OBJECTIVES

Single-arm trials are utilized by bio-pharmaceutical manufacturers for treatments that are new, or for indication expansion and in situations where placebo-controlled trials may be unethical due to availability of treatment options. However, different regulatory bodies have responded to such trial designs differently. We hypothesized that the availability of alternative treatments for patients may allow regulators to be more stringent around approving new treatments tested via single-arm trials.

METHODS:

We identified eight oncologic products approved by FDA between 2006-2017 based on single arm trials and considered their outcome for marketing authorisation in the EU. The approval data (date approved, evidence submitted, decision and rationale) for these drugs were obtained from the FDA and EMA websites. In addition, lack of availability of treatments for the same indication and/or patient population served as a proxy for unmet needs.

RESULTS:

Out of eight drugs, EMA rejected three, four were given conditional approval subject to availability of randomized controlled data, and only one product was approved due to high unmet need in a specific group of lung cancer patients. For four products, FDA’s ‘accelerated approval’ status while reciprocated by EMA’s ‘conditional approval’, more robust trial data were solicited by the authorities and thereby prolonging patient access. Lack of comparator and lack of external validity of non-randomized design were documented as primary reasons for lack of approvals. In addition, EMA appears to be more restrictive towards therapy areas where other treatment options are already available in the market, i.e. where unmet needs may not be as high.

CONCLUSIONS:

FDA and EMA decisions for approval generally overlap, but the FDA is more willing to approve a drug based on single arm trials. For manufacturers, separate clinical development options for EMA, therefore, will be an imperative especially if single-arm trial is being developed to gain FDA approval.