Ethical considerations of the dynamics of clinical trials in an epidemic context: Studies on COVID-19.

The COVID-19 epidemic has led to the intense mobilization of all health professionals, including those involved in research. From the very beginning, research ethics committees (RECs) have been called upon and mobilized to carry out the scientific and ethical evaluations of research projects to achieve a sound analysis of their risk/benefit balance. The aim of this article is to present an ethical reflection on the challenges and consequences of the fast-track procedure for the evaluation of COVID-19 research projects in the context of a public health emergency. Indeed, a large number of protocols of reduced rigor were hastily prepared without collaboration between researchers and in the absence of national regulation. As a result, a number of ethical dilemmas have emerged concerning the opposing needs of pragmatism imposed by the emergency context and the ethical principles that should govern the conduct of research. Moreover, the dispersion of these individual projects, aggravated by excessive media coverage of specific treatments, has resulted in a weakened impact of the research in the epidemic context. This article provides suggestions for the ethical management of ongoing and upcoming research, giving RECs the opportunity to adapt their evaluations to avoid allowing the pragmatism of the emergency context to subvert the inviolability of the epistemological and ethical principles of research on humans. This reflection may strengthen the ethical basis for the formulation of their decisions.

Is sleep apnea syndrome in the elderly a specific entity?

The prevalence of apneas is increased in the elderly. In the present paper, we briefly discuss the data on epidemiology, clinical significance, morbidity and mortality of sleep apnea in the elderly. We further try to identify possible mechanisms linking aging and sleep apnea that may explain the high prevalence found in aged patients. Structural changes in upper airway, increase in pharyngeal resistance, oscillations in upper airway resistance and sleep instability are among the main factors that may be involved. Last, we present data on 389 apneics consecutively diagnosed in our sleep laboratory, separated according to whether they were less or more than 65 years of age. In the group of elderly patients that cannot be extrapolated to a random sample of the general population, sleep apnea does not seem to be different in terms of severity of breathing disorders, sleep data and therapeutic implications. Further studies are needed to determine whether or not the associated morbidity is different in the elderly; these studies could lead to different diagnosis strategies and therapeutic approaches.

[Viewpoint on the methodology of drug trials affecting cognition of elderly patients]. / Point de vue sur la méthodologie des essais de médicaments à visée cognitive chez les sujets âgés.

Clinical trials for cognitive disorders in the elderly require specific methodological guidelines. They must take into account the psychosocial dimension of the patient and his family and must be based on serious neurobiologic knowledge. In degenerative dementias the progress of research concern genetics, molecular intercellular recognition and astrocytic cells. Biology of cognition like hippocampal long term potentiation provides good pharmacologic basis for trials. In normal brain aging several ways must be developed: aminergic systems, free radicals, excitotoxic amino-acid, nerves growth factors. Clinical trials bring informations for pharmacology and epidemiology. Cholinergic neurons are the main pharmacologic target but there are many other ones: GABA-ergic system, Tau protein, amyloid. A rigourous selection of patients allows to precise the nosology of illness responsible of cognitive disorders and to point-out early clinical signs that represent a more sensitive target. Diagnostic criteria are useful in Alzheimer's disease, memory impairment, vascular dementias and other dementias. Evaluation of stage and evolution of dementia, comorbidity, limits of age and caregiver are practical problems. The effects of drugs used to treat cognitive functions are subtle so it is necessary to detect them to choose the best tests in function of each trial. Laboratory investigations can be used to evaluate the response to drug administration. Ethical point of view is represented by the fact that old people with cognitive impairment must not be away from therapeutic progress. In this field we must consider carefully the consequences of cognitive impairment on patient judgment and consent to clinical trial. Legal problems are regulated by supranational rules and French directives of Huriet law.

[Anxiolytics and mnemonic ability of the aged subject. Apropos of a double-blind study between tiapride and lorazepam]. / Anxiolytiques et capacités mnésiques du sujet âgé. A propos d'une étude en double aveugle entre tiapride et lorazépam.

Starting from a study of memory performances while prescription in double blind of lorazepam (2 mg/day) versus tiapride (100 mg/day), during ten days, to patients over sixty years of age, the authors try to analyse the links between anxiety, anxiolysis and attention and memory capacities. Results seem to indicate that beyond anxiolysis, these products could have an independent action over memory performances. Statistical trial of results show significantly that performances decrease under lorazepam and increase under tiapride.

[Double-blind comparative study of lorazepam and tiapride effects on the memory capacities of subjects over 60 years of age]. / Etude comparative en double aveugle du lorazépam et du tiapride sur les capacités mnésiques du sujet âgé de plus de soixante ans.

The authors' purpose was to confirm their hypotheses based on their prior study of the effect of tiapride and lorazepam on memorizing capacities of patients over sixty years of age. The results of a two weeks, double-blind trial show that tiapride, in addition to its sedative action, produces disinhibition and enhances wakefulness, thereby improving memory performances in the elderly.

[Haloperidol decanoate. Results of an open-ended multicentric study in chronic psychotic states]. / Décanoate d'halopéridol. Résultats d'une étude ouverte multicentrique dans les états psychotiques chroniques.

UNLABELLED: An open multicentric study of 196 in-patients was carried out in 9 centres. After an initial stabilization (min. 15 days) with oral haloperidol, patients received haloperidol decanoate IM for at least 24 weeks (or a minimum of 9 injections). RESULTS: - esterification of haloperidol increased the duration of its efficacy (interval between 2 injections: average 4 weeks) without interfering with its therapeutic activity (global appreciation scale, BPRS at each injection and at the end of the treatment); - equivalent quantities of haloperidol injected at a time were 15 to 20 times those administered daily during the initial stabilisation period; - side-effects were not different with haloperidol decanoate as compared to those of the previous period (haloperidol).