CAM therapies are often dismissed as "no better than placebo;" however, this belief may be overcome through careful analysis of nonspecific factors in healing. To improve trial methodology, we propose that CAM (and conventional) RCTs should evaluate and adjust for the effects of intrapersonal, interpersonal, and environmental factors on outcomes. However, measurement of these is challenging, and there are no brief, precise instruments that are suitable for widespread use in trials and clinical settings. This paper describes the methodology of a project to develop a set of patient-reported instruments that will quantify the nonspecific or "placebo" effects that are in fact specific and active ingredients in healing. The project uses the rigorous instrument-development methodology of the NIH-PROMIS initiative. The methods include (1) integration of patients' and clinicians' opinions with existing literature; (2) development of relevant items; (3) calibration of items on large samples; (4) classical test theory and modern psychometric methods to select the most useful items; (5) development of computerized adaptive tests (CATs) that maximize information while minimizing patient burden; and (6) initial validation studies. The instruments will have the potential to revolutionize clinical trials in both CAM and conventional medicine through quantifying contextual factors that contribute to healing.