Is COVID Vaccine Research in India Failing Pregnant Women?

What the COVID vaccine trials tell us about the blind spots in clinical research.

Is a ‘lack of data’ a good enough reason to deprive pregnant women in India of the COVID vaccine?

iStock / altered by FIT

(Update: As of 13 May, the government advisory panel, The National Technical Advisory Group on Immunisation in India (NTAGI), has recommended that pregnant women in India be given the choice of taking any COVID vaccine, and that lactating women are eligible after delivery.

The recommendation will have to be reviewed by the Health Ministry's National Expert Group of Vaccine Administration (NEGVA), before it is implemented.)

In the year 1977, a freak incident involving adverse reactions to Thalidomide, a sedative, led the US FDA to decide 'women of childbearing potential' should be excluded from vaccine trials because they were deemed to be too 'complex' and 'risky'.

Sixteen years and numerous pushbacks later, the US made it compulsory by law to include women in clinical research.

This was a major step in the history of women’s representation in medical research.

However, fast-forward to a few decades later, and the vestiges of this attitude towards 'women with child-bearing potential' still have a hold on medical research.

And unfortunately, this hasn't changed with the COVID vaccine research.

A closer look at the clinical trials for the COVID vaccines remind us of the history of gender bias that lurks in medical research.

A bias that is conversely keeping these 'vulnerable' groups from receiving vital protection.

Pregnant Women and Vaccines: A Roadblock to Safety

When the vaccines were first rolled out globally in December, they came with an impossible choice for some, ‘take a vaccine that’s not been tested on pregnant people, or risk getting COVID.’

In India, this choice was made for them by the government.

But let's backtrack a bit.

Excluding pregnant and lactating women from the clinical trials of COVID vaccines stems from a long-standing obstacle of systemic exclusion.

Historically, pregnant women have been categorised as ‘too vulnerable’ and have been excluded from clinical research because of the high risk of complications they face, especially in the second and third trimesters.

But the catch 22 here is that pregnant women are also extremely vulnerable to adverse COVID complications.

"The question then becomes, shouldn't they also be considered a priority population?" says Dr Anant Bhan, Adjunct Professor & Researcher in Bioethics at Mangaluru’s Yenepoya University.

This systemic exclusion is especially problematic, considering a big portion of the healthcare workforce is made up of 'women of reproductive age'.

Speaking to FIT, Amar Jesani, Editor of the Indian Journal of Medical Ethics, says, “Not including pregnant women in the clinical trials of COVID vaccines was ethically wrong as it was known that pregnant women do face a significant risk of infection."

Shutting them out of vaccine trials means delaying the vaccine and denying protection to a subgroup of people who fall in the high-risk category.

This is exactly what's happening in India right now.

Health experts across the world, including the World Health Organization (WHO), the US FDA and CDC, and the Federation of Obstetric and Gynaecological Societies of India (FOGSI), almost unanimously assert that it is safe for pregnant and lactating women to take the COVID vaccines.

The UK National Health Services (NHS) has also announced that they will be allowing pregnant women to get vaccinated.

However, despite these strong recommendations, the Ministry of Health and Family Welfare in India continues to list pregnant women and 'women who are not sure of their pregnancy' as contraindications to the vaccine, stating that there is no data to prove its safety as they have not been part of any of the clinical trials.

This would have been a sound decision (considering the limited safety data we do have comes from retrospective studies that apply to mRNA vaccines) if efforts were underway to generate the said data in the country on an urgent basis. Why are pregnant women still being shut out?

The vaccine dilemma: Why are pregnant women still being shut out?iStock

'Vaccine for All...But at Your Own Risk': What Is the Advice With Covaxin and Covishield?

“For Covaxin, the company hasn't released any paper in a journal or pre-print, so we do not know much about the vaccine, except what has been released in press notes of the company,” says Amar Jesani.

In these, Covaxin clearly states that pregnant and lactating women should not be taking the vaccine.

Covishield, on the other hand, leaves it to the doctors to decide, giving no further information.

In fact, 'not enough data' and 'may take if the benefits outweigh the risks', are phrases one comes across often in COVID vaccine advisories across the board when it comes to pregnant women.

“It is a circular argument and we need to get around that. The reason vaccine companies don’t include pregnant women in their trial is because of liability. If anything goes wrong, the fact that she was participating in the trial leaves the company liable for paying compensation.”

Dr Gagandeep Kang, Virologist, Professor, Christian Medical College, Vellore

"They play it safe by just putting on their label that they have not evaluated the vaccines in pregnant women. You take this vaccine at your own risk," says Dr Gagandeep Kang.

“So then, if anything happens to the pregnancies, it’s not their fault. They told you, you decided to go ahead and take the vaccine.”

Dr Gagandeep Kang

In such a situation, what would be required to ensure they get the vaccine? Is it more data? Or alternatively, are we going to go ahead with it without data because the benefits outweigh the potential risks?

With the COVID vaccines, experts have taken a middle route based on available data superimposed with past knowledge and a risk-benefit analysis considering the theoretical risks.

"And that’s the exact dilemma we are having. In the absence of data, we have been forced to find other ways to make the assessment. If we had the data, we wouldn’t be arguing about it at all," adds Dr Bhan.

FOGSI, while acknowledging the lack of data, base their assessment on "basic science and animal studies" which have "not shown any teratogenic or adverse fetal or neonatal effects of the vaccine."

Speaking of retrospective studies, Dr Kang says, "Vaccines have been offered to pregnant women who are also healthcare workers in many countries. Over 35,000 women have been immunised in the US alone."

"There have been studies that have been done and published now, on pregnant women particularly with the mRNA vaccine," she adds.

In February, Pfizer became the first COVID vaccine to announce it was conducting clinical trials on pregnant women.

But can the data from mRNA vaccines really be extrapolated to apply to our vaccines, both of which are not mRNA-based?  

"You can’t even apply the data of one mRNA vaccine to another mRNA vaccine. The vaccine products are distinct even if they are on the same platform," says Dr Kang.

But she adds that in certain situations, we may have to make judgement calls based on what we know and what the situation calls for.

Should Pregnant People Get Vaccinated?

By this, Dr Kang is referring to the current COVID crisis that has gripped the country where leaving pregnant people vulnerable and unprotected could prove detrimental to them and their child.

Based on the recent risk-benefit analysis, Dr Bhan says, "The most sound thing to do is go with the recommendation of FOGSI and to cover them for now."

“Especially considering the stage of the pandemic we are currently in, it is imperative that anyone who is able to, gets vaccinated.”

Dr Anant Bhan

Dr Kang agrees, saying, “All inactivated vaccines, including Covaxin and Covishield, should be safe. I have no concern of a threat to the safety of pregnant women either."

But both Dr Bhan and Dr Kang add that extra steps, such as close monitoring over a period of time, will be needed to make up for the lack of safety data.

Dr Bhan says, "This (vaccinating pregnant and lactating people) will have to be followed up with stringent monitoring for any adverse reactions that may be linked to the vaccine."

Dr Kang adds, “Another thing that regulators can do is ask for a pregnancy registry which is essential to ensure that, when pregnant women are given the vaccine, a record is maintained of what happens during the pregnancy and after she delivers.”

Given recent risk-benefit analysis, experts agree that pregnant women should be given the COVID vaccine.iStock

The Case for Diverse Clinical Trials

In the meantime, meaningful steps must be taken to fill the gaps in safety and efficacy data.

At which point does "not enough data" stop being an acceptable answer to questions of neglected groups' safety?

"In vaccine response as well, the more data we have, the better we will be able to understand what's going on," says Dr Kang.

“So far, we have tended to ignore that women’s physiology is very different from that of men.”

Dr Gagandeep Kang

And the exclusion of pregnant women is only an extension of the lack of understanding of and consideration to women's physiologies in clinical research.

None of the COVID vaccine trials, for instance, have taken sex as a variable, even though, due to genetic factors, women tend to be at a higher risk of developing autoimmune disorders.

Women have also been reporting worse side effects after getting the vaccine. The cause for which might have been more apparent if sex was a variable in the clinical trials.

There is also the issue of blood clots.

In the last few months, two COVID vaccines – AstraZeneca and Johnson & Johnson's Janssen – have come under scrutiny for causing Thrombosis, a rare blood clotting issue.

Now, incidents of such blood clots from these vaccines are very rare occurrences. In fact, you're more likely to get blood clots from the COVID infection itself.

But considering all cases of blood clots from the J&J vaccine and most from AstraZeneca were women, segregated data in the initial trials might have given more clarity about the cause of the issue.

Subsequently, regulators would have been able to make a more informed call on the subgroups of people (if any) for whom the vaccine may be discouraged rather than throwing a wrench in the inoculation drives by pausing the concerned vaccines altogether.

Speaking specifically of the blood clots, she says, "Down the road, such a link may be established but at the moment the data is murky because of various factors and there is no evidence of any of the effects of the vaccine being predictable."

"Unless we have more granular data, we will never know," she adds.

“Rather than complaining about the absence of data, we need to be generating our data. And that onus falls on us as a country. We have a large community of trained professionals and institutions where these studies can happen with priority.”

Dr Anant Bhan

Because pregnant women are excluded in spite of being a high vulnerability group, it has led to multiple missed opportunities in the past to generate safety and efficacy data.

The global COVID pandemic has reinforced the repercussions of this oversight, as well as presented us with the opportunity to rectify it by allowing pregnant women the choice of participating in trials.

“If we don’t take the necessary steps to generate this data – obviously with the utmost field care – we’ll continue to be caught in the trap of not having enough evidence.”

Dr Anant Bhan

The norm should be ‘protection with research’ rather than ‘protection from research.’iStock

The Bottom line

Along with removing the roadblock to securing much-needed protection, clinical data would allow vulnerable groups to make a far more informed and confident choice, while also not having to take the vaccine without the safety net of clinical evidence provided to non-pregnant people.

This also includes trans women (and men) who have historically been underrepresented in clinical research and have over the decades grown to mistrust the medical industry that has treated them as afterthoughts with little consideration to the specific impact of the medicines and treatments on their bodies.

If we did have scientific data to back the claims of assurances, vaccine regulators and health authorities could then also tackle the problem of vaccine hesitancy among marginalised subgroups head-on, and encourage the uptake of their vaccines by providing confidence of their safety, instead of shifting the onus of their well-being entirely onto the consumer with an evasive, "It's your choice."

(This was first published on FIT and has been republished with permission.)