New Coronavirus Vaccine and Treatment Research: Human Challenge Trials

As a philanthropist journalist, one of the questions I most often ask about the coronavirus crisis is how the public can help.

Some things come to mind. GiveDirectly is giving money to poor Americans Suffering from unemployment and other difficulties; can also donate money to others Public health charity Help poor countries cope with the surge in demand for doctors and hospitals.

Currently, bioethicists and two epidemiologists are proposing more daring options. Volunteers infected themselves.

so Recent articles published on Journal of Infectious DiseasesBioethicist Nir Eyal and epidemiologists Marc Lipsitch and Peter G. Smith called for a “human challenge study” to test the effectiveness of the developed coronavirus vaccine. These studies involve testing the vaccine in a group of volunteers that were intentionally exposed to a novel coronavirus that causes Covid-19. It is hoped that researchers will be able to more quickly and reliably confirm the effectiveness of the proposed vaccine.

Human challenge studies are generally performed on less lethal diseases such as malaria and schistosomiasis. Colleague Kelsey Piper interviewed Malaria vaccine trial volunteer John BeshirBeshir was an active donor to antimalarial charity and saw his volunteering as an extension of his financial support for the cause.

However, malaria, when properly treated, results in lower mortality rates for young and healthy people. (Hundreds of thousands die each year, suggesting that treatment is available in seriously affected countries in Africa.) Reflects what you ca n’t do). Covid-19 is different. about 0.66% Of the infected people, they have died from the disease. And Recent research The mortality rate for young people is very low (0.03% for those in their twenties), and data based on this is in the early stages of an outbreak in China in February. There is much to be learned about the disease and its lethality.

Activist Josh Morrison, I know from his daily work Defend living kidney donor (like me),It has started Website volunteer recruitment We are willing to take on that deadly risk to speed up vaccine development. At the time of this writing, about 450 people have shown tentative interest in volunteers (including me, a single kidney may not be eligible).

Nothing is promised by registering, and the website is not looking for a current trial. No vaccine is in the development stage where human challenge trials make sense. of Milken Institute Counting 51 different vaccines currently in development, only a small Handful Phase I trials need to make sure that the vaccine is not dangerous to humans. A pilot study of efficacy will then be conducted with more samples, and a phase II study will be conducted to find the optimal dose that balances side effects with efficacy. Some studies combine phases I and II, which can speed up the process.

Eyal, Lipsitch, and Smith suggest using a human challenge trial instead of Phase III (at least, at least a few months later), where larger samples are tested for validity. Instead of the typical Phase III, human challenge tests can be performed with fewer people and in less time, as researchers do not have to wait for volunteers to be exposed to the virus. A real human challenge exam involves an intensive checkup of volunteers and a huge amount of risk disclosure to help them understand exactly what we are doing.

However, the pressure to register volunteers is forcing wider conversations on whether this kind of trial is necessary or ethical, given the number of deaths that the coronavirus threatens to kill. The ethical questions here are interconnected and depend on both empirical questions—do human challenge testing actually accelerate vaccine development? For example, how many lives can be saved by speeding up development in a month? —And cherish the questions.

The big question: is it acceptable to ask volunteers to put their lives at risk to speed up vaccine development? If so, are they eligible for nominal compensation (like lost wages) or more?

“We’re all looking for hail Mary. It’s easy to think that challenge research is exciting and has many possibilities,” said Professor of Medical Ethics at Northwestern University School of Medicine and Medical Ethics at Lurie Children’s Hospital. Says scholar Seema Shah. Wrote about Chicago Ethics of Human Challenge Trial. “But to fulfill that promise, much needs to be done properly.”

How the Human Challenge Trial works

To test something like a coronavirus vaccine, you usually collect a group of healthy people, give half an vaccine, the other half a placebo, and they get infected with the relevant disease in their daily lives Wait to do. Next, compare the groups.

The problem with the coronavirus is that healthy people who are extending their social distance will probably not be infected. This makes it difficult to actually compare the vaccinated and non-vaccinated groups. Probably both would be the same because no one in either group was exposed to the pathogen. In that case, no useful information was obtained from the trial.

In a human challenge trial, all trial volunteers are replaced by a process that is exposed to the virus that causes Covid-19 after administering the vaccine or placebo. Doing so will give you a clearer understanding of how the vaccine works when you actually face the disease you are trying to prevent.

“A standard test must take at least a few months to allow the high parts to be exposed,” said Bioethics, who co-authored an article in the Journal of Infectious Diseases requiring a human challenge test. Scholar Eyal told me. “In contrast, the challenge of coronaviruses reveals the success or failure of vaccines to protect against disease much sooner.”

In addition, human challenge trials can be performed with fewer people than standard phase III trials. Ah Covid-19 vaccine being developed at OxfordFor example, Phase III aims for 5,000 volunteers. Eyal argues that trials of human challenges can occur in as few as 100 people. Because of the need to test multiple vaccine candidates (among other reasons), the total number of participants required will probably be higher, but the number is much lower when compared to conventional studies.

Risks of conducting human challenge trials and how to mitigate them

The disadvantages of doing this are obvious. Covid-19 is a dangerous illness, especially given that the placebo group volunteers are more likely to fail all vaccines, the treatment group volunteers also get severely ill and can take weeks, And / or die.

Eyal has many answers to this objection. He expects the volunteer pool to be limited to healthy people between the ages of 20 and 45. “Existing conditions that increase the risk of failure as a result of coronavirus infection” such as Asthma and other chronic lung diseases, HIV and other immunocompromised states, obesity, diabetes, liver disease, and chronic kidney disease-“candidates should be excluded,” Eyal says. It should help reduce the probability of infection leading to death.

Current, Research published at Lancet on March 30Only 0.031% of those in their twenties infected with the virus that causes Covid-19 die. This includes people with underlying disorders. It is almost the same Risk of death from donating live kidneys, Which medical facilities should be treated as acceptable.

In addition, volunteers “will be segregated to special facilities from their families and could become influenza challenge testing facilities in some developed countries, and will be converted to this use,” said Eyal. “It should be kept in quarantine until the infection is stopped. If an infection is detected, it should provide good medical care for coronavirus disease. This refers to the general health care system in times of crisis. It’s more than you can do. “

Eyal and his co-authors have adopted “people living in high transmission environments” such as New York City, saying that “participating in the survey would have little or no net reduction in their net risk. I want to.

Reasons for anxiety

Shah, a bioethicist in the northwest, believes that the risks of human challenge testing are acceptable if the benefits are large enough. “If you really pay attention to the people you register, for example those aged 18 to 25, and evaluate them carefully against other conditions, you can lower the risk,” she explains. Risks to third parties, such as volunteer families and health care providers who treat them, should be reduced as well.

But Shah warns that we must do more than weigh the risks and benefits. “When judging the ethics of doing research, justice considerations are also important, such as whether the risks are distributed fairly,” she says. “There are other criteria: community involvement, fair choice of participants, good informed consent, and payment to make up for time and inconvenience.”

Shah warns that it is difficult to estimate the benefits of a human challenge trial, and that the magnitude of the benefits depends heavily on the coordination between the vaccine trial and the researchers. Researchers need assurance that regulatory agencies, such as the Food and Drug Administration, will actually accept human challenge testing as evidence of efficacy. The FDA may have its own ethical concerns or may be wary of avoiding standard procedures. If the FDA does not approve a vaccine that has been tested in a human challenge test, the test may not accelerate vaccine adoption at all.

Similarly, Shah states that sharing data using comparable doses will require different vaccine teams to determine which vaccines are most promising. Given the international nature of this effort, coordination needs to be done through international organizations such as the World Health Organization.

Shah warns that those ducks are not consecutive, benefits to the challenge trial may be severely diminished.

Given the distance required before the Human Challenge Trial can be applied, now is a great time to make such an adjustment. For various biotechnology companies, research institutions, and governments working on vaccines to coordinate evidence and data sharing; clinicians provide input and vaccines tested in human subjects are used in the field To be more likely to be done.

Once these factors are in place, the Human Challenge Trial case is much more compelling.

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