Observational Study Designs for Comparative Effectiveness Research: An Alternative Approach to Close Evidence Gaps in Head-and-Neck Cancer

Comparative effectiveness research (CER) has emerged as an approach to improve quality of care and patient outcomes while reducing healthcare costs by providing evidence to guide healthcare decisions. Randomized controlled trials (RCTs) have represented the ideal study design to support treatment decisions in head-and-neck (H&N) cancers. In RCTs, formal chance (randomization) determines treatment allocation, which prevents selection bias from distorting the measure of treatment effects. Despite this advantage, only a minority of patients qualify for inclusion in H&N RCTs, which limits the validity of their results to the broader H&N cancer patient population seen in clinical practice. Randomized controlled trials often do not address other knowledge gaps in the management of H&N cancer, including treatment comparisons for rare types of H&N cancers, monitoring of rare or late toxicity events (eg, osteoradionecrosis), or in some instances an RCT is simply not feasible. Observational studies, or studies in which treatment allocation occurs independently of investigators' choice or randomization, may address several of these gaps in knowledge, thereby complementing the role of RCTs. This critical review discusses how observational CER studies complement RCTs in generating the evidence to inform healthcare decisions and improve the quality of care and outcomes of H&N cancer patients. Review topics include a balanced discussion about the strengths and limitations of both RCT and observational CER study designs; a brief description of design and analytic techniques to handle selection bias in observational studies; examples of observational studies that inform current clinical practices and management of H&N cancers; and suggestions for relevant CER questions that could be addressed by an observational study design.