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 primarily based upon the premise that more frequent testing will lead to tighter anticoagulation control and thus to improved clinical outcomes, is a promising model of care. The goals of this paper are (1) to describe the strength of evidence correlating more frequent testing with improved outcomes; and (2) to discuss implications of these findings for the design of randomized controlled trials (RCTs) assessing the effectiveness and cost-effectiveness of PSM.

METHODS

We performed two literature reviews: one examining the strength of the relationship between time in target range (TTR) and the clinical outcomes of major bleeding and thromboembolism; and the second examining the strength of the relationship between frequency of testing and TTR.

RESULTS

We found that (1) the relationship between TTR and clinical outcomes is strong, thus supporting use of TTR as a primary outcome variable; and (2) more frequent testing seems to increase TTR, although the studies supporting this latter conclusion were relatively few and not definitive. Statistical analysis suggested that a study which uses clinical event rates as its primary outcome would need to be much larger than a comparable study which 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 than usual care; (2) include the maximum possible amount of self-management in the intervention group; (3) include different testing intervals in the intervention group; (4) use TTR as the primary outcome variable and event rates 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.