In September, the World Health Organization (WHO) released new guidance on best practices for clinical trials. The 76-page guidance document, called for by a resolution adopted by the 2022 World Health Assembly, seeks to improve the design, conduct, and oversight of clinical trials globally. Building upon guidance from the Council of International Organizations of Medical Sciences (CIOMS) and the Good Clinical Trials Collaborative (GCTC), the new WHO guidance seeks to reassert clinical trials as the cornerstone of both clinical and public health worldwide. In the wake of Covid-19, it provides timely updates to existing clinical trial guidance, emphasizing the need for more proactive and coordinated collaborations between global stakeholders, especially in dealing with public health emergencies. Despite its timely nature, its lengthy format risks making it less impactful than it could be. At its launch event—a webinar organized by WHO—WHO Chief Scientist Jeremy Farrar noted, “None of us [WHO] want it [the guidance document] to be known as a document which sits on a shelf, but that it is used, and of use, all of the time.” Whether or not this is the case in practice remains to be seen.
The guidance offers specific recommendations for regulatory and national health authorities, researchers, and funders. It also addresses the shortcomings of clinical trial responses during Covid-19, listing specific steps that need to be taken to facilitate rapid decision-making, clinical trial initiation, and data reporting during public health emergencies.
The guidance is divided into two parts— examining individual clinical trials as well as the global ecosystem of clinical research. Section 2, “Key Scientific and Ethical Considerations for Clinical Trials,” sets forth recommendations for “reliably informative, ethical, and efficient clinical trials,” qualifying “good” trials as those that are scientifically sound, respectful of participants, collaborative, transparent, feasible for the context, effective, and efficient. It emphasizes the need for clinical trials to be more inclusive of underrepresented groups, identifying infants and children, pregnant and lactating women, and older adults in particular, and citing their preclusion from access to certain treatments and tests because of their underrepresentation in research. The guidance also highlights the need for frequent and ongoing communication with research participants, most notably regarding consent and any safety considerations that develop during the course of a clinical trial. Strong recommendations are made around transparency throughout the guidance document, urging all stakeholders to strive towards greater collaboration and knowledge sharing.
The feasibility of clinical trials is a clear scientific and ethical priority for WHO in this guidance. It recommends that trials attend to the public health needs of the specific settings in which trials are conducted and that trials do not waste resources or the time of those participating.
The guidance takes a very useful step back to examine crucial components of what constitutes a healthy clinical trial ecosystem, both at local and global levels. It describes key pillars to ground a robust and responsive ecosystem: governance, funding, and policy frameworks, regulatory systems, ethical oversight, and infrastructure. By way of these pillars, WHO seeks to promote sustained clinical trial capabilities that attend to public health needs for diverse populations, including in times of public health emergency.
It cites the ongoing challenge of research funding, putting forth coordinated mechanisms, including public-private partnerships, as a key component of sustainable, long-term funding—a notable ethical break from prior WHO policy, which urged avoiding the private sector at all costs. Such collaborations are stressed not only with respect to funding, but also regarding resources and expertise, stressing disease- and discipline-specific consortia as crucial for enabling coordinated, efficient efforts targeting shared research priorities. The guidance also seeks to make clinical trials more accessible to patients, particularly those in lower- and middle-income countries (LMICs), by embedding the research endeavor more closely into routine health care, keeping in mind the ‘therapeutic misconception’ and the centrality of routine care. Finally, WHO stresses the need for a wider exploration into more diverse clinical trial designs that can be deployed across a range of contexts, including decentralized, platform, adaptive, and cluster-designed clinical trials.
The new guidance represents a significant step towards improving global standards for the conduct of medical research, addressing key challenges in both individual clinical trials and the larger clinical trial ecosystem. While the guidance emphasizes critical areas such as enhancing trial design, strengthening scientific and ethical standards, and promoting inclusion of underrepresented groups, its effectiveness will ultimately depend on adoption and implementation by key stakeholders worldwide. Will the document be used by national health authorities? Will it indeed “sit on a shelf” against the wishes of its authors? Will global events, such as the election of a new presidential administration with a likely hostility to all things WHO, have an impact on its uptake? These questions leave us with many unknowns about the guidance’s future impact. In an era of increasing medical misinformation, fostering trust in the clinical research enterprise has never been more crucial. The timely nature of this guidance, coupled with its comprehensive approach to addressing systemic issues in clinical trials, positions it as a potentially powerful tool for improving global health—if only it gets read.
John Massarelli, BA, is the Program Coordinator for the Working Group on Compassionate Use & Preapproval Access (CUPA) and a student at the Division of Medical Ethics, NYU Grossman School of Medicine and Department of Population Health, NYU Langone Health
Arthur Caplan, PhD, is the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at the Division of Medical Ethics, NYU Grossman School of Medicine, Department of Population Health, NYU Langone Health
@CUPAethics