OBJECTIVES: As payers decision makers increasingly become primary gate-keepers for access to novel therapies, pharmaceutical, biotech and medical device manufacturers strive to fulfill the evidentiary requests of the pharmacy benefit managers and plan medical directors. This study attempts to gather information to inform manufacturers on the need and rationale behind the payers’ requests of head-to-­head controlled studies. METHODS: We interviewed 11 medical directors (MD) and 2 pharmacy directors (PD) of commercial health insurance plans; 4 pharmacy benefit managers (PBM); and 2 MD of Medicaid programs.  The interviews focused on understanding product coverage decision making and formulary placement.  The interviewers followed a discussion guide, but encouraged deeper conversation when appropriate.  The interviews were carried out in the summer of 2012 and beginning of 2013. RESULTS:  Seven out of 13 (54%) medical directors spontaneously mentioned the need for direct comparison data in clinical trials to ensure adequate decision making.  Conversely, only one PD out of the PBMs and PDs even mentioned comparison data and that was in the context of trying to understand the clinical trial design.  Two MDs went on to further to state that if the head-to-head data showed increased efficacy that a price premium would be appropriate.  Another MD stated that the head-to-head data may assist in formulary placement decisions. CONCLUSIONS:  Payers will continue to demand head-to-head studies as long as these studies are seen as the mechanism to address their questions.  By fostering a richer dialogue with payers to explore other mechanisms for gathering the comparative data, manufacturers may be able to satisfy the payers’ needs with less risky and more relevant study designs.