CMDA's The Point

A Vaccine Trial is Not a Trial: What Participating Looks Like

September 24, 2020
05182020POINTBLOG

by Amy Givler, MD

I love vaccines. To those of you who have read my other articles on the subject (available here and here), this comes as no surprise. But, you may rightly say, “love” is an awfully strong word. Shouldn’t I only love people, not things?

I love vaccines because I love people. Millions of people are alive today only because they were vaccinated. Who are these people? Nobody knows, because the vaccine kept them from getting sick and dying. One of them could very well be me. Or you.

Soon there will be a brand-new vaccine—or multiple vaccines to protect against SARS-CoV-2, the virus that causes COVID-19. For simplicity’s sake, I will call them “COVID vaccines.” About 200 of these vaccines are in development. By no means am I following the progress of all of them, but I am keeping up with the frontrunners.

The endpoint that vaccine trials look for is prevention (not getting sick at all) or lessening of disease (getting less sick, as in not having to be hospitalized or enter the ICU, or not dying). “Disease” is different from “infection.” If someone is infected with the virus, but not sick, they are asymptomatic themselves but could still spread it to other people.

A few vaccines prevent infection, but the majority protect against disease. It would be gloriously wonderful if a COVID vaccine ends up being safe AND prevents infection. But that is not how “success” is being measured at this point. Success is being defined as 80 percent efficacy in preventing disease. That is, eight out of 10 people exposed to the virus don’t get sick, even if some of them (or all of them) still get infected.

For an update on the various vaccine candidates for COVID, listen to the first 47 minutes of a great podcast called This Week In Virology, episode 663. The host is a virologist, and he interviews Dr. Daniel Griffin, a clinician who shares the good and the bad of vaccines in general and how they work. And no, he doesn’t shy away from describing possible side effects of vaccines. And yes, he is still pro-vaccine. Vaccines benefit vastly more people than they harm.

At the end of the interview, the host asked Dr. Griffin which vaccine he would personally prefer to get, from what he knows at this point, if he was offered any of them. He said, “I really like the mRNA vaccines…I like the mRNA approach.”

“Yes!” I thought. “My feelings exactly.”

I had a particular and personal reason for agreeing with him. I signed up for the Pfizer mRNA vaccine trial and got my first shot last week.

When I first signed up for the trial, I didn’t know much about Pfizer’s vaccine. Truthfully, I didn’t think I would hear from them because I had already signed up for two other COVID vaccine trials and never heard back. But this one is only 90 minutes away from me in northern Louisiana, so maybe the others didn’t have study sites nearby.

I got a call the day after I signed up, giving me my first appointment in a week. As I hung up, I thought, “What have I done?” I was about to become a guinea pig. So I did what most science-minded people would do—I took a deep dive into the available research.

There are two potential mRNA vaccines, one developed by Moderna and one developed by Pfizer (and BioNTech). Even though they are developing “new” vaccines, these companies have been developing the expertise for 10 years.

Why is this particular vaccine platform so promising? Because it is basically a “plug and play” system that stands at the ready for when a deadly new infectious disease comes along, just as COVID-19 did 10 months ago. You just have to figure out what protein you want to make, and then insert the code for making that protein into mRNA.

Because of previous experience with Coronaviruses, scientists knew the spike protein on the surface of the virus needed to be the target for vaccines. Coronaviruses use their spike proteins to enter cells, so if you have antibodies to the spike protein, you can stop them in their tracks.

The spike protein alone is harmless. It takes the entire virus to be able to infect the cell. So mRNA vaccines work by putting the code to make the spike protein into mRNA, coating it with a fatty layer (so it gets past the cell membrane) and injecting it in the recipient’s arm.

The mRNA takes it from there. Once inside the recipient’s cells, it starts churning out the protein, and when that protein is displayed on the outside of the cells, the person’s own immune system kicks into gear. B cells make antibodies to the spike protein, and T cells make memory cells.

Any vaccine has some risk for side effects, but, after researching, I think an mRNA vaccine has a lower risk than most. That is because the immune response is mounted against only a single protein. Some vaccines are an injection of an inactivated (but otherwise whole) virus, consisting of numerous different proteins. An immune response is made to all of those different proteins, which increases the risk of side effects because of all the cross-reactions taking place.

And any risk of a vaccine has to be compared to the risk of the virus itself. In this case, it’s a virus that has already killed 200,000 people in the U.S., and nearly a million people worldwide. And it’s still going strong.

Being part of a research study felt sort of like being in a doctor’s office, and sort of not. I filled out no paperwork—the lead investigator personally asked me my medical history only after going through 19 pages of information with me, answering my several questions and getting my informed consent.

And only after that did a nurse take my vital signs, swab my nose and draw four tubes of blood. I was given a self-swab kit for me to test myself for COVID if I ever develop symptoms. I also got a debit card with $119 loaded onto it, and every time I visit the clinic, I’ll get $119 more. That was a sweet surprise. Every week I’ll answer questions on a cell phone app about symptoms, and I’ll get $5 each time. I need to let them know if I get sick anytime in the next 26 months.

Finally, I got my first injection and sat in a side room with an attentive nurse for 30 minutes. My second injection will be three weeks later, and there are four more planned visits after that, stretching out two years, for more blood draws.

So did I get the vaccine or a placebo? I was eagerly awaiting a sore arm (such as I always get with the flu shot) to tell me I had gotten the vaccine. But the next day I felt fine. No achiness, no sore arm. Drat. I hadn’t realized how much I was hoping I would get the vaccine. I really don’t want to become sick with COVID.

But then, 27 hours after the shot, I felt my arm and it was definitely tender at the injection site. Just a little, but definitely tender. So who knows?

My 96-year-old father asked me how old the people in Pfizer’s study are. “As young as 16 and as old as 85,” I said.

“So if they’re not testing it in people my age,” he said, “how will I know it is safe for me?”

Excellent question. I guess we won’t know, though I think 85 is as close to 96 as we’re going to get. But how many 85-year-olds are signing up for the trial? Men and women, a span of ages, and all genetic backgrounds need to be represented in vaccine trials if we are to know the vaccines are effective and safe.

Since the study lasts 26 months, all the data won’t be available until 2022. So I suspect the only way a vaccine will be licensed in 2021 will be under an “EUA,” an Emergency Use Authorization. As long as the data (for both safety and effectiveness) is compelling, I have no problem with that. The greatest minds in virology, immunology and statistics are working on this question. I am comforted by that.

And I’m glad to play my small part.

About Amy Givler, MD

Amy Givler is a family physician in Monroe, Louisiana. She and her husband Don met in 1980 at a CMDA student event her first year of medical school, and they have both been active members of CMDA ever since. Amy graduated from Wellesley College and Georgetown University School of Medicine, and she then completed her family medicine residency at the same indigent-care hospital where she now works part time. She also works at an urgent-care clinic and is the medical director for a Shots for Tots clinic. Amy loves to write and has written many articles and one book, Hope in the Face of Cancer: A Survival Guide for the Journey You Did Not Choose. She and Don have a heart for missions, and hope to do more short-term trips now that their three children have launched from the nest.