1. Decision making: managing risk Summary of an ISoP workshop, Berlin, 2004

2. ICH E2E Risk Management Plan –When a new drug is launched, what do you need to do to find out about, and minimise, risks –Also for new, major risks New Regulatory approach!

3. General overview Define risk, or potential for a risk for a product What type of decision is needed Best data and information for the job Patient safety and preventability –Expansion of pharmacovigilance Communication is a major area of consideration

4. Eliminating risk (not possible!) Risk specification Risk plan –Milestones Risk minimisation Start early and continue High potency, high risk products –Tripartite involvement: Prescriber Dispenser Patient

5. What kind of decision? To communicate a new risk To add information which will aid prescribers in: –Avoiding risk –The early diagnosis of harm –The management of harm that has occurred To alter the overall availability of the product

6. What kind of decision? Amending SPC requires: –Prescriber-useful information –Good communication practice –Follow up Avoiding regulatory control may require comparative effectiveness-risk assessment

7. Decision theory Context –Anticipation Definition –Simplification –Investigation –Data & information –Summation Communication /Action Follow up Impact Revision

8. Anticipating risks Pro-activity Continuity Science based evaluation in addition to spontaneous reports Multidisciplinary Consider costs & resources –Feasability & opportunity –MAH image –Win-win.

9. Anticipating risks Risk management plan started in early clinical development –Pre-clinical data –Class effects –Natural history of indication & co-morbidity Consider reasons for extra safety studies (Predict ‘real life’) –Need for multiple methods –Need for better data sources –Risk groups e.g. children, pregnancy, elderly –Anticipate off label use: paediatrics –Special drugs Orphan drugs, NCEs

10. Anticipating risks Conditional approval based on risk management plan –Should not lead to poorer pre-marketing standards Management of studies? –Joint MAH & RA ? –Academia and professional bodies Funding –Public? –Joint? Periodic refreshing of plan

11. Anticipating risks Need for definitions of terms and criteria relating to risk management and planning etc. Legal issues of compliance –Co-responsibility –Who decides protocols? Use diversity Transparency, ethical and data protection issues

12. Investigating emerging risks Multidimensional challenge Factors effecting tool –Life cycle (rarity of event; extent of use) –Complexity of ADR (terminology issues, definitions, diagnosis v. signs and symptoms ) Requirements for data source Signal –Consolidation –Confirmation (time constraint) –Choose best tool (described) –Effectiveness-risk communication –Impact

13. Investigating emerging risks What to focus on and communicate –‘Useful to clinician ‘ –What will affect patients’ choice Preventability. ADR diagnosis ADR management change in effectiveness –Interactions/additive/negative effects –Seriousness and severity issues –Quality of information –Clarity of clinical/epidemiological situation

14. Warning and communication of risk SPC – Use of PSUR –Legal v. Communication –Which section of SPC Contra indication, warning –When changed? –Design ? ‘Dear Health Professional‘ communication –Web –Design –Repeated Media Bulletins

15. Warning and communication of risk Considerable legal framework and guidelines –Governs what happens between players Particularly reporting Accuracy of information Timing important Start early? Limitation on communicating between industry and HPs and public Communication within company Structure and responsibility (personal!) ‘Communications’ v. ‘advertising’ –Responsibility of journals

16. Warning and communication of risk Players may have competing interests in communication even if public health is a common aim Personnel skills –Independent –Cope with divergent aims –Cope with uncertainty Communication and action

17. Warning and communication of risk Media –Dramatic news a priority –Internet No control When to communicate –Pro-activity Know media Call for vigilance During effectiveness/risk evaluation –Crisis (out of control, reactive) Rapid response is different Provoked by third party communication

18. Warning and communication of risk What to communicate –Rare but important –Frequent, relevant –Important negative info. –Serious quality problems –Information on imminent products

19. Warning and communication of risk To whom –MAH and RA –H Ps –Patient organisations –Public –Social security –Analysts & stock exchange? By whom –Must be competent communicator –Familiar with issues

20. Warning and communication of risk Wide range of issues possible –Difficult to predict response –Prepare for rapid and intense communication –HPs before public! –Communicating uncertainty ‘Dialogue in Pharmacovigilance’

21. Warning and communication of risk Outcomes –Follow up? Questionnaires –General Count responses? –Need more information on outcomes –Better public education –Less paternalism Better view of us! Openness –Constructive law & media interaction

22. Warning and communication of risk A hierarchy of evidence based medicine in pharmacovigilance –Signal –Hypothesis –Controlled studies Get to stronger evidence –Information –Knowledge detection UMC and IMS –andrew.bate@who-umc.org –Wisdom YOU