public health Single-arm trials for cancer drug approval and patient access

Abstract

Background: Single-arm trials (SATs) can provide an invaluable opportunity to speed up cancer drug development and approval, typically for drugs with dramatic activity in small populations with high unmet medical need. However, the inherent higher uncertainty about the drug's safety and efficacy and challenges in assessing added therapeutic value by health technology assessment (HTA) bodies and payers can negatively impact effective patient access, which shows significant variability across EU countries. Regulatory guidance addressing the SAT-specific regulatory challenges is currently limited, and harmonised value criteria for cancer drugs approved on the basis of SATs are still lacking. In practice, there appear to be divergent views across stakeholders on what might constitute compelling efficacy vs. unmet need, and variable tolerance for uncertainty. Methods: The European Medicines Agency (EMA) is addressing these challenges, in collaboration with relevant stakeholders, including clinicians, patients, developers, regulators and HTAs/payers. Results: Results will be presented from a comprehensive research project on EMA's experience with SATs in approvals and scientific advice, but also analysing value perception by HTAs and effective access in major EU markets. Conclusions: The conclusions will identify areas that could benefit from further regulatory guidance, with regard to methodology (endpoints, novel trial designs, external controls, molecularly annotated registries, supportive data, Bayesian approaches) and policy frameworks (magnitude of benefit vs. unmet need, uncertainty regarding efficacy, safety and cost-effectiveness and post-approval confirmatory evidence), with the ultimate aim of increasing predictability of the 'requirements' for patient access decisions by regulators and HTAs/payers, and facilitating early access of promising drugs to patients in need.