I am a subject of NL002-0060 and have dropped out of the COVID-19 vaccine trial | Science

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I’ve been working on a dilemma for the past few weeks. Will you stay in the COVID-19 vaccine trial that you have enrolled for 4 months? Or do you have a strong desire to succeed? Or do you drop out and take it? Already proven vaccines, and protect yourself faster? This is a question faced by thousands of test participants over the last six months, but I don’t hear much about it.

I knew I could face this dilemma from the day I drove to a huge academic center in my hometown of southeast Amsterdam and enrolled in the HERALD study. Company CureVac. I sat in a small basement with my infectious disease doctor, provided basic information about my research, gave me a signature consent form, and did a physical examination.

Then came an important moment: I was going to be randomly assigned to receive either an vaccine or a placebo. The researcher clicked a few buttons to see her screen. “The wheel of fortune will rotate,” she said. Then she read the message that popped up: “Thank you. The subject was successfully randomized.”

Thirty minutes later, the nurse gave me an injection. Neither of us knew what was in it. 12 micrograms of RNA, wrapped in small fat bubbles, may prevent illness and death. Alternatively, a few milliliters of salt water.

It was a worthy bet for me. With a high number of cases in the Netherlands, there was a 50% chance of receiving a candidate vaccine when the more contagious mutants that first appeared in the UK were taking over. The dose was low in Europe, so months before I qualified for a proven vaccine. Aside from the chance of protection, I played a small role in one of the great scientific efforts of my life and, if I was lucky, was happy to help another vaccine cross the finish line.

CureVac looked promising enough. In 2020, scientists will say that hamster And monkey.. A Phase 1 study Found almost moderate side effects, and a dose of 12 micrograms appeared to provoke a good immune response in human volunteers. Although a latecomer to the vaccination race, the vaccine named CVnCoV requires very low temperatures to maintain stability, the Pfizer-BioNTech collaboration and two other messenger RNAs (mRNAs) developed by Moderna. It has potential advantages over vaccines. In contrast, CVnCoV can be kept at room temperature for at least 3 months at 5 ° C, which is the normal refrigerator temperature, for 1 day at room temperature. This is a big advantage, especially in developing countries. (Pfizer and Moderna are also working on less vulnerable formulations.)

Headquartered CureVac Tubingen, Germany, Prompt approval from the European Medicines Agency seemed to play a major role in Europe as well.European Commission Ordered 225 million doses in November 2020, And there are 180 million more options. To meet expected demand, the company partnered with Bayer in January.

But first, the trial will have to show that it worked. Released in December 2020 In Germany, HERALD eventually registered more than 35,000 people in four European countries and six Latin American countries.

No side effects

It was safe to be the subject of research. There were no side effects from the first shot or the second shot four weeks later. Participating in the trial did not increase the risk of a well-known phenomenon in vaccine research. Given the low risk of exposure, I even wondered how useful the vaccine could be in testing its ability to prevent infection. I work from home and pay attention to social contact. I returned to the hospital for a COVID-19 test once in February when I had very mild symptoms. The test has returned to negative.

The written information I received about this study did not explain the options for participants to qualify for a proven vaccine. And at first it seemed to me that I didn’t have that choice. Vaccinations in Europe are slowly progressing, and the research team told me that the study would probably report the first data within a few months before I qualify for a licensed vaccine. CureVac planned to conduct a final analysis of the study after the outbreak of 185 confirmed COVID-19 infections. Clinical trial protocolHowever, the first interim analysis was scheduled after only 56 cases, so it shouldn’t be long. (Efficacy is calculated by comparing the number of cases of symptomatic disease in the vaccine and placebo groups.)

If the trial reaches a definite conclusion and is canceled, I will not be blinded. As researchers expected, if CVnCoV was shown to work, I basically have two options. If you receive a placebo shot, you will be vaccinated and safe. If I had received CVnCoV, it was much safer and I didn’t need anything else.

A Cureback FAQAlthough still posted, the company says it plans to publish an interim analysis in the first quarter of this year. But that deadline has passed and in April the pace of vaccination in my country began to accelerate. Starting with people over the age of 90, municipal health services went down the birth cohort.As the weeks went by, my year of 1964 Tubingen..

If that happens, I may not be blind either, the researchers said, but that would open another set of questions. If it turned out that I received a CVnCoV shot, I was altruistic and could hit the tree that the vaccine behaves like any other mRNA vaccine and stay in the test until complete. Or, I made a safety mistake, dropped out, and got whatever the government planned for me. If it turned out that I had a placebo, I had the same two options, but it would still be difficult to stay because it is not completely protected. (In that case, the trial did not provide a vaccine because its value has not yet been demonstrated.)

We sought advice from two scientists who also volunteered for the COVID-19 vaccine trial. Florian Kramer, a virologist at Mount Sinai School of Medicine and a subject of Pfizer’s efficacy study, said that analysis of study data shows that the Pfizer vaccine is highly effective. “Of course, I’m a data point, so I was thinking of staying blind,” says Krammer. “But there were many cases of COVID-19 at the time.” Moreover, if he was found to have a placebo, Pfizer provided a shot to Kramer and he remained a data point, As part of the other arm of the trial. Kramer chose not to be blinded, learned that he had a placebo, and was vaccinated in January. He is still studying.

My situation was different because CureVac didn’t have any validity data yet. Kramer said it was “noble” to stay there, but I also said I should think about myself. “Signing up for a trial is already very, very helpful,” he said. “No one can expect you to stay if there is a vaccine that prevents you from getting seriously ill or dying.” He said that dropping out now would not completely invalidate my participation. I pointed out. The last four months have already been part of the data. And this wasn’t just for me, he added: “What if you stay in a placebo group, you get infected, you get infected with someone else, and that person dies? ? “

Weill Cornell Medical College virologist John Moore faced a slightly different dilemma. He volunteered to study the efficacy of the vaccine produced by Novavax in the United States and Mexico. Started in late December 2020.. At some point in February or March, Moore said he decided to continue his research after qualifying for a hospital-certified vaccine.

Interim data from a study conducted in the UK in late January Novavax shots show 89% effectiveness, And on April 5, the company announced that its UK, US and Mexico studies would switch to “crossover design.” This means that all participants will be provided with two more shots. The first person to receive a placebo now receives the vaccine and vice versa, but everyone remains blind. The advantage for participants is that everyone knows that they are protected. For the company, it is a way to keep more people involved in the trial, for example, allowing better research on responses that correlate with immune duration and protection.

Moore accepted the crossover offer and received two shots, the last shot on May 11. He is confident that he is now protected, but remained unvaccinated for four to six weeks longer than if he dropped out. “I didn’t think the delay would cost me that much,” he says. “But if it were four to six months, of course my dynamics would have been very different.”

CureVac hasn’t said whether it will move to a crossover design. In fact, he talks very little about the dilemmas faced by volunteers. Moore also said that decisions should be made based on my own circumstances. It’s not a prison. “

Day 120

On May 16th, my age group was eligible for the mRNA vaccine. I quickly went online and confirmed my appointments for the first and second doses. I hadn’t made a decision yet, but I thought I could cancel at any time.

It happened that I was planning to have a physical examination 4 days later and 120 days after registration. During the visit, the fourth time I told the researchers that it was my turn and briefly explained the possible scenarios. Then I asked her not to blind me. She rotated the computer screen in my direction so I could see the steps I needed. And suddenly it was a “placebo”.

I didn’t have to think for a long time. I am looking forward to being safe from COVID-19. I want to regain my life in 2019, or something similar. Summer is approaching, and even with two appointments, it will take until early July to be fully protected. “I want to stop the trial,” I said. The doctor said she understood. That’s what most people in my situation did, she said.

Today, I biked to one of Amsterdam’s temporary vaccination centers, inside a large empty conference center, and received my first Pfizer-BioNtech shot. The Wheel of Fortune didn’t give me what I wanted, but I still felt very lucky.