Metal-on-metal hip implants

Transcription

1 Metal-on-metal hip implants The performance of the medical device quality assurance chain needs to be improved Utrecht, May 2013

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3 Metal-on-metal hip implants May 2013 Contents Summary 5 1 Introduction Background and importance Characteristics of metal-on-metal hip implants Regulation framework for supervision Aim of the investigation and questions addressed Study method Information procurement Incident analysis Assessment of technical files and post market surveillance The patients' perspective 14 2 Conclusions and recommendations The problem with metal-on-metal hip implants Manufacturers' responsibilities Market introduction: do products undergo sufficient clinical evaluation? Product introduction: assuring training and expertise Vigilance: risk management has to be improved Post market surveillance: improve the quality Responsibilities of the medical profession and hospitals The responsibility of notified bodies Product traceability implant register desirable Recommendations and enforcement measures 20 3 Results The problem with metal-on-metal hip implants Analysis of incidents Quality of technical files and post market surveillance Comments from notified bodies Observations from the patient's viewpoint 29 References 33 Annex 1 Research report by the National Institute for Public Health and the Environment (RIVM) 35 Page 3 of 35

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5 Metal-on-metal hip implants May 2013 Summary In 2011, the Dutch Health Care Inspectorate (the Inspectorate) started an investigation prompted by growing signs of clinical problems with metal-on-metal hip implants. The aim of the investigation was to gain more insight into the quality assurance chain for medical devices, in this case metal-on-metal hip implants. Within this chain, manufacturers, medical doctors, 'notified bodies' and others each have a distinct role and responsibility in relation to assuring the safety and responsible use of medical devices. Medical devices are subject to European regulation. The regulatory system provides a framework for market entry, market introduction, incident response and the monitoring of a product's use following its market introduction. The Inspectorate wished to establish how well that system was working and how it might be improved. The investigation involved collecting and studying information about problems involving metal-on-metal hip implants, analysing incident reports received by the Inspectorate and an assessment of the product files requested from the manufacturers of such implants. Where metal-on-metal hip implants are concerned, the European quality assurance system for medical devices appears to be inadequate in various respects. Once the product has been introduced to the market, manufacturers operate only a limited quality cycle of active product evaluation and follow-up action where necessary. There is also scope for improvement in terms of the clinical evaluation prior to market introduction, assurance of users expertise during product introduction and active response to incident reporting. The Inspectorate believes that the role of notified bodies is unduly restricted to the assessment of product file conformity during market admission. Very little active monitoring of medical devices takes place in the post market phase. The Dutch Orthopaedic Association (NOV) has advised that, until more is known about the long-term effects, metal-on-metal hip implants should no longer be used in regular patient care, but used only in the context of clinical studies. The Inspectorate endorses that advice. The Inspectorate has observed that information from the orthopaedic surgeons' own quality monitoring activities is not being exchanged with other parties in the system. The investigation confirms the need for an implant registry in the Netherlands. Patients need to be more carefully informed about the possible risks associated with certain types of implants. Furthermore, the follow-up of patients experiencing problems with metal-on-metal implants should be carried out with more uniformity and more care by orthopaedic surgeons. The Inspectorate recommends tightening up the European system in various ways. The European legislation is currently being reviewed at EU level, offering the Netherlands an opportunity to actively propose appropriate amendments. Page 5 of 35

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7 Metal-on-metal hip implants May Introduction 1.1 Background and importance Increasing indications of problems Since the middle of 2010, the Dutch Health Care Inspectorate has observed increasing indications of clinical problems with orthopaedic metal-on-metal hip implants. The indications in question were: Incident reports from manufacturers, relating to cases in the Netherlands where metal-on-metal hip implants required replacement (revision surgery) Withdrawal from the market of one particular brand and model of metal-onmetal hip implant in August 2010 A warning from a manufacturer regarding the importance of using appropriate implantation techniques and considering carefully which type of implant is indicated A report from the UK's competent authority regarding clinical problems affecting some patients with metal-on-metal hip implants The cautious stance adopted by and warnings from the Dutch Orthopaedic Association (NOV) with regard to the use of metal-on-metal hip implants Widespread problem Initially, it appeared that the problems related only to a particular metal-on-metal hip implant that was withdrawn from the market in However, it subsequently became clear that other metal-on-metal hip implants were associated with similar problems. The Inspectorate accordingly decided to initiate an investigation in Characteristics of metal-on-metal hip implants Types and groups of hip implant A hip implant or hip prosthesis is an artificial hip joint, which is used to replace the natural joint. There are various types of hip implants, which differ from one another in various ways, including their mechanical design and the materials from which the stem, the head and the cup are fabricated. For a long time, ceramic and synthetics were the materials predominantly used for the head and cup. In metal-on-metal hip implants, however, the head and cup are made from an alloy of cobalt and chromium. Hip implants may be divided broadly into two groups (see figure 1). 1 The 'total hip prosthesis' consists of an artificial head, which completely replaces the ball of the natural hip joint; a cup, which is inserted into the pelvis (acetabulum) and a stem, which is inserted into the thigh bone (femur). The associated procedure is generally referred to as 'total hip replacement'. 2 The 'resurfacing prosthesis' is a prosthetic cap that is placed over the ball of the natural hip joint, which is largely retained. This type of implant has no stem. The associated procedure is generally referred to as 'hip resurfacing'. Page 7 of 35

8 Health Care Inspectorate Figure 1. A 'total hip prosthesis' (left) and a 'resurfacing prosthesis' (right) (Source: DePuy/Johnson & Johnson) Considerable increase in use Metal-on-metal implants were developed more than thirty years ago. However, their refinement and use has increased considerably in the last ten years, driven partly by the availability of improved manufacturing techniques and partly by the anticipated durability of such implants. Greater durability should make implants of this type more suitable for younger patients and those with active lifestyles. Hip implantation brings general and specific risks All hip implant procedures involve certain general risks, such as surgical infections, haemorrhaging and adverse responses to surgical anaesthesia. Various specific post-surgical risks also exist, including the fracture, displacement, detachment and dislocation of (parts of) the prosthesis. Metal-on-metal implants appear to be associated with an additional risk. When the prosthesis is implanted, the surgeon seeks to position the head and cup in such a way as to minimise the potential for friction between them. Nevertheless, it is impossible to totally prevent friction between the head and the cup resulting in the creation of metal debris. Ions from the debris enter the surrounding tissue or the blood and appear to adversely affect the health of some patients. The need for a revision surgery can be the final outcome. One brand and model withdrawn from the market In August 2010, it became apparent that one particular brand and model of metalon-metal hip implant frequently required replacement. Data from Australia and the UK indicated that 12 to 13 per cent of the relevant implants had to be replaced. The manufacturer accordingly implemented a recall procedure [1] to withdraw the product from the market. 1.3 Regulation framework for supervision Product legislation on medical devices The admission of medical devices to the European market is governed by harmonised European product legislation, in the form of Directive 93/42/EEC, [2] which is implemented in Dutch law by the Medical Devices Act. The principle underpinning of the legislation is that a manufacturer is responsible for the safety and quality of the medical devices it places on the market. Each product must therefore carry a CE mark (CE stands for Conformité Européenne), indicating that it conforms to a number of legal requirements. One of those requirements is that the product has undergone clinical evaluation on the basis of data from clinical studies or from published scientific literature. The risks associated with the product must also have been assessed and evidence must be available demonstrating that the Page 8 of 34

9 Metal-on-metal hip implants May 2013 medical device in question is capable of performing its intended purpose. In the context of the legislation, medical devices are categorized in risk classes. Hip implants are in the highest risk class, meaning that their conformity has to be assessed by a 'notified body'. The competent authority in each member state (which in the Netherlands is the Inspectorate) supervises the activities of the notified bodies in that country. A CE-marked product is admitted to the entire European market. Vigilance: compulsory incident reporting Once a product has been admitted to the market, the manufacturer has the legal obligation of vigilance. That implies that the manufacturer must report known incidents involving the medical device to the competent authority in the country where the incident occurred. When reporting an incident, the manufacturer must provide data regarding, amongst other things, the product, the patient, the health care institution and the nature of the incident. The data must be submitted in a standardised form, according to a European model. The manufacturer must also analyse the incident and, on the basis of the findings, indicate what follow-up action (if any) is required. Post market surveillance: compulsory product monitoring Manufacturers also have a post market surveillance obligation. That implies that they must monitor their medical devices throughout their life cycle. The obligation has been created with a view to ensuring that unforeseen problems associated with clinical use or with large patient groups can be identified. If such problems are detected, the manufacturer must take appropriate action, such as modifying the product, revising the instructions for use, warning users or, in the most extreme cases, recalling the product. The competent authorities in the various European member states collectively monitor compliance with the requirements. Revision of the European Directive The European Medical Device Directive is currently undergoing review. Following discussions with the competent authorities in the various member states, the European Commission has recently put forward proposals regarding the Directive's revision. Many of the proposed revisions involve tightening aspects of the rules, making the system less noncommittal, and closer cooperation between member states. The proposals will be considered and decided upon at the European level in the period ahead. In that context, the Netherlands will have the opportunity to influence the outcome of the review. a In response to the recent problems with PIP breast implants b, the European Commissioner for Health and Consumer Policy has proposed a joint action plan in Those arrangements included various amendments tightening the present European Directive. Regulation and supervision of the use of medical devices The Inspectorate is responsible for supervising the use of medical devices, in accordance with the national Health Institutions Quality Act and the Individual Medical Professions Act. The Inspectorate is also guided by standards and guidelines of the health care professions themselves. a b Both the Inspectorate and the Ministry of Health, Welfare and Sport are represented on various European committees that will review the legislation. Breast implants manufactured by the French company Poly Implant Prostheses. Page 9 of 35

10 Health Care Inspectorate 1.4 Aim of the investigation and questions addressed Qualitative investigation for the purpose of acquiring insight and formulating views The Inspectorate's largely qualitative investigation was intended to yield insight into the quality of the chain via which medical devices are introduced and used, and to provide a basis for the formulation of associated views. The chain for the life cycle of a medical device is illustrated in figure 2. In particular, the intention was to assess the following: How well the European system of market entrance, market introduction, vigilance and post market surveillance is working, where metal-on-metal hip implants are concerned The extent to which manufacturers, notified bodies and health care professionals in the quality chain are discharging their responsibilities Figure 2. Quality chain for the medical device life cycle Questions addressed by the investigation What clinical problems are associated with metal-on-metal hip implants and how can they be characterised within the Dutch health care system? To what extent does the European system of market entrance, market introduction, vigilance and post market surveillance provide adequate assurance that the clinical use of metal-on-metal hip implants is adequate in qualitative terms? Which improvements could be made within the existing regulatory framework? How do the manufacturers of metal-on-metal hip implants carry out post market surveillance? In the context of its supervision activities, what aspects should the Inspectorate focus on in order to improve the safe and appropriate use of medical devices? Relationship to Inspectorate policy The investigation is in line with the Inspectorate's existing policy. Monitoring of the post market surveillance undertaken by the manufacturers of medical devices in the higher risk classes is one of the Inspectorate's strategic focuses. 1.5 Study method Information procurement Information sources In order to obtain insight into the clinical problems associated with metal-on-metal hip implants, the Inspectorate studied relevant information from The Page 10 of 34

11 Metal-on-metal hip implants May 2013 information was obtained from national and international scientific publications, research studies, news and media reports and information from medical professionals, counterpart authorities elsewhere, manufacturers and patients. Scope of the metal-on-metal issue in the Netherlands In order to gain insight into the extent of the problems associated with metal-onmetal hip implants in the Netherlands, the Inspectorate started by approaching the Dutch Orthopaedic Association (NOV). A National Orthopaedic Implant Registry (LROI) has been in operation under the auspices of the NOV since Orthopaedic surgeons in the Netherlands are encouraged to record all prosthetic implantation and revision procedures in the register. The register has been created from the perspective of medical science and is intended to provide information regarding the clinical effectiveness of implants (in terms of durability, complications and revision rates). The Inspectorate does not have access to the register and in 2011 therefore asked the NOV whether it was possible to provide the Inspectorate with data regarding the number and types of metal-on-metal hip prostheses implanted in the Netherlands. The Inspectorate additionally asked the manufacturers for information about the number of metal-on-metal hip implants sold in the Netherlands. International coordination Since March 2012, the Inspectorate has participated in an international conference forum concerned with metal-on-metal hip implants. The forum brings together the competent authorities of the various European member states, with the aim of exchanging information and coordinating policy. The forum initiated a request to the European Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) c, asking this body to consider the safety and the risk-benefit profile of metal-on-metal hip implants [3], in light of the uncertainty regarding the long-term health effects of such implants. SCENIHR is expected to report on the matter in the middle of Role and views of the medical profession Since late 2010, the Inspectorate has maintained contact with the NOV, with a view to learning more about the insights and views of the medical profession, so that they may be taken into account in the Inspectorate's policy on the problems associated with metal-on-metal hip implants Incident analysis Contact with manufacturer following recall Following the withdrawal of a particular model of metal-on-metal hip implant from the market in 2010, the Inspectorate has periodically made enquiries to the manufacturer regarding the situation in the Netherlands. In particular, the Inspectorate asked for the number of implants requiring revision, the follow-up of patients and the exchange of the information with orthopaedic surgeons. Analysis of incidents individually and collectively In the context of its regular supervisory activities, the Inspectorate analyses all reported incidents individually. Since 2011, the Inspectorate has additionally been analysing all manufacturers' incident reports in connection with each other. To that end, manufacturer-specific information regarding the implant, the revision surgery, the health care institution and the date of implantation and revision has been compiled and recorded. Where necessary, the Inspectorate has asked manufacturers c SCENIHR is an independent scientific advisory body at the disposal of the European Commission. Page 11 of 35

12 Health Care Inspectorate to provide additional information. In some cases, the Inspectorate was referred by a manufacturer to the company's own documentation, such as the instruction for use, an internal study report, a patient leaflet or surgical guidelines. In such cases, the relevant documentation was obtained and studied. The cumulative total number of incident reports and the cumulative number of reports per manufacturer/product have been recorded. The content of the manufacturers' vigilance reports has been analysed by the Inspectorate in order to ascertain how the manufacturers discharge their vigilance obligations. Contact with hospitals Various hospitals have informed the Inspectorate, either in the context of their regular annual discussions with the Inspectorate or by incident reports, that a substantial number of metal-on-metal hip implant revisions had to be performed. The Inspectorate asked the hospitals in question to provide information about matters such as the numbers of hip implant revisions, the provision of information to patients and the provision of information to manufacturers to facilitate incident analysis by the manufacturers Assessment of technical files and post market surveillance Selection of manufacturers In order to build up a picture of the manufacturers' post market surveillance activities, the Inspectorate requested them for the technical product files on their metal-on-metal hip implants. The manufacturers were selected on the basis of an inventory of all metal-on-metal hip implants used in the Netherlands. That inventory was compiled using information provided by the NOV and by analysing the manufacturers' product ranges. The resulting market overview is summarised in table 1. Table 1 Market overview of metal-on-metal hip implants used in the Netherlands Manufacturer DePuy/Johnson & Johnson DePuy/Johnson & Johnson Biomet Zimmer Smith&Nephew Wright Medical Technology Finsbury Orthopaedics/DePuy* 1 Stryker Corin Implantcast Orthodynamics/Eska* 2 Product name ASR Pinnacle M2a, Recap Durom Birmingham Conserve+ Adept Mitch Cormet Accis Bionik (* 1 : Finsbury was acquired by DePuy in 2009; * 2 : Eska was acquired by Orthodynamics in 2010.) Procurement of information on post market surveillance On 31 August 2011, the Inspectorate wrote to the Dutch representatives of the various manufacturers, indicating that the Inspectorate wished to study manufacturers' fulfilment of their post market surveillance obligations. They were asked to provide the Inspectorate with the following no later than 1 October 2011: Page 12 of 34

13 Metal-on-metal hip implants May 2013 A overview of the metal-on-metal hip implants supplied in the Netherlands (product name, type and numbers of products sold). The name of a contact person within the organisation representing the manufacturer in the Netherlands. A set of documentation from the product's technical file. Details of the specific documentation required and the form in which it was to be provided were given in an appendix to the letter to the manufacturers. The Inspectorate asked the manufacturers to describe their post market surveillance procedures and the follow-up activities undertaken specifically in the Netherlands. The list of technical file items requested was based on that required for the market admission of a CE-marked product and consisted of the following: 1 A description of the medical device 2 A reference to similar devices or previous generations of the device 3 The instructions for use 4 The risk analysis 5 The biocompatibility data 6 The clinical evaluation 7 The post market surveillance-procedure(s) 8 The summary and analysis of the post market surveillance data 9 The vigilance procedure(s) 10 Information regarding the training and instruction of medical professionals Assessment by the RIVM The Inspectorate asked the National Institute for Public Health and the Environment (RIVM) to assess the files provided by the manufacturers. In consultation with the RIVM, a scoring method was defined, on the basis of which each documentation item was assessed. Each file item was divided into a number of components, which were assessed individually. The scores were weighted, with the greatest weight attached to those components that the Inspectorate regarded as critical. A score for each file item was then calculated by aggregating the component scores. On the basis of its aggregate score, each item was graded 'good', 'moderate' or 'insufficient'. If any critical component was missing, the file item in question was graded 'insufficient'. The RIVM's report, describing and explaining the file assessment in detail, forms Annex 1 to this report. Second request for information In October 2011, the RIVM assessed the completeness of the files submitted to the Inspectorate. On the basis of the conclusions, the Inspectorate wrote to three manufacturers informing them that certain file items were missing or incomplete, and giving them the opportunity to provide the missing information. In December 2011, two of them provided the missing information as requested. Incomplete files were not excluded from assessment, but the missing items were scored accordingly. RIVM's final report The Inspectorate received the RIVM's final report in October The report was then sent to two notified bodies in the United Kingdom for comment, since the bodies in question had between them performed conformity assessments on eight of the eleven metal-on-metal hip implants under consideration. The two notified bodies were asked d to indicate: Their response to the results of the file assessments d The notified bodies in question are under the supervision of the Inspectorate's counterpart in the United Kingdom: the Medicines and Healthcare products Regulatory Agency (MHRA). The request was therefore made via the MHRA. Page 13 of 35

14 Health Care Inspectorate How they assessed the manufacturers' post market surveillance activities To what extent they had received vigilance reports from the manufacturers with regard to incidents involving metal-on-metal hip implants, and what they had done in response to any such reports How they assessed the manufacturers' clinical evaluation activities The patients' perspective Relevant information obtained via a lawyer s office In the Netherlands, there is a specialist lawyer s office giving legal aid to several hundreds of patients who have experienced problems with metal-on-metal hip implants. The implants in question were made by various manufacturers. In December 2012, the law firm informed the Inspectorate in writing that it had relevant information in the form of patients' statements regarding the seriousness of the health problems associated with the implants and regarding the activities of manufacturers, doctors and hospitals. The Inspectorate itself had received little information from patients directly. For that reason, the Inspectorate asked the law firm to facilitate the investigation by providing a written specification and categorisation of the statements contained in its client files. Page 14 of 34

15 Metal-on-metal hip implants May Conclusions and recommendations 2.1 The problem with metal-on-metal hip implants Metal ions from wear debris can cause clinical problems In a patient with a metal-on-metal hip implant, metal ions from the implant can cause clinical problems in the surrounding tissue. The problem is complex. The mechanism by which the problems arise is not yet fully scientifically understood. Although the conditions can necessitate revision of the implant, the percentage of hip implants requiring revision differs according to manufacturer, product and implant type. It is therefore not possible to make an absolute and generally valid statement regarding the quality of metal-on-metal hip implants as a product group. Nevertheless, literature studies and incident registries support the conclusion that the reported clinical problems constitute a critical side-effect of this type of implant. NOV recommendation: use only in the context of clinical trials If a medical device such as a hip implant does not deliver the expected outcome in some patients, that is a serious matter. The Inspectorate therefore endorses the NOV recommendation that, until more information is available regarding the longterm effects, metal-on-metal hip implants should no longer be used in regular patient care in the Netherlands, but should be reserved for use only in clinical trials. The Inspectorate regards the NOV's recommendation as a field standard for orthopaedic professionals. Is there sufficient assurance of qualitatively appropriate patient care? Under the European system for regulating the market entrance of medical devices, the possibility of a product having unexpected clinical effects cannot be excluded. The Inspectorate recognises that fact. It is therefore pertinent to consider whether the system provides sufficient assurance of qualitatively appropriate patient care. The existence of such assurance depends upon all parties in the chain being sufficiently involved in the product evaluation, adverse effects being identified in good time and appropriate action being taken in response. Final conclusion of the investigation: the performance of the medical device quality assurance chain needs to be improved The existing European regulations are intended to ensure the integrated quality assurance of medical devices. In practice, however, the quality assurance of metalon-metal hip implants appears to be inadequate in various respects. There is scope for improvement in terms of the timely identification of adverse effects and the implementation of appropriate response measures. 2.2 Manufacturers' responsibilities An effective quality cycle for product evaluation is missing None of the investigated manufacturers of metal-on-metal hip implants were found to have a quality cycle for product evaluation that was effective in practice as a means of systematically monitoring product safety and performance. The Inspectorate's conclusions and recommendations regarding the various elements of such a cycle are set out below Market introduction: do products undergo sufficient clinical evaluation? The Inspectorate was not able to establish from the information provided that the metal-on-metal hip implants underwent sufficient clinical evaluation prior to market Page 15 of 35

16 Health Care Inspectorate introduction to allow proper assessment of the intended health benefits and the possible risks. The quality, quantity and type of the clinical data used varied. Furthermore, the Inspectorate found no evidence that the manufacturers used predefined, measurable criteria to assess the acceptability of their products' performance. The Inspectorate noted that, in the clinical evaluation of the implants, the principle of relative equivalence to competing metal-on-metal hip implants was widely used. e The existing European legislation allows this approach in fulfilling the clinical evaluation. Legal requirements require tightening The Inspectorate believes that the requirements made in the European product legislation regarding supervision of the clinical evaluation of high-risk medical devices, such as implants, need to be tightened. That need is already addressed by the European Commission's current proposals regarding the revision of the European legislation. For example, the proposals would, if implemented, considerably limit the scope for applying the equivalence principle to products such as implants. The Netherlands intends to support the proposed revisions Product introduction: assuring training and expertise No evidence was found in the files to indicate that, at the time of product introduction, the manufacturers had actively and systematically trained orthopaedic surgeons in the relevant implantation skills. Some manufacturers indicated that using the correct implantation method can influence the performance of the implant. The Inspectorate would therefore like to see manufacturers pay appropriate attention to ensuring that users have the requisite expertise. Need to assure training and expertise previously highlighted In this context, the Inspectorate would draw attention to her earlier annual report: The State of the Health Care 2008 ('Risks associated with medical technology underestimated') [4]. That report already drew attention to the importance of expertise and skill in the use of medical technology. The point was subsequently emphasised by the report 'Medical technology at risk?' [5], produced by a medical technology expert group in Furthermore, the procedures necessary for assurance of the competencies and skills required to utilise medical technology were defined in the national Covenant on the Safe Use of Medical Technology in Hospitals [6], produced by the united Dutch hospitals in Vigilance: risk management has to be improved Manufacturers generally comply with their legal obligation to report any incidents that they are aware of. Nevertheless, active incident-based risk management linked to corrective actions where appropriate could be improved. The incident analyses undertaken are too product-focused. The Inspectorate believes that it is particularly important where implants are concerned that more attention is given to the relationship between the product and its clinical application. Clear acceptance criteria and intervention thresholds are lacking Moreover, in the context of incident follow-up, no clear criteria exist for determining whether a given incident percentage is acceptable or not. The European product legislation requires that, prior to market entrance, a risk analysis and assessment must be made. Nevertheless, manufacturers rarely define quantitative criteria, on the basis of which they themselves, patients, health care professionals or authorities e Application of the relative equivalence principle involves the use, for the purpose of clinical evaluation, of available clinical data regarding another similar product already been admitted to the market, if it can be demonstrated that sufficient equivalence exists between that product and the product under evaluation. Page 16 of 34

17 Metal-on-metal hip implants May 2013 may determine whether in practice a product brings greater risk than foreseen at the time of market introduction. As a result, it is unclear whether corrective action is required. In its incident monitoring activities, the Inspectorate will check whether manufacturers are in compliance with the legislation and will require them to take adequate corrective action. Limitations of the system The effectiveness of the incident vigilance arrangements for medical devices is further limited by a factor that stems from European medical device legislation being a product legislation. As such, the legislation is concerned primarily with manufacturers. Under the legislation, manufacturers are obliged to report incidents to the competent authorities. In order to do so, the manufacturers are dependent on information given to them by health care professionals and health care institutions. However, those groups have no legal obligation to report incidents to the relevant manufacturers. The Inspectorate has observed that, where metal-on-metal hip implants are concerned, the absence of any requirement to report incidents to manufacturers has been a significant impediment to obtaining a proper overview of the problem. The Inspectorate observes that manufacturers and health care providers have different interests and that the exchange of information is consequently not as transparent or as obvious as European medical device legislation envisaged Post market surveillance: improve the quality The Inspectorate believes that the post market surveillance activities of the investigated manufacturers are qualitatively lacking. There is no assured quality cycle for active product evaluation and associated intervention. Furthermore, risks and benefits are not in most cases evaluated to the initial risk analysis and riskbenefit assessment. There is consequently no basis on which to determine the need for preventive or corrective action. Nor is it apparent when manufacturers are to initiate appropriate action in response to post market surveillance findings. Systems are too limited, passive and noncommittal The systems for post market surveillance are too limited, too passive and too noncommittal to serve the function envisaged by the European medical device legislation. That legislation creates a mechanism with two primary elements: a relatively low-threshold system for market entrance on the basis of conformity, and a system under which manufacturers have a responsibility to monitor the entire life cycle of their products following market entrance. The latter responsibility is vital for assuring the safety and quality of medical device use in health care. Manufacturers' obligations need to be more strictly defined The Inspectorate advocates the stricter definition of manufacturers' post market surveillance obligations. The European legislation currently allows manufacturers too much freedom in their interpretation of what constitutes effective post market surveillance. In particular, the frequency of and criteria for intervention need to be defined in more concrete terms. In the context of the ongoing revision of the European medical device legislation, the Netherlands intends to make proposals regarding post market surveillance. The Inspectorate will require manufacturers to meet their obligations The Inspectorate intends to require manufacturers to meet their post market surveillance obligations adequately. However, the Inspectorate's ability to enforce compliance may be compromised by the fact that many manufacturers are based outside the Netherlands and by the lack of international harmonisation of enforcement activities. Page 17 of 35

18 Health Care Inspectorate 2.3 Responsibilities of the medical profession and hospitals The NOV actively advises members; adherence to guidelines requires attention In the Netherlands, the NOV actively informs and advises its members about problems with metal-on-metal hip implants. The Association highlighted the risks associated with such implants in various advisory publications for orthopaedic surgeons. Finally, the NOV advised that, in the context of the Dutch health care system, the implants should no longer be used in regular patient care, but reserved for use in clinical trials. The NOV also issued professional guidelines on periodically contacting and checking all patients with metal-on-metal hip implants. The Inspectorate considers that the profession needs to review the arrangements for ensuring that NOV guidelines are diligently followed by its members. Specialists are not sufficiently conscious of the importance of incident reporting It is desirable that orthopaedic surgeons report all revisions of hip implants as incidents to the relevant manufacturers. The manufacturers will then have the data they need to fulfil their vigilance obligations, and the removed prostheses. However, incident analysis and feedback from hospitals indicate that orthopaedic surgeons do not automatically report revisions. They are either unaware or do not fully recognise that incident reporting is essential in the context of assuring the safety of medical devices and thus the quality of care. Orthopaedic surgeons need to be encouraged to recognise that their experience with a medical device constitutes a vital link in the quality assurance chain. Clinical experiences are currently recorded only in the profession's own quality register. Incident reporting should be compulsory The Inspectorate accordingly believes that health care professionals should be obliged to report incidents involving high-risk medical devices to the relevant manufacturers. This recommendation is consistent with the action plan of the European Commissioner for Health and Consumer Policy, which calls for more to be done to involve health care professionals in highlighting undesirable incidents involving medical devices. Patients should be better informed prior to implantation The Inspectorate calls for attention to be given to improving the information given to patients prior to prosthesis implantation, with a view to ensuring that they have a clear understanding of the potential advantages and disadvantages. When the implantation of an innovative medical device whose long-term effects have not yet been properly determined is suggested to a patient, he or she must be told about alternative devices in established use and must be given objective support to help the patient arrive at a well considered personal decision. Moreover, patients must be more clearly informed about the brand and type of implant that they are ultimately given. Dissemination of information and problem monitoring appear variable The NOV recommends that patients with metal-on-metal hip implants should periodically be contacted and checked. However, that advice does not always appear to be proactively followed at the local level. Some hospitals have of their own volition organised special patient information evenings, at which patients are told about the reported problems and given the opportunity to ask questions. At the individual patient level, health issues are sometimes not detected (in time) and decision-making as to whether a hip implant revision is indicated appears to be inconsistent. Furthermore, patients apparently receive little feedback regarding the Page 18 of 34

19 Metal-on-metal hip implants May 2013 outcome of any examination of an explanted metal-on-metal hip implant. Indeed, such implants often do not undergo examination, but are simply disposed of or lost. The Inspectorate believes that the medical profession should seek to ensure that its members act more consistently and (in some cases) more diligently in the interests of the patient. Patients receive inadequate support in relation to their right to compensation The health impairment and material consequential damages suffered by some patients are considerable. However, neither manufacturers nor hospitals appear to accept any liability towards such patients. Furthermore, the pursuit of compensation from a manufacturer through the courts is a complex undertaking, because of the context. Hospitals and medical doctors appear to give patients inadequate support in relation to such matters or act in a way that is not in the patient's direct (legal) interest. Although issues of liability and compensation are not within the Inspectorate's supervisory jurisdiction, the Inspectorate considers it appropriate to record its observations. 2.4 The responsibility of notified bodies Response from notified body The Inspectorate approached two notified bodies, one of which responded. On the basis of that response, the Inspectorate makes the following observations. The notified body's response to the technical file examination was primarily procedural. Asked to comment on the observed shortcomings in manufacturers' activities, the notified body responded by describing the procedure followed. The notified body had checked whether the product files contained the relevant items and satisfied the requirements of the Directive in force at the time, on the basis of the risk classification criteria applicable at the time. The activities referred to by the notified body in its response consisted mainly of the assessment of file documents in connection with the issue of the CE declaration. So, for example, in the context of the post market surveillance, the notified body verified that the file included a plan demonstrating that the manufacturer was to gather clinical data in the future. The notified body also considered it sufficient to verify that the risk analysis and the user manual made reference to the risks specific to metal-on-metal hip implants. However, the Inspectorate found no evidence that the notified body systematically sought to verify that, following the market entrance of their products, manufacturers actually did as they said they would in their initial files. The notified body's activities in connection with incoming vigilance reports and file document revisions are regarded as passive by the Inspectorate. The notified body reported taking receipt of information from manufacturers and assessing it. The Inspectorate saw no evidence that the notified body had been proactive in its dealings with the manufacturers or the competent authorities. The notified body confirmed that the equivalence principle was applied in support of the clinical evaluation (as the Inspectorate also had observed during its examination of the product file). The role of notified bodies is too narrowly defined In relation to high-risk products, the role of the notified bodies is restricted to initial conformity assessment on the basis of product files. Rather little is currently done to actively monitor medical devices following their market entrance. The Netherlands supports proposed changes to European legislation Under the proposed changes to the European legislation, notified bodies' duties and the quality requirements that apply to them will be defined far more strictly. Page 19 of 35

20 Health Care Inspectorate Supervision of the notified bodies by the member states' competent authorities will also be tightened. The Netherlands supports the proposed changes. The Netherlands proposes joint inspections In a response to the interim action plan of the European Commissioner for Health and Consumer Policy, the Netherlands has proposed that the member states undertake joint inspections of the notified bodies. Hence, the periodic inspection of a notified body would be undertaken by a number of authorities working in tandem, and the inspection report would be available to all competent authorities. At present, supervision of each notified body is undertaken by the competent authority in that body's own country. 2.5 Product traceability implant register desirable Existing implant traceability arrangements inadequate The arrangements for ensuring traceability of orthopaedic implants in the Netherlands are inadequate at national level. If problems with an orthopaedic implant product arise, it is not possible to quickly, clearly and fully trace the patients who have received the relevant implant in the Netherlands. Similarly, in the event of a recall or the need to check the condition of patients who have received a particular device, it is not possible to identify the individual patients concerned. Central, independent implant register is desirable The Inspectorate accordingly considers a central, independent implant register to be necessary. In order to achieve the desired degree of traceability, the register should include at least the product details of each implant and the details of the patient concerned. Such a register could be used to record details not only of orthopaedic prostheses, but also of other types of implant, such as those used in cardiology and cosmetic surgery. The health care professionals that implant the products will in future be required to record the relevant data. Ministry has prepared a proposal This Inspectorate's recommendation that an implant register should be established has since been taken up by a steering committee set up by the Ministry of Health, Welfare and Sport (VWS). On 20 November 2012, the Minister of VWS submitted a proposal to Parliament [7] regarding the establishment and organisation of a national implant register for the Netherlands. Under the proposal, manufacturers and care providers will have a statutory obligation to provide the necessary data. Where possible, existing systems should be used to channel data to the implant register. The intention is also that patients should be able to consult the register in order to verify that the details of their implant are correctly recorded and to look up details of the implant they have received. Proposal in line with European plans The policy proposal outlined above is consistent with the interim action plan of the European Commissioner for Health and Consumer Policy, as referred to earlier in this report. The Commissioner's plan calls for steps to be taken to improve the traceability of medical devices. The Minister of VWS has previously expressed support for the action plan [8]. The proposal is also in line with the proposed revision to the European legislation, which make provision for the registration of medical devices. 2.6 Recommendations and enforcement measures On the basis of this investigation, the Inspectorate has formulated the following recommendations and enforcement measures: Page 20 of 34

21 Metal-on-metal hip implants May 2013 Recommendation: tighten European legislation The Inspectorate believes that the following aspects of the European Medical Device Directive should be more strictly defined: The requirements regarding the clinical evaluation of high-risk products, such as implants, prior to market introduction The requirements regarding the prior definition of measurable criteria to determine the acceptability of implant performance The requirements regarding post market surveillance by medical device manufacturers The duties of and quality requirements applicable to notified bodies. In the context of the European legislation review process, the Netherlands will make proposals to the relevant effect or lend its support to proposals already submitted. In anticipation of revision of the legislation, the interim action plan of the European Commissioner makes already provision for some of the changes outlined above. Recommendation: make reporting by health care professionals obligatory The Ministry of VWS is advised to require health care providers to report incidents involving high-risk medical devices to the relevant manufacturer. Recommendation: establish a register of 'side-effects' of medical devices The Ministry of VWS is advised to establish, in parallel to the implant register required for reasons of traceability, a system for the reporting and analysis of the 'side-effects' of medical devices, starting with implants. Measure: supervision of manufacturers The Inspectorate intends to assess whether manufacturers' vigilance reports demonstrate that the manufacturers are fulfilling their obligations adequately and will require them to take adequate corrective measures and to undertake active post market surveillance. Measure: supervision of compliance with the NOV's field standard The Inspectorate regards the NOV's recommendations that metal-on-metal hip implants should not be used any longer in regular Dutch patient care, that patients with metal-on-metal implants should be monitored and periodically checked and the way in which patients who experience problems with metal-on-metal implants should be followed up, as important field standards. The Inspectorate will accordingly ensure that these standards are adhered to, in accordance with the national Health Institutions Quality Act. Measure: consultation with orthopaedic surgeons The Inspectorate will engage in discussions with the national professional body representing orthopaedic surgeons regarding the importance of ensuring that patients are better informed about the implants they are to receive, the potential risks associated with those implants and (where relevant) the alternatives. The Inspectorate will also raise the subject of differences between orthopaedic surgeons and shortcomings in the follow-up of patients who experience problems with metal-on-metal implants. Measure: supervision of implant registration The Minister of VWS wishes to establish a national implant register in the Netherlands and to require health care providers to register relevant data. Following the establishment of such a register, the Inspectorate will supervise the registration of implants and will utilise the registered data in the context of its implant supervision activities. Page 21 of 35