Innovation in Drug Regulation: Canada as a Leader

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Innovation in Drug RegulationCanada as a Leader

• Ottawa Regional Conference
• Building Excellence in Clinical Research and
  Clinical Trials
• Robert Peterson, MD, PhD, MPH
• Director General, Therapeutic Products
  Directorate

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Positioning the US FDA for the futureM. Lumpkin,
MD Deputy Commissioner FDA 2004

• Support biomedical research and development
• Provide scientific advice during drug development
• Development new methods to contain cost of drug
  development pharmacogenomics, etc.
• Recognize value of biomedical RD
• benefit to health and to the economy
• Heart disease, diabetes, HIV, cancer
• Hundreds of billions of dollars in health costs
• Improved productivity
• Value of biomedical innovation to our economy
  equals value of innovation in all other sectors.

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Positioning Canada for the future

• Create incentives for drug development when the
  marketplace does not
• Re-think the drug approval process
• Leverage a considerable advantage in health
  delivery in Canada
• Create an involved, informed consumer
• Create an environment for preferred RD
  investment
• Raise the bar on drug safety considerations
• Allow earlier access to new medicines

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Productivity with Todays Rules
NCEs
Spending
INDs
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Recent Experience in Drug Development
From CMR data
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Greater Expectations

• The bar for licensing a new drug must be raised.
• Before a medicine is approved, the public
  should expect that enough evidence has been
  amassed to ensure its safety.
• That means completing proper safety studies
  before a drug is licensed.
• Richard Horton
• (Editor of The
  Lancet)

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Observations of a Drug Regulator

• Clinical trials are typically powered to assess
  efficacy, not safety
• Safety is a relative term and not certain at the
  time of drug authorization
• Is this a revelation?
• Authorization always based upon positive benefit
  to risk profile
• Benefit demonstrated in clinical trials, Risk is
  inferred
• Increasing focus on safety in the post-approval
  phaseis this innovative?

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Economic Drivers in Drug Development
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Present Drug Development Phase 2

• Phase 2a Proof of Concept
• Studied in Patients, numbers vary
• Dramatic toxicity may be detected
• Phase 2b Dose Determination
• Studied in Patients, strategies vary
• Prepares way for larger Phase 3 studies
• Regulators may vary in expectations

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Present Phase 3 Drug Development

• Pivotal study to confirm proof of concept
• Further confirmatory studies of the Pivotal study
  typically requiredremoves uncertainty in
  p-value lt 0.05
• Collect data on safety
• Broad panel of measurements, some focused, others
  fishing
• Very expensive, high-risk for companies,
  artificial clinical environment, rarely
  comparative to existing therapies, secretive,
  commercial decisions are involved

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Preparing for Change

• Do these present international regulatory
  requirements meet our needs?
• Three traditional phases of drug development
• Escalating cost, escalating price
• Decisions on drug development based upon
  commercialization, not necessarily disease
• Many new life-style drugs, no new antibiotic
  breakthroughs
• Are we getting the data we require?
• Safety / utility in general population?

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Drug development beyond 2004

• Greater public health involvement in drug
  development decisions
• Cost containment, risk sharing (?)
• Better early access for promising therapies
• Better data in actual drug usage
• Drug comparisons, population safety during
  development greater public disclosure
• A new paradigm for clinical trials

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Challenging the Rules

• Re-think value of expensive Phase 3 studies
• More robust Phase 2a Proof of Concept
• Better organized real world studies
• Probationary licensing after Phase 2 completion?
• Does this ever virtually occur at present?
• Healthcare system shares cost/risk in safety
  studies

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Probationary Licensing

• Start cautiously, select suitable candidates
• Move products which meet public health objectives
  rapidly into clinical use after completion of
  strong Phase 2 clinical trials
• Govt participates in decisions, shares risk and
  costs in drug development
• Access to new medicines improves
• Better data obtained in public domain
• Unique to Canada

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How does Government become involved?

• End of Phase 2 (or earlier) meeting with industry
  to assess candidate molecules
• Advisory Committee to recommend selection based
  upon established criteria
• Serious illness, unmet needs
• No traditional Phase 3 studies
• Probationary license
• Structured introduction to market
• Rigorous adherence to prescribing/reporting
• Large patient numbers to satisfy safety concerns
• Unheard of strength in dataset, relied upon by
  rest of global regulatory community

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Whats in it for Canada?

• Innovation not just in drug development, but in
  drug regulation
• Participates in drug development
• Choices based upon need, not profit margin
• Supports innovation agenda
• Better access to better data
• Structured entry of new drugs in Canada
• Public funding leads to public data
• Creates unique post-approval environment
• Decisions for NOC based upon experience in
  Canadian health delivery system

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Whats in it for Canadian Industry?

• Industry wants better drug evaluation
• Limited presently based by cost, working
  intellectual property, marketing decisions
• New scheme shares cost/risk of drug development
• Could bring earlier ROI
• Generates data for use in other jurisdictions
• Attracts global RD to Canada

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Academic Centres

• Consider partnership with government as well as
  industry
• Define the rules around late phase drug
  development
• Leverage academic expertise
• Structured introduction of NCE
• Trial design within the real world
• Define placebo requirements, comparator
  selection, blinding and randomization, open
  design safety studies
• Determine data requirements during probationary
  phase
• Review of real-time active data collection
• Public domain dataset

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Review of new regulatory path

• Preclinical requirements unchanged
• Phase 1 human volunteer studies or early Phase 2
  studies in patients for tolerability
• Robust Phase 2a Proof of Concept in patients
• Typical Phase 2b Dose determination studies
• Regulatory review with Advisory Panel
  recommendation

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Review of new regulatory path (2)

• Determine data requirements during probationary
  phase
• Probationary License
• Review of real-time active data collection
• Public domain dataset
• Revise data requirements as required
• Review labelling (approved uses)
• Consider data from special populations
  (pediatrics, geriatrics, women, aboriginals)
• NOC granted (data protection begins?)

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Unanswered questions

• How many products would qualify?
• IVDDs, Priority review drugs, Orphan drugs,
  other categories
• Would payers participate?
• Structured introduction, better public data
• Ultimate cost to healthcare system
• Negotiate with industry preferred pricing ?
• Controlled utilization during probationary phase
• Comparative data possible

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Summary

• Re-shape, re-think the process sharing the risk
  and cost in the development of important new
  therapeutic products
• Government becomes active participant
• Public participation
• Early access to important new candidate therapies
• Creates incentives for drug development which do
  not exist in the Canadian marketplace

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Or, continue with the traditional approach to
drug development.