The COVID-19 pandemic sparked a paradigm shift in clinical trials, particularly with the race to develop vaccines. Governments, academia, and the pharmaceutical industry collaborated on a scale never seen before, leading to significant advancements in public health. The UK, with its National Health Service (NHS) and the National Institute for Health and Care Research (NIHR), conducted mass trials for COVID-19 vaccines, enrolling half a million volunteers by June 2021. This collaborative effort resulted in one of the fastest vaccine rollouts globally, using vaccines from Pfizer, Moderna, and AstraZeneca. Yet, the success of this trial system wasn’t without its challenges, some of which are being addressed in a new set of guidelines by the World Health Organization (WHO).
The WHO’s recent guidelines for clinical trials advocate for a more inclusive approach, particularly in terms of participation from higher-risk populations and diverse geographical regions. This guidance follows from the findings of the UK’s James O’Shaughnessy review, which highlighted several structural barriers in clinical trials. Despite the NHS’s centralized structure, which is often seen as an advantage, the review uncovered issues such as inadequate incentives for healthcare workers and logistical obstacles, which led to many NHS staff being undercompensated or not involved in the trials.
The O’Shaughnessy review, while recognizing the UK’s vaccine rollout as one of the most successful globally, also pointed out that such successes were marred by significant inefficiencies. For example, the report noted that monetary incentives, although offered to healthcare workers participating in trials, were rarely processed, which led to frustration and a lack of motivation among NHS staff. Furthermore, the centralization of the NHS, while beneficial in some respects, created inefficiencies that delayed recruitment and hindered trial participation across the country.
This issue was compounded by the global disparities in clinical trial participation. A major concern raised by the WHO was the lack of inclusivity in trials, particularly the underrepresentation of populations in low- and middle-income countries (LMICs). In 2022, high-income countries hosted over 27,000 clinical trials, while LMICs conducted far fewer trials. This imbalance means that the benefits of medical breakthroughs, such as the COVID-19 vaccines, may not be as applicable or accessible to populations in these countries.
WHO’s Call for Inclusivity
The WHO’s new guidance highlights the importance of increasing the inclusion of high-risk participants in clinical trials. High-risk populations, such as those with pre-existing conditions or from marginalized communities, are often excluded from clinical trials, leading to skewed data that does not reflect the realities of global health. The WHO’s recommendations aim to rectify this by urging researchers and institutions to prioritize these groups in clinical trial recruitment.
In addition to diversifying participant demographics, the WHO is also calling for greater participation from countries in the Global South. Historically, clinical trials have been concentrated in wealthier nations, with limited trials taking place in LMICs. The result is a research landscape that disproportionately benefits high-income countries, further entrenching global health inequalities. WHO’s new guidelines suggest that trials should be designed to include more countries in their study populations, ensuring that research findings are globally relevant and applicable to people worldwide, regardless of their geographical location or economic status.
The Challenges of Achieving Inclusivity
While the WHO’s guidance is a step in the right direction, there are significant challenges to implementing these recommendations on a global scale. One of the main obstacles is the disparity in healthcare infrastructure between high- and low-income countries. In many LMICs, the necessary facilities, equipment, and expertise to conduct large-scale clinical trials are lacking. Even when funding is available, these countries often struggle to meet the rigorous standards required for international clinical trials.
In addition to infrastructural challenges, there are regulatory hurdles that impede the participation of LMICs in clinical trials. The lack of harmonization between regulatory bodies in different countries can create delays in trial approval and cause logistical difficulties for multinational studies. This fragmentation makes it harder to recruit participants from diverse regions and ensure that trials meet the regulatory requirements of all the countries involved.
Another challenge is the lack of financial incentives for both researchers and participants in LMICs. While wealthier countries can afford to offer compensation for trial participation, many low-income countries cannot. Without proper compensation, it becomes difficult to attract participants, especially those from vulnerable populations who may not have the means to take time off work or travel to trial sites.
The Potential Impact of WHO’s Guidance
If the WHO’s guidance is followed, it could have a profound impact on the inclusivity of clinical trials, addressing long-standing disparities in global health research. By making trials more inclusive, the benefits of medical research could be shared more equitably, helping to ensure that advancements in healthcare reach all populations, not just those in high-income countries.
One of the most immediate impacts could be the development of treatments and vaccines that are more effective for diverse populations. For example, vaccines developed during the COVID-19 pandemic were primarily tested on populations from Europe and North America, which meant that some groups—particularly those from different ethnic backgrounds—were underrepresented in trials. This led to concerns about the efficacy of these vaccines for populations with different genetic profiles or pre-existing health conditions. By including a broader spectrum of participants, future trials could result in more universally effective treatments and vaccines.
Moreover, increasing the participation of LMICs in clinical trials could lead to a more equitable distribution of healthcare resources. Many of the world’s most pressing health issues, such as malaria, tuberculosis, and HIV, disproportionately affect populations in low-income countries. By ensuring that these countries are included in the clinical trial process, the treatments developed could be more tailored to their needs, improving health outcomes in some of the world’s most vulnerable regions.
The Role of Stakeholders in Driving Change
For the WHO’s guidance to be effective, it will require the cooperation of a wide range of stakeholders, including governments, research institutions, pharmaceutical companies, and non-governmental organizations. Governments in both high-income and low-income countries will need to create the political will and infrastructure necessary to support inclusive trials. This may involve increasing funding for research, investing in healthcare infrastructure, and ensuring that regulatory systems are aligned across borders.
Research institutions and universities also have a critical role to play in promoting inclusivity. By conducting research in diverse settings and ensuring that trial participants come from a wide range of demographic backgrounds, these institutions can contribute to a more equitable global health landscape. Pharmaceutical companies, too, have a responsibility to ensure that the drugs and vaccines they develop are tested in diverse populations, to ensure that the benefits of their products are accessible to all.
Non-governmental organizations (NGOs) and advocacy groups can help raise awareness of the importance of inclusivity in clinical trials and advocate for the inclusion of marginalized populations. They can also play a vital role in facilitating access to trials in low-income countries, where logistical and financial barriers may prevent people from participating.
The WHO’s new guidance on clinical trials represents a significant step forward in addressing the lack of inclusivity in global health research. By prioritizing the inclusion of high-risk populations and more countries in each trial, the WHO aims to create a more equitable and effective global healthcare system. However, the challenges of implementing this guidance are substantial, particularly in low-income countries, where healthcare infrastructure and financial incentives are often lacking. For the WHO’s guidance to have a meaningful impact, it will require a concerted effort from all stakeholders, including governments, research institutions, and the private sector. If successful, the WHO’s approach could help bridge the gap between high-income and low-income countries, ensuring that the benefits of medical research are shared more equally across the globe.
