Decision making: managing risk

Summary of an ISoP workshop, Berlin, 2004

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!

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

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

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

What kind of decision?

• Amending SPC requires:– Prescriber-useful information – Good communication practice – Follow up

• Avoiding regulatory control may require comparative effectiveness-risk assessment

Decision theory

• Context – Anticipation

• Definition – Simplification – Investigation– Data & information – Summation

• Communication /Action • Follow up• Impact • Revision

Anticipating risks

• Pro-activity • Continuity • Science based evaluation in

addition to spontaneous reports

• Multidisciplinary • Consider costs & resources

– Feasability & opportunity – MAH image– Win-win.

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

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

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

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

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

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

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

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

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

Warning and communication of risk

• What to communicate – Rare but important – Frequent, relevant – Important negative info.– Serious quality problems – Information on imminent products

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

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’

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

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