Friday, May 8, 2020

Human Challenge Trials (aka Controlled Human Infection studies) for corona virus vaccines

What do we want?  A vaccine for covid-19.

When do we want it?  After clinical trials and peer review.

How can we get it faster?  By asking healthy young (not at too much risk) volunteers to permit themselves to get infected with covid-19, so we can try out vaccine candidates.

Is that crazy?  Well, maybe not. (But not everyone is sure of that.)

Here's a recent paper considering the proposal.

Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure 
Nir Eyal, Marc Lipsitch, Peter G Smith
The Journal of Infectious Diseases, jiaa152,
Published: 31 March 2020

Abstract: Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.

Here's another paper, in Science, 07 May 2020, by a big group of authors consisting of medical ethicists and physicians: they think it might be ok.

Ethics of controlled human infection to study COVID-19
Seema K. Shah, Franklin G. Miller, Thomas C. Darton, Devan Duenas, Claudia Emerson, Holly Fernandez Lynch, Euzebiusz Jamrozik, Nancy S. Jecker, Dorcas Kamuya, Melissa Kapulu, Jonathan Kimmelman, Douglas MacKay, Matthew J. Memoli, Sean C. Murphy, Ricardo Palacios, Thomas L. Richie, Meta Roestenberg, Abha Saxena, Katherine Saylor, Michael J. Selgelid, Vina Vaswani, Annette Rid

 Abstract: High social value is fundamental to justifying these studies

 Here are the articles opening lines:

"Development of an effective vaccine is the clearest path to controlling the coronavirus disease 2019 (COVID-19) pandemic. To accelerate vaccine development, some researchers are pursuing, and thousands of people have expressed interest in participating in, controlled human infection studies (CHIs) with severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) (1, 2). In CHIs, a small number of participants are deliberately exposed to a pathogen to study infection and gather preliminary efficacy data on experimental vaccines or treatments. We have been developing a comprehensive, state-of-the-art ethical framework for CHIs that emphasizes their social value as fundamental to justifying these studies. The ethics of CHIs in general are underexplored (3, 4), and ethical examinations of SARS-CoV-2 CHIs have largely focused on whether the risks are acceptable and participants could give valid informed consent (1). The high social value of such CHIs has generally been assumed. Based on our framework, we agree on the ethical conditions for conducting SARS-CoV-2 CHIs (see the table). We differ on whether the social value of such CHIs is sufficient to justify the risks at present, given uncertainty about both in a rapidly evolving situation; yet we see none of our disagreements as insurmountable. We provide ethical guidance for research sponsors, communities, participants, and the essential independent reviewers considering SARS-CoV-2 CHIs."

Kim Krawiec points out to me that, among the things the authors disagree about among themselves is compensation to donors:
"Members of our group disagree about the ethical permissibility of offering payment to CHI participants, and there may be relevant regulatory limits in different jurisdictions. Nevertheless, as SARS-CoV-2 CHIs require confinement and follow-up, fairness seems to demand offering participants compensation for their time. This may total several thousand dollars in the United States, assuming compensation at a fair minimum wage for unskilled labor, as in other CHIs. By contrast, incentives beyond compensation could be avoided, given the number of people already indicating willingness to participate. Concerns that the undue influence of monetary compensation compromises risk judgments are unsupported by the available data, as financial motivations are associated with greater attention to risk (15). Moreover, a rigorous informed consent process could maximize understanding. In case payment tempts participants to withhold disqualifying information, eligibility criteria should be objectively verifiable."

And here is a group of activists, at an organization called 1 Day Sooner.
You can sign up here*,

COVID-19 Human Challenge Trials
"Human challenge trials deliberately expose participants to infection, in order to study diseases and test vaccines or treatments. They have been used for influenza, malaria, typhoid, dengue fever, and cholera. Researchers are exploring whether human challenge trials could speed up the development of a vaccine for COVID-19, saving thousands or even millions of lives."

*"Sign up here if you may wish to participate in a human challenge trial for COVID-19 if one were to occur, and, potentially, advocate for safe and rapid vaccine development. "

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