BIOEQUIVALENCE OF LEVOTHYROXINE PREPARATIONS - SHORTCOMINGS AND IMPLICATIONS OF A RECENTLY PUBLISHED STUDY

A recently published report of a study that claims to demonstrate bioe quivalence between branded and generic levothyroxine products has been the center of a minor storm of controversy related to several issues. Prominent among these have been issues of suppression by industry of data unfavorable to their products, as well as their possible interfer ence with academic freedoms and the time honored peer review process. In all of the excitement over the latter issue, the fact that the stud y itself appears to be significantly flawed in both its design and its execution may have been lost. Publication of the study in spite of it s apparent flaws was viewed by the journal's editors as a conscientiou s act, but can be criticized in view of the study's faults and of the fact that the study, now 5 years old, was based on outmoded parameters , and its conclusions and inferences had been seriously questioned in another previously published analysis of the same data. In view of the importance of thyroxine bioequivalence terms of both the economics an d quality of health care to millions of thyroid patients, the study is critiqued and its history reviewed. The difference be tween classic b ioequivalency studies and those based on the pharmacodynamics of TSH r esponse is described as is the paucity of TSH data in the report. Even assuming that bioequivalence had been proven, albeit by outmoded FDA guidelines, a conclusion as to therapeutic interchangeableness would b e premature and unfounded. In view of these uncertainties, it is clear that better designed and executed studies will be required before it can be concluded that therapeutic interchange between any of the brand ed and generic levothyroxine preparations could be advised. The genesi s of the controversy surrounding the data in the study and other consi derations that could impact both clinical and research thyroidology ar e also discussed.