Paucity of Clinical Data in Oncology HTA Submissions: Key Learnings from Recent Case Studies

The European Medicines Agency has shown an increased willingness to give regulatory approval to oncology drugs on the basis of single-arm clinical trial data, leading to an increased number of Health Technology Assessment (HTA) submissions with a paucity of clinical data. Although HTA bodies are generally critical of submissions relying solely on the use of non-randomised clinical trial (RCT) evidence, manufacturers are increasingly employing complex methods and approaches to overcome these issues. By evaluating the success of oncology HTA submissions relying on single-arm trials as the main source of efficacy and safety data, this study aimed to provide strategic insight for future HTA submissions. HTA websites for members of the EU-5 were searched to identify oncology drug submissions (2011-2016) that relied on single-arm Phase II study data. The rationale, methods and approach taken by the manufactures to estimate clinical and cost-effectiveness were assessed and the HTA submissions were compared between organisations. A total of ten HTA submissions for oncology drugs without RCT data were identified. Across HTA bodies, both positive and negative recommendations were made for the following oncology drugs: sunitinib, crizotinib, bosutinib, brentuximab, vedotin, and ofatumumab. HTA submissions using novel indirect comparison techniques to account for the lack of direct comparison data were heavily criticised and not widely accepted. However, based on the high unmet need of the oncology indications, a number of positive conditional recommendations were made with restrictions on sub-populations or price. HTA bodies across Europe have differing assessment criteria and data requirements, leading to a disparity between the recommendations for oncology drugs relying on single-arm trial data. Although positive recommendations identified in this study were made with a high degree of uncertainty, the most important factor influencing the HTA recommendation appeared to be a high unmet need.