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Biomedical subjects

Gilles Bouvenot

Publications and source records attributed to Gilles Bouvenot.

18 recordsLinked to original sources
PubMed2006

Assessing chronic pain in general practice: are guidelines relevant? A cluster randomized controlled trial.

OBJECTIVES: To evaluate the impact of using pain assessment scales on the management of musculoskeletal chronic pain. METHODS: Cluster-randomized controlled multicentre trial in French general practice settings. Practices were randomized by region before patient recruitment. The inclusion concerned patients suffering from musculoskeletal chronic pain. General practitioners assigned to the scale group used two validated assessment instruments; those assigned to the control group cared for their patients according to their usual practice. The primary end-point was the level of relief obtained and the secondary changes in prescription of painkilling modalities. RESULTS: A total of 155 general practitioners included 772 successive patients suffering from musculoskeletal chronic pain. The control group reported a mean level of relief of 50.7% compared with one of 41.1% in the scale group (p<0.0001). In the intervention group, physicians decreased significantly their prescription of level two painkillers. CONCLUSIONS: In general practice, the use of pain assessment scales is not associated with greater pain relief. The lesser level of pain relief obtained in the scale group does provide evidence that using pain assessment scales does not enhance the relief of chronic pain in patients in primary care. Guidelines which recommend the systematic use of scales for the assessment and monitoring of chronic pain are not tailored to either the context or the patients encountered in the primary care setting.

Aged↗
PubMed2005

[Drug evaluation by the French National Health Authority for reimbursement decisions].

The French National Health Authority (NHA) is a scientific agency created by the French government in order to provide independent information and recommendations on health-related issues, and a coherent framework for improving healthcare practices. NHA's responsibility for periodically reviewing medicinal products for inclusion on the list of products eligible for reimbursement by the national health insurance system has been delegated to the Transparency Commission. The latter appraises the therapeutic value of medicinal products, based on clinical performance (efficacy and tolerability), the therapeutic contribution, and the expected impact on public health. If the Transparency Commission deems that a product has sufficient therapeutic value to warrant reimbursement, and if this opinion is approved by the Health Ministry, the Union of National Health Insurance Funds sets the refunding level according to the product's therapeutic value. The latter is re-assessed every 5 years, based on contemporary medical knowledge. The Transparency Commission also assesses the possible added therapeutic value of new products, i.e. their advantages over existing treatments. This is taken into account in setting the approved price. Transparency Commission opinions become part of the product's credentials, and are used by other NHA commissions to formulate "Recommendations for improving medical practices" and "Quality and distribution of medical information".

Drug Evaluation↗
PubMed2004

Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis.

BACKGROUND: Recent innovations in the pharmaceutical drug discovery environment have generated new chemical entities with the potential to become disease modifying drugs for osteoarthritis (DMOAD's). Regulatory agencies acknowledge that such compounds may be granted a DMOAD indication, providing they demonstrate that they can slow down disease progression; progression would be calibrated by a surrogate for structural change, by measuring joint space narrowing (JSN) on plain X-rays with the caveat that this delayed JSN translate into a clinical benefit for the patient. Recently, new technology has been developed to detect a structural change of the OA joint earlier than conventional X-rays. OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working party to assess whether these new technologies may be used as surrogates to plain x-rays for assessment of DMOADs. METHODS: GREES includes academic scientists, members of regulatory authorities and representatives from the pharmaceutical industry. After an extensive search of the international literature, from 1980 to 2002, two experts meetings were organized to prepare a resource document for regulatory authorities. This document includes recommendations for a possible update of guidelines for the registration of new chemical entities in osteoarthritis. RESULTS: Magnetic resonance imaging (MRI) is now used to measure parameters of cartilage morphology and integrity in OA patients. While some data are encouraging, correlation between short-term changes in cartilage structure observed with MRI and long-term radiographic or clinical changes are needed. Hence, the GREES suggests that MRI maybe used as an outcome in phase II studies, but that further data is needed before accepting MRI as a primary end-point in phase III clinical trials. Biochemical markers of bone and cartilage remodelling are being tested to predict OA and measure disease progression. Recently published data are promising but validation as surrogate end-points for OA disease progression requires additional study. The GREES suggests that biochemical markers remain limited to 'proof of concept' studies or as secondary end-points in phase II and III clinical trials. However, the GREES emphasizes the importance of acquiring additional information on biochemical markers in order to help better understand the mode of action of drugs to be used in OA. Regulatory agencies consider that evidence of improvement in clinical outcomes is critical for approval of DMOAD. Time to total joint replacement surgery is probably the most relevant clinical end-point for the evaluation of efficacy of a DMOAD. However, at this time, time to surgery can not be used in clinical trials because of bias by non disease-related factors like patient willingness for surgery or economic factors. At this stage, it appears that DMOAD should demonstrate a significant difference compared to placebo. Benefit should be measured by 3 co-primary end-points: JSN, pain and function. Secondary end-points should include the percentage of patients who are 'responder' (or 'failure'). The definition of a 'failure' patient would be someone with progression of JSN>0.5mm over a period of 2-3 years or who has a significant worsening in pain and/or function, based on validated cut-off values. The definition of the clinically relevant cut-off points for pain and function must be based on data evaluating the natural history of the disease (epidemiological cohorts or placebo groups from long-term studies). These cut-offs points should reflect a high propensity, for an individual patient, to later require joint replacement. CONCLUSION: GREES has outlined a set of guidelines for the development of a DMOAD for OA. Although these guidelines are subject to change as new information becomes available, the information above is based on the present knowledge in the field with the addition of expert opinion.

Anthraquinones↗
PubMed2004

Hypnotic and tranquillizer use among general practitioners in south-eastern France and its relation to occupational characteristics and prescribing habits.

Previous research suggests that practising physicians are more likely than the general population to use psychotropic drugs. Hypnotic and tranquillizer use in France is among the highest in Europe; most hypnotic and tranquillizer prescriptions are written by general practitioners (GPs). The objective was to compare the hypnotic and tranquillizer use of GPs in private practice in Provence (south-eastern France) with that of the general population and to study factors associated with physicians' hypnotic and tranquillizer use. A cross-sectional telephone survey was carried out with a panel of 600 GPs in Provence. The data were collected with a 53-item questionnaire about their social and demographic status, family, occupation, training, information-seeking behaviour, job satisfaction, hypnotic and tranquillizer drug use, tranquillizer and antidepressant prescriptions. The data were analysed using univariate and backward multiple logistic regressions. We found that GPs in Provence use hypnotics and tranquillizers at a significantly higher rate than the general population. We found significant associations with hypnotic and tranquillizer use only among the older group of GPs (older than 48 years). In this group, this drug use was related to the volume of services provided (billing sector), job dissatisfaction, lack of training, the 'family burden' and tranquillizer prescriptions. The strains associated with both medical practice and family burden have some influence on hypnotic and tranquillizer use among GPs; individual factors may influence prescribing attitudes and patient care as well.

Adult↗
PubMed2003

[Is it still ethical to conduct clinical trials against a placebo? A review of the ethical and methodological controversy].

UNLABELLED: A DEVELOPING CONTROVERSY: The marketing authorization for new drugs from the regulatory authorities'and ethical point of view, is only possible following convincing proof of their efficacy and safety. Between the drug registration authorities, who underline the necessity of early assessment against a placebo, on the one hand, and the ethical and consumer committees that disapprove of the use, the controversy has developed. FOR METHODOLOGISTS: Comparisons with reference drugs provide less credible results that comparisons versus a placebo. This is why their exclusive use may have deleterious effects on the reliable assessment of products to be launched on the market, in terms of efficacy and safety. Equivalence trials do not provide the expected solution since their internal validation requires a placebo arm. RETICENCE BUT NO PROHIBITION: The fifth revision of the declaration of Helsinki by the World medical association in the year 2000, which led to violent controversy regarding the drawing-up of section 29 and its clarification note, does not really help the debate progress: the authors of the texts confirm their reticence to the use of a placebo, but do not prohibit it. They have chosen a "middle of the road" solution. IN PRACTICE: The decision to conduct or not a placebo-controlled study should take into account the aims of the study (within the context or not of a marketing authorization submittal by an industrial), the early stage of the development of the drug or not and, above all, the level of efficacy and safety of the drugs already available versus the anticipated effects of the new product.

Clinical Trials as Topic↗
PubMed2003

Aminoterminal pro-brain natriuretic peptide and ventricular filling pressures in heart transplant recipients.

We tested the hypothesis that, in heart transplant recipients, plasma aminoterminal pro-brain natriuretic peptide (NT-proBNP) dosage is useful for diagnosis of high ventricular loading pressures in the absence of systolic dysfunction. We studied 60 consecutive transplanted heart recipients without systolic dysfunction at 1 to 16 years after transplantation. We found that, in these patients with frequent high ventricular filling pressures, plasma NT-proBNP was highly correlated with creatininemia and not correlated with ventricular loading pressures. These results do not support the hypothesis that NT-proBNP is useful for diagnosis of isolated diastolic dysfunction in transplanted heart recipients.

Adult↗
PubMed2002

[Generic drugs in the medical-economic context of drug prescriptions].

REIMBURSABLE DRUGS: The reimbursement, or coverage of pharmaceutical costs by the sickness benefits is governed in the French system by two conditions: the drugs must have been prescribed, and must be listed in the reimbursable drug list. Inscription in the reimbursable drugs list requires approval by the transparency commission, sole commission capable of assessing the medical service rendered (MSR) by the drugs and to propose a reimbursement rate of 65 or 35%. Exceptional drugs and those prescribed in the context of long-term treatments have a specific reimbursement status. ESTABLISHING THE PRICE: The coverage of drugs by the health insurance does not permit free pricing. The costs of drugs are established by the economic committee of health products (Comité Economique des Produits de Santé--CEPS), following approval by the transparency commission, who assesses the improvement in medical services rendered (IMSR) by new products, compared with existing products. THE ECONOMIC ADVANTAGES OF GENERICS: Physicians must be as economical as possible in terms of quality, safety and efficacy of the care they provide. Moreover, to be reimbursed by the social services, a generic must provide improved medical services or lead to savings in the cost of treatment. In such conditions one can conceive that the price of a generic (which does not provide any improvement in medical services compared with the original drug) is legitimately cheaper than the original product, and source of economy for better allocation of available funds. TWO MOTIVATING MEASURES: However, the French generic market is one of the least developed among industrialized countries. Presently, the volume of generics only represents 5% of the French drug market. Its further development is foreseen within the framework of all the plans for medicalized control of health costs. Other than the classical motives that encourage prescription of generics, i.e., citizens' awareness, labelling and the control by the French medicines agency, new determinating measures in our right for health are: the pharmacists' right to substitute and the physicians' authorization and incitement then to prescribe a product under its international non-proprietary name.

Costs and Cost Analysis↗
PubMed2002

[Critical review of the publication of a clinical trial].

THE MAIN OBJECTIVES OF THE CRITICAL REVIEW OF THE PUBLICATION OF A CLINICAL TRIAL: Are to underline the biases that may influence the validity and credibility of the results and to assess the quantity of the effect observed and the potential clinical impact. FOUR PRELIMINARY ELEMENTS: Should be taken into account: publication in a journal with a reading committee, notoriousness of the author, the interest declared by the authors and the approval of an ethics committee. EXAMINATION OF THE REPORT ITSELF: Concerns the study objectives, clearly defined and integrated within the logics of a scientific context and suggesting concrete applications. A good quality demonstrative trial is prospective, controlled, randomized, and carried out double blind. The patients included are clearly characterized in order to know to what type of patient the research results can subsequently be applied. The principle end-point, whenever possible, is of clinical significance. The choice of the comparative arm is pertinent. The required number of patients has been calculated. The author has agreed to respect Good Clinical Practice and the statistical analyses are appropriate. THE RESULTS: Presented clearly, must indicate the patients in whom the values observed have been calculated. The confidence intervals are provided. The principle analysis, in intent to treat, includes the principle end-point. The significance threshold is 5%. The extent of the difference between the results of the groups is detailed and of clinical significance. Any causal imputation is documented. The results of eventual sub-group analyses are only provided for information. THE DISCUSSION: Concerns the scope of the results, their internal and external coherence with already validated data. The conclusion, factual, evokes the eventual therapeutic benefits of the research conducted. With regard to the latter, readers will be interested in the application of the results obtained to their own patients.

Advisory Committees↗
PubMed2002

Panniculitis in a patient on methotrexate for mixed connective tissue disease.

Accelerated nodulosis during methotrexate therapy for rheumatoid arthritis has been well described. There have been recent reports of nodulosis in patients on methotrexate for other inflammatory conditions. Panniculitis is a newly discovered pathological entity in this setting. We describe a case of panniculitis in a woman receiving methotrexate for mixed connective tissue disease.

Antirheumatic Agents↗
PubMedDate not supplied

[The statins: new properties]].

The comparison of major statin trials with trials using either cholestyramine or ileal bypass has suggested that the reduction in coronary heart disease events for those patients receiving statin therapy largely result from their low density lipoprotein (LDL)-cholesterol lowering action. LDL-cholesterol lowering has several physiological consequences, including plaque stabilisation with a decrease in the inflammatory process, slowing of plaque progression, and improvement of endothelial function, as evidenced by the measurement of endothelial-dependent vasorelaxation in response to hyperhaemia or acetylcholine infusion. Statins lower C-reactive protein without any consistent effect on the other inflammation acute phase proteins. The cause and consequences of this effect are still debated. In order to explain why some statins can prevent coronary events within a few months, a direct effect of this therapy on thrombosis has also been advocated; however, the evaluation of statin antithrombotic effects in humans has produced conflicting results. By inhibiting L-mevalonic acid synthesis, statins also prevent the farnelysation of small-GTP binding proteins such as Rho and Ras. In vitro, and in animal models, the inhibition of Rho with statins results in a decrease in endothelial nitric oxide production, an inhibition of leucocyte adhesion on endothelium, decrease in PPAR alpha activation and high density lipoprotein (HDL) production by the hepatocyte, decrease in Ca2+ stores in vascular smooth cells, and a stimulation of vascular smooth muscle cell apoptosis. However, most of these effects were obtained with high statin concentrations. Further evidence is needed before a full assessment of the clinical importance of isoprenylation blockage with therapeutic concentrations of statins in humans can be made.

Animals↗
PubMedDate not supplied

[Do premarketing trials help to predict drug-related iatrogenic effects in elderly patients?].

Premarketing trials contribute poorly to predicting drug-related iatrogenic effects in elderly patients. Since their main goal is the demonstration of drug efficacy, these trials are characterised by a simplistic design, they include a limited number of young participants (volunteers only), are of a short duration, and follow a strict protocol. Results of studies in young people cannot be extrapolated to elderly people. Although licensing authorities recommend the recruitment of a meaningful number of elderly people in clinical trials (with an age distribution comparable to that expected when the drug is in routine use), even in trials that are not devoted to geriatric illnesses, elderly people remain substantially under-represented in most instances for methodological reasons (to avoid increased variance introduced by a heterogenous population), safety reasons (at this stage of drug development, it could be deleterious to include patients with comorbid conditions and unfair with regard to the brand image of the products), and ethical reasons (the decision to participate could not be taken by the elderly people alone). Exclusion of elderly participants, who are particularly exposed to drug-related iatrogenic effects, influences the generalisability of study findings. The recruitment of elderly participants, a vulnerable population, is necessary to allow valid conclusions regarding elderly people, recommendations on the appropriate dosage adjustment for elderly individuals, the avoidance of prescribing decisions based on inadequate information (with respect to a more informative summary of the characteristics of the products), and the maximum benefit for elderly people from research.

Aged↗
PubMedDate not supplied

[The French National Medicines Assessment Committee, innovation and therapeutic progress].

In France the role of the French National Medicines Assessment Committee, which is a part of the French National Authority for Health (HAS), is to evaluate the expected performance of new drugs in comparison with that of existing drug or non-drug treatments. This process includes evaluation of degree of innovation generally based on whether the drug can be considered as possibly, likely or certain to represent a factor of progress. However innovation and progress are not always synonymous. Progress is defined in terms of improvement in efficacy or tolerance determined by estimating the impact of the new product in comparison with existing modalities on the health of a subgroup of patients that can be readily defined, identified and studied. In general the committee considers any originality as positive since a new chemical or pharmacological class or a new mechanism of action may allow treatment of patients that did not respond to or tolerate existing products. However, when confronted with a concept without clear clinical benefits, the committee must distinguish between true and false innovation so that deliberation focuses more on recognition and quantification of progress than on systematic evaluation of innovation.

Clinical Trials as Topic↗
PubMedDate not supplied

[Quantification of pharmacological progress by the French National Health Authorities].

The French National Health Authority has delegated to the Transparency Commission (TC) responsibility for defining and quantifying therapeutic progress and for certifying the therapeutic added value of new drugs. It is essential to distinguish between pharmacologic innovation and therapeutic progress. The TC considers that a new product offers therapeutic progress if it: 1) improves patient management, 2) represents a significant clinical breakthrough, and/or 3) meets a previously uncovered need. Therapeutic progress must be supported by quantitative or qualitative clinical evidence of improved therapeutic tolerance, compliance or maintenance. The TC measures progress in terms of the enhancement of therapeutic value (ETV) relative to existing products. Ideally, ETV should be evaluated in head-to-head comparisons, but companies often prefer placebo-controlled studies, meaning that indirect comparisons are unavoidable. ETV is graded in five levels, ranging from I (major progress) to V (no progress), and is attributed for a specific target population. The ETV only measures expected therapeutic progress, to be confirmed in post-registration studies. TC decisions are taken into account by the commission that determines drug prices. One pending economic issue involves "me-too" products. Indeed, scientific committees cannot be expected to regulate market competition--for example, to decide when to inform decision-makers that the number of statins or betablockers on the market is sufficient to cover requirements. Another delicate problem concerns efforts by brand-name drug companies to circumvent generic drugs, notably by introducing fixed-dose combinations. Although the assessment of therapeutic progress is based on objective, verifiable and reproducible criteria, it can only be carried out fairly within a collaborative framework independent of pharmaceutical companies, healthcare insurers and consumer associations.

Drug Costs↗