Home International Normalized Ratio Monitoring: Where Evidence-Based Medicine is Exemplified in the Medicare Coverage Process

Nearly three years ago, the Centers for Medicare & Medicaid Services (CMS), formerly the Health Care Financing Administration, announced a new process for making national coverage determinations [1]. Prior to this time, the process had been criticized as inconsistent, closed, and based on a “blackbox” methodology. The new process is designed to be evidence-based, as well as open and inclusive, and relying upon scientific and clinical literature to make coverage determinations. One controversial issue that prompted the creation of the new process was the topic of home prothrombin international normalized ratio (INR) monitors. At that time, CMS was considering issuing a national noncoverage determination. Within the past year, a coalition of manufacturers, physicians, specialty societies, and patients successfully used the evidence-based process to obtain coverage of home prothrombin (INR) monitoring for patients with mechanical heart valves. This communication explains the reasoning behind this decision, particularly with respect to the coupling of testing and outcomes, and it also explores ways to possibly expand coverage, as additional information becomes available. A detailed explanation of this decision can be found on CMS’s website at www.hcfa.gov/coverage. The recent CMS Decision Memorandum on home INR monitoring embodies the use of a rigorous evidence-based approach to CMS policy decisionmaking. The construction of a desirable analytical framework for assessing the clinical effectiveness of any diagnostic test is predicated upon the notion that the results of such a test will influence patient outcomes. The ideal, randomized controlled trial for effectiveness occurs when results of the diagnostic test alter a treatment intervention, and the health outcomes associated with such treatment are included within the boundaries of that same study. However, there are possibilities where appropriate linkages of randomized controlled trials can demonstrate a similar, strong relationship between testing and health outcomes. In this latter instance, there is a coupling of surrogate (or intermediate outcomes) with eventual health outcomes. The presence of key clinical trials, particularly among patients with mechanical heart valves (MHVs) who require long-term anticoagulation, afforded CMS the opportunity to evaluate both types of analytical frameworks, which are described above. In the first case, the typical study design was comprised of a home INR test group vs. a “standard” care control group, and health outcomes are event rates (bleeding and thromboembolism). In the second analytical framework, a home INR test group was still compared against a standard care control group, but, in this instance, time-in-therapeutic range (TTR) was a more achievable surrogate outcome, given the much larger sample sizes needed to adequately compare event rates. However, since a separate body of literature has established a causal relationship between TTR and event rates, particularly as highlighted by Samsa and Matchar [2], CMS was able to rely upon such an indirect approach which is contingent upon the use of surrogate outcomes. It should be emphasized that CMS does not restrict its review of evidence to only include randomized controlled trials, but in this evaluation of home INR testing where several trials were available, it is reasonable to emphasize the strongest type of evidence that was considered. Studies involving diagnostic technologies are usually represented by crosssectional, two-by-two table analyses, which in spite of generating useful sensitivity and specificity values, do not often afford the opportunity to address outcomes, even those which are surrogate and usually more accessible. Although the Decision Memorandum contains further details, some representative supportive trials in the MHV setting (i.e., at least 50% MHV patients in both study arms) are summarized below. Horstkotte conducted one of the first randomized prospective trials related to home INR testing [3].