Monday, February 13, 2006

Assessing surrogate endpoints with the MCID

In the era of evidence based medicine we insist on meaningful clinical outcomes from research studies as a basis for making decisions. We’re interested in whether patients live longer, have a better quality of life or experience fewer hospitalizations as a result of treatment. More immediate physiologic variables which change as a result of treatment (such as blood pressure or LDL cholesterol) sometimes substitute for clinical assessment and are therefore known as surrogate endpoints. Although useful because they are more rapidly obtainable, they are not always reliable. Some surrogate endpoints such as short term suppression of ventricular arrhythmias by class I-C antiarrhythmics and hemodynamic improvement with inotropic agents do not correlate with clinical benefit at all and may even be harmful. Many surrogate variables are believed to correlate with clinical benefit but the magnitude of change necessary for meaningful outcomes is not always clear. What is the significance of a 2mm reduction in systolic blood pressure as opposed to 10mm? How do these differences translate into the incidence of stroke of myocardial infarction?

Increasingly investigators are trying to address this issue with the concept of Minimal Clinically Important Difference (MCID). For example, using one of a variety of methods researchers might attempt to estimate the minimum blood pressure change needed to translate into some meaningful outcome such as reduction of MI or stroke. One recent example comes from post publication analysis of the National Emphysema Treatment Trial (NETT) which evaluated lung volume reduction surgery [1] [2]. This analysis was discussed at the American Thoracic Society 2005 International Conference by Dr. Neil MacIntyre, linked here via Medscape. NETT helped define subsets of patients who are likely to benefit from volume reduction surgery. Among the lessons learned from the post publication analysis was the delineation of MCIDs for physiologic variable changes in emphysema. Empiric data correlations in NETT suggested that an increase in 6 minute walk distance of 121 feet, an increase in PO2 of 5 mm Hg, an increase in FEV1 of .12 L, and a 5-W increase in maximal exercise capacity were MCIDs for meaningful outcomes in emphysema.

No comments: