Introduction to Developing a Protocol for Observational Comparative Effectiveness Research: A User’s Guide

When making health care decisions, patients, health care providers, and policymakers routinely seek unbiased information about the effects of treatment on a variety of health outcomes. Nonetheless, it is estimated that more than half of medical treatments lack valid evidence of effectiveness,1-3 particularly for long-term and patient-centered outcomes. These outcomes include humanistic measures such as the effects of treatment on quality of life, which may be among the most important factors that affect patients’ decisions about whether to use a treatment. In addition, therapies that demonstrate efficacy in well-controlled experimental settings like randomized controlled trials may perform differently in general clinical practice, where there is a wider diversity of patients, providers, and health care delivery systems.4-5 The effects of these variations on treatment are sometimes unknown but can significantly influence the net benefits and risks of different therapy options in individual patients.