The Habit Formation trial of behavioral economic interventions to improve statin use and reduce the risk of cardiovascular disease: Rationale, design and methodologies.

BACKGROUND: Low adherence to statin (HMG-CoA reductase inhibitors) medication is common. Here, we report on the design and implementation of the Habit Formation trial. This clinical trial assessed whether the interventions, based on principles from behavioral economics, might improve statin adherence and lipid control in at-risk populations. We describe the rationale and methods for the trial, recruitment, conduct and follow-up. We also report on several barriers we encountered with recruitment and conduct of the trial, solutions we devised and efforts we will make to assess their impact on our study. METHODS: Habit Formation is a four-arm randomized controlled trial. Recruitment of 805 participants at elevated risk of atherosclerotic cardiovascular disease with evidence of sub-optimal statin adherence and low-density lipoprotein (LDL) control is complete. Initially, we recruited from large employers (Employers) and a national health insurance company (Insurers) using mailed letters; individuals with a statin Medication Possession Ratio less than 80% were invited to participate. Respondents were enrolled if a laboratory measurement of low-density lipoprotein was >130 mg/dL. Subsequently, we recruited participants from the Penn Medicine Health System; individuals with usual-care low-density lipoprotein of >100 mg/dL in the electronic medical record were recruited using phone, text, email, and regular mail. Eligible participants self-reported incomplete medication adherence. During a 6-month intervention period, all participants received a wireless-enabled pill bottle for their statins and daily reminder messages to take their medication. Principles of behavioral economics were used to design three financial incentives, specifically a Simple Daily Sweepstakes rewarding daily medication adherence, a Deadline Sweepstakes where participants received either a full or reduced incentive depending on whether they took their medication before or after a daily reminder or Sweepstakes Plus Deposit Contract with incentives divided between daily sweepstakes and a monthly deposit. Six months post-incentives, we compared the primary outcome, mean change from baseline low-density lipoprotein, across arms. RESULTS AND LESSONS LEARNED: Health system recruitment yielded substantially better enrollment and was cost-efficient. Despite unexpected systematic failure and/or poor availability of two wireless pill bottles, we achieved enrollment targets and implemented the interventions. For new trials, we will routinely monitor device function and have contingency plans in the event of systemic failure. CONCLUSION: Interventions used in the Habit Formation trial could be translated into clinical practice. Within a large health system, successful recruitment depended on identification of eligible individuals through their electronic medical record, along with flexible ways of contacting these individuals. Challenges with device failure were manageable. The study will add to our understanding of optimally structuring and implementing incentives to motivate durable behavior change.

Using Clinical Trial Data to Estimate the Costs of Behavioral Interventions for Potential Adopters: A Guide for Trialists.

Behavioral interventions involving electronic devices, financial incentives, gamification, and specially trained staff to encourage healthy behaviors are becoming increasingly prevalent and important in health innovation and improvement efforts. Although considerations of cost are key to their wider adoption, cost information is lacking because the resources required cannot be costed using standard administrative billing data. Pragmatic clinical trials that test behavioral interventions are potentially the best and often only source of cost information but rarely incorporate costing studies. This article provides a guide for researchers to help them collect and analyze, during the trial and with little additional effort, the information needed to inform potential adopters of the costs of adopting a behavioral intervention. A key challenge in using trial data is the separation of implementation costs, the costs an adopter would incur, from research costs. Based on experience with 3 randomized clinical trials of behavioral interventions, this article explains how to frame the costing problem, including how to think about costs associated with the control group, and describes methods for collecting data on individual costs: specifications for costing a technology platform that supports the specialized functions required, how to set up a time log to collect data on the time staff spend on implementation, and issues in getting data on device, overhead, and financial incentive costs.

Effect of Patient Financial Incentives on Statin Adherence and Lipid Control: A Randomized Clinical Trial.

Importance: Financial incentives can improve medication adherence and cardiovascular disease risk, but the optimal design to promote sustained adherence after incentives are discontinued is unknown. Objective: To determine whether 6-month interventions involving different financial incentives to encourage statin adherence reduce low-density lipoprotein cholesterol (LDL-C) levels from baseline to 12 months. Design, Setting, and Participants: This 4-group, randomized clinical trial was conducted from August 2013 to July 2018 among several large US insurer or employer populations and the University of Pennsylvania Health System. The study population included adults with elevated risk of cardiovascular disease, suboptimal LDL-C control, and evidence of imperfect adherence to statin medication. Data analysis was performed from July 2017 to June 2019. Interventions: The interventions lasted 6 months during which all participants received daily medication reminders and an electronic pill bottle. Statin adherence was measured by opening the bottle. For participants randomized to the 3 intervention groups, adherence was rewarded with financial incentives. The sweepstakes group involved incentives for daily adherence. In the deadline sweepstakes group, incentives were reduced if participants were adherent only after a reminder. The sweepstakes plus deposit contract group split incentives between daily adherence and a monthly deposit reduced for each day of nonadherence. Main Outcomes and Measures: The primary outcome was change in LDL-C level from baseline to 12 months. Results: Among 805 participants randomized (199 in the simple daily sweepstakes group, 204 in the deadline sweepstakes group, 201 in the sweepstakes plus deposit contract group, and 201 in the control group), the mean (SD) age was 58.5 (10.3) years; 519 participants (64.5%) were women, 514 (63.9%) had diabetes, and 273 (33.9%) had cardiovascular disease. The mean (SD) baseline LDL-C level was 143.2 (42.5) mg/dL. Measured adherence at 6 months (defined as the proportion of 180 days with electronic pill bottle opening) in the control group (0.69; 95% CI, 0.66-0.72) was lower than that in the simple sweepstakes group (0.84; 95% CI, 0.81-0.87), the deadline sweepstakes group (0.86; 95% CI, 0.83-0.89), and the sweepstakes plus deposit contract group (0.87; 95% CI, 0.84-0.90) (P < .001 for each incentive group vs control). LDL-C levels were measured for 636 participants at 12 months. Mean LDL-C level reductions from baseline to 12 months were 33.6 mg/dL (95% CI, 28.4-38.8 mg/dL) in the control group, 32.4 mg/dL (95% CI, 27.3-37.6 mg/dL) in the sweepstakes group, 33.2 mg/dL (95% CI, 28.1-38.3 mg/dL) in the deadline sweepstakes group, and 36.5 mg/dL (95% CI, 31.3-41.7 mg/dL) in the sweepstakes plus deposit contract group (adjusted P > .99 for each incentive group vs control). Conclusions and Relevance: Compared with the control group, different financial incentives improved measured statin adherence but not LDL-C levels. This result points to the importance of directly measuring health outcomes, rather than simply adherence, in trials aimed at improving health behaviors. Trial Registration: ClinicalTrials.gov Identifier: NCT01798784.