Regulating medical devices: a personal perspective

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Regulating medical devicesa personal perspective

• Dr Peter Wilmshurst
• Consultant Cardiologist
• Royal Shrewsbury Hospital
• Senior Lecturer in Medicine
• University of Keele

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Conflicts of interest

• No significant financial gains from involvement
  with medical device companies.
• But defending 3 defamation claims brought by NMT
  Medical for comments that I made about the MIST
  trial has cost me lots in legal fees despite
  being vindicated.

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Therapeutic agents

• Drugs
• Devices
• Devices with drugs (e.g. drug eluting stents)

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Ideal assessments of treatments

• Sufficient speed that good treatments get to
  patients rapidly.
• Sufficient checks to ensure that less effective
  or unsafe treatments are not marketed.
• Adequate post-marketing vigilance to detect
  problems.

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Equivalence for patients
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Regulatory pathways in EU
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Classes of medical devices

• Class 1 low risk e.g. stethoscopes
  manufacturers can self-declare conformity, affix
  a CE mark and register product with competent
  authority.
• Class 2 medium risk 2a monitoring equipment
  and ultrasound, 2b x-ray equipment.
• Class 3 high risk implantable devices - stents
  including drug eluting stents, pacemakers,
  prosthetic valves, prosthetic joints.
• Classes 2 and 3 must undergo a conformity
  assessment procedure.

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Licensing drugs in the EU

• A single European Medicines Agency (EMA).
• Committee for Medicinal Products for Human Use
  Europe-wide authorisation for marketing.
• Proof of safety and efficacy.
• New drugs require randomised controlled trials.
• Generic versions of existing drugs demonstrate
  same qualitative and quantitative composition and
  bioequivalence.
• EMA publishes reasons drugs were approved.
• EMA has role in post-marketing surveillance.

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Licensing devices in the EU

• Each state has own competent authority.
• Decision about CE mark is made by one of 76
  Notified Bodies (NB) - some are private
  companies.
• Satisfy requirements on safety and performance.
• Performance is defined by manufacturer.
• Do not always need to establish clinical impact.
• No need to demonstrate equivalence with other
  devices.
• Literature review if arguing device is similar to
  existing (predicate) device.

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Some problems

• Discrepancies between NB some have only 2 staff
  - forum shopping.
• NB work for the industry applicant not patients.
• Basis for granting CE mark is secret.
• Secrecy contrasts with published rationales for
  approval by EMA and FDA.
• There is no list of devices with CE marks.
• Need not prove clinical efficacy.
• Device with drug or biological component.

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Examples

• St Jude Silzone heart valve - substantially
  equivalent increased para-valvar leaks and
  thromboembolism
• Niroyal stent - substantially equivalent more
  late lumen loss.
• PFO closure introduced before evidence of
  clinical efficacy

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Conflicts of interest in clinical trials to
support licensing applications

• Clinicians invent devices (but not drugs) and
  become involved in research in devices in which
  they have financial interests.
• Andreas Gruentzig - balloon angioplasty
• Childrens Hospital Boston James Lock
  CardioSEAL STARFlex
• Martin Leon - Sapien Heart Valve, Edwards
  Lifesciences - PARTNERS Trial

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Other conflicts of interest

• Proctorships
• Consultancy payments NMT.
• Company representatives in the cath lab or
  operating theatre.
• Reporting adverse events device or operator?
• Bribes and rewards for using devices.

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Libel claims to prevent reporting

• GE Healthcare Dr Henrik Thomsen - Gadolinium
• Orbus Neich Dr Pavel Cervinka Genous
• NMT Medical MIST Trial
• I believe concerns about litigation has prevented
  some doctors reporting adverse events.

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We need to ask

• Why should standards of evidence for drugs and
  implantable devices differ?
• How do we deal with conflicts of interest around
  medical devices and clinical trial used as
  evidence for licensing?
• How do we get operators / implanters to report
  adverse events with medical devices?