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Safeguarding public health

Innovation; issues for regulators, society and industry.Overview of Conference topics

Alasdair BreckenridgeMedicines and Healthcare products Regulatory AgencyLondon 23 September 2008

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“It is a frustrating aspect of benefit-risk evaluation that there is no defined and tested algorithm or summary metric that combines benefit and risk data that might permit straightforward quantitative comparisons of different treatment options, which in turn might aid decision making”

CIOMS, 1998.

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Current perceptions

• Approval thresholds heightening

• Increased focus on safety

• Regulators dislike uncertainty

• Increasing cost of drug development

• Demand for increased transparency

• Negative perceptions of pharmaceutical industry and regulators

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• What information do regulators and industry need to enable them to undertake benefit : risk assessments?

• Are available frameworks adequate?

• How can we best communicate benefit : risk to the general public?

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Benefits of an agreed framework

• Shared understanding of issues between industry and regulator.

• Consistency in expressing benefit and risk.

• Transparency of regulatory decisions

• Tool to compare products

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Methods of assessing benefit• Nature of disease-incidence

natural historyimpact of treatmentconsequences of no intervention

• Purpose of treatment-prevention prevention of recurrence

symptomatic treatment cure

• Assessment of benefit-morbidity mortality symptoms quality of life

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Methods of assessing risk

• Development or post marketing

• ADRs affecting different systems

• Seriousness of ADRs

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Under-reporting

• Reporting bias

• Quality of reports

• Cannot estimate frequency of events

Spontaneous reports of ADRs

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Kno

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Time

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Timing of market authorisation

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Kno

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Time

Earlier to market?

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Post-licensing assessment

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“A systematic approach to population based drug safety surveillance which seeks to ascertain the number of adverse events by means of a continuous pre-organised process.”

Active Surveillance

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Record of drug exposure

• Record of outcomes

• Access to detailed information about individual cases

Data requirements for active surveillance

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Computerised databases of users and non users

• Medical records

Sources of information for active surveillance

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British Society of Rheumatology Biological Register(1)

• For patients with severe RA prescribed anti TNF α medicines.

• To receive drug, patient must be entered on central register.

• Short and long term ADRs documented.

• Cohort of similar patients prescribed conventional DMARDs

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British Society for Rheumatology Biological Register(2)

• Rheumatologists contacted 6 monthly about specific patients

•Data on severe infections and hospital admissions obtained

•Patient diaries

•Patients flagged with ONS to ascertain new cases of cancer and deaths

•Over 20000 patients on register

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GPRD: population figures

Contains 6.1 million acceptable patients from 464 active practicesCurrently collecting data on 3.58 million active patients from 405 up to standard practices

>45% of patients have 5 or more years of follow-up, >60% have at least 3 yearsContains over 40 million patient-years dataGeographically representative

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Safeguarding public health

RISK

major

minor

The worst balance

For restric

ted use only

Balance may require further study

Acceptable balance

Excellent balance

minor major BENEFIT

The Benefit-Risk Spectrum

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Principle of three

• Seriousness, duration, incidenceas applied to adverse reactions

• Seriousness, chronicity, extent of control or cureas applied to benefit

Describe verbally or numerically

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Aspirin

Disease Effectiveness of the drug

Dominant reaction

Seriousness 1 3 3

Duration 1 3 2

Incidence 3 0 2

TOTAL 5 6 7

3 = high, 2 = medium, 1 = low, 0 = no effect

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Shortcomings of models

• Do not enhance objectivity of benefit-risk decision making

• Time consuming

• Conflict between stakeholders in assessment

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Benefit-risk : outstanding issues

• Need for lexicon of terminology

• Framework for benefit: risk assessment in which different models might be used

• Different models for different situations

• Agreed framework would improve underlying science of innovation

• Importance of taking patient preferences into account

• Learning from other disciplines, including HTA

• Communication difficult but crucial