Should We Do Randomized Trials during Pregnancy?

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"It's unethical to include pregnant participants in drug trials."

This is the conventional view. Excluding them is meant to protect pregnant participants and their fetuses from unknown risks.

But consider this:

90M+

US women have given birth

That's 71% of women aged 18-85.

94%

of pregnant people use medications

On average, 3-5 different drugs during pregnancy.

But only

0.8%

of drug trials include pregnant participants

Out of 44,160 trials from 2008-2023, only 362 enrolled pregnant people.

Bilinski & Emanuel, AJOG 2025

<10%

of medications have sufficient pregnancy safety data

Among drugs approved since 1980, the vast majority lack adequate evidence.

CDC

What happens without trials?

Harmful?

Dangerous drugs go undetected

Helpful?

Beneficial treatments are delayed

Without trials, we can't distinguish safe from dangerous.
Both scenarios lead to preventable harm.

Three case studies

Slow side effect detection
Thalidomide (1956-1962)
8,000
infants with birth defects
99.6%
could have been prevented with an RCT
Delayed beneficial treatment
COVID-19 Vaccines (2020-2021)
An RCT could have prevented:
8%
of maternal COVID deaths
1%
of stillbirths
False safety alarm
Dolutegravir (2018-2019)
3,228
preventable deaths
False alarm reduced uptake of life-saving HIV drug. An RCT would have resolved this faster.

Bilinski, Emanuel & Ciaranello, Annals of Internal Medicine 2025

Three case studies

Slow side effect detection
Thalidomide (1956-1962)
8,000
infants with birth defects
99.6%
could have been prevented with an RCT
Delayed beneficial treatment
COVID-19 Vaccines (2020-2021)
An RCT could have prevented:
8%
of maternal COVID deaths
1%
of stillbirths
False safety alarm
Dolutegravir (2018-2019)
3,228
preventable deaths
False alarm reduced uptake of life-saving HIV drug. An RCT would have resolved this faster.

Bilinski, Emanuel & Ciaranello, Annals of Internal Medicine 2025

Three case studies

Slow side effect detection
Thalidomide (1956-1962)
8,000
infants with birth defects
99.6%
could have been prevented with an RCT
Delayed beneficial treatment
COVID-19 Vaccines (2020-2021)
An RCT could have prevented:
8%
of maternal COVID deaths
1%
of stillbirths
False safety alarm
Dolutegravir (2018-2019)
3,228
preventable deaths
False alarm reduced uptake of life-saving HIV drug. An RCT would have resolved this faster.

Bilinski, Emanuel & Ciaranello, Annals of Internal Medicine 2025

Three case studies

Slow side effect detection
Thalidomide (1956-1962)
8,000
infants with birth defects
99.6%
could have been prevented with an RCT
Delayed beneficial treatment
COVID-19 Vaccines (2020-2021)
An RCT could have prevented:
8%
of maternal COVID deaths
1%
of stillbirths
False safety alarm
Dolutegravir (2018-2019)
3,228
preventable deaths
False alarm reduced uptake of life-saving HIV drug. An RCT would have resolved this faster.

Bilinski, Emanuel & Ciaranello, Annals of Internal Medicine 2025

The health value of trials far exceeds their cost

$100M
cost of a trial
vs
$1-33B
in preventable harm

Across all three case studies, trial costs were dwarfed by health benefits.

The bottom line

Excluding pregnant people from trials doesn't protect them—it just prevents researchers from learning when they take medications anyway.

A path forward

Four policy levers could close the evidence gap

FDA Guidance
ICH E21 draft encourages pregnancy planning—make it binding
Require Research
Require pregnancy data like we require pediatric data
Incentivize Studies
Offer exclusivity incentives for pregnancy studies
Public Funding
Fund trials for off-patent drugs where market incentives fail

A path forward

Four policy levers could close the evidence gap

FDA Guidance
ICH E21 draft encourages pregnancy planning—make it binding
Require Research
Require pregnancy data like we require pediatric data
Incentivize Studies
Offer exclusivity incentives for pregnancy studies
Public Funding
Fund trials for off-patent drugs where market incentives fail

A path forward

Four policy levers could close the evidence gap

FDA Guidance
ICH E21 draft encourages pregnancy planning—make it binding
Require Research
Require pregnancy data like we require pediatric data
Incentivize Studies
Offer exclusivity incentives for pregnancy studies
Public Funding
Fund trials for off-patent drugs where market incentives fail

A path forward

Four policy levers could close the evidence gap

FDA Guidance
ICH E21 draft encourages pregnancy planning—make it binding
Require Research
Require pregnancy data like we require pediatric data
Incentivize Studies
Offer exclusivity incentives for pregnancy studies
Public Funding
Fund trials for off-patent drugs where market incentives fail

A path forward

Four policy levers could close the evidence gap

FDA Guidance
ICH E21 draft encourages pregnancy planning—make it binding
Require Research
Require pregnancy data like we require pediatric data
Incentivize Studies
Offer exclusivity incentives for pregnancy studies
Public Funding
Fund trials for off-patent drugs where market incentives fail

It's time to include pregnant participants in clinical trials by default.

Read the research:

JAMA: Why This Is Unethical Annals: Health Impact Model AJOG: Trial Exclusion Data One-Pager
STAT: The case for including pregnant women in RCTs STAT: Acetaminophen use in pregnancy

Research by Dr. Alyssa Bilinski (Brown University), Dr. Natalia Emanuel (Federal Reserve Bank of NY), and Dr. Andrea Ciaranello (MGH/Harvard)