Pharmacovigilance & Safety Monitoring In Clinical Trials (1).pptx

Pharmacovigilance & Safety Monitoring In Clinical Trials

1. Pharmacovigilance & Safety Monitoring In Clinical Trials PRESENTED BY : Elahe Tolideh 1st M.PHARM Dept of Pharmaceutics Al Ameen college of pharmacy Bangalore SUBMITTED TO : Prof. Dr. Ayesha Sayed Dept of Pharmaceutics Al Ameen college of pharmacy Bangalore ‹#›

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3. What is Pharmacovigilance? Pharmacovigilance (PV), as defined by WHO, is the science of detecting, assessing, understanding, and preventing adverse drug effects. Its goal is to improve patient safety by collecting and sharing reliable drug safety data. PV monitors both approved drugs and investigational products (IMPs) to: Identify new or severe adverse effects Reassess drug risk-benefit profiles Ensure accurate, updated information is shared with healthcare providers and patients ‹#›

4. Clinical Trials Phase I: Tests drug’s pharmacology and metabolism in <100 healthy volunteers or patients. Unblinded, uncontrolled, lasts <1 month. Phase II: Assesses efficacy, dosage, tolerance, and adverse effects. Includes 200–300 patients; typically placebo or active-controlled; lasts several months. Phase III: Evaluates long-term safety and efficacy in hundreds to thousands of patients. Broader participant criteria; used to determine final risk-benefit ratio before marketing. Phase IV: Post-marketing surveillance in a real-world setting to track long-term and rare adverse effects. ‹#›

5. Need for Pharmacovigilance ⚖️ 1. Balancing Efficacy vs Risk 🩺 2. ADRs Are a Major Health Concern In the US (1994), ADRs were the 4th–6th leading cause of death In the UK, it's estimated that ADRs cause ~5,700 deaths per year 30–70% of ADRs are preventable, making them a public health priority 💸 3. Economic Burden ADRs lead to increased healthcare costs (hospitalization, extended treatment) Cause loss of patient confidence in healthcare systems 🧠 4. Promotes Rational Use of Medicines Safer prescribing Monitoring of overuse/misuse Optimized benefit-risk ratio for patients ‹#›

6. Need for Pharmacovigilance 🧪 5. Limitations of Pre-Marketing Trials Clinical trials (Phases I–III) have several limitations: Small sample sizes Short duration Limited age/sex representation Specific disease focus Animal studies don’t always predict human outcomes Thus, post-marketing surveillance is essential to capture real-world adverse effects. 👥 6. Ethical and Humanitarian Responsibility Not reporting serious reactions is unethical Pharmacovigilance upholds public trust and ethical medical practice ‹#›

7. 💊 Adverse Drug Reaction (ADR) An adverse drug reaction is a noxious and unintended response to a medication that occurs at doses normally used in humans for: Prevention/Diagnosis/Treatment of diseases/Modification of physiological functions ‹#› Pharmacovigilance helps determine: Which adverse effects are acceptable considering a drug’s therapeutic benefits. Or Which side effects are worth the risk, depending on how effective the drug is in treating the disease.

8. ⚠️ Adverse Event (AE) According to ICH E6: An Adverse Event (AE) is any undesirable medical occurrence in a patient or clinical trial subject administered a pharmaceutical product, regardless of a causal relationship with the treatment. Serious Adverse Event (SAE): an AE or ADR that results in: Death Life-threatening condition Hospitalization (initial or prolonged) Persistent/significant disability or incapacity Congenital anomaly or birth defect Any medically significant event (that may jeopardize the patient or may require intervention) ‹#›

9. ❗ SUSAR – Serious, Unexpected, Suspected Adverse Reaction Serious – Fulfills any SAE criteria Unexpected – Not mentioned in the Core Safety Data Sheet of the product Suspected – Has a possible causal relationship with the drug ‹#›

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12. Sponsor’s Role Design Protocol: Defines trial steps, safety reporting, and data collection. Informed Consent Form (ICF): Informs participants about risks, benefits & study details. Data Collection: Uses Case Report Forms (CRFs) & electronic systems. Safety Reporting: Monitors and reports adverse events to authorities on time. ‹#›

13. 👥 Subjects in Clinical Trials Patients or healthy volunteers who sign the Informed Consent Form (ICF) to participate. Key Points: ICF provides clear safety info for informed decision-making. Consent must be voluntary and based on full understanding. Subjects allow collection of health data as per the protocol. Participation is optional—they can withdraw anytime without giving a reason. Phase 1 trials involve healthy volunteers (usually paid). Later phases involve patients; payment is debated due to possible coercion. ‹#›

14. 👩‍⚕️ Investigators in Clinical Trials Qualified medical professionals responsible for the care and safety of trial participants. Key Roles: Select & educate potential subjects about trial participation. Follow protocol while delivering treatment and care. Monitor & document all treatment effects, including adverse events. Report safety concerns to the ethics board (IRB) and sponsor. Ultimately responsible for the trial’s proper conduct and subject safety. ‹#›

15. Institutional Review Board (IRB) / Ethics Committee Protects the rights and safety of participants in clinical research. Key Responsibilities: Review & approve clinical trial protocols. Ensure informed and voluntary consent. Monitor ongoing trials for ethical compliance. Provide training for researchers. Can approve, reject, or request changes to trial plans. Members: Come from diverse scientific and non-scientific backgrounds for balanced decision-making. ‹#›

16. 🛡️ Data and Safety Monitoring Board (DSMB) An independent expert group overseeing one or more clinical trials. Main Roles: Regularly reviews trial data for participant safety. Assesses if there is strong evidence of benefit or harm. Ensures trial remains ethically and scientifically valid. Advises sponsor if the trial should continue, change, or stop. Who’s on the DSMB? Clinical experts (e.g., doctors, trial specialists) At least one biostatistician May include experts in ethics, pharmacology, or law ‹#›

17. 🏛️ Regulatory Authorities 🇺🇸 In the US (FDA) Before any human trial, sponsors must submit an IND (Investigational New Drug) application to the FDA. FDA reviews it (within 30 days) to ensure participant safety. In 2010, the FDA provided safety reporting guidance for drugs under IND, BA/BE studies, aligning with global standards. 🇪🇺 In Europe (EMA) The European Medicines Agency (EMA) is the EU’s counterpart to the FDA. EMA uses scientific committees to evaluate pharmaceutical applications. 🌍 Other Regions Each country has its own regulatory authority, with similar responsibilities but different legal frameworks. ‹#›

18. 🧪 PHARMACOVIGILANCE METHODS 🔹 1. Passive Surveillance Relies on voluntary reporting of adverse events. Spontaneous Reporting: → Most common method. Reports from healthcare professionals, patients, or pharma companies. → Examples: CDSCO-PvPI, WHO’s VigiBase, US FDA’s MedWatch. ✅ Useful for detecting rare and unexpected ADRs. ⚠️ Prone to under-reporting. Case Series: → Collection of individual case reports to analyze a pattern of similar events. → Often the first indication of a new safety signal. ‹#›

19. 🔹 2. Active Surveillance Proactively seeks information about adverse events using defined systems. Sentinel Sites: → Selected healthcare facilities that report all adverse events. → Provide high-quality, real-time safety data. Drug Event Monitoring: → Patients are followed up after prescription to track adverse events. → Uses prescription records and feedback from prescribers. Registries: → Databases of patients with specific diseases or treatments. → Long-term monitoring of real-world drug safety and outcomes. ‹#›

20. 🔹 3. Comparative Observational Studies Used to evaluate risk of ADRs in different patient groups. Cohort Studies: → Compare groups exposed and not exposed to a drug over time. → Estimates incidence rates of ADRs. Case-Control Studies: → Compare patients with ADRs (cases) to those without (controls). → Identifies risk factors associated with the ADR. Cross-Sectional Studies: → Snapshot of drug exposure and adverse effects at a single point in time. ‹#›

21. 🔹 4. Stimulated Reporting Encourages reporting in a focused setting (e.g., post-launch, during workshops, or under regulatory pressure). Bridges the gap between spontaneous and active reporting. Often used in newly marketed drugs or in countries with low reporting rates. 🔹 5. Targeted Clinical Investigations Special studies designed to explore specific safety concerns. May involve lab testing, clinical assessments, or focused follow-ups. Used when more precise data is needed than what observational studies provide. ‹#›

22. 💊 Pharmacovigilance Programme of India (PvPI) 🔹 Launched: 2010 by the Ministry of Health and Family Welfare Goals: Enhance patient safety by ensuring the benefits of medications outweigh the risks. Identify and assess potential adverse drug reactions (ADRs). Promote rational use of medicines. Strengthen India's drug regulatory framework. ‹#›

23. 🏛️ Governance Structure of PvPI 🔹 Indian Pharmacopoeia Commission (IPC)- GhaziAbad National Coordination Centre (NCC) for PvPI Oversees overall implementation & coordination 🔹 Central Drugs Standard Control Organization (CDSCO) Regulatory authority under Ministry of Health Works closely with IPC for regulatory decisions ‹#› 🔹 Adverse Drug Reaction Monitoring Centres (AMCs) 500+ across India Collect, analyze, and report ADRs to NCC 🔹 Healthcare Professionals Doctors, pharmacists, and nurses involved in ADR reporting 🔹 WHO-Uppsala Monitoring Centre (UMC) PvPI shares data with global database for signal detection and analysis

24. The challenges of PV in India Low awareness among healthcare providers and patients Underreporting of adverse drug reactions (ADRs) Lack of PV training in medical institutions Weak infrastructure in rural areas Language barriers across regions Limited private sector involvement Data quality and coordination issues ‹#›

25. 🏛️ Governance Structure of PvPI ‹#›

26. 🚀 Tech Transforming Safety in Clinical Trials Technology is making safety monitoring smarter and faster. 💻 Real-Time Reporting: EDC systems (Electronic Data Capture) allow for instant reporting of adverse events—no more delays. Data analytics tools can spot patterns and safety signals faster than ever, enabling quick action. 🤝 Role of CROs: Contract Research Organizations (CROs) use the latest tech to ensure better safety oversight and high-quality data in trials. ⌚ Wearables in Trials: Wearable devices are now used to track participants' vital signs 24/7. This real-time info: Improves participant safety Gives researchers deep insights Helps fine-tune treatment strategies ‹#›

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28. Conclusion Pharmacovigilance provides essential data to assess the safety profile of drugs. Active participation of healthcare professionals in reporting adverse drug reactions (ADRs) is vital for effective safety monitoring. Increasing use of electronic databases is making pharmacovigilance more proactive, organized, and efficient. Ensuring the development of safe and effective medicines for patients must be a shared priority. Patient safety monitoring is critical across all phases of drug development, especially during clinical trials. Pharmaceutical sponsors must adopt a systematic, proactive, and collaborative approach with all stakeholders. ‹#›

29. Reference Pharmacovigilance Safety Monitoring in Clinical Trials, Supriya Nikam, Anjali Jambhulkar, Kalyani Kayande, Abhilasha Ghule, Akash Inde. Sinhgad Institute of Pharmacy, Narhe, Pune, Maharashtra, India. https://www.sciencedirect.com/science/article/pii/S0165614724001676 ‹#›