Ethics and clinical research: How can the Ethics Committees (CPPs) and Committees for Research Ethics (CER) evolve?

In line with the spirit of the Giens workshops, this article reports on the recommended evolution of the Ethics Committees (CPPs) and the Committees for Research Ethics (CER) in France. These committees play a crucial role in the ethical evaluation of clinical research projects, a process that has become more complex, particularly in view of recent legislative, regulatory and methodological developments. This reflection highlights the current challenges faced by the CPPs, including the increasing workload, the complexity of the issues to be addressed and the need for better use of their resources.

Can requests for real-world evidence by the French HTA body be planned? An exhaustive retrospective case-control study of medicinal products appraisals from 2016 to 2021.

Objectives: In France, decisions for pricing and reimbursement for medicinal products are based on appraisals performed by the National authority for health ( (HAS)). During the appraisal process, additional real-world evidence can be requested as "Post-Registration Studies" (PRS) when there are uncertainties in evidence that could be resolved by additional data collection. To facilitate PRS planning, a retrospective exploratory analysis was conducted to identify the characteristics of medicinal products associated with a PRS request.

The Multidimensional Nature of Research Ethics: Letters Issued by a French Research Ethics Committee Included Similar Proportions of Ethical and Scientific Queries.

Debate is ongoing concerning the activities and functioning of Research Ethics Committees (REC), especially a possible science-or-ethics dichotomy in research ethics review. We retrospectively analyzed 145 letters issued by a French REC over 18 months. All queries were classified in three levels: qualification (definition of the problem), category (aggregation of broader topics) and finally fields (ethical, scientific, or administrative).

Pharmacoepidemiology for oncology clinical practice: Foundations, state of the art and perspectives.

Since the early 2000s, the arrival of the so-called targeted therapies and immunotherapies have prolonged survival rates in many cancers. In parallel, post-marketing surveillance of anticancer drugs through pharmacoepidemiology has gradually developed. This paper provides (i) a detailed argumentation of the foundations for pharmacoepidemiology of anticancer drugs, (ii) an overview of pharmacoepidemiological studies currently available in this field, and (iii) some perspectives to improve pharmacoepidemiology for oncology practice.

Adverse drug reactions induced by cotrimoxazole: Still a lot of preventable harm.

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs.

Ambulatory drug changes in the elderly after hospital discharge: A cohort study.

Aim: To describe the ambulatory changes in drug prescriptions 3 months after hospital discharge among elderly patients aged 75 and over, and to identify the reasons for these changes.

Methods: A prospective cohort study was conducted on subjects, discharged between 09/2016 and 01/2017 from the Bordeaux University Hospital. Prescription forms were collected from patients' pharmacists.

Added Therapeutic Value of Medicinal Products for French and German Health Technology Assessment Organizations: A Systematic Comparison.

Objectives: Determining the price and reimbursement of a new medicine is a national competence within the Member States of the European Union that is carried out by health technology authorities and is based mainly on the added therapeutic value (ATV). The primary objective of this study was to compare the ATVs granted by the French (Haute Autorité de Santé, HAS) and the German (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWIG) authorities. The secondary objective was to analyze the reasons for the discrepancies observed.

Medicine misuse: A systematic review and proposed hierarchical terminology.

Aims: Although medicine misuse is a public health issue, it has multiple meanings in the medical literature. This study aimed to characterize, classify and identify the most appropriate definitions of medicine misuse.

Methods: A systematic review was performed in Medline, ISI Web of Science, SocINDEX, PsycInfo, PsycArticles and Psychological and Behavioral Sciences Collection, using keywords related to "misuse", "appropriateness" and "medicine" between 1 November 2008 and 25 August 2020.

Overview of French databases available for studying anticancer drugs in real-life setting.

Considering their novelty and cost, post-marketing evaluation is highly relevant for new anticancer drugs. Identify and characterize available and potentially useful databases for post-marketing evaluation of these specific drugs is necessary. A review was conducted to identify available and accessible databases to study the post-marketing evaluation of drugs in real-life care setting.

[Research ethics: French regulations and applications in radiation oncology].

French regulations about research ethics are based on the so-called Jardé law, which defines researches involving human beings. Researches involving human beings require the submission of research protocols to a committee for protection of persons with a precise list of documents to submit for a favourable opinion. This law describes different categories of researches and determines the ethical procedures to apply before setting up a research protocol.

Use of benzodiazepines non-compliant with guidelines in patients with psychiatric and non-psychiatric chronic disorders.

Objective: To quantify benzodiazepine use non-compliant with guidelines in patients with psychiatric and non-psychiatric chronic diseases and assess the risk of non-recommended use associated with these diseases.

Method: A cohort study was conducted in the French health insurance databases, including 254,488 new benzodiazepine users between 2007 and 2014. Psychiatric, cardiovascular, cancer, diabetes and inflammatory diseases were identified.

Discontinuing statins or not in the elderly? Study protocol for a randomized controlled trial.

Background: The risk/benefit ratio of using statins for primary prevention of cardiovascular (CV) events in elderly people has not been established. The main objectives of the present study are to assess the cost-effectiveness of statin cessation and to examine the non-inferiority of statin cessation in terms of mortality in patients aged 75 years and over, treated with statins for primary prevention of CV events.

Methods: The "Statins in the elderly" (SITE) study is an ongoing 3-year follow-up, open-label comparative multi-centre, randomized clinical trial that is being conducted in two parallel groups in outpatient primary care offices.

Misuse of benzodiazepines: Prevalence and impact in an inpatient population with psychiatric disorders.

Aims: Use and misuse of benzodiazepine might be very prevalent in patients with acute psychiatric symptoms, whereas they might be associated with specific adverse events in this population. The study investigated their prevalence in these patients. Secondary objectives were to identify risk factors for misuse of benzodiazepines, and its impact.

Pharmacovigilance - The next chapter.

The discovery and quantification of adverse drug reactions has long relied on the careful analysis of spontaneously reported cases. Causality assessment (imputation) was a fundamental feature of individual case report analysis. This was complemented by analysis of aggregated cases, and of disproportionality analyses in spontaneous reports databases.

Appropriateness of psychotropic drug prescriptions in the elderly: structuring tools based on data extracted from the hospital information system to understand physician practices.

Background: The appropriateness of psychotropic prescriptions in the elderly is a major quality-of-care challenge at hospital. Quality indicators have been developed to prevent inappropriate psychotropic prescriptions. We aimed to select and automatically calculate such indicators, from the Bordeaux University Hospital information system, and to analyze the appropriateness of psychotropic prescription practices, in an observational study.

Requests for post-registration studies (PRS), patients follow-up in actual practice: Changes in the role of databases.

Early market access of health products is associated with a larger number of requests for information by the health authorities. Compared with these expectations, the growing expansion of health databases represents an opportunity for responding to questions raised by the authorities. The computerised nature of the health system provides numerous sources of data, and first and foremost medical/administrative databases such as the French National Inter-Scheme Health Insurance Information System (SNIIRAM) database.

Definition of indicators of the appropriateness of oral anticoagulant prescriptions in hospitalized adults: Literature review and consensus (PACHA study).

Background: Indicators of the appropriateness of oral anticoagulant prescriptions are lacking, despite the major contribution they could make to improve quality of care.

Aim: To identify and select such indicators according to their utility and operational implementation.

Methods: A literature review was conducted to identify indicators of the appropriateness of oral anticoagulant prescriptions according to the guidelines of health authorities and European learned societies.

Development and validation of hospital information system-generated indicators of the appropriateness of oral anticoagulant prescriptions in hospitalised adults: the PACHA study protocol.

Introduction: The appropriateness of oral anticoagulant prescriptions is a major challenge to improve quality and safety of care. As indicators of the appropriateness of oral anticoagulant prescriptions are lacking, the aim of the study is to develop and validate a panel of such indicators, in hospitalised adults, from the hospital information system of two university hospitals in France.

Methods And Analysis: The study will be carried out in four steps: (1) a literature review to identify indicators of the appropriateness of oral anticoagulant prescriptions and their conditions of appropriateness; (2) a Delphi consensus method to assess the potential utility and operational implementation of the selected indicators; (3) techniques of medical data search to implement indicators from the hospital information system and; (4) a cross-sectional study to assess the ability of indicators to detect inappropriate oral anticoagulant prescriptions, performance of medical data search techniques for tracking or retrieving information and the ability of tools to be transferred into other institutions.

Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: A systematic review.

Treatment of metastatic colorectal cancer (mCRC) has been modified since the launching of targeted therapies. Colorectal cancer (CRC) is common in elderly patients; their representation in randomized controlled trials (RCTs) is thus crucial. This study aimed to evaluate and quantify the inclusion of elderly/frail patients in RCTs of targeted therapies in mCRC.