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Rethinking medical deviceregulation

Carl Heneghan • Mathew ThompsonDepartment of Primary Care Health Sciences, University of Oxford, Oxford, UK

Correspondence to: Carl Heneghan. Email: carl.heneghan@phc.ox.ac.uk

Complications with Poly Implant Prosthese (PIP)breast implants1 and Metal on Metal (MoM) hipimplants2 reflect systemic failings with thecurrent regulation of medical devices. Yet, thesetwo cases highlight only a fraction of the burgeon-ing increase in medical device safety alerts3 andproblems with device recalls, and are leading toa rethink of the systems for regulatory approvalin both Europe and the USA.4

Therefore, having an understanding of medicaldevice regulation is now an important require-ment for doctors and healthcare professionalsalike. To aid this, French-Mowatt and colleaguessummarize the current medical device regulationin Europe,5 outlining the current requirementsfor CE regulation. Outside of the EuropeanUnion, Susan Lamph describes the regulatory pro-cesses across different countries and the lack ofharmonization with leads to wide variation in pre-market data requirements.6

Analysis of medical-device recalls in the UKand the USA, and the device-regulation process,reveals the increasing nature of the problems.From 2006 to 2010, the UK regulator, the MHRAissued 2,124 manufacturer field safety notices, anincrease of 1,220% over this five-year period.3 Inthe USA the number of recalls for moderate orhigh-risk devices more than doubled between2007 to 2011.7 In addition, many recalled medicaldevices in the USA were originally cleared usinga less stringent process called 510(k), or evenmore problematic, recalled devices were con-sidered to be so low-risk they were exempt fromregulatory review in the first place. This situationreflects a very low ‘bar’ currently for evidencerequirements to gain regulatory approval, evenfor high-risk devices. For instance, of 78 high-riskcardiovascular devices approved through themore stringent Pre-Market Approval (PMA)

regulatory process in the USA, fewer thanone-third had undergone randomized trials andonly half of the trials overall involved controls.8

Whilst new drugs require at least randomizedcontrolled trials to gain regulatory approval, formedical devices even under the more stringentPMA approval process, only one controlled trial(not necessarily randomized trial) is required.However, an even more worrying issue withdevice regulation in both the EU and US is theuse of ‘substantially equivalent’ in evidence sub-missions for regulatory purposes. The problemswith using ‘equivalence’ in the device approvalprocess can be traced back several decades. In1976, in the USA many devices were already onthe market, so a less burdensome alternative toPMA known as 510(k) provision was approved.The 510(k) pathway did not require clinicaltrials; the manufacturer was only required todemonstrate a device was ‘substantially equival-ent’ to another device already on the market. Theproblem now is that the definition of equivalenceis interpreted so loosely that the FDA admitsthey need to ‘clarify the meaning of “substantialequivalence.”’10

The predicate of equivalence is also usedwithin the European Union (EU) regulatorysystem for device regulation. There are three Euro-pean Directives related to device regulation.11–13

These directives, which lead to CE marking andaccess to the European market, state the extentand nature of clinical data required for approval.5

Problems occur because even for implantabledevices, the scrutiny of evidence at the outset isleft to private organizations known as NotifiedBodies;3 and secondly, clinical data required forthe equivalent route can involve as little as ‘a criti-cal evaluation of the relevant scientific literaturecurrently available relating to the safety,

DECLARATIONS

Competing interests

None declared

Funding

The authors

received no funding

Ethical approval

Not required

Guarantor

Carl Heneghan

Contributorship

Both CH and MT

contributed to the

ideas, drafted the

manuscript and

approved the final

version

Acknowledgments

None

J R Soc Med 2012: 105: 186–188. DOI 10.1258/jrsm.2012.12k030

EDITORIAL

performance, design characteristics and intendedpurpose of the device’. The use of equivalence istherefore left to the manufacturer and the NotifiedBodies to determine, without any outside scrutinyof the decision making process centrally or withineach EU country.

Even for the more stringent PMA process, thereare profound differences in evidence requirementsbetween the US and EU. For example, EUapproval of a ‘GuardWire’ developed by Percu-Surge for use during angioplasty, required a 22patient study with no control group. Yet, in theUSA, FDA regulators required an 800 patient mul-ticentre randomized controlled trial.14

Perhaps what is even more concerning than thedevice recalls and high profile cases (such as theMoM hips and PIP implants), is that manymedical device problems go unnoticed. Forexample, women participating in a breast cancerstudy were left with hundreds of tiny particles ofthe heavy metal tungsten in their breast tissuedue to a faulty device cleared under the 510(k)processes.9 Similarly, recalled device noticesoften go unheeded. In 2006 the maker of a surgicalclip, the Hem-o-lok issued an urgent recall noticewarning surgeons to stop using the clips on livingkidney donors. However, three years later asurgeon used one of the clips to tie off a 29-year-old male’s renal artery during an operation inwhich he donated a kidney to his wife. He bledto death twelve hours later when the clip malfunc-tioned.10–15 Currently we have limited ability totrace most patients in whom medical deviceshave been used (or implanted), so when problemsor recalls occur, it can be impossible to know themagnitude of the problem.

However, it seems as though the tide isturning in terms of regulatory requirements.The American system is coming under increasedscrutiny with calls for the removal of the 510(k)process. The influential Institute of Medicinehas recommended the FDA do away with the510(k) approval process and replace it ‘with anintegrated premarket and post-market regulatoryframework that effectively provides a reasonableassurance of safety and effectiveness throughoutthe device life cycle.’16 It is possible that allimplantable devices in particular will requirePMA approval and thus clinical trial data inthe future. However, more stringent regulationsare unlikely to be passed into law in the US

without a substantial battle with the medicaldevice industry.

Sprange and Clift’s analysis of manufacturers’submission challenges, to the NICE medicaltechnology program, in the supplement editionJ R Soc Med 2012;105 (S1) reveals there aresignificant issues in relation to basic and generalresearch skills that need to be addressedamongst manufacturers.17 In addition, interviewswith manufacturers highlight the current statusquo: ‘pharmaceutical and medical technologieswere also considered very different by manufac-turers.’ As such, the widespread belief is thatdevices do not require the same level of evidenceas drugs to gain access to a market and be usedin clinical practice. Sprange’s study highlightsthe need for education and research ‘tools,’which will facilitate higher quality evidence sub-missions for approval in the future.

The European Directive on medical deviceswill be revised later this year. The European Com-mission has stated it will use this opportunity tostrengthen existing legislation, particularly pro-visions relating to market surveillance, vigilanceand the functioning of notified bodies. In theUK, the House of Commons Science and Technol-ogy Committee plans to examine whether currentlegislation and regulations on safety and efficacyof medical implants are fit for purpose.18

Failures of medical devices cause harm andcost money. More stringent requirements toprovide evidence from clinical trials for the effi-cacy and safety medical devices before they areapproved should therefore be welcomed bypatients, clinicians and the medical device indus-try. Evidence for new devices must also be opento scrutiny by patients in individual countries, aswell as healthcare providers and researchers. Thepotential risk of a new device should match thetype of evidence required prior to approval foruse in clinical settings. Without these changes tocurrent systems, it is likely we will continue tosee substantial complications arising from faultydevices.

References

1 Heneghan C. The saga of Poly Implant Prosthese breastimplants. BMJ 2012;344:e306

2 Heneghan C, Langton D, Thompson M. Ongoing problemswith metal-on-metal hip implants. BMJ 2012;344:e1349

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