Structured Frameworks to Increase the Transparency of the Assessment of Benefits and Risks of Medicines: Current Status and Possible Future Directions.

Structured frameworks for benefit-risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit-risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions.

[Good practices of publication of clinical cases of pharmacovigilance: comments, Groupe de Travail sur les Bonnes Pratiques de Publication de Cliniques en Pharmacovigilance: commentary]. / Les bonnes pratiques de publication de cas cliniques de pharmacovigilance: commentaires. Groupe de Travail sur les Bonnes Pratiques de Publication de Cliniques en Pharmacovigilance: commentaires.

This paper introduces some comments on the complete text of Good Pharmacovigilance Publishing Practices, which forms appendix number 2 of the Good Pharmacovigilance Practices now published by the French Drug Agency, as was Good Clinical Practices. Each good practice is printed in italic and presented in a frame; the following comments are designed to facilitate its application. The technical terms that are used in this text are presented according to the glossary in Good Pharmacovigilance Practices.

Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases.

Fifteen cases of hepatitis related to a combination of amoxycillin and clavulanic acid are reported. Most patients were aged 60 years or more and there were more men than women (sex ratio 4:1). The amoxycillin-clavulanic acid had been given at doses ranging from 0.5 to 6 g/day (mean 2 g/day) for seven to 60 days (mean 18 days). In 11 cases, the first symptoms appeared one to four weeks after stopping treatment. Jaundice was observed in all patients and was frequently associated with pruritus. Serum aminotransferase activities were increased in all patients and were generally two to 10 times the upper limit of normal. Serum alkaline phosphatase activity was considerably increased, from two to seven times the upper limit of normal. Histological examination of the liver, performed in seven patients, showed centri- or panlobular cholestasis in all cases, associated with granulomatous hepatitis in one. The prognosis of amoxycillin-clavulanic acid induced hepatitis seemed to be good. None of the patients exhibited biological or clinical features of hepatic failure and the course of the disease was characterised by the resolution of jaundice within one to eight weeks and a complete recovery within four to 16 weeks. Taking into account the number of treated subjects and reported cases, we estimated the risk of developing hepatitis with this drug combination to be very low, probably below 1/100,000. Our data suggest that the risk of hepatotoxicity may be increased in elderly men given lengthy treatment. The association of hepatitis and signs of hypersensitivity may suggest an immunoallergic mechanism of hepatotoxicity in some patients.

[Amoxicillin as a 1st choice: 275 acute focal pneumopathies treated on an outpatient basis]. / Amoxicilline en première intention: 275 pneumopathies aiguës en foyer traitées en ville.

From December 1986 to January 1988, 100 General Practitioners and Pneumologists working outside hospital included in open unmatched series 275 patients who were diagnosed as having pneumonia at home. The study consisted of 53.2% men with an average age of 49.3 plus or minus 19.3. Their temperature on the first day (J1) was in 72.7% of cases greater than 38.5 degrees Centigrade. The doctors felt that the general state was good in 66.5% of the cases. Cough was present in 83.5% of cases but was dry in one out of every two. The patients received Amoxycillin in a dose of 2 grams per day orally (66.9%), or by injection (33.1%). On the third day (J3) 90% of the patients had a temperature below 38.5 degrees Centigrade. Their general state was improved in 94.6% of cases. The diagnosis of pneumonia at home was confirmed radiologically on 219 of the films available, confirming the good specificity of the clinical diagnosis of pneumonia at home. Ten patients were hospitalised. The apparent treatment of Amoxycillin was given in 247 cases (89.8% of cases). In 28 cases (10.2%) the treatment was changed by the addition or substitution of a Macrolide (15), or another antibiotic (5), and in 80 cases a change of treatment was not specified. 25 of these 28 cases were reviewed on the 14th day (J14) and no failures were observed after the change of treatment. In 247 patients in whom the treatment with Amoxycillin was followed 336 were reviewed on the 15th day and there had been four failures. Three were intolerant to the drug and there was one relapse.(ABSTRACT TRUNCATED AT 250 WORDS)