Enabling "Good" Clinical Research In LMICs With The Good Clinical Trials Collaborative
By Nick Medhurst, team lead, Good Clinical Trials Collaborative
Clinical trials are a cornerstone of medical advancement and improved public health. However, a complex array of challenges around resources, infrastructure, knowledge, and governance are hampering global efforts to conduct high-quality clinical trials. The result? A suboptimal evidence base and significant research waste.
The early global response to the COVID-19 pandemic illustrates this point. Out of the 2,895 registered trials between March and November 2020, a mere 5 percent were randomized and sufficiently powered to yield actionable outcomes. Additionally, only a quarter of enrolled patients contributed to adequately powered and well-controlled trials.1
While these challenges are universal across the world and to countries of all income levels, low- and middle-income countries (LMICs)2 are grappling with a unique set of barriers.
To surmount these barriers, the Good Clinical Trials Collaborative (the Collaborative) has joined forces with major clinical trial networks operating in LMICs to form Good Trials Prism. This strategic collaboration, funded by global charitable foundation Wellcome, brings together four networks with established affiliations to Wellcome: ADVANcing Clinical Evidence in infectious Diseases (ADVANCE-ID), Africa Health Research Institute (AHRI), Oxford University Clinical Research Unit (OUCRU), and The Global Health Network (TGHN).
Guided by the five scientific and ethical principles described in the Collaborative’s Guidance for Good RCTs and now incorporated in the World Health Organization’s (WHO) draft guidance3 for best practices for clinical trials, Good Trials Prism aims to enhance the quality of clinical research in Latin America, Southeast Asia, and South Africa where the networks are based, by strengthening these regional ecosystems and prioritizing collaborative, informative, and efficient research responses to pressing public health issues.
Addressing The Challenges In LMICs
The challenges LMICs face in producing reliable evidence through good trials are well documented in WHO’s draft guidance. These include the lack of fair access to affordable, safe, and efficacious interventions as well as limited availability of key resources such as technology, health workforce, infrastructure, and financing.
LMICs also continue to face high rates of infectious diseases and other communicable diseases, while rates of non-communicable diseases are similar to those in upper-middle- and high-income countries (HIC). However, most research is still conducted in HICs where demographics and clinical characteristics can be fundamentally different, making their results less applicable to LMICs.
It is therefore crucial to promote and advance good quality clinical trials in LMICs to address the significant health risks faced by their populations, ensuring equitable access to essential interventions and supporting sustained development.
Good Trial Prism partners have deep knowledge and the experience in navigating these challenges to support and deliver high-quality evidence from robust RCTs, often working internationally and across regulatory jurisdictions to coordinate informative, ethical, and efficient research.
The Guidance for Good RCTs, which complements national and local regulations by design and encourages context-specific approaches, will serve as a tool to foster common understanding among all stakeholders involved in clinical trials, emphasizing scientifically sound designs, ethical treatment of participants, collaboration and transparency, context appropriateness, and efficient quality management. Pharmaceutical companies conducting trials in LMICs can benefit from this guidance by designing trials that are tailored to low-resources settings, increasing their chances of success and bringing their vital treatments to underserved populations.
Spreading The Word: 5 Principles Of Good RCTs
1. Good RCTs are designed to produce scientifically sound answers to relevant questions.
RCTs should help resolve important uncertainties about the effects of health interventions. This requires the combination of key design features such as proper randomization to avoid selection bias, adequate sample size to minimize the play of chance, unbiased assessment of outcomes, and intention-to-treat analyses.
2. Good RCTs respect the rights, safety, and well-being of participants.
Ethical clinical trials combine seeking answers to important questions with scientific validity and appropriate protection and respect for all involved, especially participants. Independent review of proposals for new research, through a research ethics committee (or equivalent), is an important governance tool and can help ensure appropriate steps are taken to protect the rights and welfare of participants. Accessible, clear communication, and relevant consent at all stages of an RCT are at the heart of this principle.
3. Good RCTs are collaborative and transparent.
All those involved in RCTs share responsibility for building and sustaining the trust of collaborating partner organizations and clinical communities, participants, and the wider public. Trust can be undermined by lack of relevance or transparency and lack of respect for the rights and values of participants and those whose care will be influenced by the results.
4. Good RCTs are designed to be appropriate for their context.
Ensuring that a trial is set up to be practicable and produce reliable, actionable results is an important scientific and ethical duty. Consideration of the context and existing resources in a proposed trial setting can better inform effective trial design.
5. Good RCTs manage quality effectively and efficiently.
Delivery of a high-quality trial requires competent decision making and coordinated execution. Good governance and good trial quality management can help achieve these features. The focus should be on adopting risk-based proportionate approaches, identifying the key issues that would have a meaningful impact on participant well-being and safety or on decision-making based on the trial results.
Fostering Knowledge And Collaboration
Good Trials Prism serves as a platform for the partners to share their extensive clinical research expertise and promote sustained and equitable research capacity development in their regions.
The partners will develop contextually-adapted learning materials, including self-study courses, explainer resources, navigation tools, posters, and infographics, to foster understanding and widespread adoption of the principles. In addition, through workshops, seminars, conferences, and other collaborative events, the partners will facilitate the exchange of knowledge and best practices both within their networks and across partner networks. The Collaborative will provide scientific, capacity strengthening, advocacy, policy, and communication support, amplifying the collective impact of these activities.
Aligned with Good Trials Prism’s goal to foster a community of practice and establish a foundation for enduring and widespread benefits, resources curated by Good Trials Prism will be published on open access websites, freely available for others to utilize and learn from.
Vision For The Future
Ultimately, by championing the principles of good RCTs, Good Trials Prism aims to encourage all players within the global clinical research ecosystem to explore the Guidance for Good RCTs and recognize the benefits of informative, ethical, and efficient trials.
Clinical trials need robust systems and administrative functions to succeed. However, the same functions can fail to facilitate — or even deter — the pursuit of the principles of good RCTs, to the detriment of the health and well-being of the public.
Ultimately, Good Trials Prism seeks to build capacity and knowledge that helps ensure that feasibility, relevance, and efficiency are key priorities for a clinical trial. When coupled with robust design and ethical conduct, clinical trials will minimize research waste and propel healthcare progress around the world.
References:
- Bugin and Woodcock, Natural Reviews Drug Discovery 20, 254-255 (2021) doi: https://doi.org/10.1038/d41573-021-00037-3
- According to World Bank’s country classification by income level: https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups
- World Health Organization draft guidance for best practices for clinical trials, July 2023
About The Author:
Nick Medhurst is the team lead for the Good Clinical Trials Collaborative, a project committed to making it easier to do ethical and scientifically sound randomized controlled trials. Medhurst previously worked for patient representative organizations supporting people with breast cancer and cystic fibrosis (CF) and is a board member of CF Europe, a membership organization of patient representative groups, to represent and defend the interests of people with CF.