Is It OK to Enroll in a Covid-19 Vaccine Trial If I Might Drop Out?

I have the opportunity to participate next week in the AstraZeneca Covid-19 vaccine trial. I am a healthy, middle-aged, nonessential, gainfully employed New Yorker. I want to participate in the two-year trial for a number of reasons: the desire to contribute to science, (potentially); have early access to the vaccine; and simply do something other than sit horror-struck watching what is happening in health care settings.

In New York, however, maybe as early as this summer, middle-aged, nonessential people could potentially be vaccinated. Is it OK to sign up for a two-year double-blind Covid-19 trial — in which I will not know if I have been given the placebo or the vaccine — and then, without telling the trial administrators, get an antibody test to unblind my status?

If I find that I do not have Covid-19 antibodies, then it means I was likely given the placebo, and if an opportunity arises to get Pfizer/Moderna’s vaccine, I would drop out of the AstraZeneca trial. (The trial follow-up is a two-year commitment, but study enrollees can drop out at any time.) I would stay in the AstraZeneca trial if the antibody test comes back positive, indicating exposure and some presumed immunity. (I currently don’t have the antibodies.)

Is it ethical to participate in the two-year AstraZeneca trial when I know I may drop out after six or 12 months? Amy, New York

A medical trial typically has two arms; my answer has two hands. Here goes.

On the one hand: No, it’s not ethical to enroll in a trial when you’ve already formed an intention not to comply with its rules. If everybody in the trial broke the agreement and had themselves tested for antibodies, the trial would no longer be blind, and if people decided that they received the placebo and dropped out in order to receive an authorized vaccine, the study would give us less information about how safe and effective the vaccine under trial is.

Why does it matter that a trial is genuinely double blind? One reason is that knowing you’re vaccinated could itself change your behavior — by making you take bigger medical risks. Another is that an accurate assessment of “adverse events” relies on blinded comparisons; we may see worrisome side effects that turn out to be just as common in the control arm as in the treatment arm, which is the sort of thing we would never know without doing the comparison. There’s a reason that randomized controlled trials are the gold standard in medical research.

On the other hand, the availability of effective treatments poses a complication for ethical trial design. If you’re eligible for vaccination outside the trial, remaining in the trial as a placebo recipient would, medically speaking, put you at a disadvantage. A trial sponsor must not discourage participants from receiving the “standard of care” that would otherwise be their due and that they would otherwise be accorded. A trial is not a form of therapy, and participants are not patients, but a properly conducted trial does not depart from this standard of care in a way that puts participants at serious risk of harm.

As more vaccines that are already in advanced stages of their trials come on the market, there will be challenges for studying newer vaccines — vaccines that could, in theory, be safer, more protective, cheaper and easier to make or store than the ones that crossed the F.D.A. finish line earlier. Increasingly, we may be testing promising new vaccine candidates against already authorized ones, rather than against placebos. But such trials, experts have warned, will have to be of greater size and duration, raising serious financial and logistical obstacles.

Your participation would probably be of more value if you take the antibody test only when your turn approaches for receiving an authorized vaccine. Should you test positive and, as you plan, remain in the trial, researchers will be able to track (for instance) your antibody levels over time; your membership in the treatment arm can help confirm that the antibodies provide protection, especially if the control arm hasn’t dissolved. Should you test negative and drop out, there could be some usable data points from the period in which you (blindly) participated.

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Answers to Your Vaccine Questions

While the exact order of vaccine recipients may vary by state, most will likely put medical workers and residents of long-term care facilities first. If you want to understand how this decision is getting made, this article will help.

Life will return to normal only when society as a whole gains enough protection against the coronavirus. Once countries authorize a vaccine, they’ll only be able to vaccinate a few percent of their citizens at most in the first couple months. The unvaccinated majority will still remain vulnerable to getting infected. A growing number of coronavirus vaccines are showing robust protection against becoming sick. But it’s also possible for people to spread the virus without even knowing they’re infected because they experience only mild symptoms or none at all. Scientists don’t yet know if the vaccines also block the transmission of the coronavirus. So for the time being, even vaccinated people will need to wear masks, avoid indoor crowds, and so on. Once enough people get vaccinated, it will become very difficult for the coronavirus to find vulnerable people to infect. Depending on how quickly we as a society achieve that goal, life might start approaching something like normal by the fall 2021.

Yes, but not forever. The two vaccines that will potentially get authorized this month clearly protect people from getting sick with Covid-19. But the clinical trials that delivered these results were not designed to determine whether vaccinated people could still spread the coronavirus without developing symptoms. That remains a possibility. We know that people who are naturally infected by the coronavirus can spread it while they’re not experiencing any cough or other symptoms. Researchers will be intensely studying this question as the vaccines roll out. In the meantime, even vaccinated people will need to think of themselves as possible spreaders.

The Pfizer and BioNTech vaccine is delivered as a shot in the arm, like other typical vaccines. The injection won’t be any different from ones you’ve gotten before. Tens of thousands of people have already received the vaccines, and none of them have reported any serious health problems. But some of them have felt short-lived discomfort, including aches and flu-like symptoms that typically last a day. It’s possible that people may need to plan to take a day off work or school after the second shot. While these experiences aren’t pleasant, they are a good sign: they are the result of your own immune system encountering the vaccine and mounting a potent response that will provide long-lasting immunity.

No. The vaccines from Moderna and Pfizer use a genetic molecule to prime the immune system. That molecule, known as mRNA, is eventually destroyed by the body. The mRNA is packaged in an oily bubble that can fuse to a cell, allowing the molecule to slip in. The cell uses the mRNA to make proteins from the coronavirus, which can stimulate the immune system. At any moment, each of our cells may contain hundreds of thousands of mRNA molecules, which they produce in order to make proteins of their own. Once those proteins are made, our cells then shred the mRNA with special enzymes. The mRNA molecules our cells make can only survive a matter of minutes. The mRNA in vaccines is engineered to withstand the cell's enzymes a bit longer, so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.

But given your risk profile — you are not elderly and have, I gather, a job that allows you to practice social distancing and all the rest — you could reasonably decide to enroll in the study and abide by its rules. At the very least, you should tell the researchers what you plan to do and let them decide if they still want to enroll you in the trial. Right now, what you’re doing is getting a good chance of protection under false pretenses.

My elderly parents are still living in their home. They go to restaurants a couple of times a week; visit friends’ and relatives’ houses; have friends and relatives over for meals and visits, etc. They do not wear masks in their home.

I expressed my concerns about their behavior, but they say that we all have to choose the risks we are willing to take. Their feeling is that if they catch the coronavirus, they have had long and productive lives.

My concern is that they have home health aides who come in a few hours every day. I do not know if they know about my parents’ activities outside the home. I am worried that they are putting these people at risk. Do I have a moral responsibility to notify the company that provides this service? Name Withheld

Oh, dear. Your elderly parents seem to be running a trial of their own — a deeply misbegotten one and blind in all the wrong ways. According to estimates published in Nature last year, Covid-19 kills nearly one in nine of the men over 80 who gets it, and one in 17 of the women. Some of those who survive may never regain their health. Try as hard as you can to get your parents to focus on the gravity of the risks. You might relay some accounts of what being very sick with Covid-19 is like. You could point out that if one or the other of them does get sick, the last time they’ll be able to hold hands may be waiting for the ambulance.

Still, they are taking these risks knowingly; their caretakers, by contrast, may be unaware of your parents’ reckless ways, even as it increases their chances of exposure. What would be most respectful is to ask your parents to tell the people at the agency what’s happening — unless you’re the person who normally communicates with the agency, in which case you should tell your parents that this is what you plan to do.

For the sake of everyone involved, I dearly hope that they will be able to be properly vaccinated before long. Vaccine-induced immunity can take some time to develop, and if your parents were sensible, they would continue to take precautions even after they were immunized; we’re still awaiting empirical confirmation that vaccinated people won’t — at least at any significant rate — continue to spread the virus. But whatever happens, these home aides are entitled to have a clear picture of what risks they face when they are in your parents’ home.

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