A randomized trial of lottery-based incentives and reminders to improve warfarin adherence: the Warfarin Incentives (WIN2) Trial.

BACKGROUND: Previous research has suggested that daily lottery incentives could improve medication adherence. Such daily incentives include implicit reminders. However, the comparative effectiveness of reminders alone versus daily incentives has not been tested. METHODS: A total of 270 patients on warfarin were enrolled in a four-arm, multi-center, randomized controlled trial comparing a daily lottery-based incentive, a daily reminder, and a combination of the two against a control group (usual care). RESULTS: Participants in the reminder group had the lowest percentage of time out of target international normalized ratio (INR) range, the primary outcome, with an adjusted odds of an out-of-range INR 36% lower than among those in the control group, 95%CI [7%, 55%]. No other group had a statistically significant improvement in anticoagulation control relative to the control group or to each other. The only group that had significant improvement in incorrect adherence was the lottery group (incorrect adherence: 12.1% compared with 23.7% in the control group, difference of -7.4% 95%CI [-14%, -0.3%]). However, there was no relationship between changes in adherence and anticoagulation control in the lottery group. CONCLUSIONS: Automated reminders led to the largest improvements in anticoagulation control, although without impacting measured adherence. Lottery-based reminders improved measured adherence but did not lead to improved anticoagulation control. Copyright © 2016 John Wiley & Sons, Ltd.

Randomized trial of lottery-based incentives to improve warfarin adherence.

BACKGROUND: Poor adherence to medications is a major cause of morbidity and inadequate drug effectiveness. Efforts to improve adherence have typically been either ineffective or too complex to implement in clinical practice. Lottery-based incentive interventions could be a scalable approach to improving adherence. METHODS: This was a randomized, controlled clinical trial of a daily lottery-based incentive in patients on warfarin stratified by baseline international normalized ratio (INR). The trial randomized 100 patients to either a lottery-based incentive or no lottery intervention. Main outcome was out-of-range INRs. RESULTS: Over 6 months, the overall percentage of out-of-range INRs did not differ between the 2 arms (mean 23.0% in lottery arm and 25.9% in control arm, adjusted odds ratio [OR] 0.93, 95% CI 0.62-1.41). However, among the a priori subgroup with a baseline INR below therapeutic range, there was a significant reduction in out-of-range INR in the lottery arm versus the control arm (adjusted OR 0.39, 95% CI 0.25-0.62), whereas there was no such effect among those with therapeutic INRs at baseline (adjusted OR 1.26, 95% CI, 0.76-2.09, P value for interaction = .0016). Among those with low INR at baseline, there was a nonsignificant 49% reduction in the odds of nonadherence with the intervention (OR 0.51, 95% CI 0.23-1.14). CONCLUSIONS: Although a lottery-based intervention was not associated with a significant improvement in anticoagulation control among all study participants, it improved control among an a priori group of patients at higher risk for poor adherence.

Can we predict daily adherence to warfarin?: Results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study.

BACKGROUND: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy. METHODS: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin. RESULTS: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence. CONCLUSIONS: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients.

A test of financial incentives to improve warfarin adherence.

BACKGROUND: Sub-optimal adherence to warfarin places millions of patients at risk for stroke and bleeding complications each year. Novel methods are needed to improve adherence for warfarin. We conducted two pilot studies to determine whether a lottery-based daily financial incentive is feasible and improves warfarin adherence and anticoagulation control. METHODS: Volunteers from the University of Pennsylvania Anticoagulation Management Center who had taken warfarin for at least 3 months participated in either a pilot study with a lottery with a daily expected value of $5 (N = 10) or a daily expected value of $3 (N = 10). All subjects received use of an Informedix Med-eMonitor System with a daily reminder feature. If subjects opened up their pill compartments appropriately, they were entered into a daily lottery with a 1 in 5 chance of winning $10 and a 1 in 100 chance of winning $100 (pilot 1) or a 1 in 10 chance of winning $10 and a 1 in 100 chance of winning $100 (pilot 2). The primary study outcome was proportion of incorrect warfarin doses. The secondary outcome was proportion of INR measurements not within therapeutic range. Within-subject pre-post comparisons were done of INR measurements with comparisons with either historic means or within-subject comparisons of incorrect warfarin doses. RESULTS: In the first pilot, the percent of out-of-range INRs decreased from 35.0% to 12.2% during the intervention, before increasing to 42% post-intervention. The mean proportion of incorrect pills taken during the intervention was 2.3% incorrect pills, compared with a historic mean of 22% incorrect pill taking in this clinic population. Among the five subjects who also had MEMS cap adherence data from warfarin use in our prior study, mean incorrect pill taking decreased from 26% pre-pilot to 2.8% in the pilot. In the second pilot, the time out of INR range decreased from 65.0% to 40.4%, with the proportion of mean incorrect pill taking dropping to 1.6%. CONCLUSION: A daily lottery-based financial incentive demonstrated the potential for significant improvements in missed doses of warfarin and time out of INR range. Further testing should be done of this approach to determine its effectiveness and potential application to both warfarin and other chronic medications.

Risk factors for nonadherence to warfarin: results from the IN-RANGE study.

BACKGROUND: Warfarin is widely used to prevent stroke and venous thromboembolism despite its narrow therapeutic window. Warfarin nonadherence is a substantial problem, but risk factors have not been well elucidated. METHODS: A prospective cohort study of adults initiating warfarin at two anticoagulation clinics (University and VA-affiliated) was performed to determine factors affecting nonadherence to warfarin. Nonadherence, defined by failure to record a correct pill bottle opening each day, was measured daily via electronic medication event monitoring systems (MEMS) caps. A multivariable explanatory model using logistic regression for longitudinal data was used to identify risk factors for nonadherence. RESULTS: One hundred eleven subjects were followed for a median of 137 days. Warfarin nonadherence was common (4787 of 22,425 or 21% of patient-days observed). Factors independently associated with higher odds of nonadherence included education beyond high school (odds ratio (OR) 1.8 (95%CI 1.2-2.7)), lower Short Form (SF)-36 mental component score (OR 1.4 (1.1-1.6) for each 10 point decrease); and impaired cognition (< or =19 points) on the Cognitive Capacity Screening Examination (CCSE) (OR 2.9 (1.7-4.8)). Compared to currently employed subjects, unemployed (OR 0.6 (0.3-1.2)) and retired (OR 0.5 (0.3-0.8)) subjects had somewhat improved adherence; disabled subjects over age 55 had worse adherence (OR 1.8 (1.1-3.1)) than younger disabled subjects (OR 0.8 (0.4-1.5)). CONCLUSIONS: Poor adherence to warfarin is common and risk factors are related to education level, employment status, mental health functioning, and cognitive impairment. Within the carefully controlled anticoagulation clinic setting, such patient-specific factors may be the basis of future interventions to improve nonadherence.