Composite event-free-survival as an endpoint in oncology drug evaluation: Review and guidance perspectives from the Haute Autorité de Santé (HAS).

BACKGROUND: The use of right-censored composite endpoints, such as progression-free survival, has been questioned in haemato-oncology trials due to potential bias in estimated treatment effect. This may impact the accuracy of health technology evaluations. We hypothesized that there is heterogeneity and potential sources of bias in the reporting of composite endpoints to health technology assessment (HTA) bodies. METHODS: We reviewed the submissions for reimbursement of oncology drugs in 2021 and 2022 that used a composite endpoint in the pivotal trial, after appraisal by the French HTA body. The retrieved information included the clinical study report, protocol, and statistical analysis plan submitted by the industry. All events of the composite endpoint and all causes of censored observations were measured. The design characteristics and treatment effect estimates were recorded. FINDINGS: Seventy-six submissions were selected, including seven without a right-censored endpoint and four evaluating associations, resulting in 65 analysed records: 17 for haematological and 48 for solid tumours. Out these 65 submissions, 47 (72·3%) used a randomized controlled design, and 18 (27·7%) a non-comparative design. The most frequently used composite endpoint was progression-free survival, used in 54 (83·1%) of the submissions. Censoring was possibly informative in 51 (92·7%) cases, mostly due to the onset of new treatment (44/51, 86·3%) and/or discontinuation of follow-up (33/51, 64·7%). In contrast, 38 (58·5%) trials reported a quantification of censored observations, with only 12/51 (23·5%) quantifying the informative ones. The estimated treatment effect on the composite outcome increased with the amount of censoring, suggesting a higher benefit of the drug, but remained below that on survival with poor evidence of surrogacy (R-squared=0·23). INTERPRETATION: Clinical study reports should be improved in terms of reporting censoring, while stakeholders should be aware of this potential source of bias. At a minimum, sensitivity analysis that ignores intercurrent events should be requested.

[Hepatitis C infection: Therapeutic strategies]. / Infection par le virus de l'hépatite C : prise en charge thérapeutique.

The development of new direct acting antivirals has significantly modified strategies to treat chronic hepatitis C. Treatments were previously made of an interferon-based combination. This article aims to review the direct acting antivirals clinical data and to discuss the new regimens for the management of chronic hepatitis C. Direct acting antivirals combinations - with or without ribavirin - are the new chronic hepatitis C standard treatment regimen. These combinations often result in sustained viral response rate (>90%, including in patients with uncomplicated cirrhosis) after a 12-week treatment for most patients. The innovation could represent a new era for patients with unmet medical need (especially ineligible or non-responders to interferon and/or ribavirin patients). Further investigations are required to confirm the efficacy in specific population (complicated cirrhosis, pre- or post-transplantation, chronic renal failure, comorbidities, etc.) where clinical data are still limited. Other treatments are currently being developed and might lead to new perspectives, especially in terms of treatment duration or therapeutic simplification.

Medical and non-medical direct costs of chronic low back pain in patients consulting primary care physicians in France.

A retrospective, observational, cohort study in primary care. To determine the total direct medical and non-medical cost of chronic low back pain (LBP) in France and its associated factors. Chronic LBP affects 5-10% of the population its burden in France is unknown. Ninety-eight randomly selected general practitioners included 796 adult patients with chronic LBP between October 2001 and December 2002. Direct costs due to physician visits, investigations, medications, hospitalizations, and other medical and non-medical resource use were collected for the 6 months prior to study visit. Costs both reimbursed and not by the French health insurance system were considered. Quality of life (QoL) and disease severity were measured using Short Form (SF)-8 and Roland-Morris disability questionnaire (RMDQ), respectively. Costs were updated to represent 2007 prices. Men represented 50.6% of the 796 patients, mean age was 53 +/- 11.3 years, and the duration of LBP was more than 1 year in 80.9% of patients. The total mean cost per patient over six months was 715.6 euro (95% CI: 644.2-797.8). Of these costs, 22.9% related to care provided by physiotherapists and allied specialists, 19.5% to medications, 17.4% to hospitalizations, 9.6% to investigations, and 12.5% to physician fees. In multivariate analysis, the factors associated with the cost of chronic LBP were disease severity (RMDQ score) and age of the patients. LBP is a disease that is both common and costly.

Patterns and frequency of atypical antipsychotic prescribing in psychiatric medical centers: a cross-sectional national survey.

Studies describing atypical antipsychotics when compared with conventional antipsychotic drugs are few in France. This study aimed to describe the frequency and characteristics of atypical antipsychotic prescribing. A cross-sectional national survey was conducted from February to June 2003 in a random sample of 100 volunteer French psychiatrists practicing in public psychiatric medical centers. Each psychiatrist was asked to complete a questionnaire for patients to whom at least one antipsychotic was prescribed during the period of the survey. The characteristics of the patients treated with atypical antipsychotics were identified with a logistic regression model. A total of 1733 patients were included in the study. The main diagnoses were schizophrenia (46.1%) and other psychoses (40.8%), followed by mood disorders (10%) and other psychiatric disorders (2.5%). Among these patients, 56% had at least one prescription of an atypical antipsychotic, 42.1% at least one conventional antipsychotic with immediate action and 29.9% at least one conventional antipsychotic with delayed action. Seventy percent of patients were treated with single-drug atypical antipsychotics. Compared with conventional antipsychotics with immediate action, atypical antipsychotics were less likely to be prescribed to patients over 35 years of age [odds ratio (OR) 0.4; 95% confidence interval (CI) 0.3-0.6], with duration of illness >10 years (OR 0.5; 95% CI 0.3-0.7), and were less likely to be used with concomitant corrector agents for neurological side effects (OR 0.4; 95% CI 0.3-0.6). This study shows the important use of atypical antipsychotic drugs especially in schizophrenic patients and younger patients.