Practical Guidelines for Standardised Resolution of Important Protocol Deviations in Clinical Trials Conducted in Sub-Saharan Africa.

A clinical trial is any research on human subjects that involves an investigational medicinal product or device. Investigational medicinal products include unlicensed drugs or drugs used outside the product license (e.g. for a new indication) (ICH-GCP). As per the internationally accepted ICH-GCP guidelines, clinical trials should be conducted strictly per the approved protocol. However, during the lifecycle of a trial, protocol deviations may occur. Under ICH efficacy guidelines, protocol deviations are divided into non-important (minor) or important (major), and the latter can jeopardise the participant's rights, safety or the quality of data generated by the study. Existing guidelines on protocol deviation management do not detail or standardise actions to be taken for participants, investigational products, data or samples as part of a holistic management of important protocol deviations. Herein, we propose guidelines to address the current literature gap and promote the standardisation of actions to address important protocol deviations in clinical trials. The advised actions should complement the existing local institutional review board and national regulatory authority requirements.

Doxycycline vs Hydroxychloroquine + Azithromycin in the Management of COVID-19 Patients: An Open-Label Randomized Clinical Trial in Sub-Saharan Africa (DOXYCOV).

Objective We aimed to compare the safety and efficacy of a doxycycline-based regimen against Cameroon National Standard Guidelines (hydroxychloroquine plus azithromycin) for the treatment of mild symptomatic COVID-19. Methods We conducted an open-label, randomized, non-inferiority trial in Cameroon comparing doxycycline 100 mg, twice daily for seven days versus hydroxychloroquine 400 mg daily for five days and azithromycin 500 mg at day 1 and 250 mg from day 2 through 5 in mild COVID-19 patients. Clinical recovery, biological parameters, and adverse events were assessed. The primary outcome was the proportion of clinical recovery on days 3, 10, and 30. Non-inferiority was determined by the clinical recovery rate between protocols with a 20-percentage points margin. Results One hundred and ninety-four participants underwent randomization and were treated either with doxycycline (n = 97) or hydroxychloroquine-azithromycin (n = 97). On day 3, 74/92 (80.4%) participants on doxycycline versus 77/95 (81.1%) on hydroxychloroquine-azithromycin-based protocols were asymptomatic (p = 0.91). On day 10, 88/92 (95.7%) participants on doxycycline versus 93/95 (97.9%) on hydroxychloroquine-azithromycin were asymptomatic (p = 0.44). On day 30, all participants were asymptomatic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) polymerase chain reaction (PCR) test was negative on day 10 in 60/92 (65.2%) participants who were assigned to doxycycline and in 63/95 (66.3%) participants who were assigned to hydroxychloroquine-azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation. Conclusion Doxycycline 100 mg twice daily for seven days proved to be safe and non-inferior in terms of efficacy when compared to hydroxychloroquine-azithromycin for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19 and achieving virological suppression.

Evidence for an enhanced HIV/AIDS policy and care in Cameroon: proceedings of the second Cameroon HIV Research Forum (CAM-HERO) 2021.

To attain the HIV 95-95-95 goals by 2030 in Cameroon, high quality research to inform policy and patient care is of utmost importance. In the context of limited workforce and resources, collaborations, sharing of locally-adapted strategies and other field experience, leveraging on existing and innovative platforms would facilitate a coordinated and optimal AIDS response at country level. The second edition of the Cameroon HIV Research Forum (CAM-HERO) conference took place both physically and virtually on November 18 and 19, 2021 in Kribi, on the theme "Research for Policy and Care". This scientific event brought together Cameroonian HIV/AIDS researchers, experienced clinicians and regulatory authorities to foster i) the dissemination of research findings and facilitate translation into policy, ii) operational research collaboration, iii) identification of new research areas, and iv) capacity building. To achieve the set objectives during this event, a consensus on research priorities for accelerating the achievement of three 95 HIV goals in Cameroon were summarized; meeting sessions included 31 abstract presentations, 13 discussions, and presentations on various aspects of HIV research including ethics, administrative procedures and needs for capacity building; training of young scientists on guidelines for research proposal development toward ethical clearance was done; and a platform for discussion between researchers and regulatory authorities was conducted around the design and setting-up of a national HIV/AIDS research agenda. CAM-HERO 2021 brought together HIV researchers, experts and junior scientists around major programmatic challenges, evidence to translate into practice, research priorities on HIV/AIDS. Collaborations were reinforced, capacities were strengthened, and footprints were established towards a consensus on a national HIV/AIDS research agenda.

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO).

INTRODUCTION: the Treat-All remains the globally endorsed approach to attain the 95-95-95 targets and end the AIDS pandemic by 2030, but requires some country-level contextualization. In Cameroon, the specific research agenda to inform strategies for improving HIV policy was yet to be defined. METHODS: under the patronage of the Cameroon Ministry of health, researchers, policy makers, implementing partners, and clinicians from 13 institutions, used the Delphi method to arrive at a consensus of HIV research priorities. The process had five steps: 1) independent literature scan by 5 working groups; 2) review of the initial priority list; 3) appraisal of priorities list in a larger group; 4) refinement and consolidation by a consensus group; 5) rating of top research priorities. RESULTS: five research priorities and corresponding research approaches, resulted from the process. These include: 1) effectiveness, safety and active toxicity monitoring of new and old antiretrovirals; 2) outcomes of Antiretroviral Therapy (ART) with focus in children and adolescents; 3) impact of HIV and ART on aging and major chronic diseases; 4) ART dispensation models and impact on adherence and retention; 5) evaluations of HIV treatment and prevention programs. CONCLUSION: the research priorities resulted from a consensus amongst a multidisciplinary team and were based on current data about the pandemic and science to prevent, treat, and ultimately cure HIV. These priorities highlighted critical areas of investigation with potential relevance for the country, funders, and regulatory bodies.

Outcomes of the first meeting of the CAMEROON HIV RESEARCH FORUM (CAM-HERO).

Research is a vital component for the development of any country. In Cameroon, HIV Operational research is rapidly growing, however, it faces some intractable problems which can only be solved through an urgent, strategic, efficient, and collaborative approach involving key stakeholders. The Kribi meeting (09 and 10th December 2020) brought together under the auspices of the Ministry of Public Health leading HIV research organisations and connected HIV researchers and actors from different sectors. These actors disseminated and discussed recent research findings and worked out mechanisms to advance HIV research development, developed new ideas and identified priority research areas, with emphasis on translational research. The official launching and consolidation of Cam-HERO was a critical step and it is hoped that these synergistic efforts will catalyse attainment of the 95-95-95 goals in Cameroon.