Table 1.

Examples of deviations in traditional standards of evidence accepted by regulatory agencies

Population	Clinical trial used for approval was not of a sufficient size (“powered”) to confidently answer the reimbursement question pertaining to a specific population or subgroup
Intervention	Intervention may require a concomitant therapy not presently reimbursed in the respective healthcare system
Comparators	Comparators may not reflect the replaced therapies in the clinical practice or may not be present at all if single-arm trials are accepted as the evidence for approval
Outcomes	Benefit in surrogate outcomes may be used for approval, creating uncertainty in HTA stemming from not using primary outcomes in economic modelling