This Mass. doctor questioned a popular pregnancy drug. Now, he's been proven right

A baby rests in the Neonatal Intensive Care Unit at Tufts Medical Center after being born more than 11 weeks premature. (Jesse Costa/WBUR)
A baby rests in the Neonatal Intensive Care Unit at Tufts Medical Center after being born more than 11 weeks premature. (Jesse Costa/WBUR)

For two decades, Adam Urato fought the medical establishment. This past week, he was vindicated.

Here’s the backstory: The U.S. Food and Drug Administration has only ever approved one drug to prevent preterm births, which happen in about 10% of pregnancies and can cause life-long consequences.

The drug is called Makena. It was widely accepted by doctors and promoted as the best care available for high-risk pregnancies. But Urato wasn’t confident the drug worked. He publicly questioned it, testifying at the FDA and writing about it in the media and medical journals. He also helped orchestrate a citizen petition to ask the Food and Drug Administration to remove Makena from the market.

Last fall, after much debate, an  FDA advisory panel voted to recommend withdrawing the drug. The panel found no evidence that it works. And last week, the company that makes Makena said it would voluntarily pull it from the market.

WBUR spoke with Urato — an obstetrician who specializes in high-risk pregnancies at MetroWest Medical Center in Framingham — to hear what it was like to stand up against the status quo, and what he learned from the experience.

This conversation has been edited for brevity and clarity.

What convinced you to raise your voice against this popular drug and say, "Wait, something’s wrong here"?

"Approval for Makena was based on just one study, published in 2003. It started getting used like right out of the gate. But, from the get-go, it was clear that there were serious flaws with the trial.

"It was a randomized, placebo-controlled trial, but the randomization basically failed. The group that got placebo was a much higher-risk group. They had many more prior preterm births, which is the biggest risk factor for having another preterm birth.

"So, the study found the group getting Makena had a rate of preterm birth that was about 36%. And that is right about what we usually see for women who’ve had a preterm birth. So that didn't look like the drug was effective. But the placebo arm had a 55% rate of preterm birth. So it wasn't that the Makena really worked. It was just that the placebo arm had this crazy high rate of recurrent preterm birth. So, I was suspicious.

"I thought, 'This is really weak science to justify injecting a whole bunch of women with a synthetic chemical compound.' "

When did you decide to speak publicly against it?

"It was a combination of things. So, I had questions about the science, and then the observational studies that started coming out weren't showing benefit. But at the same time the company behind Makena, AMAG Pharmaceuticals [now a subsidiary of the COVIS Pharma Group], was saturating the market with advertising and showering cash on the professional medical societies.

"Each month our journal, the Journal of the American College of Obstetrics and Gynecology, would come out with a banner advertisement wrapped around it for Makena. You literally couldn't access the scientific information in the journal without interacting with this big advertisement. It was everywhere. AMAG Pharmaceuticals made billions off this drug that didn’t seem to work, so that’s what did it for me."

What was it like for you to speak out, given that the medical establishment had embraced Makena so fully?

"It was challenging. There was basically a scientific consensus that Makena was the standard of care. Everybody kind of jumped on board. A lot of colleagues I talked to didn't understand how weak the scientific foundation was for the drug.

"I did get called in once by a supervisor who sat me down and said, ‘You know, it's a little bit atypical that you're not using this drug. It's outside the standard of care.’ There was no threat per se involved, but it's your supervisor; it's your boss. And so you worry, is this going to have an effect on me and my job?"

Did you feel like it hurt your professional reputation?

"Yeah, I do. One of the big lessons I learned from this is that it's really important for us, as a human society, to try to embrace and encourage voices of dissent, voices that are going against the conventional wisdom. A lot of times those voices can be proven correct over time.

"I am sure someone would look at me and say, ‘This guy is a loose cannon for saying these things’ because the drug had become so entrenched as part of care. But ultimately my concern was for the patients and trying to stand up for them."

And how does it feel now that Makena is officially off the market?

"I'm very happy. I think this is the right decision. What we’ve basically been doing for the last 20 years is injecting pregnant women, every week, with a synthetic hormone that doesn't benefit them. It doesn't help their babies, and it carries risks. It's a really big tragedy, a big mistake.

"But I also feel bad because women that have had a prior preterm birth — and are at risk of another preterm birth — have no medications to help prevent it. It's an awful place to be in. As a physician, you want to be able to offer these patients something. And now it's clear that there's nothing.

"It’s important for people not to miss what's happened here. And for us to take steps to make sure that this sort of thing doesn't happen in the future."

Tell me, do you worry about Makena being pulled from the market in that it might discourage other pharmaceutical companies from investing in this area?

"I think it’s very unlikely that we’ll come up with a magic bullet for preterm delivery with a single pharmaceutical. It’s unlikely because the causes of preterm birth are so multifactorial.

"I'd really like to see us spend more time and effort on working in some of the other areas to try to prevent preterm births. Things like reducing smoking, reducing other drug use, trying to have better maternal health and nutrition, improving mental health.

"Preterm birth is a common problem, it’s about 10% of births. My guess is that pharmaceutical companies will want to try to come up with something."

Did this hurt your own trust in doctors and in the FDA’s system?

"We have a failed regulatory system and a failed medical establishment. I think, in large part, this is due to the influence of corporate cash, the strength of the drug and device manufacturers.

"Makena didn't work. It doesn't stop preterm birth. It doesn't lead to better health outcomes. But the reason it stuck around for so long is because it worked in a financial sense. It did work for the drug company, for the professional medical societies and for everyone that got cash showered on them from that industry. This is like a cycle that needs to be broken in an urgent way." 


Headshot of Gabrielle Emanuel

Gabrielle Emanuel Senior Health and Science Reporter
Gabrielle Emanuel was a senior health and science reporter for WBUR.



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