COLLABORATIVE EFFORTS ON PHARMACOVIGILANCE

COLLABORATIVE EFFORTS ON PHARMACOVIGILANCE DIA 2nd Latin American Regulatory Conference (LARC) November 18-20, 2009 Mexico City, MEXICO Miguel-Ángel Maciá Martínez División de Farmacoepidemiología y Farmacovigilancia AEMPS (Spanish Agency for Medicines and Healthcare Products) SUMMARY: Collaborative efforts on pharmacovigilance Introductory notes : rationale and operational framework in pharmacovigilance General principles on collaborative efforts Some key collaborations in pharmacovigilance Regulatory authorities perspective Healthcare professionals perspective Pharmaceutical industry perspective Conclusions 1

2 Reminding the rationale for pharmacovigilance Clasical limitations of the pre-marketing information regarding g adverse reactions: with a frequency of less than 1 in 1000 exposed patients Dipirone and agranulocytosis related to long term exposure to medicines Bisphosphonates and osteonecrosis of the jaws more relevant in age, gender or race subpopulations NSAIDs and serious gastrointestinal toxicity in older people in patients with comorbidities Gadolinium agents and nephrogenic systemic fibrosis in chronic renal disease in patients taking multiple other medications Cerivastatin and rabdomiolisis in gemfibrozil treated patients PHARMACOVIGILANCE: OPERATIONAL FRAMEWORK From analysis to management: Typical activities: RISK IDENTIFICATION DECISION-MAKING COMMUNICATION Record ADR case reports Perform and interpret (pharmacoepi) studies Carry out regulatory measures Inform and educate healthcare profs. and patients Prevent harm to patients

3 PHARMACOVIGILANCE: an example RISK IDENTIFICATION DECISION-MAKING COMMUNICATION Reported cases of congenital malformations asociated to the use of a new drug in pregnant women New epidemiological studies and animal data confirm the risk Contraindication in pregnancy Implementation of a pregnancy prevention program Public communications, bulletins, Direct information to prescribers, educational materials Prevent harm to patients WHO COLLABORATE IN PHV? Regulatory / Healthcare system Supranational National Local RISK IDENTIFICATION DECISION- MAKING COMMUNI CATION Pharma industry Global org. Local affiliates Healthcare Professionals Experts / Academia Clinical practice profs.

4 COLLABORATION IN PHV: SOME GENERAL PRINCIPLES Successful pharmacovigilance (risk minimization) is not possible without collaboration This should be based on clear and accepted roles and responsabilities of stakeholders The participation of each agent depends on: Specific pharmacovigilance activity Organizational scenario We will look at some key collaborations SOME KEY COLLABORATIONS IN PHARMACOVIGILANCE Drug regulation and pharmacovigilance Cooperation between countries and regions: Risk identification Decision-making Participation of healthcare professionals Risk identification Risk communication Interactions with the pharmaceutical industry Risk evaluation

5 The regulatory building The pharmacovigilance system is the roof of the regulatory building: We only remember PhV when it rains. No point in having a good roof if the building itself is not adequate. The design of a PhV system should be in proportion and fitted to the rest of the building. Therefore. The regulatory building A pharmacovigilance system can supplement but can not substitute: A system that approve drugs with proofs of efficacy, safety and quality (scientific evaluation) A system fighting against counterfeit products and fraud, in general (inspection). Activities promoting appropriate use of medicines in clinical practice (product information, medical education, guidelines)

6 Our experience in Spain as member State of the European Union EU: 27 countries Spain: 17 regions Regulatory / Healthcare system Supranational National Local KEY COLLABORATIONS IN PHV RISK IDENTIFICATION DECISION- MAKING COMMUNI CATION Pharma industry Global org. Local affiliates Healthcare Professionals Experts / Academia Clinical practice profs.

Cooperation between countries and regions in risk identification When establishing a reporting system of adverse reactions: The Local level is relevant in order to: Make possible a direct contact and feedback with the reporter (primary source of data): quality of reports Increase awareness and committment of healthcare professionals with PhV: quantity of reports Detect local issues (lack of quality, inadequate use of medicines): local management 17 Regional PhV Centres within Spain Cooperation between countries in risk identification: WHY? The Global level is relevant for: Detect new signals of rare adverse reactions: power Corroborate signals in different scenarios: external validation Common tools and standards: good pharmacovigilance practice Increase eficiency: worksharing Databases, Committes, Guidelines 7

8 Cooperation between countries in risk identification: HOW? Specific tools in Spain and Europe: ADR Databases with electronic exchange of data FEDRA (Spain) Eudravigilance (EU) (WHO VigiBase) Coordination Committes: Comité Técnico del Sistema Español de Farmacovigilancia il i Pharmacovigilance Working Party (EMEA) Shared procedures and guidelines Coordination in signal detection under development Signal evaluation driven by a reference member state in the EU Regulatory / Healthcare system Supranational National Local KEY COLLABORATIONS IN PHV RISK IDENTIFICATION DECISION- MAKING COMMUNI CATION Pharma industry Global org. Local affiliates Healthcare Professionals Experts / Academia Clinical practice profs.

9 Cooperation between countries in decision-making: WHAT DECISIONS? Relevant modifications in the product information: new contraindication, restriction of indications.. Restricted dispensation/prescription: hospitals, specialists Suspension of the authorisation Cooperation between countries in decision-making: IN WHAT SITUATIONS? The safety concern is not driven by a pure local situation The detected risk could affect different populations even with a different usage pattern of the drug There are legal tools to implement the appropriate regulatory measures in the different countries

10 Cooperation between countries in decision-making: RATIONALE: How can different decisions be explained to the population? Patients/products can move through different countries. Common market for pharmaceuticals: shared decisions at authorisation should continue afterwards. Cooperation between countries in decision-making: HOW? (New) drugs approved under coordination o procedures The same common rules will be applied for preand post-authorisation decisions. In Europe: EMEA centralized, mutual recognition. (Old) drugs approved nationally Information exchange + Discussion forum + Common decision procedures In Europe: Referral procedures

11 Regulatory / Healthcare system Supranational National Local KEY COLLABORATIONS IN PHV RISK IDENTIFICATION DECISION- MAKING Pharma industry Global org. Local affiliates COMMUNI CATION Healthcare Professionals Experts / Academia Clinical practice profs. Participation of healthcare professionals in risk identification Adverse drug reactions in the differential diagnosis in clinical practice: For already known ADRs: continuing medical education For previously unrecognized ADRs: high h level l of suspicion, i personal interest, t cluster of cases Early and effective reporting of suspected ADRs to PhV is essential

12 Participation of healthcare professionals in risk identification: HOW? Awareness: Direct communication with the pharmacovigilance professionals Effectiveness: Adecuate tools to facilitate reporting Trust in the PhV system: Scientific credibility, feedback of information ADR reporting systems: combination of local and (supra)national organizations Regulatory / Healthcare system Supranational National Local KEY COLLABORATIONS IN PHV RISK IDENTIFICATION DECISION- MAKING COMMUNI CATION Pharma industry Global org. Local affiliates Healthcare Professionals Experts / Academia Clinical practice profs.

13 Healthcare professionals and communication in PhV: OBJECTIVES In case of relevant modifications in the product information: This should influence clinical therapeutic practice In case of restricted dispensation/prescription: Prescribers should understand and apply the measures In case of suspension of the authorisation HPs are in the better place to explain the reasons to patients HPs will advice to patients on new treatment options PhV should take advantage of the direct contact of HPs with their patients Healthcare professionals and communication in PhV: HOW? Communications from Regulatory agencies Not only through the websites Direct healthcare communications from the pharma industry ( Dear Doctor Letters ) Under close supervision of healthcare authorities Drug Bulletins and local media Participation of regional pharmacovigilance units Clear, balanced, and evidence based messages should reach healthcare profs.

14 Regulatory / Healthcare system Supranational National Local KEY COLLABORATIONS IN PHV RISK IDENTIFICATION DECISION- MAKING Pharma industry Global org. Local affiliates COMMUNI CATION Healthcare Professionals Experts / Academia Clinical practice profs. Interactions with the pharmaceutical industry: Main responsabilities: Perform a continuous evaluation of the riskbenefit balance of the medicinal products: Collect and interpret data from different sources Perform post-authorization studies Immediately inform the competent authorities of any new information which might influence the overall risk-benefit evaluation or require a change in the product information.

15 Interactions with the pharmaceutical industry: Main instruments: Periodic Safety Update Reports (PSUR) International Conference of Harmonization: E2C Clinical Safety Data Management Risk Management Plans: Pharmacovigilance il Planning: ICH E2E Pro-active and continuous PhV activities implies a company Pharmacovigilance System GENERAL CONCLUSIONS The aim of pharmacovigilance activities is to prevent harm to patients Pharmacovigilance is placed in the framework of the whole regulatory building Regulators, industry and healthcare professionals are the main stakeholders Collaboration is relevant both at the local and global levels of activities. Clear roles Clear roles and responsabilities of the different agents are essential

16 A relevant example: the EAMI initiative Encuentros de Autoridades Competentes en Medicamentos de los países Iberoamericanos (Meetings of Competent Authorities for Medicines in Iberoamerica) A set of pharmacovigilance activities in the framework of the whole regulatory building among Iberoamerican regulators.

17 Grupos Técnicos: Accesibilidad y Propiedad Intelectual Ensayos Clínicos y Farmacovigilancia Medicamentos Falsificados y Fraudulentos Terapias Avanzadas y Productos Biológicos

18 Encuentros EAMI VII EAMI. Cancún, 15 a 17 de Octubre de 2008 VI EAMI. Lisboa, 16 a 18 de Octubre de 2006 V EAMI. Brasilia, 29 a 31 de Marzo de 2004 IV EAMI. San José de Costa Rica, 5 a 8 de Septiembre de 2000 III EAMI. Madrid-Granada, 13 a 15 de Octubre de 1999 II EAMI. Buenos Aires, 18 a 20 de Febrero de 1998 I EAMI. Madrid-Londres, 18 a 20 de Febrero de 1997 NEXT MEETING IN MADRID 11-14 MAY 2010. "La civilización no dura porque a los hombres sólo les interesan los resultados de la misma: los anestésicos, los automóviles, la radio. Pero nada de lo que da la civilización es el fruto natural de un árbol endémico. Todo es resultado de un esfuerzo. Sólo se aguanta una civilización si muchos aportan su colaboración al esfuerzo. Si todos prefieren gozar el fruto, la civilización se hunde José Ortega y Gasset Gracias!