As part of a cluster of articles leading up to the 2012 World Health Report and critically reflecting on the theme of “no health without research,” Trudie Lang and Sisira Siribaddana discuss the value and challenges of doing clinical trials in developing countries.

Background: Voluntary participation of a subject in research respects a subject's rights, strengthens its ethical conduct, and is formalized by the informed consent process. Clinical trials of life-saving interventions for medical emergencies often necessitate enrolment of patients where prior written individual informed consent is impossible. Although there are regulations and guidelines on protecting subjects in emergency research, these have been criticised for being limited and unnecessarily restrictive. Across Europe and the United States stringent regulations have resulted in a substantial decline of clinical trials involving emergency interventions. Methods: We are conducting a trial of fluid resuscitation in children with hypovolaemic shock in six hospitals across three malaria-endemic African countries. The design is pragmatic as children are enrolled on clinical criteria alone and is being conducted in hospitals with facilities typical of many district hospitals across Africa. The trial aims to inform strategy for managing children with febrile illness and features of shock. In order to develop appropriate consent processes for the trial, we conducted a narrative review of current international recommendations for emergency consent. Results: Practical or specific guidance was generally sparse or confusing with few examples in the literature to direct our informed consent process. For a sub-group of children who were critically sick or where parents themselves were otherwise too distressed to consider prior written consent, we opted for a modified form of deferred consent. This included verbal assent from guardians at the point of enrolment, with full written consent obtained after stabilising the child. For children who died prior to full written consent, ethical permission was received to waiver full consent. Conclusions: In light of the controversy around guidance and regulations in this area we report how and why we have used a modified system of deferred consent in an emergency intervention trial in children. Although approved by all relevant ethics committees and operational in 3 countries in Africa, formal research is now necessary to explore the perceptions and experiences of parents, health workers, researchers and ethics committees of the modified method of deferred consent.

The imperative for improving health in the world’s poorest regions lies in research, yet there is no question that low participation, a lack of trained staff, and limited opportunities for data sharing in developing countries impede advances in medical practice and public health knowledge. Extensive studies are essential to develop new treatments and to identify better ways to manage healthcare issues. Recent rapid advances in availability and uptake of digital technologies, especially of mobile networks, have the potential to overcome several barriers to collaborative research in remote places with limited access to resources. Many research groups are already taking advantage of these technologies for data sharing and capture, and these initiatives indicate that increasing acceptance and use of digital technology could promote rapid improvements in global medical science.

Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge ( www.trialforge.org ) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency. This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants’ views on the processes in the life of a randomised trial that should be covered by Trial Forge. General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a ‘go to’ website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials. Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.

Introduction In March 2020, the WHO released a Global Research Roadmap in an effort to coordinate and accelerate the global research response to combat COVID-19 based on deliberations of 400 experts across the world. Three months on, the disease and our understanding have both evolved significantly. As we now tackle a pandemic in very different contexts and with increased knowledge, we sought to build on the work of the WHO to gain a more current and global perspective on these initial priorities. Methods We undertook a mixed methods study seeking the views of the global research community to (1) assess which of the early WHO roadmap priorities are still most pressing; (2) understand whether they are still valid in different settings, regions or countries; and (3) identify any new emerging priorities. Results Thematic analysis of the significant body of combined data shows the WHO roadmap is globally relevant; however, new important priorities have emerged, in particular, pertinent to low and lower middle-income countries (less resourced countries), where health systems are under significant competing pressures. We also found a shift from prioritising vaccine and therapeutic development towards a focus on assessing the effectiveness, risks, benefits and trust in the variety of public health interventions and measures. Our findings also provide insight into temporal nature of these research priorities, highlighting the urgency of research that can only be undertaken within the period of virus transmission, as well as other important research questions but which can be answered outside the transmission period. Both types of studies are key to help combat this pandemic but also importantly to ensure we are better prepared for the future. Conclusion We hope these findings will help guide decision-making across the broad research system including the multilateral partners, research funders, public health practitioners, clinicians and civil society.