Search

Introduction: Because patients and patient organizations want to strengthen their role in the care pathway and drug evaluation and in order to improve pharmacovigilance activities, European competent authorities implemented regulations to allow direct reporting of adverse drug reactions related to medicinal products by patients in 2012. Objectives: To describe evolution and analyze determinants of patient reporting activity in France in order to assess patient involvement in pharmacovigilance. Method: Using the French national pharmacovigilance database, univariate and multivariate analyses were performed to compare the characteristics of adverse drug reaction (ADR) reports from patients and healthcare professionals (HCP) between 2011 and 2020. The relationship between regional patient ADR report activity and regional care provision and socio-professional characteristics was analyzed using the principal component analysis. Results: A significant and higher increase in ADR reports over time from patients (r = 0.89, p < 0.001) compared to HCP (r = 0.27, p = 0.002) has been observed. Patient ADR report activities compared to HCP concerned more women (80% vs. 55%, p < 0.001), younger age classes (p < 0.001), reporting through web portal (83% vs. 17%, p < 0.001), and less serious events (26% vs. 63%, p < 0.001). In the principal component analysis, regional patient reporting activity was related to socio-professional categories, age classes, and densities of hospital beds and physicians. Conclusion: Our results confirm an increasing involvement of patients in ADR report activities. The determinants of patient reporting activities are not only related to drug and medical factors but also to social factors. Digital tools may also play a role in health democracy in pharmacovigilance. [ABSTRACT FROM AUTHOR]

Shortages of drugs and medical devices have tended to increase in France and worldwide, with consequences for patients and healthcare professionals. Preventing shortages of health products has become a priority for regulatory authorities, including the French National Agency for Medicines and Health Products Safety (ANSM). To highlight perspectives for a better prevention, we described and analyzed the management of shortages in the availability of health products in France over the last 10 years. The supply chain was mapped to identify the main causes of shortages and stakeholders involved in managing shortages throughout the supply chain. National and European initiatives and regulatory measures were reviewed. A retrospective nationwide data analysis from the French reporting system of health product shortage reports was conducted over 10 years for drugs (2013-2022) and over an 18-month period for medical devices, from 1st March 2022 to 31st August 2023. An increase in drug shortage reports was observed, rising from 404 in 2013 to 3,761 in 2022 for drugs, with a relatively constant distribution of affected therapeutic classes. In 2022, the main reported causes of drug shortage risk were insufficient production capacity (27.1%), increased sales volume (21.5%), or lack of supply (13.6%). Over half of the reports on medical devices (55.4%) were objectified as indispensable, and their causes were mainly due to a lack of supply (48.2%), discontinuation of marketing (14.9%), increased sales volume (13.2%), and regulatory reasons (9.6%). ANSM and French authorities have engaged a public health policy for prevention and management of health product shortages including financial penalties, minimum safety stocks for Major Therapeutic Interest drugs, and a shortage management plan. Based on 10 years of experience, four priority measures have been identified to anticipate the risk of heath products shortages based: the importance of a national coordination from raw materials to local market, the implementation of new prevention and management actions in the supply chain, strengthening European cooperation and regulation including the establishment of a list of critical drugs, and promoting transparency and information., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Belgodère, Emmerich, Albin, Bacon, Daynes, Vignot, Vial, Renaud, Le Saulnier, Maillard-Couvreur, Cachet, Veyries, Youdarene, Oualikene-Gonin, Ratignier-Carbonneil and Maison.)

Background: Antibiotic consumption has been reported to be driven by the treatment of respiratory tract infections. Our objectives were to describe the trend of antibiotic consumption in France compared with that of other European countries; to describe the evolution of each antibiotic class in France; and to explore the relationship between antibiotic consumption and incidence of influenza-like illnesses., Methods: In this observational study, antibiotic consumption was reported as defined daily doses per 1000 inhabitants per day in the community and hospital sectors in descriptive and graphical formats, using data from the European Surveillance of Antimicrobial Consumption Network database. The total consumption and the consumption of different classes of antibiotics in France according to time and influenza-like illnesses were studied using multiple linear regression models., Results: The total consumption of antibiotics in France was constant over the 15 years. It was driven by the community sector (92.8%) and was higher than the consumption of other European Union countries (P-value < 0.001). The beta-lactam penicillins were the most consumed antibiotic class and the only class that increased with time. The multiple linear regression models showed a positive correlation between antibiotic consumption in the community sector and incidence of influenza-like illnesses [B = 0.170, 95% CI (0.088-0.252)]. Similar significant results were shown between other antibiotic classes used in the management of influenza-like illnesses (other beta-lactams, and macrolides, lincosamides and streptogramins) and influenza-like illnesses., Conclusion: Our results suggest that antibiotics used in the management of respiratory tract infections might be involved in the irrational use of antibiotics., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Objectives: The aim was to provide figures for drug shortages in France and describe their characteristics, causes and trends between 2012 and 2018., Methods: Data from the national reporting system from the Agency of Medicine and Health Product Safety (ANSM) was analysed. This database contains information regarding effective and predicted shortages of major therapeutic of interest drugs (ie, drugs whose shortage would be life-threatening or representing a loss of treatment opportunity for patients with a severe disease) which are mandatory reported by marketing authorisation holders to the ANSM. Data are presented as numbers or percentages of pharmaceutical products (ie, the product name and its formulation) reported on shortage between 2012 and 2018., Results: There were 3530 pharmaceutical products reported on shortage during the period, including 1833 different active substances. Drugs on shortage were mostly old products (63.4%) with national marketing authorisation procedures (62.8%), as well as injectable and oral forms (47.5% and 43.3%, respectively). Anti-infectives for systemic use ranked first (18%), followed by nervous and cardiovascular system drugs and by antineoplastic and immunomodulating agents (17.4%, 12.5% and 10.4%, respectively). The number of reported shortages presented a fourfold increase between 2012 and 2018 and a sharp rise in 2017 and 2018, along with a rise in the number of active substances on shortage. The therapeutic classes concerned remained similar over time. Manufacturing and material supply issues were the main reported reasons for the shortage each year (30%) and there was an overall rise of pharmaceutical market reasons., Conclusion: Drug shortages were increasingly reported in France. Preventive measures should specifically target the products most on shortage, in particular old drugs, injectable, anti-infective, nervous system and cardiovascular system drugs as well as antineoplastic and immunomodulating agents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare the regional demographic and health indicators to the pharmacovigilance activity of the regional pharmacovigilance centers in terms of number of cases collected, responses to information requests and signal detection in 2015., Methods: The pharmacovigilance activity parameters (collected cases reports, information requests, reported serious cases) were expressed in regional proportions to population size and compared to regional demographic and health indicators (population, individuals aged 60 and over, individuals aged under 20, socio-professional categories, health facilities per capita, hospital beds [medicine, surgery and obstetrics] per capita, physicians and pharmacists per capita, mortality rate and drug consumption per capita) in 12 French metropolitan areas. The Spearman correlation between these two parameters was analyzed., Results: The territorial distribution of all demographic and health indicators and pharmacovigilance activity indicators in proportion to population size was different between regions (P<0.001): individuals aged 60 and over, individuals aged under 20, socio-professional categories, health facilities per capita, hospital beds per capita, health professionals per capita, mortality rate, drug consumption per capita, reported pharmacovigilance cases, information requests and reported serious cases. The number of regional collected pharmacovigilance cases per capita was negatively correlated with the territorial distribution of managers and intermediate professions (respectively r=-0.60 and -0.68; P=0.04 and 0.02). The regional number of reported serious cases per capita was statistically correlated with the regional number of hospital beds per capita (r=0.60; P=0.04) and inversely correlated with the territorial distribution of intermediate professions (r=-0.60; P=0.04)., Conclusion: Size of population is not the only determinant of the regional level of pharmacovigilance activity. Regional demographic and health parameters (age, socio-professional categories, hospital beds and drugs consumed) may partly explain the difference between regions., (Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Aims: The aims of the present study were to describe the consumption trends of three groups of analgesics (non-opioids, and mild and strong opioids) between 2006 and 2015 in France, and compare this pattern of use with six European countries in 2015., Methods: Annual drugs sales were extracted from the French national authority's consumption database, and from the IMS Multinational Integrated Data Analysis System and national databases for European countries., Results: The use of mild opioids in France was found to have decreased by 53% over the past 10 years, owing to the declining use of dextropropoxyphene combinations, along with an increase in the use of non-opioids and strong opioids (from 72 to 93, and 2 to 2.8 defined daily doses/1000 inhabitants/day, respectively). Paracetamol, the most consumed analgesic, increased over this period, particularly for the adult high dose (+140%). The use of tramadol and codeine combinations also increased, by 62% and 42%, respectively. Morphine remained the most used strong opioid, although there were also large increases in the consumption of oxycodone (+613%) and fentanyl (+263% and +72% for transmucosal and transdermal forms, respectively). A comparison of the patterns of use in Europe in 2015 showed a higher consumption of mild and strong opioids in the UK. France ranked first and third place, respectively, for paracetamol and mild opioid consumption, whereas its use of strong opioids was among the lowest., Conclusions: Paracetamol consumption is clearly highest in France, whereas its use of strong opioids is among the lowest in Europe, although its consumption of oxycodone has increased significantly. Further studies are required specifically to monitor these drugs., (© 2018 The British Pharmacological Society.)

Background: There is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders., Methods: We performed a longitudinal study of the consent of Huntington's disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington's Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington's disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington's disease patients and 16 proxies one year later., Results: The comprehension score was high and similar for Huntington's disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year., Conclusions: Cognitively impaired patients with Huntington's disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients.

The French national agency for the safety of medicine and healthcare products created in 2005 a Medication Errors Desk which enables health professionals and patients to report directly medication errors without adverse reaction or near misses in addition of reports collected from the Pharmacovigilance System.

Purpose: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression., Methods: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score., Results: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41 ± 0.17 units per year vs. risperidone and 0.54 ± 0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05)., Conclusions: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.

Health technology assessment seeks to inform health policy- and decision-makers by promoting use of current best evidence and by addressing country specific factors, such as local context and values. In France, public health benefit (PHB) is one of the criteria used to inform decisions on the reimbursement of medicines. This article describes the methodological framework and the results after five years of assessment of PHB, by the French National Authority for Health. The semi-quantitative method used includes three dimensions that are: (1) the ability of a drug to improve the population's health status, (2) the drug's adequacy to cover public health needs, and; (3) the impact of the drug on the healthcare system. From 2005 to 2010, the PHB of 530 drugs was estimated, and 72% were assessed as having no PHB. The PHB was "low" for 88% of drugs expected to have a PHB, "medium" for 10%, and was considered to be "high" in only one case. The results of this experience show that it is feasible to assess the public health impact of drugs. But the high level of uncertainties at the time of a drug's first appraisal limits the assessment, which obviously has to be completed by reappraisal with post-marketing studies., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We previously reported that chronic heart failure (CHF) treatments reduce the duration of hospitalisation, even in elderly patients. The present study aimed to determine whether CHF treatment also provides long-term benefits in terms of reduced mortality at 8 years., Methods: A cohort of 281 patients who were admitted to a French teaching hospital with a main diagnosis of CHF were followed through the health insurance databases for 1 year and through the national mortality database for 8 years., Results: Diuretics (236 patients, 84 %) and angiotensin-converting enzyme (ACE) inhibitors (193 patients, 69 %) were the most-frequently prescribed medications. The median duration of survival was 46 months. Mortality rates were significantly lower for patients administered beta-blockers (59 %) and statins (56 %) than for patients not exposed to these drugs (82 %, p < 0.001 and 78 %, p = 0.001 respectively). No significant differences in mortality were observed for spironolactone, diuretics or ACE inhibitors. After adjustment, beta-blocker treatment remained associated with a significantly lower risk of mortality (hazard ratio, HR = 0.54 [0.34-0.84]). After adjustment, the use of two or three CHF drugs was associated with longer survival (HR = 0.53 [0.36-0.77]) than the use of zero or one CHF drug. Statins were also associated with longer survival after adjustment (HR = 0.53 [0.31-0.89]). In patients 75 years of age or older (n = 73), only beta-blocker treatment was associated with a significantly lower risk of mortality (HR = 0.31 [0.16-0.63]) in multivariate analysis., Conclusions: The use of beta-blockers was associated with better survival rates. The use of statins was also associated with better survival at 8 years. Randomised controlled trials are required to confirm these observations.

Objectives: A prophylactic anti-emetic strategy should depend on the number of nausea and vomiting risk factors. This study was undertaken to evaluate the practices of postoperative nausea and vomiting (PONV) prevention practices among obstetrician-gynaecologists, anaesthetists., Study Design: A prospective, self-administered questionnaire survey was emailed to all Club d'Anesthésie Réanimation Obstétricale (Caro) members (French Obstetric and Gynaecology Anaesthetists' Association)., Methods: The questionnaire had closed-ended questions to evaluate each Caro member's prophylactic anti-emetic practices. Questions concerned demographic datas, prophylactic anti-emetic drugs administered to the patients with or without well known risk factors for developing PONV, the existence of protocol to prevent PONV in their own department of anaesthesiology and their awareness of the existence of French Society of Anaesthesia and Intensive Care (Sfar) PONV prevention guidelines 2007., Results: Of 115 questionnaires, 66 respondents (57%) returned the questionnaires. Most of the respondents (74%) worked in a university hospital. Forty-two percent practiced exclusively in obstetric-gynaecology department. Fifty-six percent were anaesthetists for more than 20 years. Eighty-five percent of the physicians were well-informed about the SFAR's PONV prevention guidelines. Thirty seven percent of respondents assessed Apfel score systematically for all their patients. The percentages, which didn't calculate the probability of PONV with Apfel score or calculated only in cases of PONV history or travel sickness were 18% and 45% respectively. In cases of two or more risk factors, 63% used droperidol, dexamethasone and ondansetron in double or triple combinations., Conclusions: Although most surveyed practitioners were well informed about the new guidelines concerning PONV prevention, 27% not follow these guidelines regarding the administration of anti-emetic drugs. The calculation of Apfel score in the preoperative period must be also strengthened., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Having a mental illness has been and remains even now, a strong barrier to effective medical care. Most mental illness, such as schizophrenia, bipolar disorder, and depression are associated with undue medical morbidity and mortality. It represents a major health problem, with a 15 to 30 year shorter lifetime compared with the general population., Methods: Based these facts, a workshop was convened by a panel of specialists: psychiatrists, endocrinologists, cardiologists, internists, and pharmacologists from some French hospitals to review the information relating to the comorbidity and mortality among the patients with severe mental illness, the risks with antipsychotic treatment for the development of metabolic disorders and finally cardiovascular disease. The French experts strongly agreed on these points: that the patients with severe mental illness have a higher rate of preventable risk factors such as smoking, addiction, poor diet, lack of exercise; the recognition and management of morbidity are made more difficult by barriers related to patients, the illness, the attitudes of medical practitioners, and the structure of healthcare delivery services; and improved detection and treatment of comorbidity medical illness in people with severe mental illness will have significant benefits for their psychosocial functioning and overall quality of life. GUIDELINES FOR INITIATING ANTIPSYCHOTIC THERAPY: Based on these elements, the French experts propose guidelines for practising psychiatrists when initiating and maintaining therapy with antipsychotic compounds. The aim of the guidelines is practical and concerns the detection of medical illness at the first episode of mental illness, management of comorbidity with other specialists, family practitioner and follow-up with some key points. The guidelines are divided into two major parts. The first part provides: a review of mortality and comorbidity of patients with severe mental illness: the increased morbidity and mortality are primarily due to premature cardiovascular disease (myocardial infarction, stroke...).The cardiovascular events are strongly linked to non modifiable risk factors such as age, gender, personal and/or family history, but also to crucial modifiable risk factors, such as overweight and obesity, dyslipidemia, diabetes, hypertension and smoking. Although these classical risk factors exist in the general population, epidemiological studies suggest that patients with severe mental illness have an increased prevalence of these risk factors. The causes of increased metabolic and cardiovascular risk in this population are strongly related to poverty and limited access to medical care, but also to the use of psychotropic medication. A review of major published consensus guidelines for metabolic monitoring of patients treated with antipsychotic medication that have recommended stringent monitoring of metabolic status and cardiovascular risk factors in psychiatric patients receiving antipsychotic drugs. There have been six attempts, all published between 2004 and 2005: Mount Sinai, Australia, ADA-APA, Belgium, United Kingdom, Canada. Each guideline had specific, somewhat discordant, recommendations about which patients and drugs should be monitored. However, there was agreement on the importance of baseline monitoring and follow-up for the first three to four months of treatment, with subsequent ongoing reevaluation. There was agreement on the utility of the following tests and measures: weight and height, waist circumference, blood pressure, fasting plasma glucose, fasting lipid profile. In the second part, the French experts propose guidelines for practising psychiatrists when initiating and maintaining therapy with antipsychotic drugs: the first goal is identification of risk factors for development of metabolic and cardiovascular disorders: non modifiable risk factors: these include: increasing age, gender (increased rates of obesity, diabetes and metabolic syndrome are observed in female patients treated with antipsychotic drugs), personal and family history of obesity, diabetes, heart disease, ethnicity as we know that there are increased rates of diabetes, metabolic syndrome and coronary heart disease in patients of non European ethnicity, especially among South Asian, Hispanic, and Native American people. Modifiable risk factors: these include: obesity, visceral obesity, smoking, physical inactivity, and bad diet habits. Then the expert's panel focussed on all the components of the initial visit such as: family and medical history; baseline weight and BMI should be measured for all patients. Body mass index can be calculated by dividing weight (in kilograms) by height (in meters) squared; visceral obesity measured by waist circumference; blood pressure; fasting plasma glucose; fasting lipid profiles. These are the basic measures and laboratory examinations to do when initiating an antipsychotic treatment. ECG: several of the antipsychotic medications, typical and atypical, have been shown to prolong the QTc interval on the ECG. Prolongation of the QTc interval is of potential concern since the patient may be at risk for wave burst arrhythmia, a potentially serious ventricular arrhythmia. A QTc interval greater than 500 ms places the patient at a significantly increased risk for serious arrhythmia. QTc prolongation has been reported with varying incidence and degrees of severity. The atypical antipsychotics can also cause other cardiovascular adverse effects with, for example, orthostatic hypotension. Risk factors for cardiovascular adverse effects with antipsychotics include: known cardiovascular disease, electrolyte disorders, such as hypokaliemia, hypomagnesaemia, genetic characteristics, increasing age, female gender, autonomic dysfunction, high doses of antipsychotics, the use of interacting drugs, and psychiatric illness itself. In any patient with pre-existing cardiac disease, a pre-treatment ECG with routine follow-up is recommended., Concluding Remarks: Patients on antipsychotic drugs should undergo regular testing of blood sugar, lipid profile, as well as body weight, waist circumference and blood pressure, with recommended time intervals between measures. Clinicians should track the effects of treatment on physical and biological parameters, and should facilitate access to appropriate medical care. In order to prevent or limit possible side effects, information must be given to the patient and his family on the cardiovascular and metabolic risks. The cost-effectiveness of implementing these recommendations is considerable: the costs of laboratory tests and additional equipment costs (such as scales, tape measures, and blood pressure devices) are modest. The issue of responsibility for monitoring for metabolic abnormalities is much debated. However, with the prescription of antipsychotic drugs comes the responsibility for monitoring potential drug-induced metabolic abnormalities. The onset of metabolic disorders will imply specific treatments. A coordinated action of psychiatrists, general practitioners, endocrinologists, cardiologists, nurses, dieticians, and of the family is certainly a key determinant to ensure the optimal care of these patients.

Guidelines about the use of neuromuscular blocking agents based on a national consensus conference have been published in 2000. A survey was carried out to assess adherence to these guidelines. An online questionnaire was designed from the different guidelines concerning the use of muscle relaxant for tracheal intubation and surgery, monitoring and antagonism of neuromuscular blockade. In addition, question about the knowledge of the pharmacodynamics of neuromuscular blocking agents were asked. Analysis concerned 1230 answers from senior anaesthetists. Tracheal intubation is facilitated by the use of a competitive agent or by succinylcholine by 58 and 8% of responders respectively. Atracurium and cisatracurium were most frequently used (49 and 44%, respectively). The duration of effect of an intubating dose of atracurium, vecuronium or rocuronium was estimated equal or below 60 min by more than half of responders, whereas that of cisatracurium was longer. Fifty-two or 74% of responders used neuromuscular monitoring, whether a single or repeated dose of muscle relaxant was administered. Antagonism of neuromuscular blockade was systematic, frequent, and episodic or excluded by 6, 26, 55 and 13% of responders, respectively. Monitoring and antagonism of neuromuscular blockade are underused despite the guidelines. Underestimation of the risk of postoperative residual curarization is linked to the underestimation of the duration of competitive neuromuscular blocking agents.

The content of informed consent documents (ICD) is a crucial element in the process of providing information to participants in biomedical research. Clear comprehension of the information, i.e. the ability to understand its meaning and its consequences, is of utmost importance. The objective of this study was to describe the different steps in the French adaptation and preliminary validation of the Qualité de Compréhension des Formulaires d'information et de consentement (QCFic) questionnaire (http://www.lyon.inserm.fr/cic-grenoble) based on the American Quality of Informed Consent (QuIC) questionnaire. Adaptation and preliminary validation of the QuIC for use in France was composed of five principal steps: translation, scientific validation, lexical validation, edition of gold-standard answers and a pilot study. Each stage was conducted by independent groups of experts, under the coordination of the study board. Thirteen questions were added and one was suppressed. Two steps were required for the scientific validation and for lexical validation, 21 modifications were proposed. Relative to gold-standard answers, the three experts gave the same answer for 24 questions and for nine other questions, two of the three gave identical answers, which were validated by the study board. Results of a pilot study showed a global QCFic score of 88.99 (84.13-90.92) and no specific commentary was made about the content of the questions, so no more modification needed to be made. A preliminary validated French questionnaire, the QCFic, is now available to evaluate the quality of an informed consent document in phase I clinical trials. It is quick and easy to use.

Information is the keystone to the participation of subjects in biomedical research. Clear comprehension of the informed consent documents (ICDs) is primordial and a necessary requirement is that they are readable. While submission of a protocol to a French 'Comités de Protection des Personnes' (CPP) is a mandatory step with regard to the French legislation on biomedical research, no published data are available concerning its influence on ICDs readability. The aim of our study was to determine the impact of French CPP on the readability of ICDs, using lexico-syntactic readability indexes and ICDs from four clinical research centres and one clinical research unit. Twenty-five ICDs were analysed. The Flesch score was not modified after CPP review, while the Cordial score was significantly lower [from 4 (1-14) to 1 (1-13), P = 0.014]. The information was longer and more complex following CPP review. No protocol characteristics had any impact on the variation before and after review for either the Flesch or the Cordial indexes, nor on the number of syllables per word. Changes in the total number of words before and after review varied considerably between study centre, supporting heterogeneity of CPP review. Since August 2004, French CPP have to study the intelligibility of ICDs in addition to the scientific and ethic aspects of a research. We show that their current reviews do not increase the readability, while increasing the length of ICDs.

Plasma fibrinogen is strongly associated with cardiovascular morbi-mortality. We investigated in the large cohort of the D.E.S.I.R. (data from an epidemiological study on the insulin resistance syndrome) study, the relationship between change in fibrinogen concentration over a 3-year follow-up and fibrate and statin use. Fibrinogen concentrations were higher at baseline among individuals treated with statins (n=130) compared to those treated with fibrates (n=251), even after adjustment for confounding factors (including total cholesterol, HDL cholesterol and triglycerides) (mean (S.D.): 2.8 (0.6) vs. 3.1 (0.6), P<0.001). We compared change in fibrinogen concentrations at 3 years of follow-up, between individuals who started fibrate (n=126) or statin (n=127) treatment during the follow-up and individuals (n=3906) who stayed without treatment during this period. After adjustment for baseline fibrinogen level, age, sex and changes in total cholesterol, triglycerides and alcohol intake, fibrinogen concentration decreased after fibrate treatment, while it increased after statin treatment and in those not using lipid lowering drugs (-0.07 (0.54) vs. 0.10 (0.54) vs. 0.08 (0.52) g/l respectively, P=0.01). No differences were observed between different statins or different fibrates. In conclusion, fibrates in contrast with statins may combine lipid-lowering with a beneficial effect on fibrinogen. This effect is independent of changes in cholesterol and triglyceride concentrations.

Objective: To compare antihypertensive drug use between diabetics and non-diabetics and to analyse the change between the two last decennial national surveys on health and medical care in France, in 1981 and 1992., Material and Methods: These surveys included respectively 12,725 and 13,887 adults over 25 years. Use of all antihypertensive drugs marketed in France was compared between orally treated diabetics and non-diabetics who were non-insulin and non-oral anti-diabetic treated population., Results: In 1981, while diuretics were the first treatment in both populations (53% in diabetics vs 60% in non-diabetics, non significant), central inhibitors (31 vs 16% respectively, p<0.001) were the second agent among diabetic patients instead of beta blockers in non-diabetic patients (13 vs 22% respectively, p<0.05). In 1992, beta blockers were also less used in diabetics (21 versus 33%, p=0.001). In contrast, ACE inhibitors were more used (43 versus 35%, p=0.06). In both surveys and populations, other classes (reserpin, vasodilator and alpha blockers) had minor place in the strategy. The frequency of combinations of antihypertensive drugs was similar in both surveys and populations. The preferred combination treatment was in both populations reserpin with diuretics in 1981 (7 vs 9%, non significant) and ACE inhibitors with diuretics in 1992 (18 vs 18%)., Conclusion: Independently of guidelines, our data suggest that the strategy of hypertension treatment has changed last years and that prescriptions were more targeted for diabetic patients.

A new scientific discipline: Progress in scientific knowledge, advances in therapeutic innovation, the development of new drugs and the continuing need for optimal drug use impose a new approach to the rational assessment of public health needs and the risks and benefits of therapeutic intervention. In the near future, a new scientific discipline, pharmaceutical epidemiology, will play a leading role. France seems to be a bit behind other western countries in this area. Goal setting: The objectives of industrial firms do not necessarily cover all aspects of the overall goals of society. If the scientific community leaves the development and implementation of pharmaceutical epidemiology in the hands of industrial firms alone, they risk seeing its field of action limited to industrial objectives. The goals of this new discipline must be defined within an unbiased framework aimed at meeting the needs of society in general. Organization: The development of pharmaceutical epidemiology as an integral part of medical research requires a clear definition of its objectives, methods, working hypotheses and time and human allocations. In this context, pharmaceutical epidemiology should be organized within the University and scientific settings currently contributing to scientific research in France (INSERM, CNRS, ORSTOM, etc.). Creating favorable conditions: A pharmaceutical epidemiology network with adequate human and material resources is needed. The wide range of needs expressed by existing institutions (Drug Agency, Prescription and Drug Use Observatory, industrial firms, the national health insurance system, physician and pharmacist associations) pleads for a nationally organized project working in the public domain.

Despite the availability of a safe and efficacious vaccine, new cases of infection by hepatitis B virus (HBV) still occur at a substantial rate. This increases the current prevalence of chronic HBV carriers (10% of newly infected subjects) and in the long run, will raise the incidence of chronic liver disease. The surveillance of viral hepatitis commenced in December 1990 by the French sentinel network for electronic surveillance of communicable diseases. Between 1991 and 1996, a decrease in the annual incidence was observed although it was not significant (p = 0.06). The mean number of cases for this period was 12 per 100,000 inhabitants. The sex ratio (M/F) was 1.6 (p<0.01) and the median age, 32 years. Heterosexual transmission was suspected in 25% of cases, homo-bisexual transmission in 10%, use of injected drugs in 19%, percutaneous exposure in 9%, and blood transfusion or hemodialysis in 6%. Although the incidence of HBV infection is decreasing, the prevalence of chronic infection will continue to rise. However, the universal hepatitis B immunisation strategy proposed by WHO will dramatically limit the expansion of the population of chronically infected subjects if high coverage is achieved rapidly.

Objective: Antipyretic/analgesic drugs (AADs) are among the most commonly used drugs in children. Their efficacy and adverse effects have often been debated and new AADs have been introduced over the past few years. The aim of this study was to assess the characteristics of the use of AADs in children in France, and their trends., Methods: Two surveys on household health care consumption were undertaken in France, in 1981 and in 1992. They included 5060 and 4841 children, respectively. The AADs studied were aspirin, paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)., Results: The proportion of children exposed to AADs increased significantly between 1981 and 1992 (+28% in 11 years). Among them, the percentage of subjects treated with aspirin decreased (-27%). In contrast, the percentage increased for paracetamol (+ 19%) and for NSAIDs (+179%). Aspirin was the AAD most used in 1981 (57.4%) and it was replaced by paracetamol in 1992 (71.6%). Nasopharyngitis was the main reason for AAD prescription under the age of 11 years; for older children it was influenza-like syndrome, irrespective of the study year. A change in AAD choice occurred in nasopharyngitis, acute bronchitis and influenza-like syndrome irrespective of the age group, and in otitis/sinusitis between 4 and 10 years. In all these cases aspirin prescription decreased, in contrast with paracetamol and NSAIDs. Self-medication of AAD was uncommon (8.3% for aspirin and 10.3% for paracetamol in 1992) and decreased (-29% and -33%). It was used principally for nasopharyngitis, influenza-like syndrome and pain., Conclusion: The consumption of AADs in children is high and is increasing. Paracetamol and NSAIDs tend to replace aspirin prescription in children and physicians have played the main role in this change.

Trends in the use of antimicrobials in France between 1980-1981 and 1991-1992 were analyzed. Data were obtained from surveys of health and ambulatory care, which were based on national probability samples. In a 3-month period in 1980, 17% of the population of France was treated with an antibiotic, compared with 25% in 1991 (P < .001). The frequency of respiratory tract infections with a presumed viral etiology that were diagnosed and treated with antibiotics increased by 86% for adults and 115% for children in the 11-year period. The proper use of cephalosporins must be encouraged, and vigilance is required in view of the increased improper use of fluoroquinolones, mainly for respiratory tract infections with a presumed viral etiology.

Objective: To describe oral antibiotic prescription in the community., Design: Audit of anti-infective prescribing in office-based medical practice., Setting: Center of France, in the Loiret, a 600,000 inhabitant administrative division., Main Outcome Measures: Clinical hypothesis and antimicrobial drugs used as well as daily doses and durations of treatment., Results: Respiratory tract infections with a presumed viral etiology accounted for 36% of prescriptions. In children, a high percentage of antibiotic prescriptions were underdosed as compared to clinical recommendations, particularly in acute otitis media. The variability of the daily dose was high, with coefficients of variation over 40% in acute otitis media or acute tracheobronchitis. Whatever the clinical hypothesis, the duration of treatment was close to 8 days. In acute otitis media, the coefficient of variation was 14%, the lowest for all diagnoses., Conclusion: Our investigation identified two main areas for improving antimicrobial drug prescribing: (1) reduction of useless prescriptions in respiratory tract infections with a presumed viral etiology, and (2) increasing the prescribed daily dose of antimicrobials to the recommended levels.