Decision making: managing risk

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