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The concept of telemedicine was formalised in France in the 2009 "Hospital, patients, health territories" (loi hôpital, patients, santé, territoire) law and the 2010 decree through which it was applied. Many experiments have been carried out and the regulatory institutions (Ministry, Regional Health Agency [Agence régionale de santé, ARS], French National Health Authority [Haute autorité de santé, HAS], etc.) have issued various guidance statements and recommendations on its organisation and on the expectations of its evaluation. With this background, the round table wanted to produce recommendations on different areas of medical telemonitoring (the role of telemonitoring, the regulatory system, the principles for assessment, methods of use and conditions for sustained and seamless deployment). Whilst many studies carried out on new medical telemonitoring approaches have led to the postulate that it offers benefit, both clinically and in terms of patient quality of life, more information is needed to demonstrate its impact on the organisation of healthcare and the associated medico-economic benefit (criteria, methods, resources). Similarly, contractual frameworks for deployment of telemonitoring do exist, although they are complicated and involve many different stakeholders (Director General fo the Care Offering [Direction générale de l'offre de soins, DGOS], ARS, HAS, Agency for Shared Health Information Systems [Agence des systèmes d'information partagés de santé, ASIP], French National Data Protection Commission [Commission nationale informatique et libertés, CNIL], French National Medical Council [Conseil national de l'Ordre des médecins, CNOM], etc.) that would benefit from a shared approach and seamless exchange between the partners involved. The current challenge is also to define the conditions required to validate a stable economic model in order to promote organisational change. One topical issue is placing the emphasis on its evaluation and operation. Access to patient data, particularly data from the health insurance funds and the use of these data, may enable the process to be more effective. In addition, the budgetary non-fungibility of the various financial envelopes for the different areas of work, restricts the consolidation of financial impact. Funding methods will need to be adapted to this new distribution of roles, both at the centre of the healthcare system and in the industrial ecosystem. All of these changes will help the leaders of our healthcare system to bring this new ambition closer to all of the people working in the health economy., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Medical devices are many and various, ranging from tongue spatulas to implantable or invasive devices and imaging machines; their lifetimes are short, between 18 months and 5 years, due to incessant incremental innovation; and they are operator-dependent: in general, the clinical user performs a fitting procedure (hip implant or pacemaker), a therapeutic procedure using a non-implantable invasive device (arrhythmic site ablation probe, angioplasty balloon, extension spondyloplasty system, etc.) or follow-up of an active implanted device (long-term follow-up of an implanted cardiac defibrillator or of a deep brain stimulator in Parkinson's patients). A round-table held during the XXVIII(th) Giens Workshops meeting focused on the methodology of scientific evaluation of medical devices and the associated procedures with a view to their pricing and financing by the French National Health Insurance system. The working hypothesis was that the available data-set was sufficient for and compatible with scientific evaluation with clinical benefit. Post-registration studies, although contributing to the continuity of assessment, were not dealt with. Moreover, the focus was restricted to devices used in health establishments, where the association between devices and technical medical procedures is optimally representative. An update of the multiple regulatory protocols governing medical devices and procedures is provided. Issues more specifically related to procedures as such, to non-implantable devices and to innovative devices are then dealt with, and the proposals and discussion points raised at the round-table for each of these three areas are presented., (© 2013 Société Française de Pharmacologie et de Thérapeutique.)

A cohort is a group of individuals sharing some characteristics, followed longitudinally. Essential tools of epidemiology, these studies provide pieces of evidence of the relationship between an exposition and outcomes in order to guide public health policies. In France, many cohorts have been conducted over the past few years. Sometimes, initiated by independent research teams (e.g. E3N) but more often, either requested by health authorities in a global public health plan (e.g. MEMENTO in the Alzheimer plan) or conducted to investigate a safety issue (e.g. France Coag). Besides, post authorization studies often consist in prospective cohorts. Because of objectives, designs and governance arrangements diversity; participants questioned whether it was interesting for researchers, regulators and industrials to use this epidemiological tool. Some findings about difficulties met in cohorts' establishment have been shared by each other. In order to make cohorts more efficient, participants have made some recommendations., (© 2012 Société Française de Pharmacologie et de Thérapeutique.)

As the failure of several recent Phase III drug development programmes bears witness, the clinical development of "disease-modifying" drugs in Alzheimer's disease has been confronted with challenging methodological difficulties. Taking into account the financial stakes involved taking drug candidates to the Phase III stage of development, and the risk of investing time and resources fruitlessly in the evaluation of poor candidate drugs, the crucial decision remains whether to proceed from Phase II to Phase III (Go/Nogo). The aim of Phase II studies is to select a molecule likely to be effective in Phase III, but also to eliminate candidate-drugs with an inadequate effect. No consensus currently exists on the best possible design of Phase II studies to inform the Go/Nogo decision optimally. The challenges in choosing the best study design relate to the target population, the end-point criteria used, in particular the use of biomarkers, the experimental protocol, and the study duration. The objective of the Round Table (RT) was to gather the opinions of French experts from the academic, industrial, and regulatory world in order to arrive at a consensus recommendation for the best possible design to be used in Phase II studies in Alzheimer's disease., (© 2010 Société Française de Pharmacologie et de Thérapeutique.)

More and more frequently, the health authorities and the French assessment agencies are led to issue Marketing Authorizations (MAs), give opinions on the eligibility for reimbursement of drugs or to draft recommendations for clinical practice based on the results of foreign studies. The results of these studies are more or less difficult to transpose to French practice. These difficulties generate varying degrees of uncertainty concerning the effect to be expected of a drug. A more or less extensive loss of effect is sometimes even predictable. Some of the difficulties in transposition are discussed in this article and proposals for action are made in order to allow one, in the long term, to predict in the most precise manner possible the effects to be expected from a drug in the French population and be able to verify this prediction at an interval from its eligibility for reimbursement., (Copyright © 2007 Société Française de Pharmacologie et de Thérapeutique. Publié par Elsevier Masson SAS.)

The European Directive on clinical trials of medicinal products will fall within the scope of the legislation of Member States on 1 May 2004. In France, this adaptation will be carried out by a public health bill concerning, among other things, the reform of the current Huriet-Sérusclat law, and by means of regulations. For trials concerning the initial administration of a product to human subjects, the group suggested the following recommendations: In French texts, to include a deadline of 30 days for the initial authorisation by the competent authority (Afssaps [Agence française de sécurité sanitaire des produits de santé]). To maintain an observed deadline of 20 days (35 official days) for the decision of the Ethics Committee (EC) [Committee for the Protection of Persons (CPP)]. To obtain a more specific evaluation of the pharmaceutical dossier of the investigational medicinal product (IMP) from the competent authority. To provide both bodies with nonclinical and possibly clinical data concerning the IMP information of the participants and their consent. To follow the recommendations posted on the Afssaps website for the entire IMP dossier. To submit a protocol under the International Committee on Harmonisation (ICH) E6 format adapted for phase I and, possibly as a separate document, justification of a certain number of points (a total of ten) that are more specific to this trial phase to facilitate and improve the document review while also providing the expected guarantees. To limit the 'substantial' amendments to those provided for in the European guidelines. To break the blind for every serious event reported to the sponsor by the investigator, and report to the competent authority any serious adverse event related to the IMP or to the trial or without documented cause, while keeping ECs and investigators informed. Furthermore, certain points concerning the authorisations for packaging, labelling and dispensing of the batches of medicinal products for clinical trials will need to be specified for these early studies. All these recommendations are intended to help promote the development of studies involving the initial administration of medicinal products in France.

Round table no. 2 was devoted to the postmarketing evaluation of drugs. The debates involved both the questions posed by postmarketing evaluation and the methods for responding to them. The major categories of questions likely to be posed are as follows: efficacy in actual situations; safety in actual situations; prognostic factors and patients responding; place in the therapeutic strategy; impact on the healthcare care system; the 'joined' population (those who actually obtain benefit); and drug utilisation review. In addition, the methodological approaches have been divided into three categories: the experimental approach, the observational approach and the modelling approach. Each of these methodological approaches has been qualified with respect to each of the questions. The objective was neither to establish a classification of the methods according to the level of proof, nor to propose methodological formulae. Instead, the participants applied themselves to describe the strengths and the limits of the different methods for each of the questions in turn. The debates then focused on the process of identification of pertinent questions and appropriate methods. In this context, the round-table participants applied an analysis of the current system of postmarketing study projects and formulated some propositions for their improvement. Finally, the place of existing databases in the postmarketing evaluation was discussed and the participants emphasised the importance of initiating a very detailed assessment of the information that could be provided by such databases before instituting ad hoc studies.

Unlabelled: To assess the impact of cystic fibrosis (CF) and treatment on quality of life (QOL) from childhood throughout adult age, two versions of the Cystic Fibrosis Questionnaire (CFQ), were developed and validated in France: the CFQ 14+ for teenagers and adults, the CFQ Child P, a parent-proxy evaluation for children aged 8-13. They include three modules for assessing QOL, symptoms and health perception. Nine QOL dimensions were identified: physical functioning, energy/well-being, emotions, social limitations, role, embarrassment, body image, eating disturbances and treatment burden. Items were derived from 33 interviews with patients and parents. Item reduction and assessment of internal consistency, convergent and discriminant validity were based on a large cross-sectional survey among 393 patients and parents. A second study was conducted among 124 patients and 85 parents to test reproducibility and responsiveness, confirm the subscale structure and assess scalar properties using Rasch analysis. All psychometric properties were successfully demonstrated and both the CFQ 14+ and the CFQ Child P French questionnaires are now well validated. German and Spanish validated adaptations are available, an English validation is in progress., Conclusion: The CFQ 14+ and CFQ Child P are well validated, multilingual measures which allow QoL assessment in children, teenagers and adults with CF.

A drug's lifetime, whether it is short or long, may go through fantastic new developments. Such is the case with beta-blockers, some of which have long been prescribed in heart failure before having made the definite proof of their efficacy, provided they are used carefully regarding the Good Product Use. On the other hand, the development of mibefradil, a calcic antagonist prescribed in the treatment of hypertension and angina pectoris, was stopped abruptly a few weeks before its launching because of the occurrence of serious side effects in patients suffering from heart failure. These examples, which are taken amongst others, clearly show the difficulties encountered by pharmaceutical companies that are concerned in putting forward innovative, efficacious, and ... secure drugs.

Introduction: The recommendations for prescription and dispensing of Roaccutane (isotretinoid) were strengthened in 1997 in order to reduce the number of pregnancies exposed to Roaccutane. The aim of this study was to evaluate the incidence of exposed pregnancies since this time and the compliance with the new recommendations., Material and Methods: All pregnancies exposed to Roaccutane reported to French Regional Drug Monitoring Centers, to Laboratoire Roche or to the Information Center for Teratogenic Agents since the publication of these recommendations for prescription were studied (March 1997-December 1998). In addition, compliance with the new recommendations was evaluated by sampling 169 drug prescriptions dispensed at 105 pharmacies in France., Results: Thirty-seven pregnancies were exposed to Roaccutane during the risk period because of failure of contraceptive methods (28 p. 100), contraception incorrectly followed (52 p. 100) or not prescribed (20 p. 100). The incidence of pregnancies exposed to Roaccutane during the risk period evaluated at 0.6/1,000 women of child-bearing age [0.4-0.8] is very close to the incidence reported in the earlier study which prompted the new recommendations. Thirty-three percent of the 169 prescriptions studied did not carry all the legal warnings. Roaccutane was correctly prescribed for only 18 p. 100 of women, i.e. with a contraceptive method as recommended by the French Drugs Monitoring Agency and with full, correct information. Although the most important recommendations had been followed, 12 p. 100 of women were treated with Roaccutane without contraception and 16 p. 100 received a contraceptive method not recommended by the French Drugs Monitoring Agency (in particular Diane)., Discussion: The provision of information must be further improved by enforcing the modalities of prescription and dispensing of Roaccutane. However, it appears that there is no way of completely avoiding patient-related failure.

A therapeutic strategy is a hierarchical set of appropriate measures to provide an answer to a pathological state. A drug is a part of this set (together with the diagnosis, the environment and the other medicinal interventions or not). A new drug's place in a therapeutic strategy can be evaluated according to one or several referential(s) when it (or they) exist, referentials which express the state of knowledge before launch of the new drug. The drug's profile (indication or contraindication, etc.), at the point when the marketing authorization is given, is purely theoretical. One must evaluate the real place of the drug under its real conditions of use (pragmatic trials, observable surveys). A new drugs' place in a therapeutic strategy can only be evaluated in the course of time unless a therapeutic revolution occurs.

Objective: To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment., Methods: In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14., Results: Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group., Conclusions: In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.

This multicenter, noncomparative, nonrandomized study evaluated the clinical efficacy and safety of ceftriaxone for treating acute otitis media in children following clinical failure of oral antibiotic therapy. Middle-ear fluid samples were collected on day 0 and on day 3, 4, or 5 (day 3 to 5) and were used to test whether ceftriaxone therapy can eradicate Streptococcus pneumoniae isolates with increased resistance to penicillin (MIC >/= 1 mg/liter). At the first visit, on day 0, middle-ear fluid was sampled for bacteriological testing by tympanocentesis or otorrhea pus suction. Patients were administered 50 mg of ceftriaxone/kg of body weight/day, injected intramuscularly once daily, for 3 days. A second sample was collected by tympanocentesis if a pneumococcus isolate for which the MIC of penicillin was >/=1 mg/liter was detected in the day-0 sample and if the middle-ear effusion persisted on day 3 to 5. This second sample was tested for bacterial eradication. One hundred eighty-six children aged 5 months to 5 years, 10 months, with acute otitis media clinical failure were enrolled and treated in this trial. On day 10 to 12, 145 (83.8%) of the 173 patients evaluable for clinical efficacy were clinically cured. Of the 59 patients infected by pneumococci, 36 had isolates for which the MICs of penicillin were >/=1 mg/liter. Of those patients, on day 10 to 12, 32 (88.9%) were clinically cured. Middle-ear fluid samples collected by day 3 to 5 following the onset of treatment with ceftriaxone were sterile for 24 of the 27 (88.9%) patients who were infected as of day 0 by pneumococci for which the MICs of penicillin were >/=1 mg/liter and who were evaluable for bacteriological eradication. On day 10 to 12, 81.4% of S. pneumoniae-infected children and 87.5% of Haemophilus influenzae-infected children were clinically cured. No discontinuation of treatment due to adverse events, particularly due to local reactions at the injection site, were reported. Only 11 adverse events which had doubtful, probable, or possible links with the study treatment were recorded. Both the bacteriologically assessed eradication of pneumococci for which the MICs of penicillin were >/=1 mg/liter and the clinical cure rates demonstrate that ceftriaxone is of value in the management of acute otitis media unresponsive to previous oral antibiotic therapy.

Objectives: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure., Methods: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid., Results: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14., Conclusions: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.

Background: The Epidemiologic Registry of Cystic Fibrosis (ERCF) is an international registry, sponsored by Roche Laboratories, collecting data about CF patients in Europe. The aim of the our study is to compare the French data with the European data collected during the year 1995., Results: By December 31st 1995, 8,831 patients have been enrolled in Europe, including 1,457 patients in France. French CF patients are younger (mean age = 12.6 years) than European CF patients (mean age = 14.6 years). Genotype is better characterised in France (89 vs 75% for European patients), but only 49% of CF patients are homozygote for the DF508 deletion in France versus 77% in Denmark. Two clinical features of French CF patients are interesting: 1) presence of Staphylococcus aureus and Haemophilus influenzae (52%) is more frequent in France than in Europe (65 vs 48% and 52 vs 29%, respectively), 2) lung function tests (forced vital capacity [FVC]), forced expiratory volume per second [FEV1] are worse in France (P < 0.001) particularly in the older patients (> 18 years): 39% of these patients in France have a FEV1 < 40% of predicted value compared to only 29% in Europe. Similarly there are fewer patients in this age group in France (22 vs 31% in Europe) having a FVC > 90% of the predicted value in France. With regard to the treatment, three differences emerge: 1) dornase alfa is more used in France (55 vs only 34% in Europe); 2) use of prophylactic inhaled and oral antibiotics is less common in France than in all age groups; 3) the use of inhaled corticosteroids and bronchodilators is also less common in France despite the same incidence of asthma-like symptoms. Finally we notice that the mean age at death in 1995 is 18.2 years (+/- 2.38) in France and 20.6 years (+/- 0.85) in Europe., Conclusion: These results are preliminary because 1995 is the first year for ERCF in France and a low percentage of French CF patients are included for this year. Therefore they must be interpreted with caution. Nevertheless, we can hypothesise about a relationship between these results and a less aggressive treatment regimen. The impact of dornase alfa use on prognosis seems interesting to analyse in future years.

Background: Despite prominent warnings, pregnancies continue to be reported in women exposed to isotretinoin., Patients and Methods: We report results of the analysis of 318 questions asked to pharacovigilance structures in France from 1987 to 1995 because of an exposition to isotretinoin during the risk period and of a prospective inquiry concerning isotretinoin prescription in women conducted among pharmacists., Results: These 318 pregnancies began during the month after Roaccutane withdrawal (n = 104, 33 p. 100), during Roaccutane treatment (n = 163, 51 p. 100) or before Roaccutane treatment (n = 51, 16 p. 100). Of the 267 women with pregnancies conceived during treatment with isotretinoin (n = 104) or during the month after its discontinuation (n = 163), contraception was not prescribed in 28 (15 p. 100) or prescribed but with poor compliance in 109 (60 p. 100). Pregnancy was terminated voluntarily in 199 women (81 p. 100). In the 173 women who were interviewed in pharmacies, 49 (28 p. 100) did not use contraception and among them contraception was prescribed in only 59 p. 100. Only 14 p. 100 had received full information about isotretinoin and pregnancy. The teratogenic effects of isotretinoin were known by 98 p. 100 of the women and the need of contraception during treatment and for one month after discontinuation by 70 p. 100., Discussion: Insufficient compliance with warnings is the main reason for pregnancies in women receiving isotretinoin therapy. A pregnancy prevention program is needed before prescription to ensure comprehension and to obtain informed consent of patients.

Objective: We compared efficacy and impact on the comfort of ibuprofen (7.5 mg/kg per dose), aspirin (10 mg/kg/dose) and paracetamol (10 mg/kg per dose) on children with fever aged 6-24 months in an open, randomised study with three parallel groups., Methods: The main criterion for efficacy was area under the curve (AUC) of percentage temperature reduction. Comfort was assessed on scores depending on general behaviour and degree of relief. General behaviour was assessed on a verbal scale and on a visual analogue scale (VAS) and the degree of relief was assessed in relation to baseline on a verbal scale., Results: The efficacy of ibuprofen was better than that of aspirin or paracetamol. In spite of more adverse events, the comfort scores were significantly in favour of ibuprofen 6 h after the first dose of treatment.

The objective of this study was to evaluate and compare the cost and effects on quality of life [using quality-adjusted life years (QALYs)] of 2 treatments for sciatica secondary to lumbar disc herniation: chemonucleolysis and surgical discectomy. The design involved a combination of decision analysis and Rosser index, with assessment of probabilities from long term clinical series. Utility was based on patients' subjective assessment using a simplified self-administered Health Measurement Questionnaire (HMQ). 146 patients from 7 hospitals were enrolled, 2 to 3 months after chemonucleolysis or surgery. The end-points used were cost and QALYs for each intervention, every year for years 1 to 7. At the time of analysis (1990), the total cost of surgical discectomy was FF15,400, compared with FF8000 for chemonucleolysis. After 1 year, and including the costs of reoperation for failure and relapse and long term medical costs for the non-reoperated unsatisfactory results, discectomy costs were almost 40% higher than those of chemonucleolysis. Ratios remain unchanged after 7 years. QALY results reveal an additional benefit of 52 days of good health associated with chemonucleolysis.

A double-blind, randomised, parallel group study has been done comparing the efficacy and tolerability of 7.5 mg/kg ibuprofen syrup (n = 77) and 10 mg.kg-1 acetaminophen syrup (n = 77) in 154 children (6 months to 5 years) with fever (> or = 38 degrees C) associated with infectious diseases and treated with antibiotic therapy. The area under the percentage reduction in temperature curve captured the net effect of each drug and provided the best estimate for comparison of efficacy during a defined period. Temperature evolution over time was not significantly different between the two groups. Nevertheless, the temperature reduction over the first 4 h of treatment (H0-H4) was significantly higher after ibuprofen (60%) than acetaminophen (45%). Both ibuprofen and acetaminophen were well tolerated. In conclusion, significant antipyretic activity, good tolerability and its availability as a syrup make ibuprofen an effective means of fever control in children.

A multicentre, randomised, double-blind, double-dummy, parallel-group study in outpatients with rheumatoid arthritis compared the efficacy and safety of flurbiprofen 200 mg and ketoprofen 200 mg, both in sustained-release form. One hundred and sixteen patients aged 18 to 75 years were randomised to receive either one capsule of flurbiprofen sustained-release 200 mg (n = 60) or one tablet of ketoprofen sustained-release 200 mg (n = 56). Both drugs were taken once daily in the evening for 28 days. Patients were assessed at entry and after two and four weeks. Overall efficacy as evaluated on a four-point scale by the investigator and patient, and overall spontaneous pain as evaluated by the patient showed significant improvements in both treatment groups with a trend favouring greater benefit with flurbiprofen. Adverse events were recorded in 14 patients receiving flurbiprofen and 22 patients receiving ketoprofen. Neither the incidence nor the type of adverse events were significantly different in the two groups. Withdrawal rates for adverse events were very similar with both drugs. In conclusion, flurbiprofen sustained-release 200 mg is as effective as ketoprofen sustained-release 200 mg in the treatment of symptoms of rheumatoid arthritis, and exhibits a comparable safety profile.