Underrepresentation of Elderly People in Randomised Controlled Trials. The Example of Trials of 4 Widely Prescribed Drugs

BACKGROUND: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions. METHODS AND FINDINGS: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based "on-treatment" population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. CONCLUSIONS: Elderly patients are poorly represented in RCTs of drugs they are likely to receive

Utilisation en France du baclofène dans l’alcoolodépendance de 2007 à 2013 : étude à partir du SNIIRAM et du PMSI

Objectif. Quantifier et décrire pour la période 2007-2013 la population débutant en France un traitement de baclofène pour alcoolodépendance. Méthodes. Utilisation du système national d’information inter-régimes de l’Assurance maladie (SNIIRAM) et du programme de médicalisation des systèmes d’information (PMSI) pour identifier la population débutant un traitement de baclofène, déterminer par algorithme le motif de prescription, définir les caractéristiques des patients et de leur traitement. Résultats. Environ 200 000 personnes ont débuté un traitement de baclofène entre 2007 et 2013, dont 52,0 % pour alcoolodépendance. En 2013, ces personnes étaient majoritairement des hommes (62,3 %), avaient en moyenne 50,1 ans, 58,9 % avaient eu un primoprescripteur généraliste, 48,8 % étaient encore sous traitement 6 mois après leur instauration et parmi eux la moitié consommaient quotidiennement au moins 57,0 mg de baclofène. Conclusion. L’utilisation du baclofène pour une alcoolodépendance a fortement augmenté depuis 2008, avec en 2013 plus de 34 000 nouveaux utilisateurs et plus de 9 000 primoprescripteurs généralistes

The Best Use of the Charlson Comorbidity Index With Electronic Health Care Database to Predict Mortality

International audienceBACKGROUND:The most used score to measure comorbidity is the Charlson index. Its application to a health care administrative database including International Classification of Diseases, 10th edition (ICD-10) codes, medical procedures, and medication required studying its properties on survival. Our objectives were to adapt the Charlson comorbidity index to the French National Health Insurance database to predict 1-year mortality of discharged patients and to compare discrimination and calibration of different versions of the Charlson index.METHODS:Our cohort included all adults discharged from a hospital stay in France in 2010 registered in the French National Health Insurance general scheme. The pathologies of the Charlson index were identified through ICD-10 codes of discharge diagnoses and long-term disease, specific medical procedures, and reimbursement of specific medications in the past 12 months before inclusion.RESULTS:We included 6,602,641 subjects at the date of their first discharge from medical, surgical, or obstetrical department in 2010. One-year survival was 94.88%, decreasing from 98.41% for Charlson index of 0-71.64% for Charlson index of ≥5. With a discrimination of 0.91 and an appropriate calibration curve, we retained the crude Cox model including the age-adjusted Charlson index as a 4-level score.CONCLUSIONS:Our study is the first to adapt the Charlson index to a large health care database including >6 million of inpatients. When mortality is the outcome, we recommended using the age-adjusted Charlson index as 4-level score to take into account comorbidities

Characteristics of randomized controlled trials investigating drugs.

†<p>Categories not mutually exclusive.</p

Funnel plots displaying (1) mean age, (2) estimated proportion of subjects aged 65 or older and (3) estimated proportion of subjects aged 75 or older plotted for each trial against the trial's sample size.

<p>(1) Mean age, (2) proportion of subjects aged 65 or older and (3) proportion of subjects aged 75 or older in clinical practice calculated from the SNIIR-AM database were plotted as horizontal lines (plain lines) with the corresponding 95% confidence interval (95% CI; dashed lines). For each medication, the plot shows how many RCTs had a proportion of older subjects below or above the 95% CI limits (0.05 probability of exceeding these limits) (i.e., RCTs with significantly lower or higher representation of elderly people as compared with the community-based “on-treatment” population). The plot allows for assessing how the proportion of elderly people varies with trial size and time. White dots represent older trials (i.e., trial reports published before 2006) and black dots represent recent trials (i.e. trial reports published in or after 2006).</p

Flow chart of the number of published reports of randomized controlled trials identified and reviewed.

<p>Flow chart of the number of published reports of randomized controlled trials identified and reviewed.</p

Published trials with a low representation of patients aged 65 and older, defined as trials including less than half of the proportion of elderly people in the treated population.

<p>Data are number (%).</p>1<p>Fisher exact test.</p