Pharmacovigilance. Dr. Ganesh Uchit, MD Pfizer, India

Transcription

1 Pharmacovigilance 1 Dr. Ganesh Uchit, MD Pfizer, India

2 DISCLAIMER The presentation is intended for educational purposes only and does not replace independent professional judgement. Statements of fact and opinions expressed PowerPoint slides are those of the individual presenter and should not be attributed to the employer or any organization/society with which the presenter is affiliated

3 Overview Introduction & Terminology Why Pharmacovigilance? Pharmacovigilance Practices: International & Indian PVPI Drug Safety Issues in Clinical Trials Summary

4 Medicine Safety To undergo treatment you have to be very healthy, because apart from your sickness you have to withstand the medicine. Molière

5 What is Pharmacovigilance? Pharmakon: drug; vigilare: to keep awake or alert, to keep watch. Detection, assessment, understanding and prevention of any adverse event or other medicine-related problem

6 Pharmacovigilance Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem

7 Pharmacovigilance A response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. [WHO Technical Report No 498 (1972)].

8 Case 1 A patient was seen by you on Monday. He had complaints of fever, running nose, throat irritation and cough since Sunday. He was prescribed antipyretics + antihistamine + antibiotic He returns on Thursday. There is a bandage around his wrist. He also has abrasions on his hands and legs. He says he met with a minor road accident a cyclist rammed into him from behind. His cold and fever have subsided Is this an adverse event?

9 Pharmacovigilance An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Serious ADR Severe ADR Unexpected ADR

10 Why Pharmacovigilance New Medicines Pre-marketing safety data Animal Experiments: Relevant? Clinical Trials: Complete? Established Treatment Efficacy, safety & cost are of interest to the community Clinical Trials Intended for objective demonstration of clinical efficacy

11 What if we do not do any Pharmacovigilance

12 Facts about safety of Medicines Approximately 5.3% of hospital admissions associated with ADRs Higher rates found in elderly patients who are likely to be receiving multiple medications for long-term illnesses Nearly 10 20% of acute geriatric hospital admissions are related to ADRs Antiinfective drugs children and CV drugs adults & elderly Ref : The Annals of Pharmacotherapy n 2008 July/August, Volume 42

13 Facts Nearly 7% of medication errors potentially harmful but preventable ADRs Adverse Drug Reactions are among the top ten causes of mortality

14 Perception of Medical Risk Perceived Risk is an intuitive estimate of Risk Perception of risk in respect to ADRs is not consistent with other kinds of risk Extent and severity are important The media play an important role a two edged sword There is a distorted view of the risks of taking medicines The risk of death from chloramphenicol is 1 in 20,000 which is the same as the chance of dying in an air accident Everyday life carries appreciable risk Motorcycles, cars, skiing, smoking

15 The Importance of Choice Risk communication is about choice for the doctor and patient it is about shared decision making pharma companies play a part in providing information Sharing opinions, values and information maximises trust and support Many factors, some of which may appear irrational, influence patient choice personal experience, social networks, behavioural norms, media reporting, fear, trust in technology, a desire to take control Risk perception will alter with disease state

16 The certainty of reasonable uncertainty

17 Improving A E Reporting Feedback & Publication Rewards Training & Education Awareness Good Reporting Practice

18 International Organisations 18

19 WHO Collaborating Centre (Uppsala Monitoring Centre) ADR database No of reports: more than 3.5 million Each year increase ~160,000 / year Analysis Output Feedback to National Centres Signal documents 19

20 20

21 Safety Signal Detection A report or reports of an event with an unknown causal relationship to treatment that is recognised as worthy of further exploration and continued surveillance

22 Why do we need PV? Number of patients one would need to observe to have a 95% chance of detecting 1, 2, or 3 cases of an adverse reaction at a given incidence of the reaction can be gauged from this table: Expected incidence of adverse reaction Numbers of patients to be observed to detect 1, 2, or 3 events in in in in in Oxford Textbook of Clinical Pharmacology and Drug Therapy, 3 rd Edition, 2002

23 Lancet Oncol 2010; 11: Lancet Oncol 2011; 12: BMJ 2012;344:e2697 doi: /bmj.e2697 (Published 24 April 2012)

24 Pharmacovigilance in India 1986 ADR monitoring system for India proposed (12 regional centres 1997 India joined WHO-ADR monitoring programme (3 centres: AIIMS, KEM, JLN) National Pharmacovigilance prog. (2 Zonal, 5 Regional, 24 Peripheral Centres) 2010

25 Pharmacovigilance Programme of India (PVPI) Pharmacovigilance programme of India (PVPI) was launched in July Goal To ensure that the benefits of use of medicine outweighs the risks and thus safeguard the health of the Indian population

26 PvPI - Programme governance and reporting structures last accessed on 09/08/2012

27 Benefit & risk: evolving concepts One man's meat is another man's poison!!!

28 Some examples Clioquinol- subacute myelo-opticoneuropathy (SMON) in Indians (Wadia NH. Some observations on SMON from Bombay. J Neurol Neurosurg Psychiatry ;40(3): ) Phenylpropanolamine (PPA)- Hemorrhagic stroke in Indian patients (Prasad et al. Phenylpropanolamine-induced intraventricular hemorrhage. Neurol India. 2003;51(1):117-8.)

29 Corticosteroids in Herbal medicines -Eczema -Rheumatoid Arthritis - Bronchial asthma Deliberate addition of modern drugs Antiepileptics (60% commercial samples) -Sod. Valproate -Phenytoin - Carbamazepine Antidiabetics -Glibenclamide -Tolbutamide

30 Whose is responsible for Pvig. Pharmaceutical Industry Practicing Clinician Academia Nurses & Paramedics Pharmacists

31 Process in Pharmacovigilance Collect and record of AEs / ADRs Causality assessment and analysis of ADRs Collate and code in database Compute risk-benefit and suggest regulatory action Communicate for safe use of drugs among stakeholders

32 Process in Pharmacovigilance Collect and record of AEs / ADRs Causality assessment and analysis of ADRs Collate and code in database Compute risk-benefit and suggest regulatory action Communicate for safe use of drugs among stakeholders

33 Compute risk-benefit ratio One man's meat is another man's poison!!!

34 Drug safety concerns - Europe since 1995 Eur J Clin Pharmacol (2008) 64:

35 Drug Safety Issues in Clinical Trials Old requirements (Before 30 Jan 2013) New requirements (From 30 Jan 2013) Unexpected SAE Timeline = 14 calendar days EC, DCGI & other sites No pre-screening checklist No guidance on compensation Type of report Timeline Additional stakeholders Pre-screening checklist Guidance on compensation

36 What to report? Who should report? All SAEs during clinical trial Investigator, Sponsor, Ethics Committee Investigator = Within 24hrs of occurrence & due analysis report within 10 calendar days of occurrence What is the timeframe? What is the format? Sponsor EC Appendix-XI = Within 10 calendar days of occurrence = Within 21 calendar days of occurrence Whom to report? Investigator DCGI, Chairman of EC, Head of Institution, Sponsor, Sponsor DCGI, Chairman of EC, Head of Institution, EC DCGI [Chairman of Exp. Committee For death case]

37 Reporting Timeframe within 24hrs of occurrence for Investigator within 10 calendar days of occurrence (Analysis report) - for Inv.& Sponsor within 21 calendar days of occurrence for EC Too stringent occurrence Vs. awareness Hard copy submission Vs. Electronic submission Timeline is not in tune with international norms

38 What is compensation? the act or process of making amends for something or something, typically- money, awarded to someone in recognition of loss, suffering or injury. Both Schedule Y and the ICMR guidelines specify that this be an essential element of the Informed consent document (ICD). Research participants who suffer physical injury as a result of their participation are entitled to financial or other assistance to compensate them equitably for any temporary or permanent impairment or disability, according to the guidelines

39 Categories Injury occurring to the clinical trial subject Injury occurring to the trial subject is related to the clinical trial Clinical trial related death of the subject Condition For Compensation Free medical management as long as required Financial compensation & Free medical management. Financial compensation to his/her nominee(s) & Free medical management Consequences of not abiding to the condition of compensation Show cause notice Suspend or cancel the clinical trial and / or restrict Sponsor including his representative(s) to conduct any further clinical trials in the country Any other action deemed fit under the rules

40 Pharmacovigilance Promotes: Systematic & rational use Boost confidence for safety

41 References Central Drugs Standard Control Organization. Good Clinical Practices for Clinical Research in India Available from: January (GSR 53 E) Feb (GSR 63 E) System of Pre-screening for submission of reports of SAEs to CDSCO NEW Minutes of 63rd DTAB Draft Guidelines For Industry on Reporting Serious Adverse Events occurring in Clinical Trials ( pdf)

42 "Dying from a disease is sometimes unavoidable. But, dying from an adverse drug reaction is unacceptable". -Dr Vladimir Lepakhin Geneva 2005