Use of literature to make regulatory decisions: the FOLLTROPIN example
*Emily Smith, FDA Center for Veterinary Medicine 

Keywords: systematic review, meta-analysis, veterinary drug

The FOLLTROPIN approval highlights different ways in which literature may be used as part of regulatory decision-making. The sponsor conducted a systematic review and meta-analysis to provide substantial evidence of effectiveness of FOLLTROPIN, instead of conducting a traditional field study, because of the availability of a large number of published and unpublished studies. The regulatory systematic review differed from a typical systematic review (e.g. Cochrane review) in the scope of the review question, the design of the study eligibility assessment, the evaluation and inclusion of sponsor-conducted studies, and the extent of data extraction and bias assessment for individual studies. The review question was defined with a very narrow scope which included a consideration for a particular formulation of drug product, used in dairy and beef heifers and cows, under specific conditions of use. The systematic review and meta-analysis allowed the Agency to conclude that FOLLTROPIN was effective for the proposed conditions of use, that the results are likely to be repeatable, and that valid inferences can be drawn to the target population. For the target animal safety evaluation, although a systematic review was not performed, literature was used to characterize the pharmacology and toxicology of FOLLTROPIN, justify an alternative approach to the traditional margin of safety study, and identify remaining gaps in the information necessary to complete the target animal safety evaluation for FOLLTROPIN.