Risk and Reward in Utero - Ethics of Spina Bifida Clinical Trial

Their only access was through a clinical trial testing whether risky prenatal surgery was better than standard surgery after birth. Participating meant being randomly assigned to one surgery or the other.

“They take you to a room and a paper tells you what part of the trial you were randomized to,” said Jessica Thomas, 26, of Stansbury Park, Utah, assigned to prenatal surgery when pregnant with her son Tyson.“It was my only sense of hope to try to give him a better life.”

Amy Shapiro, 40, of Leander, Tex., was assigned to postnatal surgery, performed on her son Zachary the day after he was born.

“It was one of the hardest decisions I had to make to be in the study,” said Ms. Shapiro, who knew how disabling spina bifida was because her sister-in-law has it.“It was a big disappointment that we didn’t get the prenatal surgery because I knew that that was the surgery that was most likely going to help him the most, because otherwise why would they be doing the study? But at the same time, he could have died or been born prematurely from prenatal surgery. When they explained everything to us, I wanted to be in it regardless.”

Now, results are in: Fetal surgery, while increasing premature births and causing tearing at some mother’s incisions,made babies more likely to walkand less likely to have neurological problems or need shunts to drain brain fluid.

Besides the groundbreaking results, the seven-year study spotlights ethical dilemmas in research.

The surgery was becoming popular in the 1990s, even appearing on a Time magazine cover, and some experts believed that it might eventually eliminate most symptoms. But given the risks, others wanted proof that it was better than postnatal surgery.

“There were no systematic data regarding safety and efficacy,” said Dr. Jeremy Sugarman, a bioethicist at Johns Hopkins University who participated in early discussions.“Many things we believe to be true and right and appropriate ultimately are shown to be harmful and ineffective.” Spina bifida researchers believed that few women would participate if the surgery were available elsewhere, so they persuaded all but the three hospitals in the trial to stop doing the procedure, an unusual agreement.

“I frankly have a lot of problems when a group of physicians get together and in effect shut down everything so they can have a trial,” said Baruch A. Brody, director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine.“For physicians who believe in it, why should they be pressured into stopping? For families who believe they should have the surgery, why should they be told they can’t?”

But several ethicists praised the pause.“It’s impressive to see that kind of collaboration,” said Dr. Jeffrey R. Botkin, a pediatric ethicist at the University of Utah.“The sophistication surgeons need to do this is so high, it makes sense to answer research questions by allowing it only at a few centers.”

The surgery proved beneficial enough that an independent monitoring board stopped the trial, not wanting to deny more women the opportunity for prenatal surgery. But stopping trials early sometimes limits the information researchers can collect that might benefit future patients.

Monitoring boards“walk a very fine line,” said Dr. Steven Goodman, an epidemiologist at Johns Hopkins and editor of the journal Clinical Trials.“At what point is the benefit of getting more information outweighed by the consequences of not releasing results and continuing to randomize patients?”

In some trials, if one treatment proves superior, other participants can then receive that treatment. But with prenatal surgery, that isn’t possible, said Jeffrey Kahn, director of the University of Minnesota’s bioethics center.“Some people are accepting risk for the benefit of those who will come after them.”

Still, regardless of therapy,“people who enroll in clinical trials, for the most part, do better than people who don’t, because care is controlled and monitored,” Dr. Goodman said.“You simply can’t go back and say,‘In every trial people who didn’t get the winning therapy were deprived.’”

Tyson Thomas emerged from prenatal surgery with no need for a shunt and, at 22 months old, uses a walker but is almost walking independently. Zachary Shapiro, 6, has a shunt, walks with braces, and has some attention problems. Both boys, who received their surgery at the University of California, San Francisco, need catheters.

Ms. Shapiro, a kindergarten teacher, said of her son,“I do feel like he benefited, even though he didn’t benefit from the actual surgery.”

She added,“He benefited from the research that has happened about his disability.”

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