After getting my first shot in a clinical trial of a COVID-19 vaccine last month, I spent the evening feeling my forehead and raising my arm to test for soreness. Because I was not feverish, I wondered if the heat in our house was set too low.
All this in a vain attempt to figure out if I had been injected with a placebo or the real thing.
The use of the placebo in medicine was a huge advance because it helped eliminate bias that can skew the results of drug research and contribute to ineffective or unsafe products getting on the market.
But not all placebos are foolproof.
In clinical trials of pain treatments, people may suspect they did not get the real thing if their pain doesn’t get better or if they don’t feel the narcotic buzz that can occur with an opioid. In trials of smoking cessation treatments, people may be suspicious if their urge to smoke doesn’t subside.
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For COVID-19 vaccines, a possible telltale sign that the person got a placebo is if they did not have a reaction such as a slight fever, a little achiness, headache or a sore arm.
This little quirk in COVID-19 vaccine science, it turns out, is no small matter. There now are likely to be tens of thousands of people like me who volunteered for a COVID-19 vaccine clinical trial and who suspect they got a placebo.
As vaccines get approved and become available in the coming weeks and months, many of us may be weighing whether to drop out of our trials and get vaccinated with the real thing. But if we do that, we no longer are of much use to the trials we are in because the long-term data on safety and effectiveness that we can generate essentially will stop.
I have been fixated on this issue ever since Nov. 16 when I got my first injection in a clinical trial of AstraZeneca’s COVID-19 vaccine at the University of Wisconsin School of Medicine and Public Health.
The only thing I felt after getting the shot was disappointment because I did not have any of those symptoms. Though two out of every three people in the trial got the actual vaccine, and one in three got a placebo, I began thinking that I was in the placebo group.
Then I got an email from Kris Pfeiffer, another person in the trial who had the same experience.
“I had absolutely zero reactions to it,” said Pfeiffer, 49, who lives in Waukesha County. “My arm was less sore than what I’ve experienced with flu shots. My guess would be that I received the placebo, but I can’t be sure. What about you?”
Same thing, Kris. My wife felt my forehead the night I got my first shot. She said it felt clammy, which unfortunately, doesn’t appear to be one of the main reactions to the vaccine.
Maybe I’m just a non-reactor. In September, I got a high-dose flu shot and my second shingles vaccine, both on the same day. My arm was a little sore, though I did not have any other reaction.
In any event, Pfeiffer’s email changed my thinking a tiny bit. Since each of us had a one in three chance of getting the placebo, then the chance of both of us getting the placebo was one in six, essentially the same odds of losing a game of Russian roulette with a real revolver.
Recently, I’ve been looking for data on how many people in COVID-19 vaccine trials experience various reactions. Headache, muscle ache or fatigue was experienced by a minority of people after the first vaccine, and older people were less likely to have those reactions.
More people seem to have a reaction to the second shot than to the first, said William Hartman, principal investigator for the UW arm of the AstraZeneca trial.
“We hear all the time, ‘We must have gotten the placebo,’ ” said Hartman, an assistant professor of anesthesiology at UW.
So it is possible that AstraZeneca’s vaccine just doesn’t produce reactions in some people. I am going to stick with that story for a while, or at least until mid-December when I get my second shot, a booster.
But it raises some questions about what will happen with many of the AstraZeneca and other drug company trial volunteers who got shots of salt water rather than the real thing. While the AstraZeneca trial gave two real injections for one placebo, in other big trials the breakdown is 50/50.
Once effective vaccines are on the market, which likely will be in the first three months of next year, some of the volunteers may want to opt out of their trials if they think they got a placebo because they want to be protected, said Marc Lipsitch, a professor of epidemiology at Harvard School of Public Health.
It is unclear when volunteers will be told by the drug companies whether they got a placebo.
“I don’t know how it all will shake out,” he said. “You can’t stop someone, just because of the trial, from taking a measure to protect their health.”
Once their vaccines are approved, drug companies actually may offer their vaccine to trial participants who got placebos, he said, especially those in higher-risk groups. Doing so would be an acknowledgment of the person volunteering.
But there also has been talk of the placebo volunteers having to wait two years for that.
I have not decided if I will drop out because I think I got the placebo.
Would doing that be double-dealing, I wondered?
Seeking reassurance from a bioethicist, what I got was less than 100% absolution.
“On the one hand, you already did more than many people; that’s laudable,” said Jennifer Miller, an assistant professor at Yale University. “But you agreed to help test the vaccine.”
Yes. I did. The consent form that I signed states that my participation will last for two years and that I will be expected to come to the study site 13 times and provide blood draws and nose swabs. But the form also states upfront that I can later change my mind, and that will not be held against me.
I get my second shot in the clinical trial on Dec. 14. I am hoping for something a little more than clammy.