Lecture 23 - Pahrmacovigilance Flashcards
what are phase III trial limitations?
Too few data points - seldom more than 3000 patients
Too simple - patients with complicated medical conditions excluded
Too brief - trials often no longer weeks to months; precluding identification of reactions due to long term use or latent effects
Too median-aged - paediatric and elderly populations excluded
Too narrow 1 - Patients receiving concurrent meds are excluded
Too narrow 2 – Patient population may have limited ethnic diversity
what is pharmacovigilance?
Pharmacovigilance involves collecting information about suspected ADRs through national reporting systems
Reporting suspected ADRs in children is of particular importance to improve our understanding and monitoring of drug action in this patient group often excluded from clinical trials
Pharmacovigilance systems requires the effective oversight, interaction, and coordination of a range of data collection, assessment, and communication subsystems
what is the uk yellow card scheme ?
The world’s first spontaneous reporting scheme for the reporting of suspected adverse drug reactions
It is run by the MHRA with advice from the Commission on Human Medicines, and collects, collates and investigates reports on ADRs and is the cornerstone of post-marketing drug safety surveillance int he uk
describe fda psot marketing
The FDA receives over one million adverse event reports associated with medication use every year
About one third of FDA-approved drugs go on to have major safety issues
The median time from approval to the first safety event was 4.2 years
The median time from approval to the issuance of the safety communication was 4.9 years
summarise the FDA MedWatch review on drug approvals from 2008 to 2013, highlighting that around one-fifth of new drugs showed varying effects based on race/ethnicity.
Differences in skin physiology affect response to dermatologic products
Mortality rates of patients on dialysis differ
Blacks respond less well to several classes of antihypertensive agents (beta blockers and angiotensin converting enzyme (ACE) inhibitors)
Frequency of CYP2D6 poor metabolizers is higher in Whites (7-10%) and Blacks or African Americans (3-8%) than in persons of Asian heritage
HLA-B*1502 allele associated with TENS is highly prevalent in Asian populations
what are FDA actions after a report is made of an ADR?
Safety Evaluator Review of FAERS database
Further evaluation of ongoing data in Phase 4 studies
Revision of boxed warning to include new monitoring recommendations
DHCP Letter and MedWatch alert issued
what is PIDM
WHO Programme for International Drug Monitoring (PIDM)
Promotes pharmacovigilance at the country level
WHO PIDM Member States submit reports of ADRs known as Individual Case Safety Reports (ICSRs) to the WHO global database, VigiBase
VigiBase is the largest database of its kind in the world, with over 20 million reports of suspected adverse effects of medicines. Can be searched via VigiAccess.
what are reasons for not reporting ADR?
Complacency – believing that such an ADR will have already been documented
Guilt or fear of litigation – fail duty of care to patient
Improper training
Lack of recognition of a potential drug-ADR association
Indifference
what are advantages of elelctornci health record
A proactive 24/7 PV surveillance system
Big data – utilisation of a vast amount of existing longitudinal patient data – can pick up ADRs with long delays and those due to drug-drug interactions
Big data – capable of uncovering previously unknown statistical evidence of drug-ADR relationships
Big data – opportunity to identify magnitude of ADR problem
High-quality data source as they are usually created and maintained by HCPs
Once developed could be a extensive, rapid, low cost PV system
what are challenges of data mining of EHR
EHRs are often complicated by the presence of unstructured narrative information and/or complex, missing, or inaccurate data
Concomitant medications or comorbidities may interfere with, or confound, data-mining signals when analysing EHRs
The need for standardisation of vocabularies concerning diseases, drugs, and processes entered into EHRs could assist in improving signal detection and validation
Lack of access to patient medical records by drug safety surveillance experts due to patient privacy measures
There may be too few cases in an EHR database to analyse a particular drug–ADR association
