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PURPOSE: Previous cost-effectiveness analyses of colorectal cancer screening have not considered the value of patient time despite consensus recommendations to do so. The authors sought to estimate the amount and value of patient time required for screening colonoscopy. METHODS: Patients who were scheduled to undergo screening colonoscopy were recruited from a university endoscopy center. Participants completed a time diary for the screening colonoscopy process, including time spent in preparation, travel, waiting, colonoscopy, and recovery. The authors defined several time intervals and estimated their value. The primary time interval of interest, called occupied time, included preparation, travel, waiting, the colonoscopy procedure, and on-site recovery. Time was valued at the 2005 average wage rate. The authors performed sensitivity analyses to test other time intervals and wage rates. They then incorporated patient time costs into a previously published cost-effectiveness analysis of colorectal cancer screening to examine their impact. RESULTS: One hundred ten subjects completed the study. The sample was 57% female, 85% Caucasian, and 90% insured (40% Medicare, 4% Medicaid). The mean occupied time was 23.2 hours, worth $432 at the average wage rate. The authors estimate that including patient time costs in cost-effectiveness analysis would increase the cost per life-year saved with screening colonoscopy by 68%, from $13,100 to $22,000. Sensitivity analyses showed that the increase could range from 17% to 224% depending on the time interval valued. CONCLUSIONS: Patient time constitutes an important cost in colonoscopy screening and should be included in cost-effectiveness analyses. [ABSTRACT FROM AUTHOR]

Objective: To develop consensus-based recommendations guiding the conduct of cost-effectiveness analysis (CEA) to improve the comparability and quality of studies. The recommendations apply to analyses intended to inform the allocation of health care resources across a broad range of conditions and interventions. This article, first in a 3-part series, discusses how this goal affects the conduct and use of analyses. The remaining articles will outline methodological and reporting recommendations, respectively.Participants: The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS).Evidence: The panel reviewed the theoretical foundations of CEA, current practices, and alternative procedures for measuring and assigning values to resource use and health outcomes.Consensus Process: The panel met 11 times during 2 1/2 years with PHS staff and methodologists from federal agencies. Working groups brought issues and preliminary recommendations to the full panel for discussion. Draft recommendations were circulated to outside experts and the federal agencies prior to finalization.Conclusions: The panel's recommendations define a "reference case" cost-effectiveness analysis, a standard set of methods to serve as a point of comparison across studies. The reference case analysis is conducted from the societal perspective and accounts for benefits, harms, and costs to all parties. Although CEA does not reflect every element of importance in health care decisions, the information it provides is critical to informing decisions about the allocation of health care resources. [ABSTRACT FROM AUTHOR]

Objective: This article, the third in a 3-part series, describes recommendations for the reporting of cost-effective analyses (CEAs) intended to improve the quality and accessibility of CEA reports.Participants: The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, convened by the US Public Health Service.Evidence: The panel reviewed the theoretical foundations of CEA, current practices, alternative methods, published critiques of CEAs, and criticisms of general CEA methods and reporting practices.Consensus Process: The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts were solicited from federal government methodologists, health agency officials, and academic methodologists.Conclusions: These recommendations are proposed to enhance the transparency of study methods, assist analysts in providing complete information, and facilitate the presentation of comparable cost-effectiveness results across studies. Adherence to reporting conventions and attention to providing information required to understand and interpret study results will improve the relevance and accessibility of CEAs. [ABSTRACT FROM AUTHOR]

Rationales: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior nonrandomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C)., Primary Hypothesis: Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention., Design: Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of 4 modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team., Sites: University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas., Primary Outcomes: Improvement in systolic blood pressure and LDL-C., Secondary Outcomes: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention., Estimated Enrollment: 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C >100 despite being on statins and (b) had systolic blood pressure >140 at 2 recent ambulatory visits., Enrollment Dates: March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist., Current Status: Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394., Competing Interests: Conflict of interest Dr. Volpp is a Scientific Board member of THRIVE Global and a part owner of VALHealth, a behavioral economics consulting firm and has received research funding and consulting support from the American Heart Association. Dr. Asch is also a part owner of VALHealth and a Scientific Board member of THRIVE Global., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Randomized clinical trials (RCTs) often suffer from a lack of representation from historically marginalized populations, and it is uncertain whether virtual RCTs (vRCTs) enhance representativeness or if elements of their consent and enrollment processes may instead contribute to underrepresentation of these groups. In this study, we aimed to identify disparities in enrollment demographics in a vRCT, the BE ACTIVE study, which recruited patients within a single health system. We discovered that the proportions of eligible patients who were randomized differed significantly by gender and race/ethnicity (men 1.2%, women 2.0%, P < .001; White 1.8%, Black 1.3%, Hispanic 0.7%, Asian 0.9%; P < .001), and compared with White patients, non-White patients were less likely to have a valid email address on file and were less likely to click on the email link to the study webpage and begin enrollment., Competing Interests: Conflict of Interest Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To estimate the cost of Rhesus (Rh) testing and prophylaxis for first-trimester vaginal bleeding in the ambulatory setting., Study Design: We used time-driven, activity-based costing to analyze tasks associated with Rh testing and prophylaxis of first-trimester vaginal bleeding at one hospital-based outpatient and two independent reproductive health clinics. At each site, we observed 10 patients undergoing Rh-typing and two patients undergoing Rh prophylaxis. We computed the costs of blood Rh-typing by both fingerstick and phlebotomy, cost of locating previous blood type in the electronic health record (available for 69.8% of hospital-based patients), and costs associated with Rh immune globulin prophylaxis. All costs are reported in 2021 US dollars., Results: The hospital-based clinic reviewed the electronic health record to confirm Rh-status (cost, $26.18 per patient) and performed a phlebotomy, at $47.11 per patient, if none was recorded. The independent clinics typed blood by fingerstick, at a per-patient cost of $4.07. Rh-immune globulin administration costs, including the medication, were similar across facilities, at a mean of $145.66 per patient. Projected yearly costs for testing and prophylaxis were $55,831 for the hospital-based clinic, which was the lowest-volume site, $47,941 for Clinic A, which saw 150 patients/month, and $185,654 for Clinic B, which saw 600 patients/month., Conclusions: Rh testing and prophylaxis for first-trimester vaginal bleeding generates considerable costs for outpatient facilities, even for Rh-positive patients with a prior blood type on record., Implications: Rh testing and prophylaxis for first-trimester bleeding generate considerable costs even for Rh-positive patients and those with a previously known blood type. These findings highlight the need to reconsider this practice, which is no longer supported by evidence and already safely waived in multiple medical settings in the United States and around the world., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Physical activity is associated with a lower risk of major adverse cardiovascular events, but few individuals achieve guideline-recommended levels of physical activity. Strategies informed by behavioral economics increase physical activity, but their longer-term effectiveness is uncertain. We sought to determine the effect of behaviorally designed gamification, loss-framed financial incentives, or their combination on physical activity compared with attention control over 12-month intervention and 6-month postintervention follow-up periods., Methods: Between May 2019 and January 2024, participants with clinical atherosclerotic cardiovascular disease or a 10-year risk of myocardial infarction, stroke, or cardiovascular death of ≥7.5% by the Pooled Cohort equation were enrolled in a pragmatic randomized clinical trial. Participants received a wearable device to track daily steps, established a baseline, selected a step goal increase, and were randomly assigned to control (n=151), behaviorally designed gamification (n=304), loss-framed financial incentives (n=302), or gamification+financial incentives (n=305). The primary outcome of the trial was the change in mean daily steps from baseline through the 12-month intervention period., Results: A total of 1062 patients (mean±SD age, 67±8; 61% female; 31% non-White) were enrolled. Compared with control subjects, participants had significantly greater increases in mean daily steps from baseline during the 12-month intervention in the gamification arm (adjusted difference, 538.0 [95% CI, 186.2-889.9]; P =0.0027), financial incentives arm (adjusted difference, 491.8 [95% CI, 139.6-844.1]; P =0.0062), and gamification+financial incentives arm (adjusted difference, 868.0 [95% CI, 516.3-1219.7]; P <0.0001). During the 6-month follow-up, physical activity remained significantly greater in the gamification+financial incentives arm than in the control arm (adjusted difference, 576.2 [95% CI, 198.5-954]; P =0.0028), but it was not significantly greater in the gamification (adjusted difference, 459.8 [95% CI, 82.0-837.6]; P =0.0171) or financial incentives (adjusted difference, 327.9 [95% CI, -50.2 to 706]; P =0.09) arms after adjustment for multiple comparisons., Conclusions: Behaviorally designed gamification, loss-framed financial incentives, and the combination of both increased physical activity compared with control over a 12-month intervention period, with the largest effect in gamification+financial incentives. These interventions could be a useful component of strategies to reduce cardiovascular risk in high-risk patients., Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT03911141., Competing Interests: Disclosures Dr Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no conflicts.

Background and Aims: Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes., Methods and Analysis: This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated., Ethics and Dissemination: The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders., Trial Registration Number: NCT05260268., Competing Interests: Competing interests: MS reports additional grants from NIH/NIDDK/NIAAA, PCORI, and Grifols, SA., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Heart failure (HF) is one of the most common reasons for hospital admission and is a major cause of morbidity, mortality, and increasing health care costs. The EMPOWER study was a randomized trial that used remote monitoring technology to track patients' weight and diuretic adherence and a state-of-the-art approach derived from behavioral economics to motivate adherence to the reverse monitoring technology., Objective: The goal was to explore patient and clinician perceptions of the program and its impact on perceived health outcomes and better understand why some patients or clinicians did better or worse than others in response to the intervention., Approach: This was a retrospective qualitative study utilizing semi-structured interviews with 43 patients and 16 clinicians to understand the trial's processes, reflecting on successes and areas for improvement for future iterations of behavioral economic interventions., Key Results: Many patients felt supported, and they appreciated the intervention. Many also appreciated the lottery intervention, and while it was not an incentive for enrolling for many respondents, it may have increased adherence during the study. Clinicians felt that the intervention integrated well into their workflow, but the number of alerts was burdensome. Additionally, responses to alerts varied considerably by provider, perhaps because there are no professional guidelines for alerts unaccompanied by severe symptoms., Conclusion: Our qualitative analysis indicates potential areas for additional exploration and consideration to design better behavioral economic interventions to improve cardiovascular health outcomes for patients with HF. Patients appreciated lottery incentives for adhering to program requirements; however, many were too far along in their disease progression to benefit from the intervention. Clinicians found the amount and frequency of electronic alerts burdensome and felt they did not improve patient outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT02708654., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Higher levels of physical activity are associated with improvements in cardiovascular health, and consensus guidelines recommend that individuals with or at risk for atherosclerotic cardiovascular disease (ASCVD) participate in regular physical activity. However, most adults do not achieve recommended levels of physical activity. Concepts from behavioral economics have been used to design scalable interventions that increase physical activity over short time periods, but the longer-term efficacy of these strategies is uncertain., Study Design and Objectives: BE ACTIVE (NCT03911141) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of 3 strategies informed by behavioral economic concepts to increase daily physical activity in patients with established ASCVD or 10-year ASCVD risk > 7.5% who are seen in primary care and cardiology clinics affiliated with the University of Pennsylvania Health System. Patients are contacted by email or text message, and complete enrollment and informed consent on the Penn Way to Health online platform. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 33% to 50%, and are randomized 1:2:2:2 to control, gamification, financial incentives, or both gamification and financial incentives. Interventions continue for 12 months, with follow-up for an additional 6 months to evaluate the durability of behavior change. The trial has met its enrollment goal of 1050 participants, with a primary endpoint of change from baseline in daily steps over the 12-month intervention period. Key secondary endpoints include change from baseline in daily steps over the 6-month post-intervention follow-up period and change in moderate to vigorous physical activity over the intervention and follow-up periods. If the interventions prove effective, their effects on life expectancy will be compared with their costs in cost-effectiveness analysis., Conclusions: BE ACTIVE is a virtual, pragmatic randomized clinical trial powered to demonstrate whether gamification, financial incentives, or both are superior to attention control in increasing physical activity. Its results will have important implications for strategies to promote physical activity in patients with or at risk for ASCVD, as well as for the design and implementation of pragmatic virtual clinical trials within health systems., Competing Interests: Conflict of interest Dr. Fanaroff reports a career development grant from the American Heart Association. Dr. Patel is an employee of Ascension Health. Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no relevant conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Variation in operative setting and surgical technique exists when treating specialty site melanomas. There are limited data comparing costs among surgical modalities., Objective: To evaluate the costs of head and neck melanoma surgery performed with Mohs micrographic surgery or conventional excision in the operating room or office-based settings., Methods: A retrospective cohort study was performed on patients aged 18 years and older with surgically treated head and neck melanoma in 2 cohorts, an institutional cohort and an insurance claims cohort, for the years 2008-2019. The primary outcome was total cost of care for a surgical encounter, provided in the form of insurance reimbursement data. A generalized linear model was used to adjust for covariates affecting differences between treatment groups., Results: In the institutional and insurance claims cohorts, average adjusted treatment cost was highest in the conventional excision-operating room treatment group, followed by the Mohs surgery and conventional excision-office setting ( p < .001)., Conclusion: These data demonstrate the important economic role the office-based setting has for head and neck melanoma surgery. This study allows cutaneous oncologic surgeons to better understand the costs of care involved in head and neck melanoma treatment. Cost awareness is important for shared decision-making discussions with patients., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Highlights: Electronic health records are not a single system but a series of overlapping and legacy systems that require time and expertise to use efficiently.Commonly measured patient characteristics such as weight and body mass index are relatively easy to locate for most trial enrollees but less common characteristics, like ejection fraction, are not.Acquiring essential supplementary data-in this trial, state data on hospital admission-can be a lengthy and difficult process.

Lacking national direction, in 2020 Brazilian states adopted a variety of nonpharmaceutical interventions to combat COVID-19, adjusting their stringency over time. We took advantage of this variation across states and over time to estimate the independent effect of seven interventions on the growth rate ratios of COVID-19 cases and deaths. Panel regressions using daily data from March to December 2020 for twelve states show that two interventions, suspension of public events and masking mandates, significantly reduced the spread of the disease. Partial and full suspension of public events were equally effective. Full masking mandates were more effective than partial ones. Together, suspension of public events and full masking mandates reduced the growth rate ratios of both cases and deaths almost to 1, the point at which cases and deaths are no longer increasing. Policy makers may find this analysis useful as they aim to choose the most effective nonpharmaceutical interventions to reduce COVID-19's social and economic burdens.

Importance: Close remote monitoring of patients following discharge for heart failure (HF) may reduce readmissions or death., Objective: To determine whether remote monitoring of diuretic adherence and weight changes with financial incentives reduces hospital readmissions or death following discharge with HF., Design, Setting, and Participants: The Electronic Monitoring of Patients Offers Ways to Enhance Recovery (EMPOWER) study, a 3-hospital pragmatic trial, randomized 552 adults recently discharged with HF to usual care (n = 280) or a compound intervention (n = 272) designed to inform clinicians of diuretic adherence and changes in patient weight. Patients were recruited from May 25, 2016, to April 8, 2019, and followed up for 12 months. Investigators were blinded to assignment but patients were not. Analysis was by intent to treat., Interventions: Participants randomized to the intervention arm received digital scales, electronic pill bottles for diuretic medication, and regret lottery incentives conditional on the previous day's adherence to both medication and weight measurement, with $1.40 expected daily value. Participants' physicians were alerted if participants' weights increased 1.4 kg in 24 hours or 2.3 kg in 72 hours or if diuretic medications were missed for 5 days. Alerts and weights were integrated into the electronic health record. Participants randomized to the control arm received usual care and no further study contact., Main Outcomes and Measures: Time to death or readmission for any cause within 12 months., Results: Of the 552 participants, 290 were men (52.5%); 291 patients (52.7%) were Black, 231 were White (41.8%), and 16 were Hispanic (2.9%); mean (SD) age was 64.5 (11.8) years. The mean (SD) ejection fraction was 43% (18.1%). Each month, approximately 75% of participants were 80% adherent to both medication and weight measurement. There were 423 readmissions and 26 deaths in the control group and 377 readmissions and 23 deaths in the intervention group. There was no significant difference between the 2 groups for the combined outcome of all-cause inpatient readmission or death (unadjusted hazard ratio, 0.91; 95% CI, 0.74-1.13; P = .40) and no significant differences in all-cause inpatient readmission or observation stay or death, all-cause cardiovascular readmission or death, time to first event, and total all-cause deaths. Participants in the intervention group were slightly more likely to spend fewer days in the hospital., Conclusions and Relevance: In this randomized clinical trial, there was no reduction in the combined outcome of readmission or mortality in a year-long intensive remote monitoring program with incentives for patients previously hospitalized for HF., Trial Registration: ClinicalTrials.gov Identifier: NCT02708654.

Background: Despite substantial evidence on the effectiveness of non-pharmaceutical interventions (NPIs), there is still limited evidence on the individual effects of different types of NPIs on social distancing, especially in low- and middle-income countries., Methods: We used panel data analysis to evaluate the effects of mandatory social distancing rules on social distancing. We obtained data on six different categories of mandatory restrictions implemented in Brazil, by date and state, from state government gazettes (diários oficiais). We then defined a social distancing rules index (SDI) to measure the strictness of social distancing rules, assigning each a value of 2, 1, or 0 depending on whether restrictions were full, partial, or very limited/non-existent at every given time. A separate variable was defined for masking mandates. We tested whether the following variables were associated to social distancing: SDI, masking mandates, COVID-19 incidence, population socioeconomic status, and political orientation. Data is for each day between March 11th and November 10th, 2020 in the 27 Brazilian states (N = 6615)., Findings: Social distancing increased when social distancing rules were stricter, and decreased when the use of face masks became mandatory. The effects of different types of restrictions varied: suspending in-person classes and gatherings, religious/sport/cultural activities had a greater effect than other types of restrictions. Also, the effect of social distancing rules on people's behaviour decreased over time, especially when rules were stricter., Interpretation: Mandatory social distancing rules must be adopted to increase social distancing. Stricter rules have a higher impact, but result in decreased compliance over time. Policymakers should prioritize more targeted policies., Competing Interests: The authors have declared that no competing interests exist.

Rationale: A trial of four financial incentive programs, conducted at CVS Caremark, a large employer, documented their effectiveness in promoting sustained abstinence from smoking, but their cost-effectiveness is unknown, and the significant up-front cost of the incentives is a deterrent to their adoption. Objectives: To determine the cost-effectiveness of these incentives from the healthcare sector and employer perspectives. Methods: This study examines a decision model built with trial data, supplemented by data from the literature. Life-expectancy gains for quitters were projected on the basis of U.S. life tables. The two individual-oriented programs paid $800 for smoking cessation at 6 months; one required participants to deposit $150 at baseline. Payments in the two group-oriented programs varied with the group's success; again, one required participants to deposit $150. Results: Life-years, quality-adjusted life-years (QALYs), costs (2012 dollars), and cost-effectiveness ratios are described. From the healthcare sector perspective, costs ranged from $3,200 per life-year ($2,500 per QALY) for the competitive deposit program, compared with usual care, to $6,500 per life-year ($5,100 per QALY) for the individual reward program. From the employer perspective, costs ranged from $256,600 per life-year gained for the individual deposit program to $1,711,100 per life-year gained for the individual reward program; the cost per QALY ranged from $65,300 for the competitive deposit program to $128,800 for the individual reward program. Cost-effectiveness from the employer perspective improved with longer decision horizons. Including future medical costs reduced cost-effectiveness from both perspectives. Conclusions: Four financial incentive programs that paid smokers to quit are very cost-effective from the healthcare sector perspective. They are more expensive from the employer perspective but may be cost-effective for employers with longer decision horizons.

Importance: Financial incentives may improve health behaviors. It is unknown whether incentives are more effective if they target a key process (eg, medication adherence), an outcome (eg, low-density lipoprotein cholesterol [LDL-C] levels), or both., Objective: To determine whether financial incentives awarded daily for process (adherence to statins), awarded quarterly for outcomes (personalized LDL-C level targets), or awarded for process plus outcomes induce reductions in LDL-C levels compared with control., Design, Setting, and Participants: A randomized clinical trial was conducted from February 12, 2015, to October 3, 2018; data analysis was performed from October 4, 2018, to May 27, 2021, at the University of Pennsylvania Health System, Philadelphia. Participants included 764 adults with an active statin prescription, elevated risk of atherosclerotic cardiovascular disease, suboptimal LDL-C level, and evidence of imperfect adherence to statin medication., Interventions: Interventions lasted 12 months. All participants received a smart pill bottle to measure adherence and underwent LDL-C measurement every 3 months. In the process group, daily financial incentives were awarded for statin adherence. In the outcomes group, participants received incentives for achieving or sustaining at least a quarterly 10-mg/dL LDL-C level reduction. The process plus outcomes group participants were eligible for incentives split between statin adherence and quarterly LDL-C level targets., Main Outcomes and Measures: Change in LDL-C level from baseline to 12 months, determined using intention-to-treat analysis., Results: Of the 764 participants, 390 were women (51.2%); mean (SD) age was 62.4 (10.0) years, 310 (40.6%) had diabetes, 298 (39.0%) had hypertension, and mean (SD) baseline LDL-C level was 138.8 (37.6) mg/dL. Mean LDL-C level reductions from baseline to 12 months were -36.9 mg/dL (95% CI, -42.0 to -31.9 mg/dL) among control participants, -40.0 mg/dL (95% CI, -44.7 to -35.4 mg/dL) among process participants, -41.6 mg/dL (95% CI, -46.3 to -37.0 mg/dL) among outcomes participants, and -42.8 mg/dL (95% CI, -47.4 to -38.1 mg/dL) among process plus outcomes participants. In exploratory analysis among participants with diabetes and hypertension, no spillover effects of incentives were detected compared with the control group on hemoglobin A1c level and blood pressure over 12 months., Conclusions and Relevance: In this randomized clinical trial, process-, outcomes-, or process plus outcomes-based financial incentives did not improve LDL-C levels vs control., Trial Registration: ClinicalTrials.gov Identifier: NCT02246959.

Importance: Financial incentives may improve health by rewarding patients for focusing on present actions-such as medication regimen adherence-that provide longer-term health benefits., Objective: To identify barriers to improving statin therapy adherence and control of cholesterol levels with financial incentives and insights for the design of future interventions., Design, Setting, and Participants: This qualitative study involved retrospective interviews with participants in a preplanned secondary analysis of a randomized clinical trial of financial incentives for statin therapy adherence. A total of 636 trial participants from several US insurer or employer populations and an academic health system were rank ordered by change in low-density lipoprotein cholesterol (LDLC) levels. Participants with the most LDLC level improvement (high-improvement group) and those with LDLC levels that did not improve (nonimprovement group) were purposively targeted, stratified across all trial groups, for semistructured telephone interviews that were performed from April 1 to June 30, 2018. Interviews were coded using a team-based, iterative approach. Data were analyzed from July 1, 2018, to October 31, 2020., Main Outcomes and Measures: The primary outcome was mean change in LDLC level from baseline to 12 months; the secondary outcome, statin therapy adherence during the first 6 months., Results: A total of 54 patients were interviewed, divided equally between high-improvement and nonimprovement groups, with a mean (SD) age of 43.5 (10.3) years; 36 (66.7%) were women, 28 (51.9%) had diabetes, and 18 (33.3%) had cardiovascular disease. Compared with the high-improvement group, the nonimprovement group had fewer interviewees with an annual income of greater than $50 000 (11 [40.7%] vs 22 [81.5%]), worse self-reported health (fair to poor, 13 [48.1%] vs 3 [11.1%]), more Black interviewees (16 [59.3%] vs 4 [14.8%]), and lower baseline LDLC levels (>160 mg/dL, 2 [7.4%] vs 25 [92.6%]). Participants in the nonimprovement group had a greater burden of chronic illness (≥2 chronic conditions, 13 [48.1%] vs 6 [22.2%]) and were less frequently employed (full-time, 6 [22.2%] vs 12 [44.4%]). In interviews, the nonimprovement group was less focused on risks of high LDLC levels, described less engagement in LDLC level management, articulated fewer specific nutritional choices for optimizing health, and recounted greater difficulty obtaining healthy food. Participants in both groups had difficulty describing the structure of the financial incentives but did recall features of the electronic pill containers used to track adherence and how those containers affected medication routines., Conclusions and Relevance: Participants in a statin adherence trial whose LDLC levels did not improve found it more difficult to create medication routines and respond to financial incentives in the context of complex living conditions and a high burden of chronic illness. These findings suggest that future studies should be more attentive to socioeconomic circumstances of trial participants., Trial Registration: ClinicalTrials.gov Identifier: NCT01798784.

This issue of Vaccine is devoted to papers from a research project that developed two types of simulation models, static and dynamic transmission, to evaluate the cost-effectiveness of maternal immunization to prevent pertussis in infants in low- and middle-income countries (LMICs). The research was conducted by a multinational team of investigators and funded by the Bill & Melinda Gates Foundation to gain an understanding of when and where maternal immunization might be a good public health investment for LMICs. Here we review the project's central lessons for vaccine policy and research. Models require a lot of data. As most LMICs lack good data, the models were built using pertussis disease burden data from Brazil, a middle-income country with three long-established, independent information systems (disease surveillance, hospitalization, and mortality), on the hypothesis that the disease process is similar across countries. Values for key parameters, particularly infant mortality, infant vaccine coverage, and costs of vaccination and treatment, were then varied to represent other LMICs. The results show that coverage levels of infant whole cell pertussis (wP) vaccine are key to the cost-effectiveness of maternal pertussis immunization. In settings where infant wP coverage is below the threshold thought necessary to eliminate pertussis in the population, 90-95%, maternal immunization is cost-effective, even cost-saving. By contrast, it is very expensive in countries capable of maintaining infant vaccination in or above the threshold range. The research also suggests that, while static models may serve to explore an intervention's cost-effectiveness initially, dynamic transmission models are essential for more accurate estimates. These findings can help guide policies toward maternal pertussis immunization, but also show that developing better data on neonatal pertussis mortality burden and infant vaccine coverage in LMICs, and on the duration of immunity of currently available pertussis vaccines, are key priorities to support better vaccine policy., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile., Methods: We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models' different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated., Results: The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90-95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models' estimates over their different time horizons are compared at infant coverage < 90-95%, their projections fall in the same range., Conclusions: Static models may serve to explore an intervention's cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally., Clinical Trial Registry: Clinical Trial registry name and registration number: Not applicable., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Sinha was at Rutgers School of Public Health until August 2016, but is currently employed by Merck Research Laboratory, a division of Merck & Co. Dr. Andrade has received lecture fees and travel grants from GlaxoSmithKline and Pfizer. Dr. Minamisava has received travel grants from GlaxoSmithKline. The other authors have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model., Methods: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY)., Results: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage., Conclusion: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. [Dr. Sinha is currently an employee at Merck & Co and has stock holdings in that company. She was at Rutgers New Jersey Medical School when this work was conducted. Merck & Co. played no role in study design, collection, analysis, interpretation of data, writing of the report, or in the decision to submit the paper for publication. They accept no responsibility for the contents. Pej Rohani served as a paid consultant on structuring and calibrating the dynamic model.], (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pertussis is associated with significant disease burden in children worldwide. In addition to its cyclical nature, resurgences of pertussis cases, hospitalizations and deaths have been reported by many countries. We describe the dynamics of pertussis in Brazil, a middle-income country that has experienced a resurgence and that provides good quality data to allow building a dynamic transmission disease model., Methods: We conducted a descriptive analysis of pertussis burden considering data from the national disease surveillance system, national hospitalization information system and national mortality registry. Study period was 2000-2016. Absolute numbers and rates per 100,000 inhabitants over time, by age sub-groups and geographical regions are presented., Results: From 2000 to 2016, a total of 37,299 reported pertussis cases, 25,240 hospitalizations, and 601 deaths due to pertussis were reported. Although the outcomes - pertussis cases, hospitalizations, and deaths - come from independent information systems, our results document low disease burden with periodic increases every 3-4 years during the years 2000-2010, followed by a sharp increase which peaked in 2014. In both periods, disease burden is concentrated in young children, while its more serious outcomes - hospitalizations and deaths, are concentrated in infants. Pre-outbreak and outbreak disease burden as well as timing of peak during the outbreak period vary by states and within geographical regions, representing valuable resources of data for modelling purposes., Conclusion: Consistent disease burden patterns were observed over time in Brazil using a variety of data sources. Given the scarcity of good epidemiological data on pertussis available from low- and middle-income countries, our reported data provide valuable information for the assessment of the public health impact and cost-effectiveness modelling studies of newer strategies to prevent and control pertussis. These data were used to build and calibrate a national dynamic transmission model, which was used to evaluate the cost-effectiveness of maternal immunization. Clinical Trial registry name and registration number: Not applicable., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ALA has received lecture fees and travel grants from GlaxoSmithKline and Pfizer; RM has received travel grants from GlaxoSmithKline. The other authors have no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Using dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions., Methods: We tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014-2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System., Results: Based on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs., Conclusions: The same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Andrade has received lecture fees and travel grants from GlaxoSmithKline and Pfizer. Dr. Minamisava has received travel grants from GlaxoSmithKline. All other authors have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

This tutorial presents practical guidance on transforming various types of information published in journals, or available online from government and other sources, into transition probabilities for use in state-transition models, including cost-effectiveness models. Much, but not all, of the guidance has been previously published in peer-reviewed journals. Our purpose is to collect it in one location to serve as a stand-alone resource for decision modelers who draw most or all of their information from the published literature. Our focus is on the technical aspects of manipulating data to derive transition probabilities. We explain how to derive model transition probabilities from the following types of statistics: relative risks, odds, odds ratios, and rates. We then review the well-known approach for converting probabilities to match the model's cycle length when there are two health-state transitions and how to handle the case of three or more health-state transitions, for which the two-state approach is not appropriate. Other topics discussed include transition probabilities for population subgroups, issues to keep in mind when using data from different sources in the derivation process, and sensitivity analyses, including the use of sensitivity analysis to allocate analyst effort in refining transition probabilities and ways to handle sources of uncertainty that are not routinely formalized in models. The paper concludes with recommendations to help modelers make the best use of the published literature.

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.

The present study examined the association of residential instability with hospitalizations among homeless and vulnerably housed individuals over a 4-year time period. Survey data were linked to administrative records on hospitalizations. Specifically, we used data from the Health and Housing in Transition study, a prospective cohort study that tracked the health and housing status of homeless and vulnerably housed individuals in Canada. Responses from Vancouver-based participants (n = 378) from baseline and 3 follow-ups were linked to their administrative health records on hospitalizations (Discharge Abstract Database - Hospital Separation Files; 2008-2012). A generalized estimating equations model was used to examine associations between the number of residential moves and any hospitalizations during each year (none versus ≥ 1 hospitalizations). Analyses included demographic and health variables. Survey data were collected via structured interviews. Hospitalizations were derived from provincial administrative health records. A higher number of residential moves were associated with hospitalization over the study period (adjusted odds ratio: 1.14; 95% confidence interval: 1.01, 1.28). Transgender, female gender, perceived social support, better self-reported mental health, and having ≥ 3 chronic health conditions also predicted having been hospitalized over the study period, whereas high school/higher education was negatively associated with hospitalizations. Our results indicate that residential instability is associated with increased risk of hospitalization, illustrating the importance of addressing housing as a social determinant of health.

Background: Domains other than those commonly measured (physical, psychological, social, and sometimes existential/spiritual) are important to the quality of life of people with life-threatening illness. The McGill Quality of Life Questionnaire (MQOL) - Revised measures the four common domains. The aim of this study was to create a psychometrically sound instrument, MQOL - Expanded, to comprehensively measure quality of life by adding to MQOL-Revised the domains of cognition, healthcare, environment, (feeling like a) burden, and possibly, finance., Methods: Confirmatory factor analyses were conducted on three datasets to ascertain whether seven new items belonged with existing MQOL-Revised domains, whether good model fit was obtained with their addition as five separate domains to MQOL-Revised, and whether a second-order factor representing overall quality of life was present. People with life-threatening illnesses (mainly cancer) or aged > 80 were recruited from 15 healthcare sites in seven Canadian provinces. Settings included: palliative home care and inpatient units; acute care units; oncology outpatient clinics., Results: Good model fit was obtained when adding each of the five domains separately to MQOL-Revised and for the nine correlated domains. Fit was acceptable for a second-order factor model. The financial domain was removed because of low importance. The resulting MQOL-Expanded is a 21-item instrument with eight domains (fit of eight correlated domains: Comparative Fit Index = .96; Root Mean Square Error of Approximation = .033)., Conclusions: MQOL-Expanded builds on MQOL-Revised to more comprehensively measure the quality of life of people with life-threatening illness. Our analyses provide validity evidence for the MQOL-Expanded domain and summary scores; the need for further validation research is discussed. Use of MQOL-Expanded will enable a more holistic understanding of the quality of life of people with a life-threatening illness and the impact of treatments and interventions upon it. It will allow for a better understanding of less commonly assessed but important life domains (cognition, healthcare, environment, feeling like a burden) and their relationship to the more commonly assessed domains (physical, psychological, social, existential/spiritual).

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.

Background: Congestive heart failure is a major cause of morbidity, mortality, and cost. Disease management programs have shown promise but lack firm evidence of effectiveness and scalability. We describe the motivation, design, and planned analyses of EMPOWER (Electronic Monitoring of Patients Offers Ways to Enhance Recovery), a randomized clinical trial of an innovative intervention incorporating behavioral economic principles with remote monitoring technology embedded within a healthcare system., Methods and Results: EMPOWER is an ongoing, pragmatic, randomized clinical trial comparing usual care to an automated hovering intervention that includes patient-level incentives for daily weight monitoring and diuretic adherence combined with automated feedback into the clinical care pathway, enabling real-time response to concerning clinical symptoms. Identification of eligible patients began in May 2016, and implementation of the intervention is feasible. Trial processes are embedded into existing clinical pathways. The primary outcome is time to readmission for any cause. Cost-effectiveness analyses are planned to evaluate the healthcare costs and health outcomes of the approach., Conclusions: The EMPOWER trial incorporates leading-edge approaches in human motivation, derived from behavioral economics, with contemporary technology to provide scale and exception handling at low cost. The trial is also implemented within the naturalized environment of a health system, as much as possible taking advantage of the existing journeys of patients and workflows of clinicians. A goal of this pragmatic design is to limit resource utilization and also to test an intervention that would need minimal modification to be translated from research into a new way of practice., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02708654.

Objectives: In 2016, the Second Panel on Cost-effectiveness in Health and Medicine updated the seminal work of the original panel from 2 decades earlier. The Second Panel had an opportunity to reflect on the evolution of cost-effectiveness analysis (CEA) and to provide guidance for the next generation of practitioners and consumers. In this article, we present key topics for future research and policy., Methods: During the course of its deliberations, the Second Panel discussed numerous topics for advancing methods and for improving the use of CEA in decision making. We identify and consider 7 areas for which the panel believes that future research would be particularly fruitful. In each of these areas, we highlight outstanding research needs. The list is not intended as an exhaustive inventory but rather a set of key items that surfaced repeatedly in the panel's discussions. In the online Appendix , we also list and expound briefly on 8 other important topics., Results: We highlight 7 key areas: CEA and perspectives (determining, valuing, and summarizing elements for the analysis), modeling (comparative modeling and model transparency), health outcomes (valuing temporary health and path states, as well as health effects on caregivers), costing (a cost catalogue, valuing household production, and productivity effects), evidence synthesis (developing theory on learning across studies and combining data from clinical trials and observational studies), estimating and using cost-effectiveness thresholds (empirically representing 2 broad concepts: opportunity costs and public willingness to pay), and reporting and communicating CEAs (written protocols and a quality scoring system)., Conclusions: Cost-effectiveness analysis remains a flourishing and evolving field with many opportunities for research. More work is needed on many fronts to understand how best to incorporate CEA into policy and practice.

Purpose: Patient-reported outcome measures (PROMs) are frequently used in heterogeneous patient populations. PROM scores may lead to biased inferences when sources of heterogeneity (e.g., gender, ethnicity, and social factors) are ignored. Latent variable mixture models (LVMMs) can be used to examine measurement invariance (MI) when sources of heterogeneity in the population are not known a priori. The goal of this article is to discuss the use of LVMMs to identify invariant items within the context of test construction., Methods: The Draper-Lindely-de Finetti (DLD) framework for the measurement of latent variables provides a theoretical context for the use of LVMMs to identify the most invariant items in test construction. In an expository analysis using 39 items measuring daily activities, LVMMs were conducted to compare 1- and 2-class item response theory models (IRT). If the 2-class model had better fit, item-level logistic regression differential item functioning (DIF) analyses were conducted to identify items that were not invariant. These items were removed and LVMMs and DIF testing repeated until all remaining items showed MI., Results: The 39 items had an essentially unidimensional measurement structure. However, a 1-class IRT model resulted in many statistically significant bivariate residuals, indicating suboptimal fit due to remaining local dependence. A 2-class LVMM had better fit. Through subsequent rounds of LVMMs and DIF testing, nine items were identified as being most invariant., Conclusions: The DLD framework and the use of LVMMs have significant potential for advancing theoretical developments and research on item selection and the development of PROMs for heterogeneous populations.

Objective: To explore the use of cluster analysis to define groups of similar countries for the purpose of evaluating the cost-effectiveness of a public health intervention-maternal immunization-within the constraints of a project budget originally meant for an overall regional analysis., Methods: We used the most common cluster analysis algorithm, K-means, and the most common measure of distance, Euclidean distance, to group 37 low-income, sub-Saharan African countries on the basis of 24 measures of economic development, general health resources, and past success in public health programs. The groups were tested for robustness and reviewed by regional disease experts., Results: We explored 2-, 3- and 4-group clustering. Public health performance was consistently important in determining the groups. For the 2-group clustering, for example, infant mortality in Group 1 was 81 per 1,000 live births compared with 51 per 1,000 in Group 2, and 67% of children in Group 1 received DPT immunization compared with 87% in Group 2. The experts preferred four groups to fewer, on the ground that national decision makers would more readily recognize their country among four groups., Conclusions: Clusters defined by K-means clustering made sense to subject experts and allowed a more detailed evaluation of the cost-effectiveness of maternal immunization within the constraint of the project budget. The method may be useful for other evaluations that, without having the resources to conduct separate analyses for each unit, seek to inform decision makers in numerous countries or subdivisions within countries, such as states or counties.

Background: A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown., Methods: We used a decision tree model, with Markov nodes to project infants' lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy., Results: At coverage equal to the proportion of pregnant women with≥4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42-43% in Guinea-Bissau (ANC4=65%), and 55-57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries' GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses., Conclusion: Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy. Clinical Trial registry name and registration number: Not applicable., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS., Methods: Using a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease., Results: In the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of ≥70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY., Conclusions: GBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine's public health impact., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: There is international concern about the lack of compassion in healthcare systems. A valid and reliable tool for measuring compassion in healthcare systems and educational institutions is required. This comprehensive and critical narrative synthesis identified and compared existing measures of compassionate care in clinical settings., Methods: PubMed, MEDLINE, CINAHL and PsycINFO databases and grey literature were searched to identify studies that report information on instruments that measure compassion or compassionate care in clinicians, nurses, healthcare students and patients. Textual qualitative descriptions of included studies were prepared. Instruments were evaluated using the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool., Results: Nine studies containing information on the Compassion Competence Scale, a self-report instrument that measures compassion competence among Korean nurses; the Compassion Scale, the Compassionate Care Assessment Tool©, and the Schwartz Center Compassionate Care Scale™, patient-reported instruments that measure the importance of healthcare provider compassion; the Compassion Practices Scale, an instrument that measures organisational support for compassionate care; and instruments that measure compassion in educational institutions (instructional quality and a Geriatric Attitudes Scale), were included. Each instrument is associated with significant limitations. Most only measure certain aspects of compassion and lack evidence of adaptability to diverse practice settings. The EMPRO of self-report instruments revealed a lack of psychometric information on measurement reliability, validity, responsiveness and interpretability, respondent, administrative and scoring burden, and use in subpopulations., Conclusion: The findings of this narrative synthesis identified an unmet need for a psychometrically validated instrument that comprehensively measures the construct of compassion in healthcare settings.