Pharmacovigilance Workshop II 20 th June 2003 Medicines

Pharmacovigilance Workshop II 20 th June 2003 Medicines Regulation Michael Bonett

Overview • There is a need for collecting and evaluating data relating to drug safety after licensing of the medicinal product (Post-marketing) • ADR reporting - most important source of Data • Other sources of Data • Signal generation and risk quantification • Regulatory Action which can be taken • Communication

Other Data Sources • Pre-clinical data: in-vitro, animal toxicology • Pre-authorisation information: generated between the time of application and granting of license • Pre-marketing clinical trails: reported by the sponsor or investigator • Reports received from the market authorisation holder (MAH) • Reports from worldwide scientific and medical literature

Other Data Sources • Data transfer from ADR databases: from EU, World Health Organisation (WHO) • Others: Consumers, patient organisations reports • Periodic Safety Update Reports from MAH’s • Company sponsored Post-Authorisation safety studies • Data from epidemiological studies and academic centres

Signal Identification • Signal: Data constituting a hypothesis that may be relevant to the safe use of a drug • Any amount of evidence giving rise to further investigation is considered a signal • To help identify signals computer generated safety monitoring programmes and statistical methods are used

Signal Identification Examples of signals: • • Previously unidentified ADR’s Change in reporting rate Change in seriousness of reaction Identification of new risk factors for known ADR’s

Risk Quantification Once a new signal is identified, the next step will be to quantify: • the strength of the association between the ADR and the drug • the frequency of occurrence For this purpose: • Reporting rate of ADR may be calculated • MAH may perform epidemiological studies

Regulatory Action • In many instances regulatory decisions have to be taken promptly • Based on evidence from all available data • Experts and committees consulted • The most appropriate action should be chosen

Types of Regulatory Action • Further investigation: more studies needed • Update of product info to reflect new risk • Restrictions: dose reduction, limitation of length of use, restricting indications • Suspension of indications • Temporary suspension of market authorisation, until further studies are conducted • Withdrawal of the market authorisation

Communication • • • Market Authorisation Holders (MAH) Other Regulatory Agencies Healthcare Professionals Patient Groups General Public Media

Communications • Communication relating to the safety of medicines has the potential to impact on the general public, particularly if the safety issue concerned has a broad public interest • E. g. issues relating to the use of childhood vaccines • UK, media activity Re: MMR vaccine and autism - MCA: ‘The evidence does not support recent concerns’ - Confirmed safety of MMR

Conclusion Collection of Data Signal Identification Risk Quantification Regulatory Action Communication of Safety information