OBJECTIVES: This research aims to evaluate the impact of the clinical trial phase on reimbursement decisions for orphan drugs with breakthrough status in the European Union 5 (EU5: France, Germany, Italy, Spain, and the United Kingdom).

METHODS: Clinical trial and reimbursement decisions for orphan drugs with breakthrough status were assessed by reviewing EU5 health technology assessments (HTAs) from 2015 to 2018. A total of 437 HTAs were chosen because they reported clinical trials in their clinical analyses. A comparison was drawn between clinical trial phases and reimbursement decisions. A logistic regression was performed to determine the likelihood of approval increases when the trial phases increase.

RESULTS: Of the 437 HTAs, 84.44% (n = 369) had positive decisions. Of those positive decisions, 83.47% (n = 308) reported a phase 3 clinical trial in their clinical analysis, 15.72% (n = 58) reported a phase 2 clinical trial, and 0.81% (n = 3) reported a phase 1 clinical trial. Of the negative decisions (n = 68), 67.65% (n = 46) reported a phase 3 clinical trial in their clinical analysis, 30.88% (n = 21) reported a phase 2 clinical trial, and 1.47% (n = 1) reported a phase 1 clinical trial. The odds ratio of the regression was 2.18, indicating the odds of having a higher phase trial with a positive decision was 2.18 times that of a negative decision, and the p-value was 0.004, indicating a statistical significance.

CONCLUSIONS: The statistical significance of the logistic regression indicates that, as the trial phase increases, there is a higher likelihood of approval in the EU5. However, further research into factors such as the specific HTA agency, disease condition, and drug in addition to the clinical trial phase should be conducted to further determine the likelihood of approval.