Relationship between test frequency and outcomes of anticoagulation: A literature review and commentary with implications for the design of randomized trials of patient self-management

Background: Patient self-management (PSM) of anticoagulation, which is prim arily based upon the premise that more frequent testing will lead to tighte r anticoagulation control and thus to improved clinical outcomes, is a prom ising model of care. The goals of this paper are (1) to describe the streng th of evidence correlating more frequent testing with improved outcomes; an d (2) to discuss implications of these findings for the design of randomize d controlled trials (RCTs) assessing the effectiveness and cost-effectivene ss of PSM. Methods: We performed two literature reviews: one examining the strength of the relationship between time in target range (TTR) and the clinical outco mes of major bleeding and thromboembolism; and the second examining the str ength of the relationship between frequency of testing and TTR. Results: We found that (1) the relationship between TTR and clinical outcom es is strong, thus supporting use of TTR as a primary outcome variable; and (2) more frequent testing seems to increase TTR, although the studies supp orting this latter conclusion were relatively few and not definitive. Stati stical analysis suggested that a study which uses clinical event rates as i ts primary outcome would need to be much larger than a comparable study whi ch is based upon TTR. Conclusions: When designing randomized trials of PSM, the design should (1) use as its control group high quality anticoagulation management rather th an usual care; (2) include the maximum possible amount of self-management i n the intervention group; (3) include different testing intervals in the in tervention group; (4) use TTR as the primary outcome variable and event rat es as a secondary outcome; and (5) base the sample size calculations upon a 5-10% absolute improvement in TTR. Additional RCTs are needed in order to determine how the promise of PSM can best be fulfilled.