Selection of trial sites where the outbreak is growing, possibly in regions where the implementation of control measures has been resisted, might make ideal trial locations
Following the news that China trials of Gilead Sciences Inc’s antiviral drug remdesivir in patients with mild symptoms of coronavirus (Covid-19) have been suspended due to lack of eligible patients; Michael Breen, Associate Director of Infectious Diseases at GlobalData, a leading data and analytics company, provides his view:
“As the Covid-19 outbreak becomes controlled, we must acknowledge that developers will increasingly face difficulties in recruiting infected patients for trials. In fact, as Gilead experienced in China, companies may have plans in place to initiate a trial, but when it comes to begin enrollment, there may be insufficient numbers of patients to power the study. Furthermore, as the number of developers burgeons, there will be increasing competition for a contracting pool of trial enrollment candidates. Thus, selection of trial sites where the outbreak is growing, possibly in regions where the implementation of control measures has been resisted, might make ideal trial locations due to a potentially richer pool of infections to treat or prevent.
“This situation is reminiscent of the Zika virus epidemic of 2015-2016, where developers rapidly began intense development of therapeutic and prophylactic interventions. However, as the outbreak was contained less than two years after its initiation due to implementation of mosquito control measures, developers had no patients left to include in trials for treatments. Similarly, a lack of spread of the virus also meant it would be near impossible to demonstrate any effectiveness of a vaccine; thus, the development of nearly all Zika virus interventions came to a halt.
“If patient pools for inclusion in trials continues to shrink, developers may have to rely on predicting which regions may not effectively control the outbreak, which is extremely difficult. They may also try to anticipate areas where a second wave or rebound of the outbreak could occur, but must also consider than if faced with a second wave, authorities may impose even more strict restrictions than for the first wave in order to rapidly control the outbreak, which would again limit patient pools.
“One potential way of demonstrating a vaccine’s effectiveness could be challenge studies, where patients receive a vaccine, and then are challenged with a given pathogen. While not an acceptable substitute for standard clinical trials, this type of study could be useful for determining which vaccines should be moved into proper clinical studies, and ease competition for what might be a vanishing patient pool.
“Challenge studies are great for proof of principle, but they have their limitations. They might not reflect protection conferred by whatever strain of the pathogen is circulating, and they cannot be conducted with pathogens which are associated with severe disease for ethical reasons. Additionally, they are used largely for vaccines, not treatments, so should numbers of infected patients decrease substantially, we may see trials for treatments postponed until the outbreak re-emerges.”