Booties on the ground

In his excellent review of Annie Murphy Paul's new book, Origins: How the Nine Months Before Birth Shape the Rest of Our Lives in the New York Times Book Review on Sunday, physician/author Dr. Jerome Groopman wrote:

Of necessity, research on fetal development involves observing pregnant women in their daily lives; no one would purposefully have one group eat in a possibly risky way or be exposed to a potentially dangerous substance, and compare outcomes with an unperturbed control group. We have, at best, only correlations between a mother’s lifestyle and her child’s future health, not clear causation.

And, in "The Case Against Breast-Feeding," Hanna Rosin's 2009 article in The Atlantic, she wrote, "An ideal study would randomly divide a group of mothers, tell one half to breast-feed and the other not to, and then measure the outcomes. But researchers cannot ethically tell mothers what to feed their babies."

Really? Why not? Both Groopman and Rosin are writing about how vulnerable observational studies are to being tainted by hidden variables. Controlled trials are a better system for testing what works and what doesn't.

But if I am reading their statements correctly, Groopman and Rosin are saying that we cannot even think about practicing actual, rigorous science if babies and fetuses are involved.

Building up a body of "evidence-based medicine" around a segment of the population that is exempted from clinical trials — depending entirely on observational research, that is — seems unwise to me. We don't need to wonder what a worst-case scenario involving babies would look like;  we have the 50-year-old thalidomide catastrophe as a demonstration. Thousands of children around the world were born with deformed limbs after their mothers took the drug.

Subjecting drugs and behaviors that can affect unborn children to standard scientific trials that include pregnant women might save the population from potentially massive damage from those behaviors, and from the drugs once they are put on the market. This is especially true now that we suspect the experience in the womb has a huge influence on the course of an individual's life — the subject of Paul's book, Origins.

Now I understand why the medical ethicist Ruth Macklin, writing in The Lancet last winter, called for the inclusion of pregnant women in drug trials, and retaining women who get pregnant in such trials. Conventional wisdom seems to have rendered the concept so unthinkable that a call for change is necessary.

What do you think about including pregnant women in clinical trials? I would love to read your comments.

Medicine is only as good as its evidence.

People talk about "evidence-based medicine" in obstetrics, and in the holistic birthing community as well, as if it's a sleek, shiny package tied up with a bow and ready for Christmas morning.

But evidence-based medicine is a shambling, messy thing, always on the move, only as reliable as the researchers who conduct it -- and as the research that has gone before and serves as its foundation.

The Lancet's retraction earlier this month of a 1998 study that appeared to establish a link between the development of autism in young children and the vaccine for measles, mumps and rubella is a good demonstration of the fallibility of evidence-based medicine.

One reason the original Lancet study collapsed was that other researchers could not duplicate lead author Andrew Wakefield MD et al.'s results. But even while 10 of the 13 original co-authors withdrew their support for the study, the public absorbed the idea that a cause-effect relationship exists between vaccination and autism.  That idea has not been eradicated by the Lancet's retraction.

And while such a retraction is unusual, it is unfortunately not unheard of.

Last July, anesthesiology researcher Scott S. Reuben MD of Baystate Medical Center in Springfield, Mass., was revealed to have falsified results in at least 21 studies that appeared in several peer-reviewed journals. Anesthesia and Analgesia alone retracted 10 of Dr. Reuben's articles.

Dr. Reuben specialized in multimodal analgesia, a drug-delivery system designed to control the pain of surgery.

In January, Dr. Reuben pleaded guilty to fraud for such audacious creations as a 2005 trial of Pfizer's drug Celebrex as an agent in a multimodal analgesia model. Dr. Reuben accepted $74,000 from Pfizer to conduct the study, simply did not do the work, and then published fabricated results in Anesthesia and Analgesia.

Unfortunately, other researchers based their own work on those phony results.

The collapse of Reuben's data has left multimodal analgesia “in shambles....The big chunk of what people have based their protocol on is gone,” said Jacques Chelly,  an anesthesiologist at the University of Pittsburgh Medical Center, in Anesthesiology News last March.