Améliorer la compréhension et la gestion des conflits d’intérêts des experts conseillant la prise de décisions en santé publique

Étude de cas / Case studyAu Québec, au Canada et ailleurs dans le monde, des comités consultatifs d’experts conseillent et orientent les décideurs gouvernementaux dans le choix de nouveaux médicaments, de vaccins à utiliser ou encore d’interventions à mettre en place. Parallèlement, ces experts bénéficient d’un appui de plus en plus important d’entreprises privées pour réaliser leurs recherches ou en diffuser les résultats. Cette situation les met à risque de conflits d’intérêts et peut, éventuellement, miner la confiance de la population envers la prise de décision publique. Cette étude de cas suscite des réflexions pertinentes quant à ce qui constitue une gestion saine et optimale des situations de conflits d’intérêts par les membres experts et les organisations dans lesquelles ils ont un rôle-conseil.In Québec, in Canada and elsewhere in the world, expert advisory committees advise and guide government decision-makers in the choice of new drugs, vaccines to be used or interventions to be put in place. In parallel, these experts are receiving increasing support from private companies to conduct their research or to disseminate the results of their research. Such situations place them at risk of conflicts of interest and may eventually undermine confidence in public decision-making. This case study stimulates reflection into what constitutes sound and optimal management of conflict of interest situations by expert members and the organizations in which they have an advising role

Portrait of blood-derived extracellular vesicles in patients with Parkinson's disease.

The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EV were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD

Cartographie des mesures de soutien à la santé mentale des étudiant.es et des employé.es de l’UQAC

Cartographie des mesures de soutien à la santé mentale des étudiant.es et des employé.es de l’UQA

Santé mentale et population universitaire : un laboratoire-vivant au service de la communauté : rapport de recherche

Cette étude a trois objectifs : 1) Identifier les principaux enjeux de santé des étudiant·es et des employé·es de l’UQAC en contexte pandémique, 2) Répertorier l’ensemble des mesures de soutien à la santé mises à la disposition des étudiant·es et des employé·es de l’UQAC, et 3) Identifier de nouvelles solutions à mettre en place afin de pallier les manques et de soutenir les étudiant·es et les employé·es de l’UQAC

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Decriminalizing Payment of Gamete Donors and Surrogates in Canada

On 29 May 2018, the Liberal MP Anthony Housefather tabled Bill C-404 titled An Act to amend the Assisted Human Reproduction Act which seeks to decriminalize the payment of gamete donors and surrogates across Canada. Although Prime Minister Justin Trudeau indicated the importance of having a societal debate on the subject, the bill was read only once by the House of Commons before it died on the Order Paper. Bill C-404 aimed to increase the number of Canadian gamete donors and surrogates to fulfill Canada's domestic needs, which are purportedly not being met because of a lack of economic incentives on the supply side and the existence of a grey market that deters some Canadians in acting as donors or surrogates and causes intending parents to fear being criminally sanctioned if the reimbursement they pay is deemed unrelated or unreasonable. While Bill C-404 has not been adopted by Parliament, this paper seeks to analyze the policy tensions at the heart of the decriminalization of payment of donors and surrogates—tensions that may well resurface in the future. As long as the alleged shortage of donors and surrogates persists, stakeholders are likely to continue to advocate for legislative change.  Le 29 mai 2018, le député libéral Anthony Housefather a déposé le projet de loi C-404 intitulé Loi modifiant la Loi sur la procréation assistée, qui vise à décriminaliser le paiement des donneurs de gamètes et des mères porteuses au Canada. Bien que le premier ministre Justin Trudeau ait souligné l'importance d'avoir un débat de société sur le sujet, le projet de loi n'a été lu qu'une seule fois par la Chambre des communes avant de mourir au feuilleton. Le projet de loi C-404 visait à augmenter le nombre de donneurs de gamètes et de mères porteuses pour répondre aux besoins intérieurs du Canada qui ne seraient pas satisfaits en raison du manque d'incitatifs économiques et de l'existence d'un marché gris qui dissuade certains Canadiens d'agir comme donneurs ou mères porteuses et qui fait en sorte que les parents craignent de possibles sanctions criminelles si le remboursement qu'ils offrent est jugé non-relié ou déraisonnable. Bien que le projet de loi C-404 n'ait pas été adopté par le Parlement, le présent document cherche à analyser les tensions politiques qui sont au coeur de la décriminalisation de la rémunération des donneurs et des mères porteuses—tensions qui pourraient bien réapparaître dans l'avenir, car la pénurie alléguée de donneurs et de mères porteuses est susceptible de persister et il est probable que les intervenants continueront à plaider pour un changement législatif

Améliorer la compréhension et la gestion des conflits d’intérêts des experts conseillant la prise de décisions en santé publique

In Québec, in Canada and elsewhere in the world, expert advisory committees advise and guide government decision-makers in the choice of new drugs, vaccines to be used or interventions to be put in place. In parallel, these experts are receiving increasing support from private companies to conduct their research or to disseminate the results of their research. Such situations place them at risk of conflicts of interest and may eventually undermine confidence in public decision-making. This case study stimulates reflection into what constitutes sound and optimal management of conflict of interest situations by expert members and the organizations in which they have an advising role

Experts sous influence? Quand la non-divulgation des conflits d’intérêts met à risque la confiance du public

L’érosion actuelle de la confiance du public envers les campagnes de vaccination et les décisions de politiques publiques qui y sont associées, aggravée par des scandales comme ceux relatifs à la pandémie H1N1 et l’utilisation du Tamiflu™, risque de diminuer de façon significative l’efficacité de ces interventions importantes pour la santé publique. Un manque de confiance de la population envers les acteurs de santé publique peut conduire à une méfiance accrue face aux interventions, pouvant ainsi compromettre l’atteinte des objectifs recherchés par une intervention spécifique et, conséquemment, avoir un impact important sur les bénéfices attendus pour la population visée par cette intervention. Dans la production des avis d’experts, les membres des comités consultatifs d’experts en immunisation (CCEI) peuvent avoir une influence importante sur la prise de décision publique, notamment, sur la sélection par les décideurs de santé publique de vaccins en particulier et la façon dont les campagnes de vaccination seront déployées. En contrepartie de cette influence sur les décisions publiques, une indépendance et une transparence sont attendues de leur part puisque des mécanismes de divulgation et de gestion de conflits d’intérêts (CI) imparfaits peuvent affecter négativement la confiance du public à l’égard de telles décisions. Il apparaît donc important de s’assurer que des mécanismes de gestion des CI, transparents et robustes, existent pour ces comités. Dans cette étude, les avis ou rapports d’évaluation de la pertinence de la vaccination préparés par un CCEI au Québec ont été examinés pour quatre types de maladies évitables par la vaccination (infections invasives à méningocoques et à pneumocoques, coqueluche et virus du papillome humain). Le but était de : 1) identifier les CI divulgués par les membres du CCEI dans leurs rapports comparativement à ceux déclarés dans leurs publications scientifiques pour ces mêmes infections ; 2) analyser la nature des CI (réel, potentiel, apparent, personnel, financier, institutionnel, etc.) et l’impact potentiel (risque) sur la prise de décision impartiale et sur la confiance du public ; et 3) évaluer les mécanismes de gestion de CI actuellement utilisés par ce CCEI. Les résultats de cette étude montrent que très peu de rapports du CCEI contiennent une section sur les CI par rapport à la pléthore divulguée dans les publications scientifiques publiées par les membres du CCEI. De plus, les CI divulgués dans les rapports fréquemment ne correspondent pas à ceux décrits dans les publications scientifiques. Il serait donc important d’introduire des mesures visant à accroître la transparence des experts en immunisation et d’améliorer les mécanismes de divulgation et de gestion des CI afin de veiller à ce que la confiance du public envers les décideurs en santé publique soit maintenue et améliorée