Article

Quelles études pour évaluer des nouveaux dispositifs médicaux ?

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Currently, regulatory agencies have serious difficulty in obtaining high-quality scientific proof that demonstrates the clinical efficacy of new medical devices. These difficulties are specific to medical devices and to the medical environment that uses them. Schematically the clinical development of a new medical device has two stages: feasibility studies and studies to demonstrate clinical benefits. Feasibility studies are proposed immediately after the preclinical phase. The type of study that is methodologically appropriate is a noncomparative trial that responds to questions about patient selection, the development of implantation techniques, clinical efficacy, and complications. The demonstration of clinical benefits depends on the performance of a randomized control trial, although the feasibility studies are taken into account. The construction of the trial should be based on the formulation of a clear, specific, and pertinent principal objective. Eligible patients should correspond to those for whom the new device is intended in daily practice. The choice of a control group depends on the reference strategy or treatment, determined from the literature. A single principal endpoint should be proposed, consistent with the principal objective, which should be clinical (whenever possible), pertinent, and validated. The measure used to determine the endpoint must be as objective as possible. Multicenter trials are preferable to facilitate patient recruitment and minimize the inclusion period. Moreover, the results of multicenter studies can be extrapolated more readily. Nonetheless, the teams likely to participate in a multicenter trial must have stabilized their learning curve. To meet the methodological requirements of clinical trials for new medical devices, clinical research must improve its structure, especially by promoting the links between industry, clinicians, and academics.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Les items analysés par projet sont résumés dans le Tableau 19. nouveaux DM [54,162]. Plus particulièrement, cela permettrait d'éviter que certaines innovations soient développées en réponse à un problème de santé identifié et non du fait de progrès technologiques, à la recherche de solutions d'application [51]. ...
... Enfin, cela favoriserait l'utilisation encadrée de l'innovation dans les établissements de santé [54]. ...
... Les méthodologistes et les autorités réglementaires doivent être impliqués très tôt, a minima au moment de la préparation des premières études cliniques de faisabilité [54,134]. Dans notre expérience, la HAS a été informée avant la formalisation de l'action et a accepté [154]. ...
Article
Medical devices are health products representing a heterogeneous set of more than 500 000technologies, from the simplest to the most complex ones. Unlike drugs, there is no formalframework for the stages of clinical development of medical devices, especially those with ahigher degree of risk.The objective of this thesis was to describe clinical data available in France when a medicaldevice is launched, and suggest some options to improve the quality and quantity of clinicalstudies performed. To this end, we explored two ways: supporting enterprises for theimplementation of clinical studies that meet the expectations of all stakeholders; and usingregistries to improve the level of available evidence by generating additional post-marketingclinical data.The clinical evaluation of medical devices is complex and difficult, and must go through thelearning of industrials and interactions with health authorities. However, the level of clinicalevidence should and can be improved, including the specialization of methodologists and theaccompaniment of enterprises through platforms close to the clinical field.
... • le centre d'évaluation du dispositif médical (CEDM) qui est une structure de l'AP-HP d'aide à la conception et à la réalisation d'études d'évaluation clinique développée en partenariat avec la direction régionale de l'industrie, de la recherche et de l'environnement et le pôle de compétitivité MEDICEN Paris-Région. Elle s'adresse aux industriels quelle que soit la phase de développement de leur produit (avant ou après le marquage CE) [47] ; • la plateforme d'évaluation des DM du CHU de Toulouse qui a été lancée en 2012 en partenariat avec une association d'industriels de la santé de la région Midi-Pyrénées ; • l'action collective Rhône-Alpes qui est une action pilote et expérimentale des HCL menée en partenariat avec la direction régionale de l'industrie de la recherche et de l'environnement, du conseil régional de Rhône-Alpes, de l'agence régionale du développement et de l'innovation Rhône-Alpes santé et OSEO [48]. Son objectif est d'inciter, par la formation et l'accompagnement, les petites et moyennes entreprises du secteur à réaliser des évaluations cliniques et médico-économiques de leurs DM [43]. ...
Article
Innovative medical devices offer solutions to medical problems and greatly improve patients' outcomes. Like National Health Technology Assessment (HTA) agencies, hospitals face numerous requests for innovative and costly medical devices. To help local decision-makers, different approaches of hospital-based HTA (HB-HTA) have been adopted worldwide. The objective of the present paper is to explore HB-HTA models for adopting innovative medical devices in France and elsewhere. Four different models have been conceptualized: "ambassador" model, "mini-HTA" model, "HTA unit" model and "internal committee". Apparently, "HTA unit" and "internal committee" (or a mixture of both models) are the prevailing HB-HTA models in France. Nevertheless, some weaknesses of these models have been pointed out in previous works. Only few examples involving hospital pharmacists have been found abroad, except in France and in Italy. Finally, the harmonization of the assessment of innovative medical devices in France needs a better understanding of HB-HTA practices.
... • le centre d'évaluation du dispositif médical (CEDM) qui est une structure de l'AP-HP d'aide à la conception et à la réalisation d'études d'évaluation clinique développée en partenariat avec la direction régionale de l'industrie, de la recherche et de l'environnement et le pôle de compétitivité MEDICEN Paris-Région. Elle s'adresse aux industriels quelle que soit la phase de développement de leur produit (avant ou après le marquage CE) [47] ; • la plateforme d'évaluation des DM du CHU de Toulouse qui a été lancée en 2012 en partenariat avec une association d'industriels de la santé de la région Midi-Pyrénées ; • l'action collective Rhône-Alpes qui est une action pilote et expérimentale des HCL menée en partenariat avec la direction régionale de l'industrie de la recherche et de l'environnement, du conseil régional de Rhône-Alpes, de l'agence régionale du développement et de l'innovation Rhône-Alpes santé et OSEO [48]. Son objectif est d'inciter, par la formation et l'accompagnement, les petites et moyennes entreprises du secteur à réaliser des évaluations cliniques et médico-économiques de leurs DM [43]. ...
Article
Innovative medical devices offer solutions to medical problems and greatly improve patients’ outcomes. Like National Health Technology Assessment (HTA) agencies, hospitals face numerous requests for innovative and costly medical devices. To help local decision-makers, different approaches of hospital-based HTA (HB-HTA) have been adopted worldwide. The objective of the present paper is to explore HB-HTA models for adopting innovative medical devices in France and elsewhere. Four different models have been conceptualized: “ambassador” model, “mini-HTA” model, “HTA unit” model and “internal committee”. Apparently, “HTA unit” and “internal committee” (or a mixture of both models) are the prevailing HB-HTA models in France. Nevertheless, some weaknesses of these models have been pointed out in previous works. Only few examples involving hospital pharmacists have been found abroad, except in France and in Italy. Finally, the harmonization of the assessment of innovative medical devices in France needs a better understanding of HB-HTA practices.
... Des méthodologies rigoureuses, propres aux essais cliniques de ce domaine, seront mises en oeuvre pour obtenir des preuves objectives et adaptées au degré de maturation de l'innovation [10]. ...
Article
Full-text available
The network of CIC-IT is in the heart of the innovation process. From a sharing of experiences, this article aims at specifying the maturation process of innovative technologies, from the genesis of an idea to the evaluation of the medical service delivered to a target population. After having reported concepts in connection with innovative technologies in the health field and after having identified the main actors, a description of an innovation process is proposed. It is organized according to scientific and technical, regulatory, economic and industrial dimensions. This brief description is completed by the identification of potential funding sources in this field and is illustrated by a practical example of an innovation. This paper underlines the strategic matter of a close work between different actors to gain efficiency, these collaborations which can really be boosted within the shared space offered by the network of CIC-IT.
Article
Introduction Since 2003, the AP–HP medical devices committee (CODIMS) assess the therapeutic relevance of innovated medical device (MD) for the French AP–HP hospitals’ group. To accomplish this task, the CODIMS asks manufacturers to bring out clinical arguments to justify the use of their MD in hospital. This work analyses retrospectively after 8 years, all assessed MD until March 2011 and the scientific quality of the clinical data submitted by manufacturers to the CODIMS to purchase their MD. Method All MD were classed according to their certification's level (I, IIa, IIb, III, DMIA). The quality of available clinical studies (CS) provided by manufacturers for each case was assessed and classed according to five clinical relevance levels based on the evidence-based medecine standards (1–2: high methodology; 3–5: low methodology). Results One hundred and three MD files (80 % of class IIb and III MD) were analysed by the CODIMS (630 CS). Our results highlight the lack of relevance of files that are provided to assess innovated MD: 29 files without any CS; concerning class IIb (32 DMS, 221 CS) and III (50, 342 CS) MD, only 6 % of CS presented a correct clinical relevance level. And the situation did not get better during this assessment period. Discussion/Conclusion The CODIMS deplore the poor clinical relevance of files provided to assess MD (wrong comparator, inappropriate ends-points, insufficient follow-up to assess long-term security, small population studied). Future legislative developments for MD assessment are expected to improve this situation.
Article
The drug and medical devices Committee of the University Hospital of Lyon faces the weakness of clinical data available to justify medical devices purchase. The Hospital of Lyon has worked with several organisms of the Rhône-Alpes region to set up a pilot programme aimed at encouraging small and medium enterprises (SMEs) to realise clinical studies for the evaluation of their medical device. We report the results of this experiment which took place from 2007 to 2010. Eligible projects were selected on the basis of their scientific interest. A specific structure for regulatory and methodological support was set up. Twenty companies applied, seventeen were selected. Eight research protocols were written; four clinical studies were implemented. These studies were performed by micro-companies for medical devices that could be considered as innovative device or substantial novelty. Two draft protocols were started but deferred by choice of the company. For projects that did not lead to a research protocol or study, the main causes were: a longer than expected development phase (n=3); a problem linked to methodological feasibility (n=1); the unsuccessful search for a principal investigator (n=2); or the company's choice (n=5). This pilot experience in France has supported and trained regional SMEs in clinical research. Its continuation could encourage manufacturers to conduct clinical trials of good quality.
Article
Full-text available
Under the mandate of the Educational Committee of the European Association of Endoscopic Surgery (E.A.E.S.), three consensus development conferences (CDCs) were performed in order to assess the current status of the endoscopic surgical approaches for the treatment of cholelithiasis, appendicitis, and inguinal hernia. Consensus panels for the different disease states (10-13 members each) selected by the education committee on the basis of members' clinical expertise, academic activity, community influence, and geographical location weighed the evidence on the basis of published results according to the criteria for technology assessment: feasibility, efficacy, effectiveness, economy. Draft statements were prepared, discussed by the panels, and presented at plenary sessions of the 2nd European Congress of the E.A.E.S. in Madrid September 15-17, 1994. Following discussions final consensus statements were formulated to provide specific answers for each topic to a minimum of the following questions: 1. What stage of technological development is the endoscopic surgical procedure at (in September 1994)? 2. Is endoscopic surgery safe and feasible? 3. Is it beneficial to the patients? 4. Who should undergo endoscopic surgery? 5. What are the training recommendations? Laparoscopic cholecystectomy is the procedure of choice for symptomatic cholelithiasis. Laparoscopic appendectomy is presently at the efficacy stage of development, because most of the data on feasibility and safety originate from centers with special interest in endoscopic surgery: it is not yet the gold standard for acute appendicitis. Endoscopic hernia repair is presently a feasible alternative for conventional hernia repair if performed by experienced endoscopic surgeons. It appears to be efficacious in the short-term. The full text of the consensus panel's statements is given in this publication.
Article
Full-text available
Objectives: (1) To describe systematically studies that directly assessed the learning curve effect of health technologies. (2) Systematically to identify 'novel' statistical techniques applied to learning curve data in other fields, such as psychology and manufacturing. (3) To test these statistical techniques in data sets from studies of varying designs to assess health technologies in which learning curve effects are known to exist. METHODS - STUDY SELECTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW): For a study to be included, it had to include a formal analysis of the learning curve of a health technology using a graphical, tabular or statistical technique. METHODS - STUDY SELECTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): For a study to be included, it had to include a formal assessment of a learning curve using a statistical technique that had not been identified in the previous search. METHODS - DATA SOURCES: Six clinical and 16 non-clinical biomedical databases were searched. A limited amount of handsearching and scanning of reference lists was also undertaken. METHODS - DATA EXTRACTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW): A number of study characteristics were abstracted from the papers such as study design, study size, number of operators and the statistical method used. METHODS - DATA EXTRACTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): The new statistical techniques identified were categorised into four subgroups of increasing complexity: exploratory data analysis; simple series data analysis; complex data structure analysis, generic techniques. METHODS - TESTING OF STATISTICAL METHODS: Some of the statistical methods identified in the systematic searches for single (simple) operator series data and for multiple (complex) operator series data were illustrated and explored using three data sets. The first was a case series of 190 consecutive laparoscopic fundoplication procedures performed by a single surgeon; the second was a case series of consecutive laparoscopic cholecystectomy procedures performed by ten surgeons; the third was randomised trial data derived from the laparoscopic procedure arm of a multicentre trial of groin hernia repair, supplemented by data from non-randomised operations performed during the trial. RESULTS - HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW: Of 4571 abstracts identified, 272 (6%) were later included in the study after review of the full paper. Some 51% of studies assessed a surgical minimal access technique and 95% were case series. The statistical method used most often (60%) was splitting the data into consecutive parts (such as halves or thirds), with only 14% attempting a more formal statistical analysis. The reporting of the studies was poor, with 31% giving no details of data collection methods. RESULTS - NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH: Of 9431 abstracts assessed, 115 (1%) were deemed appropriate for further investigation and, of these, 18 were included in the study. All of the methods for complex data sets were identified in the non-clinical literature. These were discriminant analysis, two-stage estimation of learning rates, generalised estimating equations, multilevel models, latent curve models, time series models and stochastic parameter models. In addition, eight new shapes of learning curves were identified. RESULTS - TESTING OF STATISTICAL METHODS: No one particular shape of learning curve performed significantly better than another. The performance of 'operation time' as a proxy for learning differed between the three procedures. Multilevel modelling using the laparoscopic cholecystectomy data demonstrated and measured surgeon-specific and confounding effects. The inclusion of non-randomised cases, despite the possible limitations of the method, enhanced the interpretation of learning effects. CONCLUSIONS - HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW: The statistical methods used for assessing learning effects in health technology assessment have been crude and the reporting of studies poor. CONCLUSIONS - NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH: A number of statistical methods for assessing learning effects were identified that had not hitherto been used in health technology assessment. There was a hierarchy of methods for the identification and measurement of learning, and the more sophisticated methods for both have had little if any use in health technology assessment. This demonstrated the value of considering fields outside clinical research when addressing methodological issues in health technology assessment. CONCLUSIONS - TESTING OF STATISTICAL METHODS: It has been demonstrated that the portfolio of techniques identified can enhance investigations of learning curve effects. (ABSTRACT TRUNCATED)
Article
Full-text available
The quality and quantity of randomised trials of surgical techniques is acknowledged to be limited. According to Peter McCulloch and colleagues, however, some aspects of surgery present special difficulties for randomised trials. In this article they analyse what these difficulties are and propose some solutions for improving the standards of clinical research in surgery.
Article
Full-text available
Throughout the world, healthcare innovations have put pressure on limited resources while governments and patients have demanded top quality, yet cost effective, services. This makes it increasingly difficult for anyone who plans, provides, or receives health services to judge which intervention to use—what works, how well, at what cost, for whom, in what circumstances, and with what impact? Health technology assessment (HTA) is a multidisciplinary specialty whose purpose is to bring together the evidence to answer those questions.1 It boasts a thriving international scientific society (Health Technology Assessment International; www.htai.org) and a global network of more than 40 public sector agencies (International Network of Agencies for Health Technology Assessment; www.inahta.org). It evaluates the costs, effectiveness, and sometimes the wider impact of any intervention used in the care of patients, including medicines, devices, techniques, and skills. In the UK, for example, the HTA programme (www.ncchta.org) has produced more than 300 reports that have had an impact on services, including novel research as well as syntheses of evidence on cost effectiveness on topics ranging from left ventricular assist devices to isolation procedures for containing Staphylococcus aureus.2-5 It also provides much of the evidence base for the guidance which the National Institute for Health and Clinical Excellence (NICE) provides for the NHS.6
Article
Full-text available
Intensive self-management with frequent self-monitoring of blood glucose (SMBG) is important in type 1 diabetes to achieve good metabolic control (1–3). Nevertheless, many patients still experience episodes of unrecognized hypo- and hyperglycemia (4). Novel technologies for continuous glucose monitoring (CGM) that provide information about glucose excursions are now available. Previous studies reported the benefits of retrospective evaluation of CGM data (5–11), but few assessed effects on glycemic control (5,12–14), and only one showed improvements compared with SMBG (14). We evaluated the effect of a new real-time glucose monitor on glycemic control in patients with poorly controlled type 1 diabetes. The device, Guardian RT (Medtronic MiniMed, Northridge, CA), allows users to see glucose readings and set hypo- and hyperglycemic alarms and provides trend information on changing glucose values. The study included 81 children (median age 14.4 years [range 8.0–18.9]) and 81 adults (age 39.1 years [19.0–59.5]) with stable type 1 diabetes. All had adhered to intensified insulin treatment (continuous subcutaneous insulin infusion, n = 78; multiple daily injection, n = 84) but had HbA1c (A1C) levels ≥8.1%. Informed consent was obtained from patients regularly attending the eight participating centers. Subjects were randomly assigned 1:1:1 for 3 months to Guardian RT continuously (arm 1) or biweekly for 3-day periods every 2 weeks (arm 2) or to continue conventional SMBG (control). Treatment adjustments made by physicians and patients were based on SMBG profiles in control subjects and on real-time glucose profiles in arms 1 and 2. Patients were instructed to perform confirmatory SMBG measurements before therapeutical interventions or corrective action if hypo- or hyperglycemic alarms or symptoms occurred. …
Article
Full-text available
The use of left ventricular assist devices is an accepted therapy for patients with refractory heart failure, but current pulsatile volume-displacement devices have limitations (including large pump size and limited long-term mechanical durability) that have reduced widespread adoption of this technology. Continuous-flow pumps are newer types of left ventricular assist devices developed to overcome some of these limitations. In a prospective, multicenter study without a concurrent control group, 133 patients with end-stage heart failure who were on a waiting list for heart transplantation underwent implantation of a continuous-flow pump. The principal outcomes were the proportions of patients who, at 180 days, had undergone transplantation, had cardiac recovery, or had ongoing mechanical support while remaining eligible for transplantation. We also assessed functional status and quality of life. The principal outcomes occurred in 100 patients (75%). The median duration of support was 126 days (range, 1 to 600). The survival rate during support was 75% at 6 months and 68% at 12 months. At 3 months, therapy was associated with significant improvement in functional status (according to the New York Heart Association class and results of a 6-minute walk test) and in quality of life (according to the Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaires). Major adverse events included postoperative bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in two patients. A continuous-flow left ventricular assist device can provide effective hemodynamic support for a period of at least 6 months in patients awaiting heart transplantation, with improved functional status and quality of life. (ClinicalTrials.gov number, NCT00121472 [ClinicalTrials.gov].).
Article
Full-text available
Conventional dual-chamber pacing maintains atrioventricular synchrony but results in high percentages of ventricular pacing, which causes ventricular desynchronization and has been linked to an increased risk of atrial fibrillation in patients with sinus-node disease. We randomly assigned 1065 patients with sinus-node disease, intact atrioventricular conduction, and a normal QRS interval to receive conventional dual-chamber pacing (535 patients) or dual-chamber minimal ventricular pacing with the use of new pacemaker features designed to promote atrioventricular conduction, preserve ventricular conduction, and prevent ventricular desynchronization (530 patients). The primary end point was time to persistent atrial fibrillation. The mean (+/-SD) follow-up period was 1.7+/-1.0 years when the trial was stopped because it had met the primary end point. The median percentage of ventricular beats that were paced was lower in dual-chamber minimal ventricular pacing than in conventional dual-chamber pacing (9.1% vs. 99.0%, P<0.001), whereas the percentage of atrial beats that were paced was similar in the two groups (71.4% vs. 70.4%, P=0.96). Persistent atrial fibrillation developed in 110 patients, 68 (12.7%) in the group assigned to conventional dual-chamber pacing and 42 (7.9%) in the group assigned to dual-chamber minimal ventricular pacing. The hazard ratio for development of persistent atrial fibrillation in patients with dual-chamber minimal ventricular pacing as compared with those with conventional dual-chamber pacing was 0.60 (95% confidence interval, 0.41 to 0.88; P=0.009), indicating a 40% reduction in relative risk. The absolute reduction in risk was 4.8%. The mortality rate was similar in the two groups (4.9% in the group receiving dual-chamber minimal ventricular pacing vs. 5.4% in the group receiving conventional dual-chamber pacing, P=0.54). Dual-chamber minimal ventricular pacing, as compared with conventional dual-chamber pacing, prevents ventricular desynchronization and moderately reduces the risk of persistent atrial fibrillation in patients with sinus-node disease. (ClinicalTrials.gov number, NCT00284830 [ClinicalTrials.gov].).
Article
Full-text available
The global medical technology industry brings thousands of devices to market every year. However, significant gaps persist in the scientific literature, in the medical device approval process, and in the realm of postmarketing surveillance. Although thousands of drugs obtain approval only after review in randomized controlled trials, relatively few new medical devices are subject to comparable scrutiny. To improve health outcomes, we must enhance our scrutiny of medical devices, and, without simply deferring to the Food and Drug Administration, we must ask ourselves: Who is responsible for evaluating the safety and effectiveness of medical devices? Technology assessments by independent organizations are a part of the solution to this challenge and may motivate further research focused on patient outcomes.
Article
The quality and quantity of randomised trials of surgical techniques is acknowledged to be limited. According to Peter McCulloch and colleagues, however, some aspects of surgery present special difficulties for randomised trials. In this article they analyse what these difficulties are and propose some solutions for improving the standards of clinical research in surgeryThe improvement in the quality of clinical research in the past decade is to be welcomed, but it carries its own dangers. Some have extrapolated the advantages of the randomised controlled trial (RCT) into the dogma that it is the only valid method for comparing treatments,1 ignoring the difficulties that have hampered the use of RCTs in some disciplines. The RCT has theoretical advantages over other study designs, but experimental studies comparing treatment effect estimates in randomised and non-randomised studies have not consistently confirmed this, 2 3 w1-w3 and the superiority of RCTs should not therefore be accepted as axiomatic.Small, poorly conducted RCTs are more likely to result when RCTs are difficult to conduct, and these may then be misleading because their design affords them unwarranted credibility. Surgery seems to be such an area. Until recently, most studies of operations were retrospective case series, with RCTs accounting for less than 10% of the total.w4-w6 RCTs declined from 14% of research articles in the British Journal of Surgery in 1985 to 5% in 1992. 4 5 Treatments in general surgery are half as likely to be based on RCT evidence as treatments in internal medicine. 6 7 Methodological quality was poor in 56% of RCTs comparing cancer surgery techniques.8 Only 58% of these studies described satisfactory randomisation, and few significant outcome differences were found, probably because of type II statistical errors.Why is surgery so deficient? Some of the obstacles militate against all …
Article
The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris. We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months. At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group. As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.
Article
Throughout the developed world, economic evaluation of costly new pharmaceuticals and medical devices became increasingly widespread and systematic during the 1990s. However, serious concerns remain about the validity and relevance of this economic evidence, and about the transparency and accountability of its use in public sector reimbursement decisions. In this article, we summarise current concerns in Europe, based on interviews with European health economists from industry, universities, research institutes and consulting firms. We identify five challenges for European policy-makers, and conclude that there is considerable scope for improving decision-making without damaging incentives to innovate. The challenges are: (1). full publication of the economic evidence used in reimbursement decisions; (2). the redesign of licensing laws to improve the relevance of economic data available at product launch; (3). harmonisation of economic evaluation methodologies; (4). development of methodologies for evaluation of health inequality impacts; and (5). negotiation of price-performance deals to facilitate the use of economic evidence in post-launch pricing review decisions, as information is gathered from studies of product performance in routine use.
Article
Endovascular aneurysm repair (EVAR) is a new technology to treat patients with abdominal aortic aneurysm (AAA) when the anatomy is suitable. Uncertainty exists about how endovascular repair compares with conventional open surgery. EVAR trial 1 was instigated to compare these treatments in patients judged fit for open AAA repair. Between 1999 and 2003, 1082 elective (non-emergency) patients were randomised to receive either EVAR (n=543) or open AAA repair (n=539). Patients aged at least 60 years with aneurysms of diameter 5.5 cm or more, who were fit enough for open surgical repair (anaesthetically and medically well enough for the procedure), were recruited for the study at 41 British hospitals proficient in the EVAR technique. The primary outcome measure is all-cause mortality and these results will be released in 2005. The primary analysis presented here is operative mortality by intention to treat and a secondary analysis was done in per-protocol patients. Patients (983 men, 99 women) had a mean age of 74 years (SD 6) and mean AAA diameter of 6.5 cm (SD 1). 1047 (97%) patients underwent AAA repair and 1008 (93%) received their allocated treatment. 30-day mortality in the EVAR group was 1.7% (9/531) versus 4.7% (24/516) in the open repair group (odds ratio 0.35 [95% CI 0.16-0.77], p=0.009). By per-protocol analysis, 30-day mortality for EVAR was 1.6% (8/512) versus 4.6% (23/496) for open repair (0.33 [0.15-0.74], p=0.007). Secondary interventions were more common in patients allocated EVAR (9.8% vs 5.8%, p=0.02). In patients with large AAAs, treatment by EVAR reduced the 30-day operative mortality by two-thirds compared with open repair. Any change in clinical practice should await durability and longer term results.
Article
Binary angiographic and clinical restenosis rates can vary widely between clinical studies, even for the same stent, influenced heavily by case-mix covariates that differ among observational and randomized trials intended to assess a given stent system. We hypothesized that mean in-stent late loss might be a more stable estimator of restenosis propensity across such studies. In 46 trials of drug-eluting and bare-metal stenting, increasing mean late loss was associated with higher target lesion revascularization (TLR) rates (P<0.001). When the class of bare-metal stents was compared with the class of effective drug-eluting stents, late loss was more discriminating than TLR as measured by the high intraclass correlation coefficient (rho) (late loss, rho=0.71 versus TLR, rho=0.22; 95% CI of difference=0.33, 0.65). When the individual drug-eluting stents and bare-metal stents were compared, late loss was a better discriminator than TLR (0.68 versus 0.19; 95% CI of difference=0.24, 0.60). Greater adjustments of study covariates are needed to stabilize assessments of TLR compared with late loss because of greater influence of reference vessel diameter on TLR than on in-stent late loss. Optimization of late loss with the use of a novel method of standardization according to diabetes prevalence and mean lesion length resulted in minor adjustments in late loss (<0.08 mm for 90% of reported trials) and an ordered array of mean late loss values for the stent systems studied. Late loss is more reliable than restenosis rates for discriminating restenosis propensity between new drug-eluting stent platforms across studies and might be the optimum end point for evaluating drug-eluting stents in early, nonrandomized studies.
Article
Surgeons and patients seeking improved treatment often forget that a new technique is not necessarily a better one New surgical technology that offers the promise of improved patient care is attractive. Intrigued, and with an intuitive certainty, surgeons—cheered on by their patients—may adopt new technologies, despite little evidence of either their efficacy or their superiority over existing procedures. The argument that randomised clinical trials of surgical procedures are unethical because the new treatment is better than alternative treatment or no treatment is based on presumption more than fact, and arguments to the contrary are compelling. 1 Surgical procedures that are later found to be ineffective waste resources and endanger lives. Understanding why such procedures come to be offered as treatment can inform us—whether we are well intended perpetrators or unsuspecting patients. New medical technology may come in the form of a drug, a device, a procedure, a technique, or a process of care. In surgery, innovation is generally either a new procedure that uses existing devices or drugs, such as chymopapain for lumbar disc disorders, or an existing procedure that uses new devices, such as those for spinal fusion. Factors that determine the adoption and diffusion of a new technology fall into two categories: characteristics of the technology itself (box 1) and contextual factors that promote it (box 2). Surgeons are attracted to the new technology if it can be passively observed, easily and quickly learnt, and added to their existing practice with minimal disruption. If the potential contribution to their practice is sufficiently great, surgeons are more likely to invest time and effort and tolerate disruption of their routine to gain the competitive advantage that a new technology offers. Social observers have advanced pivotal theories regarding the adoption and diffusion of technologies. Everett Rogers described an S—curve portraying the …
L’essai thérapeutique chez l’homme
  • D Schwartz
  • R Flamant
  • J Lellouch
Schwartz D, Flamant R, Lellouch J. L'essai thérapeutique chez l'homme. Ed. Flammarion, 1981.
Commission d’évaluation des produits et des prestations. Les avis sur les dispositifs médicaux
  • Haute Autorité De Santé
Haute Autorité de santé. Commission d'évaluation des produits et des prestations. Les avis sur les dispositifs médicaux, 2009, http://www.has-sante.fr/portail/jcms/c 5274/dispositifs.