OBJECTIVES: Randomized controlled trials (RCTs) are the gold standard for assessing new medicines. However, single arm trials (SATs) can also provide valuable evidence in some situations, particularly for rare diseases or when RCTs are not feasible. This study reviews HTA reports issued by the Haute Autorité de Santé (HAS) in France for oncology drugs with SAT as pivotal evidence, and to analyze the factors driving ratings of clinical added value (ASMR).

METHODS: Using the NaviHTA database, HAS reports for oncology drugs with submission including SAT evidence only, published from 2018 to 2023, were selected. Frequencies of different products and disease landscape characteristics by appraisal outcome were computed. Justifications supporting ASMR were summarized for different ASMR categories.

RESULTS: Forty-five assessment cases involving 36 products, including 6 gene therapies and some with multiple indications, were identified. All assessed conditions were severe or life-threatening and 40 cases related to rare conditions. Nine cases were not reimbursed and restrictions were decided for 8. Results of indirect treatment comparisons were considered in only 3 out of 30 cases. Low (IV) and moderate (III) ASMRs were issued in 11 cases, including the single case where a comparison to historical controls was presented. The analysis of the ASMR justifications showed that the agency acknowledged the effect size from pivotal studies and the unmet need in all 11 cases. ITC results were acknowledged in 2 of 11 cases, and an expected improvement in care due to convenience of use in 2/11. The main uncertainties raised were the absence of long-term data and significant drug toxicity (8/11), and the lack of direct comparative data ( 7/11).

CONCLUSIONS: Added clinical value was acknowledged by the HAS for a few products in absence of any comparative evidence. These situations were characterized by high unmet needs, disease rarity and exceptional clinical outcomes.