OBJECTIVES: Several novel targeted combination therapies have been shown to improve health outcomes, but are often associated with significant costs. With the advances in oncology innovation (e.g., checkpoint inhibitors), and the move toward double- or triple-therapy regimens, payers’ perception of these potentially high-cost regimens is uncertain. This analysis evaluates if the current HTA process is sufficient to capture the complexities/innovations of brand+brand regimens by evaluating if agencies treat brand+brand combinations differently than single brands.

METHODS: HTA reviews for six brand+brand combinations and their single agents, between 2005-March 2017, were identified in the Context Matters data model. A total of 194 reviews published by G-BA, HAS, NICE, PBAC, pCODR, SMC, HIRA, and TLV were analyzed. Reimbursement decision, clinical and economic drivers of the decision, and key agency criticisms were compared between assessments of brand+brand combinations and single brands.

RESULTS: HTAs for brand+brand combinations were more likely to receive “Do-not-recommend” decisions than single brands (46% vs. 29%, respectively), and were less likely to receive “Recommend” decisions (39% vs. 51%, respectively). However, there were similar rates of recommendations with restrictions and types of restrictions. Key drivers and criticism showed that both single brands and brand+brand combinations showed efficacy gains over single agent comparators, but the gains were larger for single brands. Also, single brands were usually approved first, often addressing an unmet need. Both brand+brand combinations and single brands were criticized for uncertain cost-effectiveness, despite discounts/PASs.

CONCLUSIONS: Brand+brand targeted oncology combinations struggled to gain reimbursement compared to their single agents despite efficacy gains over single brands and discounts/PASes. It is concerning that brand+brand combinations which offer improvements in survival (overall or progress-free) over current standards-of-care are less likely to receive positive decisions from HTA agencies. Traditional assessment processes do not seem to capture the complexities of brand+brand combinations and the innovations they offer.