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

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 Risk minimisation Start early and continue High potency, high risk products
Tripartite involvement:
Prescriber Dispenser Patient

Milestones

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 Management of studies? Funding
Joint MAH & RA ? Academia and professional bodies Public? Joint? Should not lead to poorer pre-marketing standards

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 When changed? Design ? Web Design Repeated

Contra indication, warning

Dear Health Professional communication

Media Bulletins

Warning and communication of risk

Considerable legal framework and guidelines
Governs what happens between players
Particularly reporting Accuracy of information

Timing important

Communication within company

Responsibility of journals

Start early? Limitation on communicating between industry and HPs and public Structure and responsibility (personal!)

Communications v. advertising

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