Five COVID-19 Related Challenges for Trials in Low-to-Middle Income Countries
Challenges faced by researchers conducting clinical trials in low- and middle-income countries are examined.
COVID-19 has dramatically impacted clinical trials in high-income countries because of site closures, stay-at-home orders, supply chain issues, and participant reluctance to visit doctors’ offices and hospitals, among other barriers. Many of these difficulties have been exacerbated-and accompanied by new ones-in low- and middle-income countries (LMICs). COVID-19 also is amplifying some of the difficulties that are always present in clinical trials in LMICs.
While the substantial majority of clinical trials still take place in countries classified by the World Bank as high income,a review of clinical trial registrations on the WHO International Clinical Trials Registry Platform and clinicaltrials.gov shows that a significant and growing number are being conducted in LMICs, with major centers in Eastern Europe, the Middle East, Brazil, China, India, and South Africa. Even very low-income LMICs without large numbers of investigators and sites trained in ICH GCP have dozens or hundreds of trials.
Five critical challenges faced by researchers conducting clinical trials in LMICs are examined below.
Regulator guidance
Several LMICs, including
,
Unavailable participants
Quarantines and internal travel restrictions will impact the ability of participants and research staff to go to clinical trial sites. Both the
Monitoring visits
While remote trial monitoring is an important way to continue research during the pandemic, as the FDA has noted, there are often components of an on-site monitoring visit that cannot be completed remotely. External travel restrictions, which are in place almost everywhere as of this writing, are limiting in-person monitoring of studies that have monitors from outside the country. Some countries, such as Vietnam, are requiring
Supplies
The availability of necessary supplies and disruptions to supply chains as a result of the pandemic will in general impact LMICs more than high-income countries. COVID-19 will likely have a long-lasting
Informed consent and ethical issues
Protocol changes and other circumstances that may impact the risks and benefits of a clinical trial have implications for the participants’ ongoing informed consent and the ethics oversight of the trial. In-person study visits may be riskier in some LMICs than in high-income countries during the pandemic as a result of PPE (and eventually vaccine, antibody, or other preventative) availability. Virtual/remote visits could be riskier, where they are allowed, because living arrangements may not facilitate privacy, and internet cost and speed will often prevent video conferencing. Participation in general may be riskier in LMICs because of the capability of the health system to treat COVID-19 or study injuries during the pandemic and because of the privacy concerns government anti-COVID-19 measures may create, such as China's QR
In addition, the Declaration of Helsinki, FDA regulations, ICH GCP E6, and influential
containing estimates of the impact of COVID-19 on global poverty as of April 2020. Many will not have access to clean drinking water or running water in their homes to wash their hands to prevent COVID-19. Many also will be food insecure; the
Conclusion
As clinical trial sponsors work with their CROs and sites to address the challenges posed by COVID-19 in their LMIC-based studies, they should be sure to follow any regulatory guidance available in the countries where the sites are located, either specific to clinical trials or those that generally pertain to the healthcare sector. For those LMICs without regulatory guidance, following the general principles articulated in FDA’s guidance is advisable to the extent possible. Participant safety must be the priority, so when trials are started or ongoing during the pandemic, decreased in-person study visits and monitoring should be implemented wherever possible. Every protocol deviation and missing data element should be documented. Finally, informed consent forms and study IRB/IEC approvals may need to be revisited in light of local conditions.
Clint D. Hermes is an attorney at Bass, Berry & Sims. He can be reached at
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