Regulating medical devices: a personal perspective

1. Regulating medical devices:a personal perspective Dr Peter Wilmshurst Consultant Cardiologist Royal Shrewsbury Hospital & Senior Lecturer in Medicine University of Keele

2. 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.

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

4. 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.

5. Equivalence for patients

6. Regulatory pathways in EU

7. 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”.

8. 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.

9. 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.

10. 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.

11. 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

12. 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 • Children’s Hospital Boston & James Lock –CardioSEAL & STARFlex • Martin Leon - Sapien Heart Valve, Edwards Lifesciences - PARTNERS Trial

13. 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.

14. 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.

15. 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?