Transcript Document
Regulating medical devices: a personal perspective Dr Peter Wilmshurst Consultant Cardiologist Royal Shrewsbury Hospital & Senior Lecturer in Medicine University of Keele 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. Therapeutic agents Drugs Devices Devices with drugs (e.g. drug eluting stents) 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. Equivalence for patients Regulatory pathways in EU 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”. 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. 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. 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. 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 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 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. 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. 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?