Our article on the secret legacy of thalidomide spawned more questions and surfaced more people injured by thalidomide in U.S "clinical trials."
In part one of our follow-up series, we focused on how Richardson-Merrell abused a system that didn't monitor drug trials. In part two, we explain why 17 infants injured by thalidomide is a gross underestimate, given the alleged 207 pregnant "participants" (also hugely underestimated) did not know they were being given thalidomide, let alone that they were part of a study.
The Numbers Don't Add Up
Thalidomide's damages were said to include only a "flipper-like limb," occurring in the first two months of gestation. However, reporters from the London Sunday Times, who wrote the authoritative book on thalidomide, Suffer the Children, cited heart and other organ defects, as well as genital, visual and auditory damages.
The estimates of U.S. injuries must be false:
- given the 2.5 million tablets of thalidomide dispensed;
- given one obstetrician alone administered 109,000 tablets;
- given 20,000 patients received thalidomide in the United States;
- given one obstetrician alone admitted giving the drug to 80 pregnant women;
- given 1,267 physicians administered the drug to patients on routine office visits;
- given organ, visual, auditory, genital and other defects were often left out of the estimates, and heart, lung, kidney and reproductive damages would not reveal themselves until years later.
"Drug Studies" Managed by a Marketing Division of a Drug Company
Dr. Ray Nulsen, a Cincinnati obstetrician and fraternity brother of Richardson-Merrell's executive, Don Merrell, lied about delivering two stillborns, whom he called "flukes," and three babies with multiple defects. He also admitted giving pre-samples of thalidomide to 80 pregnant patients.
Dr. Nulsen and 1,266 other physicians were chosen for this study, run by Richardson-Merrell's marketing and sales staff, not its medical staff.
In the midst of the Baby Boom, when one in seven Americans were being prescribed sedatives, Richardson-Merrell found a cash-cow in thalidomide. Who suffers from insomnia more than pregnant women? When are there more pregnant women than in the midst of a Baby Boom?
Obstetrician-gynecologists, psychiatrists and general practitioners would have been top recruits. Given Richardson-Merrell's direction to not keep medical records, it's impossible to estimate how many pregnant patients were involved. These patients, on routine office visits, were not told they were part of a study. On page 70 of Suffer the Children the authors note, "Richardson-Merrell distributed 2,528,412 thalidomide tablets to 1,267 doctors, who gave them to some 20,000 patients -- in containers that bore nothing more than directions for use. Actually, the trials were not clinical ones in the true sense of the term."
Our first piece linked to a 2009 Northwestern paper stating Dr. Frances Kelsey, a then-FDA pharmacologist, "was concerned that there were not yet any results available from U.S. clinical trials of the drug. Even if these data were available, however, they may not have been reliable." May not? Of the physicians participating in these trials, the Northwestern report says "that few tracked their patients after dispensing the drug." After? They weren't tracking patients right there in their offices. The Northwestern paper quoted the FDA's estimate of 207 pregnant women, but an FDA under attack might have wanted to minimize the damage.
In our original post we unintentionally misidentified the widely reported number of 20,000 patients as all pregnant women, yet no one knows how many were pregnant or women. The Northwestern study merely echoes numbers offered by the FDA after the drug was off the market, according to Dark Remedy.
When "Mad Men" Ruled the Drug Regulation Industry
Here is where the personalities take over the story. Dark Remedy offers elaborate descriptions:
New FDA recruit Dr. Frances Kelsey was assigned the Richardson-Merrell thalidomide application as her first case by then-FDA Commissioner George Larrick, who started his FDA career in, of all places, Cincinnati. As detailed on page 42 of Dark Remedy, Larrick protected his friends, such as FDA-colleague Henry Welch, who accepted "over a quarter of a million dollars in private fees from the antibiotics industry while he was certifying the efficacy and safety of their medications ... [Larrick] was everything the drug companies could have hoped for."
On page 46 of Dark Remedy the authors describe that Dr. Kelsey wore short, straight hair, flat heels and was thorough. "Her well-mannered, business-like attitude did not suggest a troublemaker." This mattered to Larrick, who wanted the opposite of Barbara Moulton, an FDA employee deemed a troublemaker after rejecting applications. Moulton resembled Eleanor Roosevelt, and took pride in it. But even Moulton could not get around corrupt superiors. One man crashed her meeting with drug representatives, snatched up the application before animal study results had been submitted and signed his own approval, usurping her authority.
It's hard not to wonder if Barbara Moulton might have shut down thalidomide's "clinical trials." While Frances Kelsey's actions were never less than correct, as one of us is a woman injured by the effects of thalidomide, born in Cincinnati without lower legs, it's a question that haunts: Why didn't Kelsey shut the study down, given her fears about pregnant women included in the studies?
The Gender Gap
The answer is not in the structure, not in the players, but in the nature of human relationships. In every detail about a doctor, a drug company executive, a regulatory agency, there was a woman working behind the scenes. One secretary stuffing pills in a doctor's mailbox, another co-authoring a "medical paper" with a male superior, and still another promoted into a system that had not broken free of its "good ol' boy" network.
Frances Kelsey was unable to shut down that study because she lacked the authority.
Yet Dr. Frances Kelsey's work and persistence, documented and celebrated, prevailed. Thalidomide was denied FDA approval and was banned for use by pregnant women in the U.S. in 1961.
She, as well as Dark Remedy co-author Dr. Rock Brynner, among other figures in the fight against thalidomide, is interviewed in a vital video report by The New York Times.
While this chapter of FDA history is behind us, the damages of thalidomide's "clinical trials" continue to reveal themselves more than 50 years later.