Overall survival (OS) and validated patient-reported outcomes (PROs) are clinical end points in oncology clinical trials that are intrinsically meaningful to patients. The US Food and Drug Administration (FDA) has the ability to approve cancer treatments on the basis of surrogate end points, such as response rate (RR) or progression-free survival (PFS). These end points may arrive sooner than OS, thereby speeding approval, which is a benefit for ultimately effective drugs. At the same time, surrogate end points carry the disadvantage of greater uncertainty for clinical efficacy, potentially allowing drugs that do not improve clinically meaningful end points to enter the market. In addition to high-profile examples in which surrogate end points failed to determine survival benefit, such as bevacizumab in metastatic breast cancer, an umbrella meta-analysis of oncology clinical trials demonstrated a weak association between commonly used surrogate end points and OS in most cancer types.

Although it is widely asserted that RR and PFS reduce development times, we are unaware of any empirical analysis that sought to estimate the extent to which study duration is reduced. One underdiscussed aspect of surrogate end points is that the FDA often relies on both RR and duration of response prior to approval (to show responses are enduring, not fleeting), and this additional follow-up time may decrease the time saved from using RR end points. Prior work has suggested that development times—from early clinical trials to drug approval—can range from an average of 5.8 to 15.2 years, and quantifying the benefit of surrogates in this context would be valuable...