[The Jardé law: What does change]. / La loi Jardé : ce qui change.

The Jardé law has been voted in 2012 but was only enforced in November 2016, after the publication of its decree. Introduction of non-interventional researches in the scope of the "researches involving human beings" and random allocation of ethics committees are the main novelties of the new law. Global consent, which authorizes future researches on existing data without informing the study participant, has also been introduced. Submission of collections of biological samples and genetic studies on existing samples have been simplified. CNIL has revised the rules of data protection ("Reference Methodologies").

French Jardé's law and European regulation on drug trials: Harmonization and implementation of new rules.

Jardé's law, concerning research studies in humans, was enacted in March 2012 but did not come into force until November 2016. This delay is largely explained by the adoption of a European regulation on clinical trials on medicinal products that will probably not be applicable until October 2018. In addition to covering the respective areas of the French and European legislation, the round table provided an opportunity to discuss the principal measures that will apply to future research, particularly those concerning the operational procedures of the ethics committees and the national committee for research in humans, as well as measures relating to the management of serious adverse effects, more specifically in phase I studies in subjects not presenting with any disorder. This round table also enabled the formulation of recommendations to better anticipate the practical difficulties that the regulatory changes might engender. Finally, we highlight the numerous challenges in terms of training that these important regulatory changes impose and the absolute necessity to best adapt the restrictions to those that are planned in numerous other European countries so that France remains competitive in terms of clinical research and so that French patients may continue to benefit rapidly from the most innovative treatments.

The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency.

How can the quality of medical data in pharmacovigilance, pharmacoepidemiology and clinical studies be guaranteed?

The development of medicinal products is subject to quality standards aimed at guaranteeing that database contents accurately reflect the source documents. Paradoxically, these standards hardly address the quality of the source data itself. The objective of this work was to propose recommendations to improve data quality in three fields (pharmacovigilance, pharmacoepidemiology and clinical studies). The analysis was focused on the data and on the critical stages presenting critical quality problems, for which the current guidelines are insufficiently detailed, unsuitable and/or poorly applied. Finally, recommendations have been proposed, mainly focused on the origin of the data and its transcription.

Decreasing the adverse effects of endotracheal suctioning during mechanical ventilation by changing practice.

BACKGROUND: Little is known about the incidence of and risk factors for adverse effects from endotracheal suctioning. We studied the incidence and risk factors, and evaluated the effect of suctioning practice guidelines. METHODS: During a 3-month period, in 79 mechanically ventilated subjects, we recorded the adverse effects in 4,506 suctioning procedures. Then practice guidelines were implemented, and 1 year later, during another 3-month period, in 68 subjects, we recorded the adverse effects in 4,994 suctioning procedures. RESULTS: In the first period, adverse effects occurred frequently: oxygen desaturation in 46.8% of subjects and 6.5% of suctionings, hemorrhagic secretions in 31.6% of subjects and 4% of suctionings, blood pressure change in 24.1% of subjects and 1.6% of suctionings, and heart rate change in 10.1% of subjects and 1.1% of suctionings. After guidelines implementation, all complications, both separately and all together, were reduced. The incidence of all complications together decreased from 59.5% to 42.6% of subjects, and from 12.4% to 4.9% of procedures (both P < .05). PEEP > 5 cm H2O was an independent risk factor for oxygen desaturation. Receiving > 6 suctionings per day was a risk factor for desaturation and hemorrhagic secretions. The use of guidelines was independently associated with fewer complications. CONCLUSIONS: Endotracheal suctioning frequently induces adverse effects. Technique, suctioning frequency, and higher PEEP are risk factors for complications. Their incidence can be reduced by the implementation of suctioning guidelines.

Fever control using external cooling in septic shock: a randomized controlled trial.

RATIONALE: Fever control may improve vascular tone and decrease oxygen consumption, but fever may contribute to combat infection. OBJECTIVES: To determine whether fever control by external cooling diminishes vasopressor requirements in septic shock. METHODS: In a multicenter randomized controlled trial, febrile patients with septic shock requiring vasopressors, mechanical ventilation, and sedation were allocated to external cooling (n = 101) to achieve normothermia (36.5-37°C) for 48 hours or no external cooling (n = 99). Vasopressors were tapered to maintain the same blood pressure target in the two groups. The primary endpoint was the number of patients with a 50% decrease in baseline vasopressor dose after 48 hours. MEASUREMENTS AND MAIN RESULTS: Body temperature was significantly lower in the cooling group after 2 hours of treatment (36.8 ± 0.7 vs. 38.4 ± 1.1°C; P < 0.01). A 50% vasopressor dose decrease was significantly more common with external cooling from 12 hours of treatment (54 vs. 20%; absolute difference, 34%; 95% confidence interval [95% CI], -46 to -21; P < 0.001) but not at 48 hours (72 vs. 61%; absolute difference, 11%; 95% CI, -23 to 2). Shock reversal during the intensive care unit stay was significantly more common with cooling (86 vs. 73%; absolute difference, 13%; 95% CI, 2 to 25; P = 0.021). Day-14 mortality was significantly lower in the cooling group (19 vs. 34%; absolute difference, -16%; 95% CI, -28 to -4; P = 0.013). CONCLUSIONS: In this study, fever control using external cooling was safe and decreased vasopressor requirements and early mortality in septic shock.

Evolution of requests to hasten death among patients managed by palliative care teams in France: a multicentre cross-sectional survey (DemandE).

BACKGROUND: Strongly marked ideological positions on the impact of palliative care and limited hard data plague the debate on physician-assisted death. METHODS: A national cross-sectional study on the requests to hasten death (RHD) was conducted among 789 French palliative care organisations. Data were collected for all patients with RHD encountered during year 2010. Data on patients' characteristics, medical, psychological and social context, symptoms, nature of palliative management, patient's evolution and palliative care team's interpretation of the request were obtained. FINDINGS: A majority of centres responded and 342 teams provided descriptions of 783 RHD, 476 by a patient, 258 by relatives or close friends and 49 by the nursing staff. Cancer was the most frequent pathology (72%) and 68% of the patients had entered terminal stage. Patients rarely appeared with uncontrolled pain (3.7%), but had difficulties with feeding (65%), moving (54%), excretion (49%), or were cachectic (39%); 31% were considered to be anxio-depressive; 79% did not give physical reasons for their request; 37% of RHD were maintained and 24% fluctuated despite provision of regular follow-up by a palliative care team to 83% of all cases; 68% of patients died within a month; the interpretation of RHD by the staff was a wish for relief (69%), patient's inextricable situation (44%), actual desire not to continue living (36%) or to be helped to die (30%). INTERPRETATION: The large number of described cases provides, for the first time, comprehensive hard data on the evolution of RHDs in a country that has not legalised euthanasia. Whatever the way RHD are expressed, they are frequently maintained despite adequate palliative care with suitable control of pain and psychological support by specialists.