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      Towards achieving transnational research partnership equity: lessons from implementing adaptive platform trials in low- and middle-income countries

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          Abstract

          Background

          Use of adaptive clinical trials, particularly adaptive platform trials, has grown exponentially in response to the coronavirus disease (COVID-19) pandemic. Implementation of these trials in low- and middle-income countries (LMICs) has been fostered through the formation or modification of transnational research partnerships, typically between research groups from LMICs and high-income countries (HICs). While these partnerships are important to promote collaboration and overcome the structural and economic disadvantages faced by LMIC health researchers, it is critical to focus attention on the multiple dimensions of partnership equity.

          Methods

          Based on informal literature reviews and a meeting with leaders of one of the multinational COVID-19 adaptive platform trials, we describe some important considerations about research partnership equity in this context.

          Results

          We organize these considerations into eight thematic categories: 1) epistemic structures, 2) funding, 3) ethics oversight, 4) regulatory oversight, 5) leadership, 6) post-trial access to interventions, data, and specimens, 7) knowledge translation and dissemination, and 8) research capacity strengthening and maintenance. Within each category we review normative claims that support its relevance to research partnership equity followed by discussion of how adaptive platform trials highlight new dimensions, considerations, or challenges.

          Conclusion

          In aggregate, these observations provide insight into procedural and substantive equity-building measures within transnational global health research partnerships more broadly.

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          Most cited references95

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          Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

          Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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            The FAIR Guiding Principles for scientific data management and stewardship

            There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
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              Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19

              Abstract Background Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials. Methods In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality. Results The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P=0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine. Conclusions Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.)
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data CurationRole: Formal AnalysisRole: InvestigationRole: MethodologyRole: Writing – Original Draft Preparation
                Role: ConceptualizationRole: MethodologyRole: Writing – Review & Editing
                Role: ValidationRole: Writing – Review & Editing
                Role: ConceptualizationRole: ValidationRole: Writing – Review & Editing
                Role: ValidationRole: Writing – Review & Editing
                Role: ValidationRole: Writing – Review & Editing
                Role: Data CurationRole: VisualizationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Funding AcquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – Original Draft Preparation
                Journal
                Wellcome Open Res
                Wellcome Open Res
                Wellcome Open Research
                F1000 Research Limited (London, UK )
                2398-502X
                6 December 2023
                2023
                : 8
                : 120
                Affiliations
                [1 ]Berman Institute for Bioethics, Johns Hopkins University, Baltimore, MD, 21205, USA
                [2 ]Division of Infectious Diseases, Johns Hopkins Medicine, Baltimore, Maryland, 21205, USA
                [3 ]Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, Maryland, 21205, USA
                [4 ]Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, 21205, USA
                [5 ]School of Public Health, University of Zambia, Lusaka, Zambia
                [6 ]Uganda National Council for Science and Technology, Kampala, Uganda
                [7 ]Family Health International Clinical/Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia, Liberia
                [8 ]Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, 21205, USA
                [1 ]European and Developing Countries Clinical Trials Partnership, University of Stellenbosch Global Health Department, Cape Town, South Africa
                [1 ]Northumbria University, Newcastle upon Tyne, UK
                Johns Hopkins Medicine, USA
                [1 ]European and Developing Countries Clinical Trials Partnership, University of Stellenbosch Global Health Department, Cape Town, South Africa
                Johns Hopkins Medicine, USA
                [1 ]Liverpool School of Tropical Medicine, Liverpool, UK
                Johns Hopkins Medicine, USA
                Author notes

                Competing interests: Jeremy Sugarman is a member of Merck KGaA’s Ethics Advisory Panel (formerly, Bioethics Advisory Panel) and Stem Cell Research Oversight Committee; a member of IQVIA’s Ethics Advisory Panel; a member of Aspen Neurosciences Clinical Advisory Panel (and previously Scientific Advisory Board); a member of a Merck Data Monitoring Committee; and a consultant to Biogen. None of these activities are related to the material described in this paper. All other authors have no competing interests to declare.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0001-9005-9812
                https://orcid.org/0000-0001-7022-8332
                https://orcid.org/0000-0003-1187-032X
                https://orcid.org/0000-0002-4767-2512
                Article
                10.12688/wellcomeopenres.18915.2
                10714106
                38089903
                4f0ab26e-d3b1-46bf-b178-219089a3ea12
                Copyright: © 2023 Modlin C et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 November 2023
                Funding
                Funded by: Wellcome Trust
                Award ID: 221719
                Funded by: Wellcome Trust
                Award ID: 214711
                This work was supported by Wellcome [214711, <a href=https://doi.org/10.35802/214711>https://doi.org/10.35802/214711</a>, 221719, <a href=https://doi.org/10.35802/221719>https://doi.org/10.35802/221719</a>]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Articles

                international research partnership; equity; adaptive platform trials; adaptive clinical trials; public health emergencies

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