Outpatient healthcare and clinical trials in the care pathway: Organisational and regulatory aspects and tools.

Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue. However, this type of research has specific characteristics that differentiate it from clinical research conducted in a hospital setting and requires an adaptation of its conditions of practice: in terms of organisation, the development of research in outpatient healthcare relies on the appropriation of its fundamentals by the investigators, which implies their presentation, upstream, from the initial cycle, and the participation of practitioners in training modules adapted to research in primary care, such as those already organised by several GIRCI (Groupement Inter régional de la Recherche Clinique et de l'Innovation [French Interregional Clusters for Clinical Research and Innovation]). To compensate for the fragmented nature of their location, on the model of the EMRCs (équipes mobiles de recherche clinique [mobile clinical research teams]) in oncology, mobile research teams should enable general medical practices to participate in clinical trials. This presupposes, on the one hand, the allocation of earmarked funding to ensure the sustainability of a base of dedicated personnel and, on the other hand, the impetus of a national dynamic through the setting up of a multi-organisation thematic institute for "research in primary care" associated, at the operational level, with a national scale investigation network supported by a platform of excellence. The use of digital tools and innovations (telemedicine; data collection via connected tools; e-consent; electronic signature) which make it possible to digitise and relocate all or part of the research procedures for both the participant and the investigation teams. An adaptation of the legal framework in order to bring the place of research closer to the patient and not the other way round, which means moving the equipment and investigations closer to the patient. Taking into account the acceptability of the patient, thus limiting the disruption that may be caused by his or her participation in a research protocol and motivating the practitioner by valuing his or her contribution and providing all the guarantees of scientific relevance and independence of practice. In view of the contextual analysis, positive feedback and the availability of organisational and digital support points facilitating the delocalisation and digitisation of the conduct of research activity as close as possible to the patient and his or her doctor, the round table concluded that opportunities exist today which favour the development of clinical research in general practice. It is important to seize this opportunity and make the most of it without delay.

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. These databases, although developed for other purposes, have already been used for many years with regard to post-registration studies (PRS). The use thereof will continue to increase with the recent creation of the French National Health Data System (SNDS [2016 health system reform law]). At the same time, other databases are available in France, offering an illustration of "product use under actual practice conditions" by patients and health professionals (cohorts, specific registries, data warehouses, etc.). Based on a preliminary analysis of requests for PRS, approximately two-thirds appeared to have found at least a partial response in existing databases. Using these databases has a number of disadvantages, but also numerous advantages, which are listed. In order to facilitate access and optimise their use, it seemed important to draw up recommendations aiming to facilitate these developments and guarantee the conditions for their technical validity. The recommendations drawn up notably include the need for measures aiming to promote the visibility of research conducted on databases in the field of PRS. Moreover, it seemed worthwhile to promote the interoperability of health data warehouses, to make it possible to match information originating from field studies with information originating from databases, and to develop and share algorithms aiming to identify criteria of interest (proxies). Methodological documents, such as the French National Authority for Health (HAS) recommendations on "Les études post-inscription sur les technologies de santé (médicaments, dispositifs médicaux et actes). Principes et méthodes" [Post-registration studies on health technologies (medicinal products, medical devices and procedures). Principles and methods] should be updated to incorporate these developments.

Comparison of Paliperidone Palmitate and Risperidone Long-Acting Injection in Schizophrenic Patients: Results From a Multicenter Retrospective Cohort Study in France.

PURPOSE/BACKGROUND: The study objective was to compare the impact of being treated by paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) on the length of stay on initial hospitalization, rehospitalization risk, and treatment duration in schizophrenic patients. METHODS: We conducted an observational retrospective cohort study in 43 centers in France, including schizophrenic patients who initiated a treatment by PP or RLAI during initial hospitalization. The follow-up periods started in September 2012 for the RLAI group (median follow-up duration, 233 days) and in June 2013 for the PP group (259 days). Statistical analyses were based on Cox regression models, with propensity score weighting to account for differences in patients' characteristics. FINDINGS/RESULTS: The analysis included 347 patients: 197 in the PP treatment group and 150 in the RLAI group. Compared with patients on RLAI, patients on PP were significantly more likely to have nonpsychiatric comorbidities, to have been on previous antipsychotic therapy, or to have been hospitalized for psychiatric care in the previous year. With regard to length of stay on initial hospitalization, there was no statistically significant difference between both groups (hazard ratio, 1.13 [0.97; 1.31]). Being on PP was associated with similar times to first rehospitalization compared with RLAI (hazard ratio, 0.92 [0.65; 1.30]). IMPLICATIONS/CONCLUSIONS: We observed nonsignificant differences in initial hospitalization duration and time to rehospitalization between PP and RLAI, potentially due to lack of statistical power. A trend was observed in favor of PP with regard to time to treatment discontinuation, although this result was compromised by patients who switched between RLAI and PP.

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.

Prostatic hyperplasia is highly associated with nocturia and excessive sleepiness: a cross-sectional study.

OBJECTIVES: The objective of this study is to assess the impact of nocturia on sleep in patients with lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE) (nocturia≥2). DESIGN: Cross-sectional survey. SETTING: 798 urologists and general practitioners randomly selected from the overall population of urologists and general practitioners of every French region. PARTICIPANTS: A total of 2179 LUTS/BPE men (aged 67.5±7.5 years old) were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Validated patients' self-administered questionnaires were used to assess the severity of LUTS/BPE (the International Prostate Symptom Score), sleep characteristics (sleep log) and sleep disorders (the International Classification of Sleep Disorders (ICSD-2) and the DSM-IV). Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). The volume of 24 h diuresis (1500 ml) was measured. RESULTS: Participants had on average 2.9±0.9 nocturia episodes (three or more episodes in 67%) and the International Prostate Symptom Score of 15.8±5.7; 60.9% complained of insomnia according to the ICSD-2, 7.9% of restless leg syndrome and 6.4% of obstructive sleep apnoea. 32.3% had excessive sleepiness (ESS >10) and 3.1% severe excessive sleepiness (ESS >16). Insomnia was mainly nocturnal awakenings with an average wake after sleep onset of 89±47 min. The number of episodes of nocturia per night correlated significantly with wake after sleep onset and ESS but not with total sleep time and sleep latency. CONCLUSION: Nocturia is significantly associated with sleep maintenance insomnia and sleepiness in men with BPE.

[Frequency of psychotic-like symptoms among adults consulting general practitioners]. / Fréquence des symptômes d'allure psychotique observés chez l'adulte en consultation de médecine générale.

OBJECTIVES: To assess the frequency of the most frequently observed psychotic-like symptoms in adults consulting general practitioners and to describe their principal characteristics and management. METHODS: Observational epidemiologic survey of 1200 randomly selected general practitioners, distributed throughout France. The symptoms considered were those modified from the BPRS (Brief Psychiatric Rating Scale). During the two-week survey, practitioners recorded the total number of children and adults consulting them and the number with psychotic-like symptoms. They described the characteristics and management of the first three adults with these symptoms (chronological selection). RESULTS: The mean rate of adults with psychotic-like symptoms was 4.9 +/- 8.1% (95% confidence interval: 4.4, 5.4%) during the 12 618 consultation days assessed. The mean age of these patients was 52 years, with equal numbers of men and women. At the consultation, 18.6% were disabled or on short-term sick-leave from work because of the psychiatric disorder; 35.3% of the patients had no known history of psychiatric disorders. Nearly all these patients (95.2%) had more than one psychotic-like symptom. The principal such symptoms were: "changes in behavior, presentation, or interpersonal relations" (62.0%), "bizarre behavior" (48.2%), "depression" and "anxiety" (49.7 and 42.2%), "unusual thought content" or "conceptual disorganization" (29.3 and 26.9%). Most patients received outpatient pharmaceutical management. CONCLUSION: We observed a greater frequency of psychotic-like symptoms in adults consulting general practitioners than expected.

Relationship between severity of symptoms and quality of life in 858 patients with irritable bowel syndrome.

AIMS: Heath-related quality of life (QoL) is decreased in patients with irritable bowel syndrome (IBS) but the relationship between symptom intensity of IBS and QoL remains largely unknown. The aim of this prospective survey was to investigate the relationship between intensity of IBS and changes in QoL. METHODS: Eight hundred and fifty-eight patients with IBS, according to Rome II criteria, completed a symptom questionnaire to measure intensity of IBS, and the gastrointestinal quality of life (GIQLI) questionnaire, which is a general QoL measure in patients with gastrointestinal disorders. RESULTS: 37.2% of the patients had constipation-predominant type IBS, 37.3% had diarrhea-predominant IBS and 25.4% had alternating diarrhea and constipation type symptoms. IBS was considered to be in remission or mild in 8.3% of patients; 41.3% had moderate IBS and 50.4% had severe IBS. The mean GIQLI score was 88 +/- 20. There was a significant correlation between symptom intensity and changes in QoL. Other significantly related factors were the type of bowel abnormality and gender. CONCLUSION: In IBS patients, symptom intensity and type of IBS have a negative impact on health-related QoL.