Pfizer study of covid-19 vaccine in pregnant women delayed by slow enrollment5 min read . Updated: 22 Sep 2021, 06:43 PM IST
- Changing guidelines, possibility of being given placebo made trial unappealing to some expectant mothers
A study led by Pfizer Inc. and BioNTech SE evaluating their Covid-19 vaccine in expectant mothers has been complicated by slow enrollment, researchers say, delaying results that could help inform physicians about how the shots affect pregnant women and their babies.
Pfizer closed enrollment at many U.S. sites this summer, after fewer than expected numbers of subjects entered the study, researchers say. The slow enrollment was driven by revised guidelines from government and physician groups that recommend pregnant women receive the shots based on new real-world research, according to trial-site researchers. They also say increased vaccine supply made a trial that included the possibility of being given a placebo instead of a vaccine unappealing to expectant mothers and raised questions about the ethics of seeking volunteers.
“It’s hard to enthusiastically recommend the study when you’ve got a vaccine out there," said Dr. Andrew Wagner, an obstetrician-gynecologist whose Saginaw, Mich.-based practice enrolled fewer than a dozen subjects, mostly in the spring before the vaccine became widely available. “The scientist hat I wear says you want those patients, but obviously the clinician in me says, ‘You’ve got to get your vaccine.’ "
Pfizer also had trial sites overseas, according to a government database. A company spokeswoman didn’t comment on the overseas enrollment, but said that due to the updated guidance and expanded vaccine availability in the U.S., it decreased the number of subjects in the trial after a few months of study. Pfizer plans to share safety results and still plans to complete the trial, the spokeswoman said.
The revised vaccine guidelines were driven by observational studies—conducted by government and academic researchers but not vaccine makers—that showed Covid-19 shots work safely in pregnant women. Vaccine makers also found their shots to be safe in studies of pregnant animals and their babies.
Amid the sluggish enrollment, Pfizer has missed public targets for the results of the study of pregnant women. Safety data was forecast by early August with full results by the end of the year. The drugmaker now expects results early next year, Pfizer Biopharmaceuticals President Angela Hwang said at an investor conference last week.
Maternal and fetal medicine experts say Pfizer’s study is important because the best way to see if a vaccine works is to conduct a trial in which some participants randomly receive a placebo and researchers compare infection rates with a vaccinated group. They also say a trial could confirm findings of other studies that showed antibodies in mothers are transferred to babies.
Expectant mothers are more likely to have severe Covid-19 than women who aren’t pregnant, and have a higher chance of having a preterm delivery if they contract the disease, according to studies. The number of pregnant women who are vaccinated remains relatively low compared with the national average.
Johnson & Johnson is enrolling women who are between 16 and 38 weeks pregnant for a mid-stage study in which all subjects are given the vaccine. Moderna Inc. isn’t conducting a trial of its shot in pregnant women.
Pfizer excluded pregnant women from participating in its large late-stage study last year because it wanted to first test the vaccine in people who weren’t pregnant, the company has said.
For its pregnancy trial, Pfizer in February began enrolling healthy adults who were 24 weeks to 34 weeks pregnant, hoping to study 4,000 women. Pfizer said it chose that stage of pregnancy because it is a period when expectant mothers can safely receive some other vaccines. Antibodies for other shots have also been shown to transfer to babies in that time period, the company said.
Enrollment started strong, researchers at more than a half-dozen sites said, because the trial was a way for women to potentially get vaccinated when the U.S. had scarce supply. The women learned if they received a placebo or vaccine after giving birth. Those who received the placebo were then offered the vaccine.
Researchers also said that some women liked the extra care they received from being in a trial when there wasn’t clarity from health authorities about whether pregnant women should get the shot.
Madison Omdal, 28 years old, was eligible for the vaccine as a college sports athletic trainer but joined Pfizer’s study in March because of uncertainty at the time over how the shot could affect pregnancy. Though Ms. Omdal ultimately received the vaccine in the trial, she said she was willing to receive a placebo because her pregnancy was categorized as low risk.
“They were still not 100% recommending it," Ms. Omdal, who lives in Salt Lake City and gave birth to a girl in June, said of the vaccine. “It was a pretty stressful time to be pregnant."
Initially, the U.S. Centers for Disease Control and Prevention, and two maternal-medicine groups—American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine—didn’t outrightly recommend vaccination for pregnant women, saying instead that they should make the decision after discussion with their doctors.
Then in April, the CDC recommended pregnant women become vaccinated, citing data from a large study by its researchers. It reiterated that recommendation in August, after it found that pregnant women who received an mRNA vaccine during the first 20 weeks of pregnancy didn’t have an increased risk of miscarriage.
Data from three national safety monitoring systems didn’t find safety concerns for women who were vaccinated late in pregnancy, or for their babies.
ACOG and SMFM revised their guidelines, too, suggesting pregnant women become vaccinated, based on the recent research.
Enrollment at U.S. sites began to lighten, and Pfizer began halting recruitment at multiple locations starting in late June, researchers say. Some sites stopped accepting new subjects and others that planned to participate backed out because they found it unethical to ask patients to risk receiving a placebo.
Northwestern Medicine in Chicago planned to serve as a trial site but backed out when data showed shots were safe for pregnant women, said Dr. Emily Miller, assistant professor in Northwestern’s Division of Maternal-Fetal Medicine.
“There’s been an enormous amount of science that’s filled the chasm that was left by the exclusion of pregnant people from the trials," she said. “We thought that we can’t really ethically randomize people or give people placebo when they had access to get the vaccine."
At Bingham Memorial Hospital in Blackfoot, Idaho, slow enrollment was partly due to the changing recommendations, which contributed to vaccine hesitancy, said Kim Lowe, who oversees clinical research. She said that women who were interested in receiving the vaccine wanted to get it earlier in their pregnancies than the trial permitted.
Ms. Lowe said the hospital enrolled fewer than a dozen people before Pfizer stopped recruitment at the site in the summer.
University of Utah Health enrolled about 30 subjects by the start of summer but decided, with Pfizer, it wouldn’t enroll more women because of emerging data and the revised recommendations, said Torri Metz, associate professor of obstetrics and gynecology.
“It’s really a shift in the way we talk with patients about it, and the advice that’s out there for them," Dr. Metz said.
This story has been published from a wire agency feed without modifications to the text
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