JNTU B.Pharmacy IV PHARMACOVIGILANCE Previous Question Paper (March-2021 - R17)

Adverse Drug Reactions (ADRs) are classified based on the Rawlins and Thompson classification system into six types:

• Type A (Augmented): Dose-dependent and predictable reactions related to the pharmacological action of the drug (e.g., hypoglycemia with insulin).
• Type B (Bizarre): Dose-independent, unpredictable, and idiosyncratic reactions (e.g., anaphylaxis with penicillin).
• Type C (Chronic): Reactions related to long-term use and dose (e.g., HPA axis suppression with corticosteroids).
• Type D (Delayed): Reactions that occur long after drug exposure, such as carcinogenicity or teratogenicity.
• Type E (End-of-use): Reactions occurring upon drug withdrawal (e.g., rebound hypertension).
• Type F (Failure): Unexpected failure of therapy, often due to drug interactions.

Detection of ADRs: Detection occurs through pre-marketing clinical trials (Phase I-III) and post-marketing surveillance (Phase IV). Methods include:

• Spontaneous Reporting: Voluntary reporting by healthcare professionals to national centers.
• Active Surveillance: Systematic monitoring through hospital-based programs or prescription event monitoring.
• Cohort Studies and Case-Control Studies: Observational research to establish causal links between drug exposure and specific outcomes.
• Electronic Health Record (EHR) Mining: Using automated algorithms to identify potential safety signals in patient databases.

Reporting of ADRs: The reporting process follows a structured pathway:

• Documentation: The reporter completes an ADR reporting form (e.g., CIOMS or MedWatch) capturing patient demographics, drug details, reaction description, and outcome.
• Submission: The report is submitted to the local Pharmacovigilance Center or the Marketing Authorization Holder (MAH).
• Causality Assessment: Experts evaluate the relationship between the drug and the event using tools like the Naranjo Algorithm or WHO-UMC criteria.
• Signal Detection and Database Entry: Data is entered into regional or global databases (e.g., VigiBase) to detect safety signals, which may lead to regulatory actions such as labeling changes or product withdrawal.

Safety monitoring of medicines, or pharmacovigilance, is essential to ensure that the benefits of therapeutic agents outweigh their risks. Clinical trials are conducted on limited populations over short durations, meaning rare, delayed, or idiosyncratic adverse drug reactions (ADRs) often remain undetected until a drug is used by a broader, more diverse population in real-world settings. Continuous monitoring is critical to identify previously unknown safety signals, assess risk-benefit profiles, detect drug-drug or drug-food interactions, and prevent medication errors, ultimately safeguarding public health and improving patient outcomes.

The WHO International Drug Monitoring Programme was established in 1968 following the thalidomide tragedy to create a global system for identifying and reporting ADRs. Its key components and functions include:

• Uppsala Monitoring Centre (UMC): The UMC acts as the operational hub of the program, located in Sweden. It collects, manages, and analyzes individual case safety reports (ICSRs) submitted by member countries.
• VigiBase: This is the WHO global database of ICSRs, which serves as the world's largest repository of suspected ADR reports. It allows for data mining and signal detection using advanced statistical methods.
• Signal Detection: The program employs systematic methods to identify potential safety signals—information on a new or known adverse event that may be caused by a medicine—which are then shared with member states for further investigation.
• Global Collaboration: The program facilitates the exchange of safety information between national pharmacovigilance centers, regulatory authorities, and the pharmaceutical industry, fostering a standardized approach to drug safety.
• Capacity Building: The WHO provides technical support, training, and guidelines to assist member countries in establishing and strengthening their own national pharmacovigilance systems, ensuring that safety monitoring is effective even in resource-limited settings.