Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.

BACKGROUND: Older patients who are hospitalized for acute decompensated heart failure have high rates of physical frailty, poor quality of life, delayed recovery, and frequent rehospitalizations. Interventions to address physical frailty in this population are not well established. METHODS: We conducted a multicenter, randomized, controlled trial to evaluate a transitional, tailored, progressive rehabilitation intervention that included four physical-function domains (strength, balance, mobility, and endurance). The intervention was initiated during, or early after, hospitalization for heart failure and was continued after discharge for 36 outpatient sessions. The primary outcome was the score on the Short Physical Performance Battery (total scores range from 0 to 12, with lower scores indicating more severe physical dysfunction) at 3 months. The secondary outcome was the 6-month rate of rehospitalization for any cause. RESULTS: A total of 349 patients underwent randomization; 175 were assigned to the rehabilitation intervention and 174 to usual care (control). At baseline, patients in each group had markedly impaired physical function, and 97% were frail or prefrail; the mean number of coexisting conditions was five in each group. Patient retention in the intervention group was 82%, and adherence to the intervention sessions was 67%. After adjustment for baseline Short Physical Performance Battery score and other baseline characteristics, the least-squares mean (±SE) score on the Short Physical Performance Battery at 3 months was 8.3±0.2 in the intervention group and 6.9±0.2 in the control group (mean between-group difference, 1.5; 95% confidence interval [CI], 0.9 to 2.0; P<0.001). At 6 months, the rates of rehospitalization for any cause were 1.18 in the intervention group and 1.28 in the control group (rate ratio, 0.93; 95% CI, 0.66 to 1.19). There were 21 deaths (15 from cardiovascular causes) in the intervention group and 16 deaths (8 from cardiovascular causes) in the control group. The rates of death from any cause were 0.13 and 0.10, respectively (rate ratio, 1.17; 95% CI, 0.61 to 2.27). CONCLUSIONS: In a diverse population of older patients who were hospitalized for acute decompensated heart failure, an early, transitional, tailored, progressive rehabilitation intervention that included multiple physical-function domains resulted in greater improvement in physical function than usual care. (Funded by the National Institutes of Health and others; REHAB-HF ClinicalTrials.gov number, NCT02196038.).

Development and testing of patient-centered education about hormone replacement therapy for women at high genetic risk of breast and ovarian cancer.

OBJECTIVE: In this study, we aimed to develop education to assist BRCA mutation carriers in making informed decisions about HRT in the context of risk-reducing surgery, while simultaneously clarifying their treatment-specific values and reducing decisional conflict. METHODS: We enrolled premenopausal BRCA mutation carriers ages 19-49 without prior cancer or risk-reducing salpingo-oophorectomy to structured interviews in which they reviewed education about the risks and benefits of HRT. Materials included literature-derived data demonstrating associations between HRT and commonly considered health outcomes (breast cancer, vasomotor symptoms, sexual functioning, cardiovascular disease, osteoporosis, and blood clots). Participants completed the 16-item Decisional Conflict Scale (DCS) before and after education, communicated their preferences by rating and ranking the six outcomes, and provided feedback to inform iterative revisions of the educational content. RESULTS: 25 participants completed interviews. DCS scores decreased significantly from 54.6 to 22.8 following education (p < 0.001); sub-scores for uncertainty (71.7 to 37.3), informed (71.7 to 15.3), values clarity (53.7 to 17.0), effective decision (44.2 to 25.5), and support (35.0 to 17.7) also decreased significantly. Participants ranked cardiovascular disease as the most important outcome to consider, followed by breast cancer, osteoporosis, blood clots, decline in sexual function, and hot flashes. Participants with prior mastectomy (N = 10) ranked breast cancer as the most important outcome 25% of the time, compared to 80% in participants without mastectomy (N = 15). CONCLUSION: Following education, BRCA mutation carriers had significantly less decisional conflict regarding the choice to use HRT. This pilot study was successful in generating a prototype educational aid for further testing.

Quantifying patients' preferences on tradeoffs between mortality risk and reduced need for target vessel revascularization for claudication.

BACKGROUND: In 2019, the US Food and Drug Administration issued a warning that symptomatic relief from claudication using paclitaxel-coated devices might be associated with an increase in mortality over 5 years. We designed a discrete-choice experiment (DCE) to quantify tradeoffs that patients would accept between a decreased risk of clinically driven target-vessel revascularization (CDTVR) and increased mortality risk. METHODS: Patients with claudication symptoms were recruited from seven medical centers to complete a web-based survey including eight DCE questions that presented pairs of hypothetical device profiles defined by varying risks of CDTVR and overall mortality at 2 and 5 years. Random-parameters logit models were used to estimate relative preference weights, from which the maximum-acceptable increase in 5-year mortality risk was derived. RESULTS: A total of 272 patients completed the survey. On average, patients would accept a device offering reductions in CDTVR risks from 30% to 10% at 2 years and from 40% to 30% at 5 years if the 5-year mortality risk was less than 12.6% (95% CI: 11.8-13.4%), representing a cut-point of 4.6 percentage points above a baseline risk of 8%. However, approximately 40% chose the device alternative with the lower 5-year mortality risk in seven (20.6%) or eight (18.0%) of the eight DCE questions regardless of the benefit offered. CONCLUSIONS: Most patients in the study would accept some incremental increase in 5-year mortality risk to reduce the 2-year and 5-year risks of CDTVR by 20 and 10 percentage points, respectively. However, significant patient-level variability in risk tolerance underscores the need for systematic approaches to support benefit-risk decision making.

The Impact of Hearing Loss and Its Treatment on Health-Related Quality of Life Utility: a Systematic Review with Meta-analysis.

BACKGROUND: Hearing loss significantly impacts health-related quality of life (QoL), yet the effects of current treatments on QoL utility remain uncertain. Our objective was to describe the impact of untreated and treated hearing loss on QoL utility to inform hearing healthcare policy. METHODS: We searched databases for articles published through 02/01/2021. Two independent reviewers screened for articles that reported elicitation of general QoL utility values for untreated and treated hearing loss health states. We extracted data and quality indicators from 62 studies that met the inclusion criteria. RESULTS: Included studies predominately used observational pre/post designs (61%), evaluated unilateral cochlear implantation (65%), administered the Health Utilities Index 3 (HUI3; 71%), and were conducted in Europe and North America (84%). In general, treatment of hearing loss improved post-treatment QoL utility when measured by most methods except the Euro-QoL 5 dimension (EQ-5D). In meta-analysis, hearing aids for adult mild-to-moderate hearing loss compared to no treatment significantly improved HUI3-estimated QoL utility (3 studies; mean change=0.11; 95% confidence interval (CI): 0.07 to 0.14) but did not impact EQ-5D-estimated QoL (3 studies; mean change=0.0; 95% CI: -0.03 to 0.04). Cochlear implants improved adult QoL utility 1-year post-implantation when measured by the HUI3 (7 studies; mean change=0.17; 95% CI: 0.11 to 0.23); however, pediatric VAS-estimated QoL utility was non-significant (4 studies; mean change=0.12; 95% CI: -0.02 to 0.25). The quality of included studies was limited by failure to report missingness of data and low survey response rates. Our study was limited by heterogeneous study populations and designs. FINDINGS: Treatment of hearing loss significantly improves QoL utility, and the HUI3 and VAS were most sensitive to improvements in hearing. Improved access to hearing healthcare should be prioritized. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021253314.

Mapping Factors That Affect the Uptake of Digital Therapeutics Within Health Systems: Scoping Review.

BACKGROUND: Digital therapeutics are patient-facing digital health interventions that can significantly alter the health care landscape. Despite digital therapeutics being used to successfully treat a range of conditions, their uptake in health systems remains limited. Understanding the full spectrum of uptake factors is essential to identify ways in which policy makers and providers can facilitate the adoption of effective digital therapeutics within a health system, as well as the steps developers can take to assist in the deployment of products. OBJECTIVE: In this review, we aimed to map the most frequently discussed factors that determine the integration of digital therapeutics into health systems and practical use of digital therapeutics by patients and professionals. METHODS: A scoping review was conducted in MEDLINE, Web of Science, Cochrane Database of Systematic Reviews, and Google Scholar. Relevant data were extracted and synthesized using a thematic analysis. RESULTS: We identified 35,541 academic and 221 gray literature reports, with 244 (0.69%) included in the review, covering 35 countries. Overall, 85 factors that can impact the uptake of digital therapeutics were extracted and pooled into 5 categories: policy and system, patient characteristics, properties of digital therapeutics, characteristics of health professionals, and outcomes. The need for a regulatory framework for digital therapeutics was the most stated factor at the policy level. Demographic characteristics formed the most iterated patient-related factor, whereas digital literacy was considered the most important factor for health professionals. Among the properties of digital therapeutics, their interoperability across the broader health system was most emphasized. Finally, the ability to expand access to health care was the most frequently stated outcome measure. CONCLUSIONS: The map of factors developed in this review offers a multistakeholder approach to recognizing the uptake factors of digital therapeutics in the health care pathway and provides an analytical tool for policy makers to assess their health system's readiness for digital therapeutics.

Cost-Effectiveness of Tumor Genomic Profiling to Guide First-Line Targeted Therapy Selection in Patients With Metastatic Lung Adenocarcinoma.

OBJECTIVES: A cost-effectiveness analysis comparing comprehensive genomic profiling (CGP) of 10 oncogenes, targeted gene panel testing (TGPT) of 4 oncogenes, and no tumor profiling over the lifetime for patients with metastatic lung adenocarcinoma from the Centers for Medicare and Medicaid Services' perspective was conducted. METHODS: A decision analytic model used 10 000 hypothetical Medicare beneficiaries with metastatic lung adenocarcinoma to simulate outcomes associated with CGP (ALK, BRAF, EGFR, ERBB2, MET, NTRK1, NTRK2, NTRK3, RET, ROS1), TGPT (ALK, BRAF, EGFR, ROS1), and no tumor profiling (no genes tested). First-line targeted cancer-directed therapies were assigned if actionable gene variants were detected; otherwise, nontargeted cancer-directed therapies were assigned. Model inputs were derived from randomized trials (progression-free survival, adverse events), the Veterans Health Administration and Medicare (drug costs), published studies (nondrug cancer-related management costs, health state utilities), and published databases (actionable variant prevalences). Costs (2019 US$) and quality-adjusted life-years (QALYs) were discounted at 3% per year. Probabilistic sensitivity analyses used 1000 Monte Carlo simulations. RESULTS: No tumor profiling was the least costly/person ($122 613 vs $184 063 for TGPT and $188 425 for CGP) and yielded the least QALYs/person (0.53 vs 0.73 for TGPT and 0.74 for CGP). The costs per QALY gained and corresponding 95% confidence interval were $310 735 ($278 323-$347 952) for TGPT vs no tumor profiling and $445 545 ($322 297-$572 084) for CGP vs TGPT. All probabilistic sensitivity analysis simulations for both comparisons surpassed the willingness-to-pay threshold ($150 000 per QALY gained). CONCLUSION: Compared with no tumor profiling in patients with metastatic lung adenocarcinoma, tumor profiling (TGPT, CGP) improves quality-adjusted survival but is not cost-effective.

Patient preferences pertaining to treatment options for drug-resistant focal epilepsy.

OBJECTIVE: To determine patient acceptability of benefit-risk trade-offs in selecting treatment options for drug-resistant mesial temporal lobe epilepsy, including open brain surgery, laser ablation (laser interstitial thermal therapy [LITT]), and continued medications. METHODS: A discrete-choice experiment survey was developed, consisting of 20 versions that were randomly assigned to respondents. Each version had 8 sets of constructed treatment alternatives, representing open brain surgery, LITT, or continued medical management. For each set, respondents indicated the treatment alternative they would choose first. Treatment alternatives were characterized by varying levels of chance of seizure freedom for at least 2 years (20-70%), risk of 30-day mortality (0-10%), and risk of neurological deficits (0-40%). Respondents' choices were analyzed using random-parameters logit models to quantify acceptable benefit-risk trade-offs. Preference heterogeneity was evaluated using latent-class analysis. RESULTS: The survey was administered to 2 cohorts of adult patients with drug-resistant epilepsy: a Duke cohort identified using diagnostic codes (n = 106) and a web-recruited panel with a self-reported physician diagnosis of drug-resistant epilepsy (n = 300). Based on mean preference weights, respondents who indicated a willingness to consider surgical intervention would accept a reduction in chance of seizure freedom from 70% to a minimum-acceptable benefit (MAB) of 23% if they could undergo LITT rather than open brain surgery. For a reduction in 30-day mortality from 1% to 0%, MAB was 52%. For a reduction in risk of long-term deficits from 10% to 0%, MAB was 39%. Latent-class analysis revealed additional choice patterns identifying respondent groups that more strongly favored continuing medications or undergoing surgery. CONCLUSION: Patients who are receptive to surgery would accept significantly lower treatment effectiveness to undergo a minimally invasive procedure relative to open brain surgery. They also were willing to accept lower treatment benefit to reduce risks of mortality or neurological deficits.

Chemoradiation treatment patterns among United States Veteran Health Administration patients with unresectable stage III non-small cell lung cancer.

BACKGROUND: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States (US). Among VHA patients, the rate of use of concurrent chemoradiation therapy (CCRT) among those with unresectable, stage III non-small cell lung cancer (NSCLC) is unknown. The objective was to report recent CCRT treatment patterns in VHA patients and identify characteristics associated with receipt of CCRT. METHODS: Using Department of Veteran Affairs (VA) Cancer Registry System data linked to VA electronic medical records, we determined rates of CCRT, sequential CRT (SCRT), radiation therapy (RT) only, chemotherapy (CT) only, and neither treatment. RESULTS: Among 4054 VHA patients who met study criteria, CCRT rates slightly increased from 44 to 50% between 2013 and 2017. Factors associated with decreased odds of CCRT receipt compared to any other treatment included increasing age (adjusted odds ratio [aOR] per 10 years = 0.67; 95% CI: 0.60-0.76) and Charlson-Deyo comorbidity score (aOR = 0.94; 95% CI: 0.91-0.97). White race was associated with increased odds of CCRT receipt (aOR = 1.24; 95% CI: 1.004-1.53). In a chart review sample of 200 patients, less than half (n = 85) had a documented reason for not receiving CCRT. Among these, 29% declined treatment, and 71% did not receive CCRT due to "not being a candidate" for reasons related to frailty or lung nodules being too far apart for radiation therapy. CONCLUSIONS: CCRT rates among VHA patients with unresectable, stage III NSCLC slightly increased from 2013 to 2017; however in 2017, only half were receiving CCRT. Older patients and those with multiple comorbidities were less likely to receive CCRT and even when controlling for these factors, non-white patients were less likely to receive CCRT.

The preferences of women with ovarian cancer for oral versus intravenous recurrence regimens.

OBJECTIVE: To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. METHODS: A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%-60%); probability of PFS at 2 years (10%-20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). RESULTS: Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. CONCLUSIONS: These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens.

Quantifying Value of Hope.

BACKGROUND: 'Hope' is a construct in patient-centered value frameworks, but few studies have attempted to measure the value of hope separately from treatment-related gains in quality of life and survival to support its application in economic evaluation. OBJECTIVE: To generate quantitative information on the "value of hope". METHODS: We designed a discrete-choice experiment in which treatment alternatives varied the probability of achieving 10-year survival, expected survival as the weighted sum of short-term and long-term survival, health status, and out-of-pocket cost. Two-hundred patients with cancer or history of cancer recruited by Cancer Support Community each completed 10 choice questions. We used mixed-logit and latent-class models to analyze the choice data. RESULTS: Relative to fixed survival periods of two, three or five years with 0% chance of 10-year survival, participants positively valued treatments with 5% and 10% chances of 10-year survival. However, participants negatively valued a 20% chance of 10-year survival that required an offsetting 80% chance of shorter survival. This finding was particularly strong when expected survival was two years. Compared to a 0% chance, dollar-equivalent values of 5% and 10% chances of long-term survival were $5,975 and $12,421, respectively, independent of health status or expected survival. The corresponding value for 20% versus 0% chance of long-term survival was negative. Latent-class analysis revealed 4 groups with distinct preference patterns. CONCLUSIONS: Our findings affirm positive value for hope independent of expected survival and health status. However, this finding does not universally hold in all situations nor across all groups.

Cytomegalovirus in Allogeneic Hematopoietic Transplantation: Impact on Costs and Clinical Outcomes Using a Preemptive Strategy.

Cytomegalovirus (CMV) results in significant morbidity and mortality following hematopoietic cell transplantation (HCT). Establishing the cost and clinical impact is imperative to the selection of appropriate CMV preventative strategies. This is a retrospective cohort study of consecutive patients undergoing their first allogeneic HCT between January 1, 2009, and December 31, 2013. Detailed clinical and institutional cost data were obtained from the start of conditioning through 1-year post-transplantation. Baseline characteristics, resource utilization, costs, and outcomes were compared between patients with and without clinically significant CMV infection (csCMVi). One hundred seventy out of 388 patients (44%) developed csCMVi within 1 year after HCT. Within the first year post-HCT, patients with csCMVi had a significantly longer transplantation-related length of stay (mean, 91.7 days versus 78.3 days; P < .0001) and more frequent and prolonged hospitalizations (mean, 2.4 versus 1.7 admissions [P < .0001]; mean, 39.1 versus 31.5 inpatient days [P = .001]) without significantly more admissions to the intensive care unit (28.2% versus 21.6%; P = .408). The use of granulocyte colony-stimulating factor was greater in patients with csCMVi (73.5% versus 54.1%; P = .0001), although no significant differences were demonstrated in mean platelet or red blood cell (RBC) transfusions. Total costs were also higher in patients with csCMVi (mean cost difference, $45,811; 95% CI, $26,385 to $67,544). However, the incidence of graft-versus-host disease (GVHD) and selected infectious complications was not significantly different between the 2 groups. There were no significant differences in 1-year and 5-year post-transplantation overall survival (OS) or nonrelapse mortality (NRM) between those with and those without csCMVi, although relapse of underlying disease was significantly lower in the csCMVi group. Overall, our data show that allogeneic HCT recipients with csCMVi had significantly greater medical resource utilization and costs than those without csCMVi. However, clinical outcomes, including GVHD, infections, and mortality, were similar in the 2 groups. Further study is needed to determine the cost-effectiveness of CMV preventive modalities.

Variation Among Patients With Crohn's Disease in Benefit vs Risk Preferences and Remission Time Equivalents.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) must make decisions about their treatment. We aimed to quantify patients' preferences for different treatment outcomes and adverse events. We also evaluated the effects of latent class heterogeneity on these preferences. METHODS: An online stated-preference survey was completed by 812 individuals with CD in the Crohn's and Colitis Foundation Partners cohort (IBD Partners). Patients were given information on symptoms and severity of active disease; duration of therapy with corticosteroids; and risks of serious infection, cancer and surgery. Patients were asked to assume that their treatment was not working and to choose an alternative therapy. The primary outcome was remission-time equivalents (RTE) of a given duration of symptom severity or treatment-related risk. Latent class choice models identified groups of patients with dominant treatment-outcome preferences and associated patient characteristics with these groups. RESULTS: Latent class analysis demonstrated 3 distinct groups of survey responders whose choices were strongly influenced by avoidance of active symptoms (61%), avoidance of corticosteroid use (25%), or avoidance of risks of cancer, infection or surgery (14%) when choosing a therapy. Class membership was correlated with age, sex, mean short CD activity index score and corticosteroid avoidance. RTEs in each latent class differed significantly from the mean RTEs for the overall sample, although the symptom-avoidant class most closely approximated the overall sample. CONCLUSIONS: In an online survey of patients with CD, we found substantial heterogeneity in preference for medication efficacy and risk of harm. Physicians and regulators should therefore not assume that all patients have mean-value preferences-this could result in significant differences in health-technology assessment models.

Patient preferences for maintenance PARP inhibitor therapy in ovarian cancer treatment.

OBJECTIVE: To measure preferences of women with ovarian cancer regarding risks, side effects, costs and benefits afforded by maintenance therapy (MT) with a poly ADP ribose polymerase (PARP) inhibitor. METHODS: A discrete-choice experiment elicited preferences of women with ovarian cancer regarding 6 attributes (levels in parentheses) relevant to decisions for MT versus treatment break: (1) overall survival (OS; 36, 38, 42 months); (2) progression-free survival (PFS; 15, 17, 21 months); (3) nausea (none, mild, moderate); (4) fatigue (none, mild, moderate); (5) probability of death from myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML; 0% to 10%); (6) monthly out-of-pocket cost ($0 to $1000). Participants chose between 2 variable MT scenarios and a static scenario representing treatment break, with multiple iterations. Random-parameters logit regression was applied to model choices as a function of attribute levels. RESULTS: 95 eligible participants completed the survey; mean age was 62, 48% had recurrence, and 17% were ever-PARP inhibitor users. Participants valued OS (average importance weight 24.5 out of 100) and monthly costs (24.6) most highly, followed by risk of death from MDS/AML (17.9), nausea (14.7), PFS (10.5) and fatigue (7.8). Participants would accept 5% risk of MDS/AML if treatment provided 2.2 months additional OS or 4.8 months PFS. Participants would require gains of 2.6 months PFS to accept mild treatment-related fatigue and 4.4 months to accept mild nausea. CONCLUSIONS: When considering MT, women with ovarian cancer are most motivated by gains in OS. Women expect at least 3-4 months of PFS benefit to bear mild side effects of treatment.

Patient preferences for attributes of primary surgical debulking versus neoadjuvant chemotherapy for treatment of newly diagnosed ovarian cancer.

BACKGROUND: Randomized trials have reported conflicting findings on survival for advanced-stage ovarian cancer treated with primary debulking surgery (PDS) versus neoadjuvant chemotherapy with interval debulking; surgical complications and mortality are higher with PDS. We assessed women's preferences for tradeoffs related to this important clinical decision. METHODS: Ovarian cancer patients were recruited to complete a discrete-choice experiment (DCE) consisting of 8 choice tasks presenting experimentally designed treatment alternatives in terms of treatment order, extent of surgery including risk of ostomy, chance of death from surgical complications (1%-10%), readmission for surgical complications (5%-50%), progression-free survival (1-3 years), and overall survival (3-5 years). Random-parameters logit regression was applied to model participants' choices as a function of attribute levels. RESULTS: A total of 101 ovarian cancer survivors completed the DCE survey; of these participants, 30% were receiving chemotherapy at the time, and 33% had prior recurrence. Overall survival was of greatest importance to participants (36/100), followed by risk of readmission due to complications (23/100), progression-free survival (19/100), surgical mortality (16/100), extent of surgery (4/100), and order of surgery and chemotherapy (2/100). Overall, the participants would tolerate a 15-percentage point increase in risk of major complications (95% confidence interval [CI], 3%-29%) or a 4-percentage point increase in the risk of surgical mortality (95% CI, 2%-13%) in order to increase their expected overall survival from 3 to 3.5 years. CONCLUSIONS: Patients would accept a moderately higher risk of perioperative complications and surgical mortality in exchange for substantial gains in survival. These quantitative findings provide clinicians with a framework to discuss preferences with patients and to incorporate preferences into clinical trial design.

Chemotherapy Costs and 21-Gene Recurrence Score Genomic Testing Among Medicare Beneficiaries With Early-Stage Breast Cancer, 2005 to 2011.

BACKGROUND: This study examined whether associations between 21-gene recurrence score (RS) genomic testing and lower costs among patients with early-stage, estrogen receptor-positive breast cancer are observable in real-world data from the Medicare population. METHODS: A retrospective cohort study was conducted using SEER-Medicare data for a nationally representative sample of Medicare beneficiaries diagnosed from 2005 through 2011. The main outcomes were associations between RS testing and overall and chemotherapy-specific costs. The primary analysis was restricted to patients aged 66 to 75 years. RESULTS: The primary analysis comprised 30,058 patients. Mean costs 1 year after diagnosis were $35,940 [SD, $28,894] overall, $51,127 [33,386] for clinically high-risk disease, $33,225 [$27,711] for intermediate-risk disease, and $26,695 [$19,532] for low-risk disease. Chemotherapy-specific costs followed similar trends. In multivariable analyses, RS testing was associated with significantly lower costs among high-risk patients in terms of both relative costs (cost ratio, 0.88; 99% CI, 0.82-0.94) and absolute costs ($6,606; 99% CI, $39,223-$9,290). Higher costs among low-risk and intermediate-risk patients were mainly caused by higher noncancer costs. In sensitivity analyses that included all patients aged ≥66 years (N=64,996), associations between RS testing and costs among high-risk patients were similar but less pronounced because of lower overall use of chemotherapy. CONCLUSIONS: RS testing was associated with lower overall and chemotherapy-related costs in patients with high-risk disease, consistent with lower chemotherapy use among these patients. Higher overall costs for patients with intermediate-risk and low-risk disease were driven largely by non-treatment-related costs.

The Internal Validity of Discrete Choice Experiment Data: A Testing Tool for Quantitative Assessments.

OBJECTIVES: To develop a tool for testing internal validity of discrete choice experiment (DCE) data, deploy the program, and collect summary test results from a sample of active health researchers to demonstrate the practical utility of the tool in a wide range of health applications. METHODS: A previously developed Gauss program had been in use for testing internal validity. The program was translated to MATLAB and adapted, compiled, and deployed. Sixty-seven authors who had coauthored one or more published DCE studies between 2013 and 2016 were contacted by email; provided access to the tool, instructions, and an example data file; and invited to submit test summaries for tabulation. RESULTS: Twenty-one researchers from 10 countries contributed test results from a total of 55 DCE data sets. Fifty-one studies included at least two out of a possible six tests. Attribute dominance was the most common test, and stability had the highest failure incidence. Only three summaries included a transitivity test, and no failures were detected. CONCLUSIONS: It was possible to evaluate multiple internal validity checks for most data sets even when the experimental design did not explicitly include tests. Nevertheless, internal validity is rarely reported. Free availability of the tool for testing data quality could improve both reporting and more careful design of DCE studies to help validate and interpret stated preference data.

Comparing the Noncomparable: The Need for Equivalence Measures That Make Sense in Health-Economic Evaluations.

BACKGROUND: The popularity of quality-adjusted life years (QALYs) has been resistant to concerns about validity and reliability. Utility-theoretic outcome equivalents are widely used in other areas of applied economics. Equivalence values can be derived for time, money, risk, and other metrics. These equivalence measures preserve all available information about individual preferences and are valid measures of individual welfare changes. OBJECTIVE: The objective of this study was to derive alternative generalized equivalence measures from first principles and illustrate their application in an empirical comparative-effectiveness example. METHODS: We specify a general-equilibrium model incorporating neoclassical utility functions, health production function, severity-duration preferences, and labor-market tradeoff function. The empirical implementation takes advantage of discrete-choice experiment methods that are widely accepted in other areas of applied economics and increasingly in health economics. We illustrate the practical significance of restrictive QALY assumptions using comparative-effectiveness results based on both QALYs and estimates of welfare-theoretic time-equivalent values for anti-tumor necrosis factor and prolonged corticosteroid treatments for Crohn's disease in three distinct preference classes. RESULTS: The QALY difference between the two treatments is 0.2 months, while time-equivalent values range between 0.5 and 1.3 months for aggregate and class-specific differences. Thus, the QALY-based analysis understates welfare-theoretic values by 60%-85%. CONCLUSION: These results suggest that using disease-specific equivalence values offer a meaningful alternative to QALYs to compare global outcomes across treatments. The equivalence values approach is consistent with principles of welfare economics and offers several features not represented in QALYs, including accounting for preference nonlinearities in disease severity and duration, inclusion of preference-relevant nonclinical healthcare factors, representing preferences of clinically-relevant patient subpopulations, and including utility losses related to risk aversion.

Something Is Better Than Nothing: The Value of Active Intervention in Stated Preferences for Treatments to Delay Onset of Alzheimer's Disease Symptoms.

BACKGROUND: The objective of the study was to understand respondents' willingness to accept hypothetical treatment-related risks in return for the benefit of additional time with normal memory from potential Alzheimer's disease interception therapies. METHODS: A US web-based discrete-choice survey was administered to respondents ages 60 to 85 years with no Alzheimer's disease diagnosis and no cognitive symptoms. Choice questions required respondents to indicate whether they preferred a constant, no-treatment condition described as 4 years of normal memory followed by 3 years of cognitive impairment and 5 years of dementia or an interception treatment with chosen risks of disabling stroke and death, but with increased duration of normal memory. The study design included internal validity tests to verify data quality. RESULTS: On average, respondents were willing to accept a 5% to 13% risk of stroke or death in the first year for treatments that could provide 1 or more additional years with normal memory. Nevertheless, 30% of respondents failed a simple internal-validity test question where the treatment alternative offered no improvement in disease progression but had significant side effects. These respondents also were more likely to choose active treatment in the subsequent series of choice questions. This unexpected finding is consistent with hopeful attitudes of patients with debilitating and potentially fatal conditions. CONCLUSION: Pro-treatment attitudes are clinically relevant and can affect the analysis and interpretation of stated-preference data. Internal-validity tests generally are underutilized in preference research. This study demonstrated how analysis of apparent validity failures can yield important insights about patient preferences.

INITIAL ADOPTION OF RECOMBINANT HUMAN THYROID-STIMULATING HORMONE FOLLOWING THYROIDECTOMY IN THE MEDICARE THYROID CANCER PATIENT POPULATION.

OBJECTIVE: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved for diagnostic (1998) and therapeutic (2008) indications in conjunction with radioactive iodine (RAI) administration post-thyroidectomy. Potential benefits of rhTSH, including avoidance of hypothyroidism side effects and shorter, less costly hospital stays, have not been assessed at the population level within the United States. In this study we quantify utilization, outcomes, and associated costs of rhTSH within the nationally representative Surveillance, Epidemiology, and End Results (SEER)-Medicare patient population. METHODS: We conducted a retrospective analysis of beneficiaries aged >65 years diagnosed within the SEER-Medicare data with differentiated thyroid cancer. Endpoints examined included ( 1) rhTSH utilization in the 2 years post-thyroidectomy (patients diagnosed 1996-2011 [utilization cohort]) and ( 2) comparison of resource utilization and costs as a function of rhTSH receipt in the 30 days prior to and 1 year following therapeutic RAI administration (patients diagnosed 2008-2011 [resource use cohort]). All costs were adjusted to reflect 2013 dollars. RESULTS: A total of 6,482 patients met inclusion criteria, of which, 1,363 (21.0%) received rhTSH. Receipt varied by region and was higher in the South (18%), Northeast (28%), and West (44%) compared to the Midwest (10%), and lower in census tracts in the bottom quartile of high school education rates (odds ratio 0.68, 95% confidence interval [CI] 0.55-0.83). rhTSH receipt was not associated with patient sex, age, comorbidities, or stage. Post-therapeutic RAI, 1,444 patients were assessed for resource utilization (2008-2011). The average cost of rhTSH was $905 per patient, with $2,483 being spent on average among patients who received rhTSH in association with therapeutic RAI. rhTSH receipt was not significantly associated with total inpatient days or number of outpatient and emergency department visits. Multivariable analyses showed similar overall costs among patients who did versus did not receive rhTSH (cost ratio [CR] 0.96, 95% CI 0.86-1.09), partially due to increased mean outpatient costs ($5,213 vs. $4,190) being offset by lower inpatient costs ($3,493 vs. $6,143). Overall costs were significantly higher in multivariable analyses among patients with distant metastatic disease (CR 1.92, 95% CI 1.58-2.32) and multiple comorbidities (CR 2.15, 95% CI 1.83-2.53). CONCLUSION: rhTSH recipients had higher outpatient, lower inpatient, and similar total Medicare payments as those not receiving rhTSH in conjunction with RAI, lending support to the use of rhTSH as a cost-neutral treatment option from the payer perspective. ABBREVIATIONS: CI = confidence interval; CMS = Centers for Medicare & Medicaid Services; CR = cost ratio; HCPCS = Healthcare Common Procedure Coding System; IQR = interquartile range; mCi = millicurie; OR = odds ratio; PET = positron emission tomography; RAI = radioactive iodine; rhTSH = recombinant human thyroid-stimulating hormone; RR = risk ratio; SEER = Surveillance, Epidemiology, and End Results.

Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).

AIMS: TECOS, a cardiovascular safety trial (ClinicalTrials.gov identifier: NCT00790205) involving 14 671 patients with type 2 diabetes and cardiovascular disease, demonstrated that sitagliptin was non-inferior to placebo for the primary composite cardiovascular outcome when added to best usual care. This study tested hypotheses that medical resource use and costs differed between these 2 treatment strategies. MATERIALS AND METHODS: Information concerning medical resource use was collected on case report forms throughout the trial and was valued using US costs for: Medicare payments for hospitalizations, medical procedures and outpatient visits, and wholesale acquisition costs (WAC) for diabetes-related medications. Hierarchical generalized linear models were used to compare resource use and US costs, accounting for variable intercountry practice patterns. Sensitivity analyses included resource valuation using English costs for a UK perspective. RESULTS: There were no significant differences in hospitalizations, inpatient days, medical procedures, or outpatient visits during follow-up (mean and median 3.0 years in both groups). Hospitalization rates appeared to diverge after 2 years, with lower rates among sitagliptin-treated vs placebo patients after 2.5 years (relative rate, 0.90 [95% CI, 0.83-0.97]; P = .01). Mean medical costs, exclusive of study medication, were 11 937 USD in the sitagliptin arm and 12 409 USD in the placebo arm (P = .06). Mean sitagliptin costs based on undiscounted WAC were 9978 USD per patient. Differential UK total costs including study drug costs were smaller (911 GBP), primarily because of lower mean costs for sitagliptin (1072 GBP). CONCLUSIONS: Lower hospitalization rates across time with sitagliptin slightly offset sitagliptin treatment costs over 3 years in type 2 diabetes patients at high risk for cardiovascular events.