ATA and Endocrine Sister Societies urge FDA to consider expert opinion and the health of millions of thyroid patients

May 26, 2004

Steven Galson, M.D.
Acting Director, Center for Drug Evaluation and Research
Food and Drug Administration
5600 Fishers Lane, HFD-240
Rockville, MD 20857

Dear Dr. Galson:

We are writing to you again on behalf of our societies–the American Thyroid Association (ATA), The Endocrine Society (TES), and American Association of Clinical Endocrinologists (AACE)–to express our continuing and heightened concern that FDA has postponed a thoughtful and complete review of information regarding thyroxine therapeutic equivalence.

The agency has not taken advantage of the opportunity to hear and consider thoroughly the views of the clinical experts who guide thinking regarding management of the 13 million Americans who take levothyroxine products. The FDA’s sole public solicitation of expert opinion about this critical matter has been the March 13, 2003 Pharmacokinetic Advisory Panel meeting. FDA has agreed with our societies that the panel’s advice was naive from a clinical perspective. Furthermore, we believe that it was not deliberate in its consideration of serious questions regarding thyroxine bioequivalence criteria. We are even more concerned about this matter in light recent direct experimental evidence that raises valid concerns about FDA’s current thyroxine bioequivalence methodology.¹ These are important data that a regulatory body must take seriously.

We are discouraged that FDA appears prepared to withdraw from its commitment to hold a workshop addressing all of the relevant issues: thyroxine bioequivalence testing baseline correction, optimal test subjects, and acceptable confidence limits; and TSH as a pharmacodynamic measure. Failure by FDA to move ahead with this workshop will be a lost opportunity. Any program held after a decision regarding approval of additional thyroxine formulations has already been made will be a meaningless exercise.

We strongly urge FDA–as we did in our September 29, 2003 and March 19, 2004 letters–to 1) suspend approval of new thyroxine formulations until these matters are resolved, and 2) not make a final decision regarding equivalence testing until you have heard from representatives of the real experts in this field— more than 4,600 clinical endocrinologist members of our societies–at the workshop that your agency proposed.

To ignore our request that FDA simply take the time to listen to thoughtful and careful consideration of these issues with experts in clinical endocrinology is, in our view, a disservice to the millions of Americans whose health depends daily on precise thyroxine dosing.

We look forward to hearing from you personally.

Yours truly,


Paul W. Ladenson, MD	E. Chester Ridgway, MD	Carlos R. Hamilton, Jr., MD, FACE
President-Elect	President	President
American Thyroid Association	The Endocrine Society	American Association of Clinical Endocrinologists