Implementing adaptive platform trials

This topic aims at supporting activities that are contributing to one or several of the expected impacts for this call. To that end, proposals under this topic should aim for delivering results that are contributing to all the following expected outcomes:

• More clinicians and researchers in sub-Saharan Africa have the capacity to design, implement and maintain large-scale, multi-centre and multi-country adaptive platform trials allowing the simultaneous evaluation of multiple interventions in an adaptive manner;
• A number of large-scale, multi-centre and multi-country adaptive platform trials, investigating treatments and/or treatment regimens for infectious diseases are implemented in sub-Saharan Africa, having the operational capability to rapidly include treatment approaches for infectious diseases outbreaks with epidemic or pandemic potential;
• Health care providers and professionals in sub-Saharan Africa have a better understanding on how to treat and reduce the burden of infectious diseases within the scope of the GH EDCTP3 programme in this call topic;
• Trial sites across multiple institutions and countries belong to a coordinated network of clinical sites and facilities such as research laboratories with the capacity to deliver efficiently robust clinical evidence derived from a diverse population, through harmonized research methods, data collection and sharing and joint analysis;
• More clinical investigators and researchers at the earlier stages of their career (e.g. Master’s, PhD candidates, or post-doctoral level), including increasing proportions of women scientists, are able to develop a scientific career in sub-Saharan Africa and establish themselves as scientific leaders in sub-Saharan Africa.

During the COVID-19 pandemic the research community has seen the emergence and success of large-scale, multi-country adaptive platform trials to evaluate therapeutics for COVID-19. Adaptive platform trials have the ability to evaluate simultaneously multiple interventions in one trial answering multiple questions based on a master protocol^[1]. The adaptive design of the trial provides the flexibility for promising new therapies to enter clinical evaluation and for poor-performing ones to discontinue based on interim evaluations, paving a pathway for efficient clinical trial research. Adaptive platform trials help to establish an efficient research ecosystem that can build clinical trial capacity for long-term sustainability in a coordinated and collaborative manner across institutions in different countries.

The COVID-19 pandemic has shown a lack of COVID-19-related large-scale clinical trials in sub-Saharan Africa, while this region could greatly benefit from more resource-efficient clinical trials that are investigating novel treatments for existing infectious diseases and that are able to react to future threats. Implementation of adaptive platform trials in sub-Saharan Africa has the potential to improve the identification of safe and efficacious interventions and save resources that are particularly scarce in this region of the world. In addition, the conduct of adaptive platform trials with the in-built operational ability to rapidly implement clinical evaluation of treatment options for when an epidemic-prone pathogen strikes, is key to being prepared for infectious disease epidemics or pandemics.

This topic aims to support the implementation of adaptive platform trials for the evaluation of candidate treatments for infectious diseases in sub-Saharan Africa. These trials should also be able to rapidly evaluate treatments in response to an emerging infectious disease threat.

Pathogens within the scope of this call topic are those that cause lower respiratory tract infections, emerging and re-emerging infections, neglected infectious diseases, and diarrheal diseases. Special attention should be paid to infections that lack treatment options or where treatments are inadequate. This includes for example infections that are hard to treat due to antimicrobial resistance. HIV, malaria and tuberculosis are excluded from this call topic due to previous investments in these areas.

As appropriate, using rapid multiplex platforms for diagnosis of parasitic, bacterial, fungal and/or viral infections should be considered,

The proposals should address all of the following:

• Implementation of adaptive platform trials in sub-Saharan Africa that are routinely evaluating treatment options for infectious diseases within the scope of this topic in ‘inter-epidemic’ times, while also considering in their trial design the ability to be ‘epidemic-fit’ and ready for the timely assessment of treatments in the face of an infectious diseases outbreak with epidemic or pandemic potential;
• Training on clinical trial implementation and laboratory analysis, harmonized data collection and management systems to run the adaptive platform trials and at the same time create a coordinated network of clinical trial sites and research laboratories for longer-term usability;
• Hurdles related to ethical, administrative, regulatory and logistical aspects should be addressed in order to allow smooth implementation of adaptive platform trials and avoid such barriers when the trial needs to adapt in response to an epidemic or pandemic;
• Outreach to sub-Saharan African clinical researchers and biostatisticians to build and increase the capacity for the design and implementation of further adaptive platform trials across sub–Saharan Africa;
• Promotion of close communication between clinical experts, patient communities, regulators, health care workers and policy makers to increase understanding of and trust in adaptive platform trials as an efficient design for clinical research in sub-Saharan Africa;
• Interaction with relevant national public health institutes, Africa CDC, World Health Organisation - Regional Office for Africa and/or other regional and international relevant organisations to adequately address health research systems needs in adaptive platform trial study design;
• Sex and gender aspects should be taken into account. All data should be disaggregated by sex, age and other relevant variables, such as by measures of socioeconomic status (i.e. take into account the socioeconomic gradient).

Populations for intervention development and evaluation should also include vulnerable populations which need treatment options, including children, pregnant women, people with co-infections and co-morbidities, older people, and people living in hard-to-reach communities.

Collaboration and coordination with existing adaptive platform trials in Africa and Europe, EDCTP’s Networks of Excellence and other EDCTP funded initiatives is expected, where relevant.

[1] https://www.nature.com/articles/s41573-019-0034-3.pdf