RiskBenefit Implications for Pharmaceutical Marketing

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Risk/Benefit Implications for Pharmaceutical
Marketing
PMCQ Education Day - Emerging Trends in
Pharmaceutical MarketingMontreal, October 20,
2005
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Topics Covered

• Recent Regulatory Decisions re Safety
• Response in the Regulatory Arenas
• Public Response
• Implications for Marketing
• I would like to acknowledge IMS Canada and its
  publication, Provincial Reimbursement Advisor, in
  preparing this presentation.

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Safety Letters Posted on Health Canada Website
2000-2005
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Antidepressants and Suicide Potential

• Late 2003 - Public concern about possibility of
  antidepressants and suicide potential.
• February 2004 Scientific Advisory Panel held
• Recommended stronger warnings
• May 2004 SSRIs updated to warn re potential of
  self-harm.
• Class warning patients under the age of 16

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VIOXX

• Market withdrawal of VIOXX on September 30, 2004
• December 2004 US Congressional Report
  criticized how Merck and the FDA had disseminated
  information related to safety of VIOXX.
• June 2005 Canadian Expert Advisory Panel
  recommends that VIOXX be returned to the Canadian
  market with updated labelling.
• July 2005 A US judge rules that a nationwide
  class action lawsuit could be brought by a labour
  union helaht plan on behalf of all 3rd party
  payers.

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VIOXX

• July 2005 EU advises that compliance of VIOXX
  ADR reporting will be investigated.
• August 2005 Merck loses first case re VIOXX and
  must pay 253 million to family in Texas.
• September 2005 Ontario Superior Court hears
  arguments requesting class action be allowed.

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Adderall XR

• Feb 9, 2005 marketing of ADDERALL XR suspended
• Based on sudden deaths (20) reported in PMS.
• 14 in children
• Aug 26, 2005 New Drug Committee Hearing held.
• Product can be remarketed with changes to Product
  Monograph.

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Long-Acting Beta-2 Agonists

• October 4, 2005 possible increased of
  asthma-related deaths
• SMART study
• Began in 1996 at request of FDA.
• Study of approximately 30,000 patients was
  prematurely halted in January 2003
• FDA advisory committee in July 2005

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Questions Being Asked

• How closely tied are the regulatory authorities
  to pharmaceutical companies?
• How transparent are the decisions made by
  regulatory authorities?
• How do pharmaceutical companies comply with
  disclosure regulations
• Do pharmaceutical companies spin safety
  information to their own ends?
• How much does the public have a right to know?
• How much is really known about a drug when it is
  first marketed?

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Controversy re safety

• Unless the Canadian public can be assured that
  Health Canada is adequately monitoring the safety
  of marketed drugs, then confidence in the use of
  therapeutic products will suffer, and so will the
  health of Canadians.
• Lexchin J. Drug withdrawals from the Canadian
  market for safety reasons, 1963-2004. Canadian
  Med Assoc J 2005172765-8.

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Response in the Regulatory Arena
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Transparency

• Canadian public want to know the basis on which
  decisions are made.
• Provincial governments and other payers also want
  to know the basis on which these decisions are
  made
• To address these concerns, Health Canada has
  taken a number of recent steps to disclose how
  decisions are made.

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Office of Public Ombudsman

• April 16, 2005 Health Canada announced the
  creation of the Office of Public Ombudsman
• Will receive complaints, concerns and feedback
  about how Health Canada fulfills its
  responsibilities.
• To date no Ombudsman has been appointed.

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Public Expert Advisory Committee Meetings

• June 9, 2005 first public EAM held on COX-2
  drugs
• Any interested parties could attend and address
  the Panel.
• Reort posted on Health Canadas website, together
  with all documentation given to Panel to consider
• Sept 2005 second public advisory committee held
  on breast implants.

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Summary Basis of Decision

• In the past, when new drugs were approved, the
  basis on which the decision was made was not
  disclosed.
• Health Canada have announced that they will
  provide a Summary Basis of Decision for all drugs
  approved after Jan 1, 2005.
• To date, six have issued Crestor, Fabrazyme,
  Lyrica, Velcade, Zemplar and Macugen

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Clinical Trial Information

• There is a belief that industry does not
  disclose negative results from clinical trials.
• Several leading journals (including CMAJ) have
  announced that they will no longer publish
  articles on clinical trials unless the trials
  were registered in a public database, meeting
  certain minimum criteria.
• FDA has a database that meets requirements.
• July 7, 2005 Health Canada announced that they
  would be setting up such a database in Canada.

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Public Listing of Recalls

• As of April 2005, all recalls are listed on
  Health Canada website.
• Information available product, lot numbers,
  reason for recall, hazard level and recalling
  firm.

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Public Disclosure of ADRs

• May 25, 2005 new web-based database for ADRs
  launched by Health Canada
• Called MedEffect
• Provides access to the latest advisories,
  warnings and recalls
• Promotes the reporting of adverse drug reactions
• Patients can report directly
• ADR Database also available
• Anyone can search ADRs and drugs for all data
  submitted to Health Canada since the early 60s.

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Office of Pediatric Initiatives

• Concern that little is known about drugs in
  children and how to use them, specifically the
  dose.
• This office has been set up to promote research
  in children.
• Proposed legislation changes in Canada would
  allow some exclusivity related to companies doing
  research in children.

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Upgrading Pharmacovigilance

• In addition to transparency, Health Canada has
  focused on upgrading the collection and
  interpretation of pharmacovigilance data.
• This includes providing money to Health Canada to
  upgrade Health Canada oversight of safety
• Feb 2005 - 170 million over 5 years provided.

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MOU with US

• Rare ADRs occur in less than one in 10,000
  patients.
• Can only be detected post-marketing and by using
  large databases.
• June 29, 2005 Canada signed a MOU with the US
  Consumer Product Safety Commission to share data
  with the US.
• Includes postmarketing surveillance and
  enforcement activities.

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Mandatory Reporting of ADRs

• Companies are required to report ADRs but
  physicians are encouraged to report them.
• Some countries have mandatory reporting systems
  France, Sweden, Norway, Austria, Italy
• Canada has mandatory reporting of child abuse,
  chemical intoxication and some infectious
  diseases.
• Health Canada has announced that they want to
  establish mandatory reporting and are currently
  setting consultation on what this would mean.

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Upgrade of Canadas ADR System

• Program is underway to upgrade and modernize
  Health Canadas systems
• Provide for greater on-line public query capacity
• Integration of foreign safety
• Automated signal detection
• Electronic filing.
• Provincial governments could more easily monitor
  drugs.
• Could assist limited reimbursement or delayed
  reimbursement.

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Establishment of New Regional Centers

• April 2005 new centers opened in Alberta and
  Manitoba.
• Now seven centers Halifax, Montreal, Toronto,
  Winnipeg, Saskatoon, Edmonton, Vancouver.

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Need for Pharmacovigilance Plans in Submissions?

• As of November 2005 required in Europe
• Post approval stability protocols required in
  Canada.
• Easy to make this a post approval
  pharmacovigilance protocol.
• I believe this will occur in the next year.

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Federal/Provincial Conference on Drug Safety

• September 2005 Federal Health Minister and BC
  Health Minister (leaders of the National
  Pharmaceuticals Strategy) held a meeting to
  discuss this issue.
• Involved provincial representatives, health care
  providers, patient reps, industry and researchers
• Press release indicated that Health Ministers
  were to evaluate how to strengthen real-world
  drug safety and effectiveness and to provide
  report by June 16, 2006.

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Response International - Regulatory
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New Guidelines

• US has issued three new guidelines on how to
  document and assess adverse reaction data.
• WHO organization has issued a new guideline on
  assessing ADRs in clinical trials (CIOMS).
• Europe is requiring pharmacovigilance protocols
  in submissions.
• Expectation is that ICH will enter this arena.

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Response in Academia
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Conflict of Interest

• April 2005 The Drug Trial published
• A book focused on the drug trial at the Hospital
  for Sick Children and Dr. Olivieri
• In Hamilton, the Spectator conducted a 3-month
  investigation of McMasters Faculty of Health
  Sciences
• Approximately 100 faculty members had financial
  relationships with industry
• Research funding, clinical trial contracts,
  honoraria, speaking fees, consultancies, stock
  options, sitting on Boards of Directors

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Response of Public
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Public Response

• New publications
• The Drug Trial
• Dangerous Doses
• Xx
• Movies/TV
• The Constant Gardener.
• Spring 2006 new movie looking at the
  pharmaceutical industry.
• Law Order episodes.

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Public Response

• Public Opinion Polls
• Show distrust of pharmaceutical industry at an
  all-time high.
• Public response to perceived safety issues is
  that industry is holding back negative data and
  putting their health at risk.

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Implications for Marketing
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Public Relations

• There has never been a time for a greater need
  for the industry to tell its side of the story.
• Trade associations and individual companies need
  to get the benefits that this industry brings to
  the forefront. Otherwise, it will not be told.
• Stories regarding these benefits need to be
  brought to the public media, e.g., Law and Order.
  Counterfeit medications would be one way to do
  this.

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Litigation

• With the greater disclosure of ADR information
  and risk/benefit data that support decision
  making, there will be more data available for
  litigation purposes.
• Companies should routinely be monitoring what is
  on this ADR website regarding their products.

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Time to Approval

• Given the concerns about safety, agencies are
  likely to make conservative decisions and to ask
  for more data.
• Approval of non-life threatening drugs may be
  delayed or consensus requested from advisory
  committees.

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Post Approval Commitments

• We will see the Canadian system develop to
  require post-approval commitments, either through
  a change to the system, the use of more
  conditional NOCs or the use of postmarketing
  protocols
• Will focus on safety assessments in
  sub-populations.
• Monitoring ADRs in a small environment in real
  life, e.g., a teaching hospital.
• These post-marketing commitments will likely have
  an impact on listings for reimbursement.

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Use of Large Databases

• As regulatory agencies try to get at rare ADRs
  (lt1/10,000 patients), large databases will be the
  best place to get this information.
• We will see large databases adapt themselves
  better to be able to provide this data.
• We will see regulatory agencies requesting
  companies to use these databases more.

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Patient Access to Data

• Patients will have far greater access to data.
• They will review the data and share it among
  themselves via the internet.
• They will begin filling their own ADR forms,
  particularly the patient groups that are
  well-organized and can assist one another.

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Direct To Consumer Advertising

• Ban on Direct to Consumer advertising will
  continue.
• US DTC Advertising may well find itself
  restricted.
• US Trade organization has recently issued new
  guideline that it expects its members to abide by
  regarding DTC advertising.

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Risk Management

• Risk Management in its broadest sense will become
  a strategic function within pharmaceutical
  companies.
• Pharmacovigilance and safety is one component of
  risk management for a company.
• Paramount in the assessment would be the risk to
  the patient.
• How that risk is explored and defined may need to
  be tightened i.e., move from art to science
  with predetermined numbers and probabilities.

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Parting Message

• As of October 31, 2005, the US have adapted SPL
  labelling for ALL drug product subject to an NDA.
  
• Company submits in SPL. FDA provides SPL to
  National Library of Medicine (NLM). NLM
  maintains database of all approved labelling
  which HMOs and others can use to develop their
  patient labelling etc.
• Approved labelling is transmitted to NLM within
  10 minutes of approval. From there it is
  available throughout the country.
• Compare this to the industry stance in Canada
  where we have no electronic database of Product
  Monographs. Nor do we want one because we cant
  be sure that the English version is the same as
  the French version.

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Conclusions

• We have entered a new environment focused on
• The relationship that industry has with
  regulators.
• How transparent we are in sharing safety data on
  our products.
• How close we are to researchers.
• How much information our patients and customers
  have access to regarding our products.
• The old environment will never come back. We
  need to learn to function in this new environment
  and address the concerns that are coming to us.