Worldwide, teams of researchers are racing to develop COVID-19 vaccines and therapies to stem the spread of the virus. Many of these drugs, including 7 vaccines, are in phase 3 clinical trials — the final stage of drug development. That means that they’re already being administered to thousands of people in the general public.
But not everyone has the opportunity to take part in these trials. Pregnant women are among those populations excluded because new drugs have a unique potential to harm mom and her fetus and including pregnant women in studies can interfere with study results. The exclusion is standard practice for new vaccines. Not everyone is happy. There are major downsides to this routine exclusion — ones that are particularly pressing with COVID-19.
Excluding pregnant women from clinical trials leaves us with limited data on that population and delays their access to treatment. For years, regulatory bodies, including the U.S. Institute of Medicine and the National Institutes of Health, have advocated for the inclusion of pregnant women in drug trials. A recent article published in Ethics and Human Research argued that in light of coronavirus, the scientific community needs to change its approach. Fatherly spoke to Dr. Rachel Pope, an obstetrician-gynecologist at University Hospitals Cleveland Medical Center and co-author of the paper about the risks of including pregnant women in clinical trials — and of leaving them out.
What are the risks of including pregnant women in clinical trials?
We know that women’s immune systems are slightly altered during pregnancy. It’s not that they’re weakened but they do respond to things a little bit differently. And so that makes things more complicated. She may not react the same as the average non-pregnant woman.
And then the other complexity is that there’s a developing fetus. You have cells that are rapidly dividing, and developing organs. Anything that could potentially interfere with that process is potentially dangerous.
But when you look at therapies for COVID-19, many of the medications that are being studied are things that already exist. Like hydroxychloroquine, remdesivir, azithromycin — these are all things that have been used for other purposes. And the interesting thing is that many of them have actually been used for pregnant women for years, but for other reasons. Azithromycin has been used for treatments of sexually transmitted infections in pregnancy with no concern at all. Hydroxychloroquine has been used by pregnant women with lupus or other autoimmune diseases. But now that they’re being repurposed for COVID-19, suddenly we’re seeing that pregnant women are being excluded from those trials.
“It comes from good intentions of wanting to protect the fetus from things that are unknown, but it may come at the price of the health of a woman.”
So, why exclude pregnant women?
One reason could be that they want to give doses that are very high, and maybe those doses haven’t been studied in pregnancy.
Then when you think about studying pregnant women, you have a mom and you worry about her side-effects, and then you have the fetus, you worry about side-effects to the fetus. The same way that people are hesitant to study new medications in children, they don’t study them in pregnant women, because they don’t want to expose the fetus.
It comes from good intentions of wanting to protect the fetus from things that are unknown, but it may come at the price of the health of a woman. I think that brings in the whole ethical question of well, who are we valuing here? And if we think that this medication is otherwise safe, then why would you not offer it to her and let her make the decision whether to expose the fetus or not?
There are also the hurdles that you have to jump in order to clear your regulatory or ethical reviews. That deters people. There are more forms, you have to explain not only that you know the risks to the mother, but also to the fetus. You may have to consult the father of the fetus. There’s just a whole other layer of complication that comes in.
“The implications could be years of delayed treatment or years of delayed access to vaccination.”
What happens when we exclude pregnant women from clinical trials? What are the risks?
A lot of people feel like, well, we’ll study this for the general population, and then we’ll look at pregnant women. But the implications of that could be years of delayed treatment or years of delayed access to vaccination.
One example of that is Ebola. As a vaccine has been developed for Ebola, pregnant women have been excluded from it. Keeping them out of those initial trials meant that their access to the vaccine was subsequently delayed as well.
It could be risks that are not just health-related but also socio-economic. So if we continue on, and most people are able to get vaccinated, but pregnant women aren’t — imagine the rest of us kind of getting on with their lives, but then pregnant women being stuck. I think that could have pretty damaging effects on their careers and livelihoods and potentially also emotional and mental health.
How has the conversation around this played out in the scientific community?
It’s actually encouraged to include women who are pregnant, but I don’t think that that’s the reality. I mean, personally, I think it’d be better to have the option. Then women can decide whether they want to take the risk or not. But yeah, but I think that’s a big disconnect.
In an ideal world, what would clinical trials look like, with pregnant women?
There should either be an option to offer it to pregnant women and they decide that for themselves, you know, understanding that we have little idea about whether the drug will work for them, its side-effects. I mean, it’s the same thing as a man or non-pregnant woman who decides to take the vaccine. We have no idea.
The other way to go if we’re going to fast-track a vaccine, is we think about these other populations like pregnant women, and we fast-track them as well. So as soon as things are deemed to be safe enough for the general population, then the trials for the subpopulations, like pregnant women and children are started and similarly fast-tracked. So that there’s not this huge delay: we have this rush to find a vaccine that gets to the general population, we find something and then we slow down and we don’t push the same way for pregnant women.
That’s kind of what I imagine happening. I hope I’m wrong.