Saturday, June 03, 2023

A conversation with Dr. Zvi Loewy.

(Courtesy of Touro College of Pharmacy)
Rabbi Dr. Zvi Loewy, of Fair Lawn, is associate dean of research and professor of pharmaceutical and biomedical science at Touro College of Pharmacy. He recently authored an article on clinical trials for COVID- 19 vaccines in the newly released “Medical Halachah Annual, Volume 1: The Pandemic and Its Implications,” published by Touro University and New York Medical College in conjunction with Mosaica Press. Professor Loewy addressed halachic perspectives in volunteering for open label clinical trials. Here, he answers some of the most commonly-asked questions about vaccine trials and halacha.

Can you describe the discovery and development of the first vaccines?

The history of vaccines actually dates back to smallpox when they used a process called variolation, during which people were exposed to material from smallpox sores and pustules. Doctors took some of that matter and injected it into people or had them inhale it and noticed that the death rate from smallpox plummeted to 2%-3% as compared to people who contracted smallpox naturally. The first time this was done was in the early 1700s. Then in 1796, a physician named Edward Jenner injected people with cowpox and showed that it protected against smallpox. This was the beginning of the vaccine era.

It has been reported that the COVID vaccine differed from the standard childhood vaccines that are commonly given. Can you explain in what way the COVID vaccine is different? Is it completely new or is it similar to the other standard vaccines?

Just to give some background, there are four broad classes of vaccines. The first is inactivated virus, which is when scientists take a virus and make it inactive and essentially kill it so it can’t thrive in human cells.

The second one is called attenuated virus, and that’s when the virus is weakened. The measles and polio vaccines are examples of inactivated and attenuated vaccines.

The third type of vaccine is subunit vaccine, or when scientists take a component of a virus and inject it into an individual to create a new response. The hepatitis B vaccine is an example of this type. It’s a protein that’s injected that is part of the virus but not the whole virus.

The fourth type of vaccine is nucleic acid-based. This is the family of vaccines of which the COVID-19 vaccine is a part. The RNA molecule that corresponded to the spike protein of the virus responsible for COVID-19 was injected into people.

Everyone thought this vaccine used new technology, but in actuality the technology has been around for decades. Nearly 50 years ago, RNA was transferred into cells with a liposome, which is a drug delivery vehicle that is composed of fats. This basic technology was developed in the 1970s to deliver drugs. There have been key iterations building upon the foundational technology for decades, enabling the Pfizer and Moderna COVID-19 vaccines. The technology had been developed years earlier; for COVID it was just used in a different way, to deliver vaccines instead of drugs.

Normally, a clinical trial for a vaccine takes a number of years. Can you please explain why the COVID vaccine was available in such a short period of time?

The nucleic acid sequence of the virus that caused COVID-19 was identified very rapidly, so the design of the vaccine began very early on in the pandemic. How did it go from design to development to clinical trials in nine months as opposed to many years? Normally in clinical trials, each phase is done sequentially so you go through phase one, then phase two. then phase three, and for each successive phase you keep increasing the number of new participants as well as adding different trial sites nationally and internationally to demonstrate that what you’re developing is safe and efficacious and has broad geographical applicability.

During COVID, the trial phases were done in parallel instead of sequentially, which shaved off a lot of time, and that’s how they were able to release it in record time, at “warp speed.” Everything that is normally done was done; they didn’t skip steps; they just did it all at once and then analyzed the data from the phases that were going on concurrently. Participants in the clinical trials included different ages, races and ethnicities right from the start, to demonstrate that it would have broad applicability

At the end of the day, the safety profile of the COVID vaccine that was developed in an accelerated mode was higher than the safety profile of the flu vaccine that most people take without thinking. The learnings from this initiative will be used in the future. Moderna is already using this technology to try to develop oncology therapies and other vaccines.

In your opinion, what are the halachic and ethical issues involved in volunteering to be part of a clinical trial for new medications and vaccines?

We are privileged to have poskim who can weigh in on these situations, and they should be consulted for halachic direction. That said, there are two halachic questions that arise.

The first centers on one’s obligation to engage in an action to save another person. Is one obligated to participate in a trial based on the premise that he may save someone else’s life? Although the Beis Yosef obligates an individual to assume potential danger to save the life of someone facing definite danger, many of the rishonim do not address the issue, suggesting that they were possibly opposed to taking risk. It is believed that the rishonim omit the obligation for assuming risk consistent with the opinion of the Talmud Bavli. Interestingly, the Talmud Yerushalmi advocates taking risk. Practically, a posek familiar with these issues should be consulted.

The second question is: How much risk can you possibly take when you are volunteering to test a new drug or vaccine? In the “Medical Halachah Annual,” Rabbi Mayer Twersky offers a lengthy discussion, based on an analysis of rishonim and acharonim, on risk-taking in halacha, and he quantifies the risk that would be acceptable to take.

Is there ever a time that Jewish law and ethics would demand participation in a vaccine or medication trial?

Most halachic sources discuss participation in trials, not in terms of demanding it, but rather permitting it. Rabbi Yitzchak Zilberstein, a renowned medical halacha posek and son-in-law of Rav Elyashiv, has written in his seforim based on a Gemara in Shabbos and a teshuva of the Chasam Sofer, that participation in such trials is encouraged if participation will provide benefit based upon the uniqueness of the Jewish population. However, Rabbi Zilberstein notes his father-in-law’s opinion that if participation in a clinical trial can lead to adverse effects, or if treatment may be withheld since one may receive a placebo, then participation is unequivocally prohibited. Rav Elyashiv was opposed to participating in placebo-based trials. Those considering participation should check with their own poskim.

What are your thoughts on a challenge trial? Is it ethical?

A challenge trial is basically where you have two populations—both are infected with the virus. One group gets the vaccine and the second group receives a placebo. As opposed to being naturally exposed to someone who has the virus, in challenge trials scientists are directly exposing the participants to the virus to see if they elicit a protective response.

From an ethical perspective with the COVID trials, it has been reported that risks associated with a challenge trial will subject fully informed volunteers to an approximate 1% chance of hospitalization and a 0.03% (or less) chance of death. From an ethical perspective, it seems that these trials should be permitted based on the common rule that governs research on human subjects, which states that “risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.” Challenge trials for COVID-19 can meet this requirement.

It is important to note that there is also a strong argument against challenge trials. If a trial is not consistent with the accepted standard of care, it is unethical. So, if we don’t infect an unvaccinated control group as standard of care, then to do so in a challenge trial would be unethical. It’s dangerous for medical research to sanction intentional inflicting of harm on some individuals to benefit others.

Halachically, Rav Elyashiv would oppose participation in challenge trials. It’s important to look at both sides of the issues, but ultimately to seek out a posek to guide your decision.

The “Medical Halachah Annual” contains 14 essays by key rabbis and doctors on the intersection of medicine and halacha. To order the book visit https://mosaicapress.com/product/medical-halachah-annual/

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