Greater Expectations in a Cancer Trial: Absolute More Than Relative Survival Increases, Community More Than Academic Clinicians

Abstract

There is no consensus on how the difference between control and experimental outcome rates, the clinically important difference, should be estimated when designing a clinical trial. We sought to determine whether community and academic clinicians had different perceptions as to what would constitute a clinically important increase in survival, when asked to respond in absolute or relative terms, before a trial was started rather than when the results were already known. A telephone survey of 25 practicing Canadian oncologists was performed. Questions were asked as to the importance of acceptable and minimally acceptable improvements in survival for a hypothetical trial of pancreatic cancer where the baseline survival was expected to be between 2 and 8 months. Responses were sought for absolute (additional months) or relative gains (percent improvement) in survival. The mean absolute additional survival expectations corresponded to at least a doubling of baseline survival and tended to be greatest when the prognosis was poorest (p = 0.06). Relative expectations for improved survival varied with baseline survival (p < 0.001). When improvement in survival was requested in relative terms, the median expected improvement was 25%. This is highly significantly different than when survival improvements were requested in absolute terms (p < 0.0001). Median absolute survival expectations were greater for community as compared with academically affiliated physicians (p = 0.046). We found that physicians are inconsistent in their interpretation of qualitative data. What constitutes a potentially clinically important treatment effect differs whether viewed in relative or absolute terms before the performance of a trial. Expectations were greatest when the prognosis was poorest and differed between community and academic physicians