A mapping of 115,000 randomized trials revealed a mismatch between research effort and health needs in non–high-income regions

Abstract

Background

Concerns exist as to whether the allocation of resources in clinical research is aligned with public health needs. We evaluated the alignment between the effort of clinical research through the conduct of randomized controlled trials (RCTs) and health needs measured as the burden of diseases for all regions and a broad range of diseases.

Methods

We grouped countries into seven regions and diseases into 27 groups. We mapped all RCTs initiated between 2006 and 2015 that were registered at the WHO International Clinical Trials Registry Platform to regions and diseases. The burden of diseases in 2005 was mapped as disability-adjusted life years (DALYs), based on the 2010 Global Burden of Diseases study. Within regions, we defined a research gap when the proportion of RCTs concerning a disease in the region was less than half the relative burden of the disease.

Results

We mapped 117,180 RCTs planning to enroll 42.6 million patients and 2,220 million DALYs. In high- versus non–high-income countries, 130.9 versus 6.9 RCTs per million DALYs were conducted. We did not identify any research gap in high-income countries. We identified research gaps for all other regions. In particular, for Sub-Saharan Africa, we identified research gaps for common infectious diseases (CID) and neonatal disorders (ND): 5.8% (95% uncertainty interval 4.7–6.9) and 2.0% (0.9–4.5) of RCTs in Sub-Saharan Africa concerned CID and ND, although these diseases represented 22.9% and 11.6% of the burden in the region, respectively. For South Asia, we identified research gaps for the same two groups of diseases.

Conclusions

In non–high-income regions, the conduct of RCTs was misaligned with the distribution of major causes of burden, in particular infectious diseases and neonatal disorders in Sub-Saharan Africa and South Asia.

Introduction

The conduct of clinical trials, in particular randomized controlled trials (RCTs), helps creating evidence on the efficacy and safety of health interventions. Conducting RCTs worldwide might be particularly of interest to increase the external validity of treatment effects or to find local solutions when known solutions are not efficient or applicable in specific settings [1]. Concerns have been raised regarding the alignment of the allocation of clinical research and public health needs [2], [3]. Clinical research activities, and in particular the conduct of RCTs, may be driven by specific interests or constraints that may differ from local health priorities [4]. Although not encompassing all types of clinical research effort, a comprehensive mapping of RCTs may be helpful to understand the processes guiding clinical research, and to steer limited resources toward local health priorities, particularly in low-resource settings [2], [5].

Several studies have shown that research is lacking in low-income countries [6], [7] and that diseases receiving the most research attention are those that are predominant in high-income countries [2], [8]. Other studies have suggested that in low-income regions such as Sub-Saharan Africa, the conduct of RCTs is aligned with the burden across diseases [9]. However, previous studies focused on specific regions or specific diseases, and a global-scale analysis may bring novel insights.

We evaluated the alignment between the research effort (measured as the number of RCTs conducted) and the burden of disease across all world regions and a broad range of diseases. Within each region, we estimated the research effort across diseases and identified the diseases for which the research effort was too low as compared with the burden they cause. At a global level, for each disease, we estimated the research effort across non–high-income regions and identified the regions for which the research effort was too low as compared with the regional disease burden.