile
- Taking into consideration overall info from clinical studies, post-marketing experience & balancing pros & cons of…
- -> efficacy & safety data, therapeutic alternatives, type of disease, impact on population, ability to mitigate risk
Risk minimisation & management
i) Favourable R/B Analysis
- enhancement of warnings in package inserts
- change indications to mitigate new risks
- new contraindication
- post-market studies; registries
ii) Unfavourable R/B Analysis
- suspend sales, recall pdct, withdraw pdct
Risk communication
- Minimise risk & enhance safe use of drugs
- Update & inform audience of safety issues in a timely, transparent & unbiased manner
Organisations involved in Pharmacovigilance
WHO & UMC (Uppsala Monitoring Centre) - looks at ADR globally
CIOMS - non-profit organisation, reviews laws & methods of regulatory science
ICH
Min information needed for an Individual Case Safety Report
- identifiable report
- identifiable patient
- at least one identifiable drug
- at least one identifiable suspected ADR
Casuality Assessment
1) Pharmacological plausibility
2) Chronology
- temporal r/s
3) Synergistic Pharmacokinetic (eg. serotonin syndrome)
4) Synergistic (in a broad sense)
- Cause whole quantitative degree of the effect when in combination
5) Alternative
Criteria for causality classes
A) Certain - AE pharmacologically clear & plausible B) Probable - AE pharmacologically plausible C) Possible - > 1 drug - casuality pharmacologically not excludable D) Unlikely E) Unclassified/Unassessable
What is the CIOMS/RUCAM Scale
Diagnosis of Drug-Induced Liver Injury (DILI)
Based on the:
- hx of ingestion of drugs (incl complementary medications) within 12mths of onset of illness
- -> exclusion of viral serology
- -> -ve metabolic screen
- -> daily alcoholic intake < 20g
- -> absence of biliary or focal liver pathology on ultrasound or CT scan of abdomen
