This editorial appeared in Journal of the American Medical Association in 1997.
In the late 80’s, Synthroid, the dominant drug for thyroid hormone replacement, contracted Betty Dong, PharmD at UCSF to do research that would determine bioequivalence amongst different thyroid hormone replacement medications. This research had not been done previously. Bioequivalence is the property whereby two drugs with the same active ingredient produce the same physiological effect. Hypothyroidism is a condition where the body does not produce enough thyroid hormone to properly regulate the body’s metabolism leading to symptoms such as fatigue, feeling cold, and others. Synthroid, the first synthetic thyroid replacement medication, had been the favorite medication for treating hypothyroidism since it came on the market in 1958. Prior to this, animal extracts were used. The makers of Synthroid wanted the study done to prove the superiority of their product because the state of Massachusetts was considering adding a competitor’s formulation to the state formulary.
Betty Dong had written favorably on Synthroid in the past. She signed a contract with Synthroid’s manufacturers to conduct the new research comparing the bioequivalence of multiple thyroid replacement preparations. The contract specified all of the research parameters and statistical methods to be used. The company maintained a close eye on her work, visiting her several times a year to oversee the research. Except for a few minor adjustments, the work proceeded as anticipated. And then the results came in. All of the thyroid preparations being tested turned out to be equivalent to one another. It was calculated that using generic preparations instead of Synthroid would save $356 million per year.
Synthroid’s manufacturers immediately began a campaign to discredit the research and Dong. They met with the university. Lawyers got involved. Dong stood by her results and the statistical analysis (done using the exact methods as agreed upon in the contract.) The study and Dong’s conclusions were sound. The university supported her. This was important information that the medical community would benefit from knowing as no other study had rigorously tested the bioequivalence of various thyroid replacement preparations before. When Dong and her team went to publish, they were blocked by the makers of Synthroid. A clause in the contract required Synthroid’s written permission to publish the study and its results. Synthroid’s executives threatened to sue Dong and the other researchers if they published the paper. They withdrew the article from publication at the last minute.
Synthroid then published the data using different statistical methods to show that it was superior to other preparations. They did this with their own physician listed as the lead author in a journal of which he was the editor. Credit was not given to Dong or any of her colleagues who worked on the study.
Eventually Dong’s original research paper was published with the consent of Synthroid after they decided the negative press they were receiving was more egregious to them than having the actual study published.
The editorial gives a behind-the-scenes look at what can happen in the world of medical research. The conflict of interest between academic researchers and the commercial interests that fund them highlights the struggle to control the dissemination of medical knowledge. In this case, a commercial interest attempted to suppress information beneficial to the medical community (and public) to protect its investments and profit margins.
Realizing that behind every study lies interests beyond those of medical knowledge helped me to read the medical literature more critically. While you can’t read the backstory of every paper published, you can learn to read between the lines. I now look to see who funded a study before I even consider reading it. Protecting patients from commercial interests that go against their own is part of my duty to them as a physician.
I encourage you to read the entire editorial originally published in JAMA that can be found here. There is also a write up of the full story from the Wall Street Journal that can be found here. Both of these recount the story in more detail. Remember Thyroid Storm whenever you read about a new medical study reported in the press.
©2013 by Luc Readinger, MD