LEC 7 Pharmacovigilance l Flashcards
Range of therapeutic products regulated by HSA (7)
- Investigational drugs / Clinical trials drugs
- Therapeutic products
- Medical devices
- CPM
- Cosmetics
- Advanced therapy products (CTGT)
- Tobacco products
Health product regulation (pre-market) (3)
- Clinical trials
- Product registration/listing
- Dealers licensing
Health product regulation (post-marketing) (4)
- Vigilance
- Surveillance
- Compliance monitoring
- to GDP/GMP - Enforcement
Health product regulation (placing on market) (3)
- Storage and distribution
- Advertising
- Supply and sale
How are the levels of risks assessed? (2)
Titrate risk based on :
- Types of health product & its inherent risks (CPM vs Therapeutic products)
- therapeutic products have higher risks - Treatment for diseases
- treatment for more serious diseases means higher risk tolerance
Controls on products (high risk vs low risk)
More stringent control for high risks products
HSA approval of drug use into the market
Benefits outweigh the risks for the intended population and use
Are all product risk-free?
No
Efficacy vs Effectiveness
Efficacy
- under controlled conditions
- shown in clinical trials
Effectiveness
- under clinical conditions
Adverse Drug Reaction (WHO definition)
A reaction that is
- noxious/harmful
- unintended
- occurs at doses normally used in man for prophylaxis, diagnosis or treatment of disease of the modification of physiological function (normal therapeutic doses)
- excludes overdosage, drug abuse and medication errors
Side effects
Any unintended effect occurring at doses normally used in humans that is related to the pharmacological properties of the drug
- can be positive or negative side effects
eg discovery of new SE can lead to the off-label use of the drug
ADR vs SE (2)
ADR
- negative reactions
- may or may not be related to pharmacological properties
SE
- can be positive or negative reactions
- related to pharmacological properties
Adverse Events vs Adverse Reactions
Adverse Events
- causality not implied
Adverse Reactions
- causality assumed
Rule of Three
- 95% confidence
- point estimate for the frequency of that ADR is not higher than 3 in the size of the investigated population
eg clinical trial sample size = 1,800 (no ADR)
- there is 95% confidence that the true frequency of the ADR is less than 1/600
Limitations of clinical trials (5)
- Mainly test efficacy only
- Detect common ADR only (1/100 to 1/1,000)
- Detect short term ADR
- Small number of exposed patients (1,500-3,000)
- Short duration (1-3y)
Pharmacovigilance
- is the science of collecting, monitoring, researching, assessing and evaluating information
- from healthcare providers and patients
- on the adverse effects
- of health products
- with a view to :
1. Identifying new information about hazards
2. Preventing harm to patients
Pharmacovigilance framework (4)
- Signal/Risk detection
- Risk assessment
- assess benefit/risk profile - Risk minimisation
- implement appropriate regulatory actions
- maintain product in market > remove product in market - Risk communication
What are ‘signals’ (3)
- what does it provide?
- an early indicator or warning of a potential new problem with a drug or class of drug
- more than 1 report to generate a signal
- new ADR or additional info about known ADR
Source of a signal (4)
- International Data
- Local Data
- Pre-market Data
- Post-market Data
Can liver toxicity be a signal of paracetamol?
No because it is not a new problem with paracetamol.
It is already known that paracetamol can cause liver toxicity
International data (3)
- WHO International Drug Monitoring Programme
- Environmental Scanning
- literature
- media reports
- information from other regulatory agencies - International Regulatory Exchanges
Local data (4)
- Healthcare Professionals
- Autopsy Reports & Toxicology Lab
- Active Surveillance Initiatives
- CMIS
- Sentinel Sites (vaccines)
- Registries for selected drugs - Mandatory Reporting (Drug companies)
- serious reports within 15 days
Advantages of ADR reporting (5)
- Operates for all drugs given to patients
- Operates throughout the whole lifespan of the drug
- Relatively inexpensive to operate
- Accessible to all healthcare providers
- Can provide rapid identification of newly identified adverse drug reactions
Disadvantages of ADR reporting (4)
- Low level of reporting
- 2-4% of all ADR
- <10% of serious ADR are reported - Schemes requires HCPs to recognise ADR
- recognition is complicated by many ADR mimic naturally-occurring illnesses - Data collected relate to suspected association only
- not confirmed causality - Unable to provide incidence rate
- only the frequency / prevalence
- due to the lack of denominator
Given the limitations of ADR reporting, is ADR reporting still important?
Yes.
It is the only way of monitoring the safety of a drug throughout its marketed life
Is ADR reporting confidential?
Yes.
Any information related to the identities of the reporter and the patient will be kept confidential
Channels of ADR reporting (6)
- Phone
- Fax
- Online reporting
- E-reporting linked to medical records
- Critical Medical Information Store (CMIS)
Methods of assessing Signal detection (2)
- Qualitative methods
2. Quantitative methods
Qualitative methods of signal detection (5)
Case by case basis
- Frequency
- Nature/Type of event
- Time of onset
- Duration
- Rechallenge/Dechallenge
Quantitative methods of signal detection
- Frequentist method
2. Bayesian approaches
Follow up on signal detection (2)
To confirm causality
- Hypothesis testing
2. Epidemiological study
Steps for conducting Risk/Benefit assessment (2)
- Review safety signals and further confirmatory studies/data
- Determine the benefit vs risk profile
- efficacy data
- safety data
- therapeutic alternatives
- type of disease
- impact on population
- ability to mitigate risks
Risk minimisation & management classes (2)
- Retention of product in market (favourable)
2. Removal of product in market (unfavourable)
(( favourable ))
Risk minimisation & management if product is retained in market
- more common (4)
- less common (3)
More common :
- enhancement of warnings in package insert
- change of indications to mitigate new risk
- new contraindications to use
- postmarket studies and registries
Less common :
- restriction of use to certain medical disciplines
- restriction of access to certain patients only
eg when treatment resistant
- black box warning (sternest warning)
Risk minimisation & management if product is removed from market (3)
- suspension of sales
- recall of product
- withdrawal of product (or voluntary withdrawal)
Risk communication aim (1)
- to minimise risk and enhance safe use of drugs by updating and informing intended audience of safety issues in a timely, transparent and unbiased manner
Risk communication methods
- Dear Healthcare Professionals Letters
- Public advisories
- Posters
Impact of ADR (3)
- Increase length of hospital stays
- Increase costs
- Risks of mortality
Relevance / Importance of pharmacovigilance (4)
- Clinical trials limitations
- Genetic & environmental influence
- Ageing population (polypharmacy, comorbidities)
- Rising use of Complementary Proprietary Medicines (CPM)
