Friday, April 24, 2020

1_DAY_SOONER COVID-19 Human Challenge Trials


                How could challenge trials help speed up vaccine development?

Excerpts from

The proposed trial method would potentially cut the wait time for the rollout of an efficacious vaccine. Challenge studies (which always directly expose all participants to a pathogen to assess efficacy) generally require fewer participants, followed over a shorter period than do standard efficacy studies (in which many participants are never exposed). Rollout of an efficacious vaccine to age groups not included in the challenge studies may depend on immunological bridging, but this would be a component of the expanded safety studies discussed above. It is possible that this process could take several months shorter than reliance on standard phase 3 testing to assess efficacy. While rollout to other populations might require initial bridging studies, these could be conducted relatively quickly.

It seems clear that, in the absence of an efficacious vaccine, the global death toll from COVID-19 will be enormous. A recent modelling study suggests that, even with mitigation strategies focusing on shielding the elderly and slowing but not interrupting transmission, there may be 20 million this year [10]. If the use of human challenge helped to make the vaccine available before the epidemic has completely passed, the savings in human lives could be in the thousands or conceivably millions. Intense social distancing and related control measures, held in place for many months between now and the availability of vaccine, will themselves take a toll on economies, societies, and population health. Advancing the registration and rollout of an efficacious vaccine, even by a few months, could save many thousands of lives, and commands enormous societal value.

But a remaining key question, for deeming human challenge studies ethical, pertains to risk. Are the risks to participants, even when they are justified by the social importance of the trial and backed by participants’ willful permission, also being kept to the necessary minimum? And do the risks fall below a postulated cap on the acceptable risk of medical trials, even ones of the highest social value and with participants’ consent [15]?

The proposed challenge studies seek to contain the risk to participants in 6 different ways. First, the study will recruit only healthy patients from age groups in which the risk of severe disease and death following SARS-CoV-2 infection is low. Second, there is the possibility that the vaccine candidate will protect at least some of those who are vaccinated. Third, in the absence of an effective vaccine, a high proportion of the general population is likely to be naturally infected with SARS-CoV-2 at some point [17], including those who might participate in a challenge study; by volunteering to be artificially infected they may be just hastening an event that is likely to occur in later months anyhow. Fourth, only people with an especially high baseline risk of getting exposed during or soon after the trial period should be recruited (eg, people residing in areas with high transmission rates). Fifth, participants would be monitored carefully and frequently following the challenge and afforded the best available care if needed (eg, guaranteed access to state-of-the-art facilities of the health system, notwithstanding the possibility of severe shortages of medical care during the evolving pandemic). Sixth, by the time vaccine candidates are being tested, some therapeutics may be approved, which may reduce participants’ risk of morbidity and mortality further. For these 6 reasons, mortality and morbidity from participation notwithstanding, net mortality and morbidity from participation should remain low or negative.