SPL standard � regulatory impact by MnOIcySD


									  Risk/Benefit Implications
     for Pharmaceutical

  PMCQ Education Day - Emerging
Trends in Pharmaceutical Marketing
    Montreal, October 20, 2005
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.
Safety Letters Posted on Health Canada
Website – 2000-2005






           2000   2001   2002   2003   2004   2005*

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
        Class warning – patients under the age of 16

   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.

 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.
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
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
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?
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

          Lexchin J. Drug withdrawals from the Canadian market for
safety reasons, 1963-2004. Canadian Med Assoc J 2005;172:765-8.
Response in the Regulatory Arena

  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
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.
Public Expert Advisory Committee Meetings

   June 9, 2005 – first public EAM held on COX-2 drugs
      Any interested parties could attend and address the
       Reort posted on Health Canada’s website, together
     with all documentation given to Panel to consider
  Sept 2005 – second public advisory committee held
on breast implants.
Summary Basis of Decision

  In the past, when new drugs were approved, the
basis on which the decision was made was not
  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®
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.
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.
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 60’s.
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
   Proposed legislation changes in Canada would allow
some exclusivity related to companies doing research in
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.
MOU with US

  Rare ADRs – occur in less than one in 10,000
   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
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.
Upgrade of Canada’s ADR System

 Program is underway to upgrade and modernize
Health Canada’s systems
       Provide for greater on-line public query capacity
       Integration of foreign safety
       Automated signal detection
       Electronic filing.
  Provincial governments could more easily monitor
      Could assist limited reimbursement or delayed
Establishment of New Regional Centers

 April 2005 – new centers opened in Alberta and
  Now seven centers – Halifax, Montreal, Toronto,
Winnipeg, Saskatoon, Edmonton, Vancouver.
Need for Pharmacovigilance Plans in

   As of November 2005 – required in Europe
   Post approval stability protocols required in Canada.
  Easy to make this a post approval pharmacovigilance
        I believe this will occur in the next year.
Federal/Provincial Conference on Drug

  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.
Response International - Regulatory
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
   Expectation is that ICH will enter this arena.
Response in Academia
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 McMaster’s 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
Response of Public
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.
Public Response

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

   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.
Time to Approval

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

  As regulatory agencies try to get at “rare” ADRs
(<1/10,000 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.
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.
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.
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.
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 can’t be sure that the
English version is the same as the French version.

   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
        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.

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