Challenge trials in humans are being promoted to develop a coronavirus vaccine

Challenge trials in humans are being promoted to develop a coronavirus vaccine

By
Benjamin Mateus

May 5, 2020

Without much fanfare, news reports on coronavirus vaccines have focused on ways to accelerate vaccine development through challenging human trials. Simply put, such trials would deliberately infect healthy volunteers with the coronavirus after receiving the experimental vaccine, to determine its efficacy.

Democratic Rep. Bill Foster of Illinois, leading the effort with 34 other members of the House of Representatives, sent a letter to the Food and Drug Administration, saying: “A more tolerant development process is likely appropriate. to risk in the case of COVID-19 vaccine. The enormous human cost of the COVID-19 epidemic alters the optimization of the risk / benefit analysis “.

Josh Morrison, a member of an alleged grassroots effort, 1 Day Sooner, said Nature magazine, “We want to recruit as many people as possible who want to do this, and prequalify them to participate in challenge trials if they occur. At the same time, we believe that public policy decisions around challenge trials will be better informed. if they highlight the voice of people interested in participating in such trials. ” According to the group, thousands from more than 50 countries have volunteered.

Vaccine trials are notoriously long, with optimistic estimates of 12 to 18 months for vaccine launch. Much of the time in vaccine trials is spent testing the safety and efficacy of a vaccine. These phase three placebo-controlled trials, in which one group receives the vaccine and the other receives a placebo, generally involve several thousand participants who are followed long enough to assess differences in the incidence of disease.

Human challenge tests have been conducted for hundreds of years, but they are tests of last resort and are conducted under special circumstances and with much supervision. In the case of COVID-19, they were first raised in late March in a proposal published in the Infectious journal reiseases by authors Nir Eyal, Marc Lipstich and Peter G. Smith. They wrote in their summary: “By replacing conventional phase three tests of vaccine candidates [with human challenge trials]Such trials can subtract months from the licensing process, making effective vaccines available more quickly. “

The role of vaccines in global health cannot be underestimated. Smallpox was eradicated in 1977, the last case occurred in Somalia. Poliomyelitis was eliminated in the United States in 1979. After a worldwide campaign launched in 1994 by the Food and Agriculture Organization of the United Nations, rinderpest, a viral infection of cattle and domestic buffalo with close mortality at 100 percent, it was last confirmed in 2001 and declared eradicated in June 2011.

Measles, a virus for which only humans act as a host, killed 7 to 8 million children annually until a decade of work finally led to the development of a vaccine in 1963. Still, and despite the fact that there is a Effective vaccine available, measles infects more than half a million people worldwide, killing more than 140,000 people annually, mostly children under the age of five. The countries with the highest incidence include the Democratic Republic of the Congo, Liberia, Madagascar, Somalia and Ukraine; these five represent almost half of all cases worldwide.

The vaccination program in the United States, according to the CDC, has prevented more than 21 million hospitalizations and 732,000 deaths among children born in the past 20 years. In addition to the morbidity and mortality associated with vaccines, the economic benefits translate into $ 295 billion in direct costs and $ 1.38 billion in total social costs.

Efforts have been made to develop a vaccine against the SARS-CoV-2 virus. Many see a vaccine as the only solution to the pandemic. Without pharmaceutical treatments that have shown clear mortality benefits, current public health measures and supporting medical care remain essentially the only means of addressing coronavirus and its impact on human populations.

According to the World Health Organization (WHO), there are currently six human trials in the race to develop a SARS-CoV-2 vaccine. Moderna, which works in association with NIAID, and INOVIO Pharmaceuticals are US-based trials. Both in Phase I. Modern was the first to begin human testing in mid-March, building on previous work on other coronaviruses. The University of Oxford, in Great Britain, is in phase I / II, using a non-replicative viral vector. The study is being led by Dr. Sarah Gilbert, who previously led the work on “Disease X”, a hypothetical pathogen with pandemic potential adopted by WHO on its restricted list of priority diseases. The other three trials are from China: CANSINO Biological, SINOVAC and Beijing Institute of Biological Products. Seventy-seven other trials are in the preclinical evaluation stage.

In October 2016, the World Health Organization issued a statement on regulatory considerations for vaccine trials that pursue challenge trials in humans to accelerate the development of these critical preventive treatments. They write: “It is essential that challenge studies be conducted within an ethical framework in which truly informed consent is given. When carried out, human challenge studies should be carried out with abundant foresight, caution and supervision. The information to be obtained must clearly justify the risks to humans. “

The WHO notes that if a pathogen has a high case fatality rate and there are no existing therapies to prevent or lessen the impact of the disease and prevent death, then such trials would be inappropriate. They reportedly plan to publish a response to the proposed COVID-19 human challenge trials soon.

The authors Eyal et al., Regarding concerns about a human challenge trial for COVID-19, admit that it might be possible that any protection demonstrated by a vaccine in a human challenge study cannot be replicated when the vaccine is used in the general population.

Furthermore, there is no attenuated SARS-CoV-2 virus that can help participants avoid the risks associated with COVID-19, as outlined in the WHO guideline, nor is there a therapeutic treatment that can safely reduce the mortality risk after participants are infected. More troubling, they write, is that “some coronavirus vaccine constructs may induce more severe disease after infection, as reported in animal models of SARS and MERS vaccine candidates.” For this reason, they recommend challenging small groups sequentially to address this problem.

In support of the proposal, they affirm that these volunteers will have voluntarily consented to assume these risks. They write: “In the present case, the study would involve multiple tests of understanding of all the risks so that the decision is deeply informed and voluntary.” These participants would be isolated in the treatment facilities and would receive the best possible care.

They also justified conducting the trial by claiming that 1) the study will only recruit healthy participants, 2) the vaccine will likely benefit some of the trial participants, 3) in the absence of a vaccine, they are likely to be infected anyway, 4 ) only people with a high initial risk of exposure should be recruited, 5) participants would be provided with the best care available, and 6) potentially some therapies might be available to improve morbidity or mortality.

Dr. Beth Kirkpatrick, professor and chair of the University of Vermont Department of Microbiology and Molecular Genetics, who heads a human challenge testing unit, explained to STAT that human challenge models for COVID-19 do not exist. She said it would take more than two years to design and approve one, given all the ethical and regulatory constraints that come with it.

One of the main considerations with this human challenge trial is to establish appropriate endpoints for symptoms (flu-like illness or pneumonia) and their implications for vaccine efficacy. Until now, scientists are still baffled about why some people get sick while others don’t, and why symptomatic patients have a constellation of symptoms compared to others. Additional concerns raised include whether the data from that study will translate into efficacy across all age categories, as the population being evaluated is young and healthy. Information on vaccine safety would also be compromised in these smaller trials.

The working class must be very skeptical about the claimed benefits of such treatments and how such studies are conducted, especially in the face of a pandemic with a new coronavirus that has at all times surprised and puzzled scientists and researchers. Given the despair and disruption caused by this pandemic, the volunteers for these trials are likely to come from workers who are at the highest risk of contracting the infection due to the “essential” nature of their work.

It is deeply troubling that these tests of human defiance are being vigorously supported by the political establishment. Normal feelings of mistrust, caution, and vigilance to protect the people involved seem absent. Ultimately, the race for vaccine development rests on capitalist relationships that provide a tremendous profit incentive for the corporations that manufacture them, in addition to general concern in governing circles about promoting a return-to-work policy. . Challenge tests in humans become a facilitator for both purposes.

Attempts to reduce corners and streamline trials have already led to abject failures, which ultimately only delay the need to determine which therapeutics and vaccines will work and are inherently safe and which have adverse profiles. In the face of the frenzy and despair that is causing social tensions, it becomes even more necessary to adhere rigorously to scientific principles. Even in desperate times, these principles will save time, life, and resources.

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