PRO13 Nice Assessment of Orphan Treatments Supported By Single-Arm Trials

Abstract

The EMA grants orphan drug designation for treatments of rare diseases (prevalence of ≤5 in 10,000 in the EU). Single-arm clinical trials (SATs) may be used to assess efficacy of treatments for rare diseases, as patient populations are too small to make randomised control trials feasible. Indirect treatment comparisons (ITCs) are needed to provide estimates of relative treatment effects in the absence of randomised evidence. We reviewed the methods used, outcomes, and key drivers of NICE assessments, and decisions for orphan treatments supported by SATs and ITCs. The EMA website was searched to identify orphan treatments approved between 1st January 2010 and 31st May 2020, and which treatments were supported only by SATs. The NICE website was searched for assessments of these treatments. ITC methods, decision outcomes, and key drivers were evaluated. Between 2010 and May 2020, the EMA approved 123 orphan treatments, of which 17 were supported by clinical evidence only from SATs. As of June 2020, 10 of these treatments were assessed by NICE and all were recommended. Four used a matched ITC, five used a naïve ITC, and one used an historical comparison. NICE generally critiqued the lack of available data due to small patient populations and uncertainties related to the use of naïve ITCs. Further data collection was required for six treatments. Most oncology treatments (five out of seven) were recommended through the Cancer Drugs Fund. Of the three non-oncology treatments, one required a managed access agreement (MAA). Orphan treatments supported by SATs make up approximately 14% of all orphan treatments approved by the EMA in the last 10 years. NICE recommended all assessed orphan treatments supported exclusively by SATs (2010-2020). However, an MAA was required for most of these treatments as further data collection was required to address uncertainties in the clinical evidence.