Urgently seeking efficiency and sustainability of clinical trials in global health

Abstract

This paper shows the scale of global health research and the context in which we frame the subsequent papers in the Series. In this Series paper, we provide a historical perspective on clinical trial research by revisiting the 1948 streptomycin trial for pulmonary tuberculosis, which was the first documented randomised clinical trial in the English language, and we discuss its close connection with global health. We describe the current state of clinical trial research globally by providing an overview of clinical trials that have been registered in the WHO International Clinical Trial Registry since 2010. We discuss challenges with current trial planning and designs that are often used in clinical trial research undertaken in low-income and middle-income countries, as an overview of the global health trials landscape. Finally, we discuss the importance of collaborative work in global health research towards generating sustainable and culturally appropriate research environments.

Figure 1:. Global overview of clinical trial research

(A) Percentage of registered randomised clinical trials worldwide. (B) Percentage of trials that are cluster-randomised, by country, from the WHO International Clinical Trials Registry Platform from Jan 1, 2010, to Nov 5, 2019. (C) Number of master protocols registered or undertaken worldwide as of Dec 11, 2019.

Figure 2:. Conventional fixed trial designs and common adaptive trial designs

(A) A two-arm randomised clinical trial with conventional fixed trial design. (B) A two-arm trial with SSR. If the first interim analysis shows worse results than expected, an SSR can be carried out by use of the interim results. An SSR is not permitted in a traditional non-adaptive trial, so even when the original planned sample size is reached, the trial might be underpowered. If SSR is permitted, the sample size could be increased to ensure that the trial is adequately powered. (C) A two-arm trial with response adaptive randomisation. The response adaptive randomisation design allows for preferential assignment of interventions that show favourable interim results. In this example, the response adaptive randomisation design allows for an increased allocation ratio to treatment 1 based on the interim results. SSR=sample size reassessment.