AimsClinical trials constitute the gold standard to assess the efficacy and safety of new medicines. However, because they are conducted in standardized conditions far from the real world of prescription and use, discrepancies in patient selection or treatment conditions may alter both the effectiveness and risks. On the basis of three examples, our objectives were to study the differences between the characteristics of treated populations and treatment patterns in clinical trials and in postmarketing settings and to discuss the potential consequences on actual efficacy and safety. MethodsTreated populations were compared with patients included in premarketing clinical trials. Comparisons were made on the basis of demographic characteristics and treatment patterns. ResultsWhatever the indicator and the drug studied, differences were observed: from 0.04% to 63% for tacrine, from 0% to 37% for celecoxib and from 6% to 52% for simvastatin, with possible consequences on the effectiveness and safety of the drug concerned. Our results confirm the under-representation of women and elderly patients in premarketing clinical trials, e.g. an M : F ratio of 4.6 in clinical trails of simvastatin vs 1.0 in the joint population. Moreover, the concomitant use of medicines was made extremely restrictive by the protocols of these trials while this was not the case in the postmarketing phase. This has possible consequences on the effectiveness and safety of the drug concerned. ConclusionsThese results plead for systematic ad hoc observational postmarketing studies for any novel and/or expensive medicine to assess the relevance of premarketing data.

To assess the incidence of hospital admissions related to adverse drug reactions (ADRs) in France and the frequency of preventable ADRs in France, a prospective study was conducted among a representative randomly selected sample of medical wards in public hospitals between December 2006 and June 2007; all patients admitted during a 2-week period were included. An ADR-related hospitalization case was defined as a hospital admission because of an ADR, and an independent committee reviewed and validated all potential cases. Preventability was assessed using the French ADR preventability scale. Data were extrapolated to the population of France. Among 2692 admissions, 97 were related to an ADR (incidence 3.6%, 95% confidence interval, CI [2.8-4.4]). Patients admitted for an ADR were significantly older than those admitted for other reasons (P < 0.001). A third (32.0%) of ADR-related hospitalizations were 'preventable', 16.5% 'potentially preventable'. Drug interactions accounted for 29.9% of ADR-related hospitalizations. The most frequent causes of ADR-related hospitalizations were vascular disorders (20.6%), mainly bleeding complications, central nervous system disorders (11.3%), gastrointestinal disorders, and general disorders (9.3%). Antithrombotic and antineoplastic agents were the most frequently involved (12.6% each), followed by diuretics and analgesics (9.0% each). Vitamin-K-antagonists (VKAs) were the most common drugs associated with admission. The estimated annual number of ADR-related hospitalizations in France was 143 915 (95% CI [112 063-175 766]). ADRs were a significant cause of hospital admission in 2006-2007, in particular those due to VKAs. As new oral anticoagulants (NOACs) have been marketed, more attention needs to be paid to ensure a safe use of antithrombotic agents.

Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.