Implications of comparative effectiveness research for radiation oncology

The essence of comparative effectiveness research (CER) is to understand what health interventions work, for which patients, and under what conditions. The objective of this article is to introduce the relative strengths and weaknesses of several forms of evidence to illustrate the potential for CER evidence generation within radiation oncology.

We introduce the underlying concepts of effectiveness and efficacy. We describe the design of traditional explanatory randomized trials (RCTs). We introduce the rationale, strengths, and weaknesses of several alternative study designs for comparative effectiveness, including pragmatic clinical trials, adaptive trials, and observational (nonrandomized) studies.

Explanatory RCTs are designed to assess the efficacy of an intervention while achieving a high degree of internal validity. Pragmatic clinical trials (PCTs) are prospective studies performed in typical, real-world clinical practice settings. The emphasis of PCTs is to maintain a degree of internal validity while also maximizing external validity. Adaptive trials can be modified at interim stages using existing or evolving evidence in the course of a trial, which may allow trials to maintain clinical relevance by studying current treatments. Observational data are becoming increasingly important, given substantial funding for clinical registries and greater availability of electronic medical records and claims databases, but need to address well-known limitations such as selection bias.

With the rapid proliferation of new and evolving radiotherapy technologies, it is incumbent upon our field to invest in building the evidence base for radiotherapy CER and to actively participate in current initiatives for generating comparative evidence.