Faculty Bibliography

OBJECTIVES: We compared the effectiveness of diabetes-focused messaging strategies at increasing enrolment in a healthy food programme among adults with diabetes. METHODS: Vitality is a multifaceted wellness benefit available to members of Discovery Health, a South Africa-based health insurer. One of the largest Vitality programmes is HealthyFood (HF), an incentive-based programme designed to encourage healthier diets by providing up to 25% cashback on healthy food purchases. We randomised adults with type 2 diabetes to 1 of 5 arms: (1) control, (2) a diabetes-specific message, (3) a message with a recommendation of HF written from the perspective of a HF member with diabetes, (4) a message containing a physician's recommendation of HF, or (5) the diabetes-specific message from arm 2 paired with an 'enhanced active choice'(EAC). In an EAC, readers are asked to make an immediate choice (in this case, to enrol or not enrol); the pros and cons associated with the preferred and non-preferred options are highlighted. HF enrolment was assessed 1 month following the first emailed message. RESULTS: We randomised 3906 members. After excluding those who enrolled in HF or departed from the Vitality programme before the first intervention email, 3665 (94%) were included in a modified intent-to-treat analysis. All 4 experimental arms had significantly higher HF enrolment rates compared with control (p<0.0001 for all comparisons). When comparing experimental arms, the diabetes-specific message with the EAC had a significantly higher enrolment rate (12.6%) than the diabetes-specific message alone (7.6%, p=0.0016). CONCLUSIONS: Messages focused on diabetes were effective at increasing enrolment in a healthy food programme. The addition of a framed active choice to a message significantly raised enrolment rates in this population. These findings suggest that simple, low-cost interventions can enhance enrolment in health promoting programmes and also be pragmatically tested within those programmes. TRIAL REGISTRATION NUMBER: NCT02462057.

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

BACKGROUND: Randomized clinical trials provide gold-standard evidence for the efficacy of interventions, but have limitations, including highly selected populations that make inference on effectiveness difficult and a lack of ability to adapt and change midstream. METHODS: We propose two innovations for pragmatic trial design. RESULTS: Evidence-based evolutionary testing, a framework that allows adaptation of interventions and rapid-cycle innovation, preserves the power of randomization while acknowledging the need for adaptation and learning. An opt-out consent framework increases the fraction of the target population who participate in trials, but may lead to dampening of effect sizes. CONCLUSION: Pragmatic trials offer numerous advantages in the evaluation of behavioral interventions in health. Statistical innovations, including evidence-based evolutionary testing and opt-out framing of consent and enrollment processes, can enhance the power of pragmatic trials and lead to more rapid progress.

OBJECTIVES: Diagnostic imaging may be a major source of cancer-related distress, a condition known as "scanxiety". Scant scholarly work has been performed to evaluate scan-associated distress in cancer. We sought to characterize risk factors for scan-associated distress among patients with Non-Small Cell Lung Cancer (NSCLC), and to evaluate the impact of scan-associated distress on quality of life. MATERIALS AND METHODS: We conducted a cross-sectional survey study of patients with recurrent/metastatic NSCLC treated at an academic medical center. Clinical and demographic variables were obtained through chart abstraction and patient self-report. We used a modified version of the Impact of Event Scale 6 (IES-6) to specifically assess distress associated with scans, and quality of life was measured using the Functional Assessment of Cancer Therapy - Lung (FACT-L). RESULTS: Among 103 participants (survey response rate 76.3%), median age was 67, 61.2% were women, and 82.5% were white. At the study visit, 72.8% of subjects discussed a recent scan, and 83% reported some scan-associated distress. Scan-associated distress was not associated with whether the patient had a recent scan, progressive disease or time from diagnosis. Scan-associated distress was associated with impaired quality of life (p=0.004); each unit increase in IES-6 corresponded to an approximately one-unit decrease in FACT-L score. CONCLUSION: Scan-associated distress is a common problem among patients with NSCLC, and is associated with impaired quality of life. Scan-associated distress severity was not associated with time since diagnosis or whether a recent scan was discussed at the study visit, which implies scan-associated distress may be a persistent problem.

The substantial nationwide investment in inpatient palliative care services stems from their great promise to improve patient-centered outcomes and reduce costs. However, robust experimental evidence of these benefits is lacking. The Randomized Evaluation of Default Access to Palliative Services (REDAPS) study is a pragmatic, stepped-wedge, cluster randomized trial designed to test the efficacy and costs of specialized palliative care consultative services for hospitalized patients with advanced chronic obstructive pulmonary disease, dementia, or end-stage renal disease, as well as the overall effectiveness of ordering such services by default. Additional aims are to identify the types of services that are most beneficial and the types of patients most likely to benefit, including comparisons between ward and ICU patients. We hypothesize that patient-centered outcomes can be improved without raising costs by simply changing the default option for palliative care consultation from opt-in to opt-out for patients with life-limiting illnesses. Patients aged 45 years or older are enrolled at 11 hospitals using an integrated electronic health record (EHR). As a pragmatic trial designed to enroll between 12,000 and 15,000 patients, eligibility is determined using a validated, EHR-based algorithm, and all outcomes are captured via the EHR and billing systems data. The time at which each hospital transitions from control, opt-in palliative care consultation to intervention, opt-out consultation, is randomly assigned. The primary outcome is a composite measure of in-hospital mortality and length of stay. Secondary outcomes include palliative care process measures and clinical and economic outcomes. The REDAPS trial was registered with clinicaltrials.gov, NCT02505035 on July 16, 2015.

BACKGROUND: Coronary artery disease is the single leading cause of death in the United States, and medications can significantly reduce the rate of repeat cardiovascular events and treatment procedures. Adherence to these medications, however, is very low. METHODS: HeartStrong is a national randomized trial offering 3 innovations. First, the intervention is built on concepts from behavioral economics that we expect to enhance its effectiveness. Second, the implementation of the trial takes advantage of new technology, including wireless pill bottles and remote feedback, to substantially automate procedures. Third, the trial's design includes an enhancement of the standard randomized clinical trial that allows rapid-cycle innovation and ongoing program enhancement. RESULTS: Using a system involving direct data feeds from 6 insurance partners followed by mail, telephone, and email contact, we enrolled 1,509 patients discharged from the hospital with acute myocardial infarction in a 2:1 ratio of intervention:usual care. The intervention period lasts 1 year; the primary outcome is time to first fatal or nonfatal acute vascular event or revascularization, including acute myocardial infarction, unstable angina, stroke, acute coronary syndrome admission, or death. CONCLUSIONS: Our randomized controlled trial of the HeartStrong program will provide an evaluation of a state-of-the-art behavioral economic intervention with a number of important pragmatic features. These include a tailored intervention responding to patient activity, streamlining of consent and implementation processes using new technologies, outcomes centrally important to patients, and the ability to implement rapid-cycle innovation.

Synchronizing medication refills-renewing all medications at the same time from the same pharmacy-is an increasingly popular strategy to improve adherence to medication regimens, but there has been little research regarding its effectiveness. In light of increasing policy interest, we evaluated the impact of a pilot refill synchronization program implemented by a large national insurer. A random sample of Medicare Advantage patients receiving mail-order refills for common maintenance medications (antihypertensive, lipid-lowering, or antidiabetic agents) were invited to join the program and followed for twelve months. On average, the absolute increase in the proportion of patients deemed adherent during follow-up was 3-10 percentage points for the intervention group, compared to 1-5 percentage points for the control group. Patients with poorer baseline adherence showed larger increases in the absolute proportion deemed adherent in intervention (23-26 percentage points) compared to a control group (13-15 percentage points). Synchronizing refills might be a promising intervention to improve adherence to maintenance medications, especially among Medicare patients with low baseline adherence.

BACKGROUND: Next-generation sequencing (NGS) of surgically resected solid tumor samples has become integral to personalized medicine approaches for cancer treatment and monitoring. Liquid biopsies, or the enrichment and characterization of circulating tumor cells (CTCs) from blood, can provide noninvasive detection of evolving tumor mutations to improve cancer patient care. However, the application of solid tumor NGS approaches to circulating tumor samples has been hampered by the low-input DNA available from rare CTCs. Moreover, whole genome amplification (WGA) approaches used to generate sufficient input DNA are often incompatible with blood collection tube preservatives used to facilitate clinical sample batching. METHODS: To address this, we have developed a novel approach combining tumor cell isolation from preserved blood with Repli-G WGA and Illumina TruSeq Amplicon Cancer Panel-based NGS. We purified cell pools ranging from 10 to 1000 cells from three different cell lines, and quantitatively demonstrate comparable quality of DNA extracted from preserved versus unpreserved samples. RESULTS: Preservation and WGA were compatible with the generation of high-quality libraries. Known point mutations and gene amplification were detected for libraries that had been prepared from amplified DNA from preserved blood. CONCLUSION: These spiking experiments provide proof of concept of a clinically applicable workflow for real-time monitoring of patient tumor using noninvasive liquid biopsies.

PURPOSE: To test whether employer matching of employees' monetary contributions increases employees' (1) participation in deposit contracts to promote weight loss and (2) weight loss. DESIGN: A 36-week randomized trial. SETTING: Large employer in the northeast United States. PARTICIPANTS: One hundred thirty-two obese employees. INTERVENTIONS: Over 24 weeks, participants were asked to lose 24 pounds and randomized to monthly weigh-ins or daily weigh-ins with monthly opportunities to deposit $1 to $3 per day that was not matched, matched 1:1, or matched 2:1. Deposits and matched funds were returned to participants for each day they were below their goal weight. MEASURES: Rates of making >/=1 deposit, weight loss at 24 weeks (primary outcome), and 36 weeks. ANALYSIS: Deposit rates were compared using chi(2) tests. Weight loss was compared using t tests. RESULTS: Among participants eligible to make deposits, 29% made >/=1 deposit and matching did not increase participation. At 24 weeks, control participants gained an average of 1.0 pound, whereas 1:1 match participants lost an average of 5.3 pounds (P = .005). After 36 weeks, control participants gained an average of 2.1 pounds, whereas no match participants lost an average of 5.1 pounds (P = .008). CONCLUSION: Participation in deposit contracts to promote weight loss was low, and matching deposits did not increase participation. For deposit contracts to impact population health, ongoing participation will need to be higher.