Why drugs fail health technology assessment: a comparative analysis of health technology assessment rejections across seven OECD countries

While a substantial amount of evidence exists on factors associated with positive health technology assessment (HTA) outcomes, the evidence on the same regarding rejections is scarce. Using a proprietary dataset of HTA outcomes in seven Organisation for Economic Co-operation and Development (OECD) countries, we empirically examine the factors associated with HTA rejections and study the magnitude of inter-agency differences in technology appraisals. Data were extracted from HTA reports between 2009 and 2020. The primary outcome was the probability of rejection, which was examined with respect to several regulatory, disease-related, evidence (clinical and economic) and unaddressed uncertainty variables. Multivariate logistic regression analysis was used. Out of N = 1,405 HTA assessments, the rejection rate was 12.9% (n = 181). Significant predictors of HTA rejection were submissions for drugs with cancer or orphan indications (but not both), low quality of evidence and the presence of uncertainties surrounding clinical benefit, cost-effectiveness, and economic model utility inputs. Systematic differences between agencies in their propensity for rejecting the same drugs were revealed, particularly in relation to cancer and rare diseases. Despite the low rejection rate, our findings suggest that it is critical to improve quality of evidence, focus on risk mitigation strategies as a means of reducing the impact of uncertainties and share HTA practices across borders to increase consistency in decision-making.