Patient-Informed Value Elements in Cost-Effectiveness Analyses of Major Depressive Disorder Treatment: A Literature Review and Synthesis.

OBJECTIVES: Prior work identified 6 key value elements (attributes of treatment and desired outcomes) for individuals living with major depressive disorder (MDD) in managing their condition: mode of treatment, time to treatment helpfulness, MDD relief, quality of work, interaction with others, and affordability. The objective of our study was to identify whether previous cost-effectiveness analyses (CEAs) for MDD treatment addressed any of these value elements. A secondary objective was to identify whether any study engaged patients, family members, and caregivers in the model development process. METHODS: We conducted a systematic literature review to identify published model-based CEAs. We compared the elements of the published studies with the MDD patient value elements elicited in prior work to identify gaps and areas for future research. RESULTS: Of 86 published CEAs, we found that 7 included patient out-of-pocket costs, and 32 included measures of productivity, which were both priorities for individuals with MDD. We found that only 2 studies elicited measures from patients for their model, and 2 studies engaged patients in the modeling process. CONCLUSIONS: Published CEA models for MDD treatment do not regularly include value elements that are a priority for this patient population nor do they include patients in their modeling process. Flexible models that can accommodate elements consistent with patient experience are needed, and a multistakeholder engagement approach would help accomplish this.

Impact of Undertreatment of Depression on Suicide Risk Among Children and Adolescents With Major Depressive Disorder: A Microsimulation Study.

Undertreatment of depression is common among children and adolescents, but evidence of the impact of undertreatment of depression on risk of suicide is limited due to the low base rate of suicide in the population and lack of sufficient data sources. We developed a microsimulation model that uses evidence from multiple sources to study the impact of different durations of antidepressant treatment on suicide risk in a synthesized sample that is nationally representative of children and adolescents with major depressive disorder. Compared with receiving no treatment, suicide rate and risk of suicide attempt both decreased with increasing duration of antidepressant treatment (for 12 weeks, suicide rate ratios = 0.78 (95% credible interval (CrI): 0.58, 1.15), 36 weeks, 0.65 (95% CrI: 0.44, 0.90), and 52 weeks, 0.63 (95% CrI: 0.45, 0.72); for suicide attempt: 12 weeks, suicide risk ratios = 0.68 (95% CrI: 0.62, 0.69), 36 weeks, 0.56 (95% CrI: 0.52, 0.57), and 52 weeks, 0.55 (95% CrI: 0.51, 0.56). The suicide rate and risk of suicide attempt were lower in children than in adolescents. Males had a lower risk of suicide attempt but higher suicide rate than females. The findings from the microsimulation model show that completion of 12-36 weeks of antidepressant treatment may reduce suicide attempt and suicide among children and adolescents with major depressive disorder.

Eliciting Low-Risk Thyroid Cancer Treatment Preferences Using Clinical Vignettes: A Pilot Study.

OBJECTIVE: While surgical resection has been the traditional standard treatment for small (≤1 cm), differentiated thyroid cancers, active surveillance (AS) and radiofrequency ablation (RFA) are increasingly considered. The aim of this study was to explore patient preferences in thyroid cancer treatment using a series of clinical vignettes. METHODS: Thyroid cancer survivors and general population volunteers were recruited to rank experience-driven clinical vignettes in order of preference. Rankings were compared using Wilcoxon signed rank. Formative qualitative methods were used to develop and refine clinical vignettes that captured 4 treatments-thyroid lobectomy (TL), total thyroidectomy (TT), AS, and RFA-along with 6 treatment complications. Content was validated via interviews with 5 academic subspecialists. RESULTS: Nineteen volunteers participated (10 survivors, 9 general population). Treatment complications were ranked lower than uncomplicated counterparts in 99.0% of cases, indicating excellent comprehension. Counter to our hypothesis, among uncomplicated vignettes, median rankings were 1 for AS, 2 for RFA, 3.5 for TL, and 5 for TT. Trends were consistent between thyroid cancer survivors and the general population. AS was significantly preferred over RFA (P = .02) and TT (P < .01). Among surgical options, TL was significantly preferred over TT (P < .01). CONCLUSION: When treatments for low-risk thyroid cancer are described clearly and accurately through clinical vignettes, patients may be more likely to choose less invasive treatment options over traditional surgical resection.

Exploring the Use of State Medical Cannabis Legislation as a Proxy for Medical Cannabis Use Among Patients Receiving Chemotherapy.

OPINION STATEMENT: The use of medical cannabis is expanding in the USA. Due to conflicting, low-quality evidence, many oncologists may not feel confident to recommend it to patients. Given the potential for legal and financial risks when conducting clinical trials with medical cannabis, the use of observational data should be explored. Observational data that directly capture medical cannabis use in relation to prescription medications and track the prevalence and patterns of cannabis use is sparse. To gain insights into the role medical cannabis plays in the pharmaceutical landscape, proxies such as cannabis legislation need to be explored. In the context of recommendation-nonadherent antiemetic prescribing among patients experiencing chemotherapy-induced nausea and vomiting, medical cannabis may be a suitable alternative to an antiemetic in states that allow medical cannabis. Findings suggest that legislation may impact the use of certain antiemetics in states with cannabis legislation in place. The presence or absence of legislation regarding medical cannabis use may serve as an early, observable surrogate marker of medical cannabis use in the community. In light of the paucity of clinical trials and observational datasets that capture cannabis use, there remains a tremendous need for the development of methodologies or standardized datasets that appropriately and reliably capture the use of medical cannabis to facilitate research into its clinical application and effect on prescription medication use. Standardizing the reporting and destigmatizing use could eliminate the dependence upon proxy measures as a substitute for more extensive data and go a long way in improving data capture, thus allowing us to generate knowledge and hypotheses from observational data until research conditions improve and allow for expanded clinical trials involving medical cannabis.

Initiation of Transdermal Fentanyl Among US Commercially Insured Patients Between 2007 and 2015.

INTRODUCTION: This study examined patterns of initial transdermal fentanyl (TDF) claims among US commercially insured patients and explored the risk of 30-day hospitalization among patients with and without prior opioid exposure necessary to produce tolerance. DESIGN: A retrospective cohort study of initial outpatient TDF prescriptions. SETTING: A 10% random sample of commercially insured enrollees within the IQVIA Health Plan Claims Database (formerly known as PharMetrics Plus). SUBJECTS: Individuals with a claim for TDF between 2007 and 2015. METHODS: The primary exposure was a new transdermal fentanyl claim, and the primary outcome was guideline concordance based on time and dose exposure. RESULTS: Among the 24,770 patients in the cohort, 4,848 (20%) patients had sufficient time exposure to opioids before TDF. Among those with sufficient time exposure, 3,971 (82%) had adequate opioid exposure based on the US Food and Drug Administration (FDA) package insert dosing guidance. Overall, 3,971 of the 24,770 (16%) patients received guideline-consistent TDF. An exploratory analysis of 30-day hospitalization after a TDF claim did not detect a difference in odds between guideline-consistent or -inconsistent groups when adjusted for variables known to influence the risk of opioid-induced respiratory depression. CONCLUSIONS: A majority of patients met FDA opioid dose thresholds for TDF but had insufficient time exposure based on package insert recommendations for tolerance. Exploratory analysis did not detect a difference in odds for all-cause hospitalization or respiratory-related 30-day hospitalization between guideline-consistent or -inconsistent TDF claims. Prescribers should continue to adhere to FDA TDF labeling, although certain aspects of the labeling should be reevaluated or clarified.

Future of Patients in Healthcare Evaluation: The Patient-Informed Reference Case.

The "Reference Case" was developed to facilitate comparability among published cost-effectiveness analyses intended to contribute to decisions about the broad allocation of healthcare resources. Although the societal perspective is recommended for Reference Case analyses, empirical estimations rarely adequately represent the patient perspective, and more often, healthcare system or payer perspectives are used. In this commentary, we discuss the evolution of the Reference Case over the past 20 years and how it now needs to further evolve. This should begin with a patient-informed societal perspective. A realignment of the societal perspective to better include patient perspectives in CEA creates a conduit for patient inclusion. Engaging patients to both derive patient-informed value elements and prioritize value elements using stated preference methods will lead to patient inclusion in the societal perspective and a patient-informed Reference Case analysis.

Returns to scientific publications for pharmaceutical products in the United States.

Drug-specific clinical and health economic and outcomes research (HEOR) publications have amassed, but their effect on drug sales is largely unknown. We estimated the impact of publications on pharmaceutical sales in 3 markets (statins, rheumatoid arthritis, and asthma drugs) with varying generic competition. An event-study approach with fixed effects and difference-in-fixed-effects modeling was used to estimate the causal effects of drug-specific publications on subsequent quarter's drug-specific sales and volume. High-impact clinical and HEOR publications have significant positive effects on sales (mediated through price) and volume in the statin market (high generic competition). High-impact clinical publications have a significant positive effect on sales (mediated through volume) in low-generic competition market (asthma). The effects of publications in the rheumatoid arthritis market (no generic competition) on sales were null. Manufacturers' investment in clinical and HEOR publications needs to be strategic and should be anticipated and complemented by public investments in such studies.

Mortality and Associated Morbidities Following Traumatic Brain Injury in Older Medicare Statin Users.

OBJECTIVE: To assess the relationship between posttraumatic brain injury statin use and (1) mortality and (2) the incidence of associated morbidities, including stroke, depression, and Alzheimer's disease and related dementias following injury. SETTING AND PARTICIPANTS: Nested cohort of all Medicare beneficiaries 65 years of age and older who survived a traumatic brain injury (TBI) hospitalization during 2006 through 2010. The final sample comprised 100 515 beneficiaries. DESIGN: Retrospective cohort study of older Medicare beneficiaries. Relative risks (RR) and 95% confidence interval (CI) were obtained using discrete time analysis and generalized estimating equations. MEASURES: The exposure of interest included monthly atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin use. Outcomes of interest included mortality, stroke, depression, and Alzheimer's disease and related dementias. RESULTS: Statin use of any kind was associated with decreased mortality following TBI hospitalization discharge. Any statin use was also associated with a decrease in any stroke (RR, 0.86; 95% confidence intervals (CI), 0.81-0.91), depression (RR, 0.85; 95% CI, 0.79-0.90), and Alzheimer's disease and related dementias (RR, 0.77; 95% CI, 0.73-0.81). CONCLUSION: These findings provide valuable information for clinicians treating older adults with TBI as clinicians can consider, when appropriate, atorvastatin and simvastatin to older adults with TBI in order to decrease mortality and associated morbidities.

Hepatitis C Treatment Regimens Are Cost-Effective: But Compared With What?

BACKGROUND: Numerous economic models have been published evaluating treatment of chronic hepatitis C virus (HCV) infection, but none provide a comprehensive comparison among new antiviral agents. OBJECTIVE: Evaluate the cost-effectiveness of all recommended therapies for treatment of genotypes 1 and 4 chronic HCV. METHODS: Using data from clinical trials, observational analyses, and drug pricing databases, Markov decision models were developed for HCV genotypes 1 and 4 to compare all recommended drugs from the perspective of the third-party payer over a 5-, 10-, and 50-year time horizon. A probabilistic sensitivity analysis (PSA) was conducted by assigning distributions for clinical cure, age entering the model, costs for each health state, and quality-adjusted life years (QALYs) for each health state in a Monte Carlo simulation of 10 000 repetitions of the model. RESULTS: In the lifetime model for genotype 1, effects ranged from 18.08 to 18.40 QALYs and total costs ranged from $88 107 to $184 636. The lifetime model of genotype 4 treatments had a range of effects from 18.23 to 18.43 QALYs and total costs ranging from $87 063 to $127 637. Grazoprevir/elbasvir was the optimal strategy followed by velpatasvir/sofosbuvir as the second-best strategy in most simulations for both genotypes 1 and 4, with drug costs and efficacy of grazoprevir/elbasvir as the primary model drivers. CONCLUSIONS: Grazoprevir/elbasvir was cost-effective compared with all strategies for genotypes 1 and 4. Effects for all strategies were similar with cost of drug in the initial year driving the results.

Treatment Charges for Traumatic Brain Injury Among Older Adults at a Trauma Center.

OBJECTIVE: To provide charge estimates of treatment for traumatic brain injury (TBI), including both hospital and physician charges, among adults 65 years and older treated at a trauma center. METHODS: We identified older adults treated for TBI during 2008-2012 (n = 1843) at Maryland's Primary Adult Resource Center and obtained hospital and physician charges separately. Analyses were stratified by sex and all charges were inflated to 2012 dollars. Total TBI charges were modeled as a function of covariates using a generalized linear model. RESULTS: Women comprised 48% of the sample. The mean unadjusted total TBI hospitalization charge for adults 65 years and older was $36 075 (standard deviation, $63 073). Physician charges comprised 15% of total charges. Adjusted mean charges were lower in women than in men (adjusted difference, -$894; 95% confidence interval, -$277 to -$1512). Length of hospital and intensive care unit stay were associated with the highest charges. CONCLUSIONS: This study provides the first estimates of hospital and physician charges associated with hospitalization for TBI among older adults at a trauma center that will aid in resource allocation, triage decisions, and healthcare policy.

Patterns of Statin Use in Older Medicare Beneficiaries With Traumatic Brain Injury.

BACKGROUND: In addition to lowering lipids, statins also may be beneficial for older adults sustaining a traumatic brain injury (TBI), as statin use prior to and following trauma may decrease mortality following injury. However, despite statins' potential to reduce mortality, there is limited research regarding statin use among older adults. OBJECTIVE: To characterize and investigate factors associated with statin use among older adults with TBI. METHODS: A retrospective drug utilization study was used to characterize statin use among Medicare beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 and with continuous Medicare Parts A, B, and D coverage 6 months prior and 12 months following TBI. Logistic regression was used to investigate the factors associated with statin use. The exposure of interest was statin use prior to and following TBI. RESULTS: Of the 75 698 beneficiaries included in the study, 37 874 (~50%) of beneficiaries used a statin at least once during the study period. The most common statin used was simvastatin, while fluvastatin was the least used statin. Statin users were more likely to have cardiovascular diseases when compared to nonusers. Hyperlipidemia was a major factor associated with statin use and had the greatest impact on statin use compared to nonuse (odds ratio = 9.54; 95% confidence interval = 9.07, 10.03). CONCLUSIONS: This national sample of older adults with TBI suggests that statins are commonly used. Future studies must next examine the impact of statin use on mortality and secondary injury in order to shape pharmacological therapy guidelines following TBI.

In-Hospital Mortality Following Traumatic Brain Injury Among Older Medicare Beneficiaries, Comparing Statin Users With Nonusers.

BACKGROUND: Traumatic brain injury (TBI) is a significant public health concern for older adults. Small-scale human studies have suggested pre-TBI statin use is associated with decreased in-hospital mortality following TBI, highlighting the need for large-scale translational research. OBJECTIVE: To investigate the relationship between pre-TBI statin use and in-hospital mortality following TBI. METHODS: A retrospective study of Medicare beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 was conducted to assess the impact of pre-TBI statin use on in-hospital mortality following TBI. Exposure of interest included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. Beneficiaries were classified as current, recent, past, and nonusers of statins prior to TBI. The outcome of interest was in-hospital mortality. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) comparing current, recent, and prior statin use to nonuse. RESULTS: Most statin users were classified as current users (90%). Current atorvastatin (OR = 0.88; 95% = CI 0.82, 0.96), simvastatin (OR = 0.84; 95% CI = 0.79, 0.91), and rosuvastatin (OR = 0.79; 95% CI = 0.67, 0.94) use were associated with a significant decrease in the risk of in-hospital mortality following TBI. CONCLUSIONS: In addition to being the most used statins, current use of atorvastatin, rosuvastatin, and simvastatin was associated with a significant decrease in in-hospital mortality following TBI among older adults. Future research must include clinical trials to help exclude the possibility of a healthy user effect in order to better understand the impact of statin use on in-hospital mortality following TBI.

Translating Pharmacometrics to a Pharmacoeconomic Model of COPD.

BACKGROUND: A model-based meta-analysis (MBMA) is a type of meta-regression that uses nonlinear mixed-effects models estimated on trial-level data to relate patient and trial characteristics, dosing, biomarkers, and outcomes of treatment. OBJECTIVES: To use a pharmacometric MBMA within a pharmacoeconomic model of chronic obstructive pulmonary disease (COPD). METHODS: A Markov microsimulation model was developed to estimate monthly changes in the key disease severity metrics of COPD (forced expiratory volume in 1 second [FEV1] and exacerbations) to compare a hypothetical drug that increases FEV1 to usual care. The MBMA was used to predict a baseline exacerbation rate in a group of actual trial patients, given their known baseline FEV1. The hypothetical drug increased FEV1, thereby decreasing individuals' predicted exacerbation rates. Individual patient simulations allowed stochastic changes in monthly FEV1 decline. RESULTS: In a sample of 1097 trial patients with a mean FEV1 of 50%, the MBMA predicted 0.93 exacerbations per year on average. The exacerbation rate ranged from 0.52 to 1.3 per year across moderate and severe patient subgroups. A hypothetical anti-inflammatory drug that increased FEV1 by 50 ml decreased exacerbations by 26%. Given a simplified estimation of costs and quality-adjusted life-years (QALYs) associated with COPD, a drug with a 50-ml increase priced at €35/mo had an incremental cost-effectiveness ratio ranging from €13,000/QALY to approximately €207,000/QALY across patient severity subgroups. CONCLUSIONS: The synergistic aspects of MBMA and pharmacoeconomic modeling are highlighted in this hypothetical example. Markov microsimulation modeling allows the finer predictions of MBMA to inform parameters. Such an approach has utility in both early-phase cost-effectiveness estimations and trial design.

Asthma control in the United States, 2008-2010: indicators of poor asthma control.

BACKGROUND: An estimated 23 million Americans have asthma, of whom at least 12 million experience an asthma exacerbation every year. Clinical practice guidelines focus on asthma control, with an emphasis on reducing both impairment and risk. OBJECTIVE: We sought to explore broad patterns of asthma prevalence, self-reported medication use, and indicators of control in a nationally representative sample. METHODS: The 2008, 2009, and 2010 Medical Expenditure Panel Surveys were used to examine the national prevalence of self-reported asthma, trends in medication use, and demographic characteristics of asthmatic patients. History of lifetime asthma and current diagnosis were ascertained based on self-report. Asthma management and control were examined by using patient-reported medication use. RESULTS: Of the 102,544 subjects asked about an asthma diagnosis, 9,782 reported lifetime asthma, and 8,837 reported current asthma. Five thousand five subjects (4.8% of the population) reported experiencing an asthma exacerbation in the previous year. Four thousand five hundred twenty-one subjects used a quick-relief inhaler for asthma symptoms, and 14.6% used more than 3 canisters of this type of medication in the past 3 months. Of this group, 60% were using daily long-term control medication but still required significant use of quick-relief inhalers, whereas 28% had never used long-term control medication. Of those who had a recent exacerbation, 29% were using daily preventive medication, whereas 54% had never used long-term control medication. CONCLUSIONS: Improvement of asthma control continues to be a US public health concern. Results suggest suboptimal asthma control with underuse of long-term control medications, overuse of quick-relief inhalers, and a significant number of self-reported asthma exacerbations.

Dynamic medication adherence modeling in primary prevention of cardiovascular disease: a Markov microsimulation methods application.

BACKGROUND: Real-world patients' medication adherence is lower than that of clinical trial patients. Hence, the effectiveness of medications in routine practice may differ. OBJECTIVES: The study objective was to compare the outcomes of an adherence-naive versus a dynamic adherence modeling framework using the case of statins for the primary prevention of cardiovascular (CV) disease. METHODS: Statin adherence was categorized into three state-transition groups on the basis of an epidemiological cohort study. Yearly adherence transitions were incorporated into a Markov microsimulation using TreeAge software. Tracker variables were used to store adherence transitions, which were used to adjust probabilities of CV events over the patient's lifetime. Microsimulation loops "random walks" estimated the average accrued quality-adjusted life-years (QALYs) and CV events. For each 1,000-patient microsimulations, 10,000 outer loops were performed to reflect second-order uncertainty. RESULTS: The adherence-naive model estimated 0.14 CV events avoided per person, whereas the dynamic adherence model estimated 0.08 CV events avoided per person. Using the adherence-naive model, we found that statin therapy resulted in 0.40 QALYs gained over the lifetime horizon on average per person while the dynamic adherence model estimated 0.22 incremental QALYs gained. Subgroup analysis revealed that maintaining high adherence in year 2 resulted in 0.23 incremental QALYs gained as compared with 0.16 incremental QALYs gained when adherence dropped to the lowest level. CONCLUSIONS: A dynamic adherence Markov microsimulation model reveals risk reduction and effectiveness that are lower than with an adherence-naive model, and reflective of real-world practice. Such a model may highlight the value of improving or maintaining good adherence.

The relationship between asthma, asthma control and economic outcomes in the United States.

OBJECTIVE: Asthma, a serious chronic lung disease affecting approximately 26 million Americans, remains clinical and economic burdens on the healthcare system. Although associations between uncontrolled asthma and poor health outcomes is known, the extent of this impact of uncontrolled asthma on economic outcomes in the United States (US) is unknown. We sought to determine the relationship between asthma, asthma control and economic outcomes in the US. METHODS: The 2008-2010 Medical Expenditure Panel Surveys were used to estimate the impact of uncontrolled asthma (asthma-related emergency department [ED] visit, use of >3 canisters of quick-relief inhaler in past 3 months or asthma attack in past 12 months) on medical expenditures, utilization and productivity. Estimates were generated using multivariate regression controlling for sociodemographics and comorbidity. RESULTS: Medical expenditures attributable to asthma were up to $4423 greater for those with markers of uncontrolled asthma compared with those who did not have asthma. Frequency of hospital discharges were up to 4.6-fold greater for those with uncontrolled asthma than those without asthma (p < 0.01), while all others with asthma did not have significantly more discharges. ED visits were up to 1.8-fold greater for those with uncontrolled asthma compared with those without asthma (p < 0.01). Productivity was significantly (p < 0.01) decreased (more likely to be unemployed, more days absent from work and more activity limitations) for those with uncontrolled asthma. CONCLUSIONS: In recent national data, individuals with asthma and markers of uncontrolled asthma had higher medical expenditures, greater utilization and decreased productivity.

Evidence inventory: A patient-centered framework for Centers for Medicare & Medicaid Services to assess the clinical benefit of drugs to inform its maximum fair price negotiation.

The Inflation Reduction Act passed in August 2022 empowers the Centers for Medicare & Medicaid Services (CMS) to negotiate maximum fair prices for certain expensive drugs. In the process of determining maximum fair prices, CMS gathers evidence on the clinical benefits of these drugs as compared with their therapeutic alternative(s) from various sources. As patients are the primary beneficiaries of the treatment, we recommend that CMS should embrace an approach that prioritizes patient experience when evaluating such diverse sources of evidence in the assessment of the clinical benefit. Thus, we propose to draw on several existing frameworks to support the concept of "evidence inventory," a patient-centered approach to systematically evaluate benefits of drugs under consideration. This 4-step process to develop an evidence inventory includes the following: (1) Formulate the research question-in a PICO(T) (P = population, I = Intervention or exposure, C = comparator, O = outcome, and T = time frame) format, (2) Synthesize evidence, (3) Evaluate the evidence-using evidence inventory, and (4) Reevaluate evidence as new information become available. Patients and other relevant stakeholders play a critical role in each of these 4 steps. The proposed evidence inventory holds the potential to provide a structured and transparent patient-centered framework for evaluating the clinical benefits of drugs as compared with their therapeutic alternative(s) informing CMS maximum fair price negotiation.

Age-stratified comparison of active surveillance versus radiofrequency ablation for papillary thyroid microcarcinoma using decision analysis.

BACKGROUND: Papillary thyroid microcarcinomas may be treated with radiofrequency ablation, active surveillance, or surgery. The objective of this study was to use mathematical modeling to compare treatment alternatives for papillary thyroid microcarcinomas among those who decline surgery. We hypothesized that radiofrequency ablation would outperform active surveillance in avoiding progression and surgery but that the effect size would be small for older patients. METHODS: We engaged stakeholders to identify meaningful long-term endpoints for papillary thyroid microcarcinoma treatment-(1) cancer progression/surgery, (2) need for thyroid replacement therapy, and (3) permanent treatment complication. A Markov decision analysis model was created to compare the probability of these endpoints after radiofrequency ablation or active surveillance for papillary thyroid microcarcinomas and overall cost. Transition probabilities were extracted from published literature. Model outcomes were estimated to have a 10-year time horizon. RESULTS: The primary outcome yielded a number needed to treat of 18.1 for the avoidance of progression and 27.4 for the avoidance of lifelong thyroid replacement therapy for radiofrequency ablation compared to active surveillance. However, as patient age increased, the number needed to treat to avoid progression increased from 5.2 (age 20-29) to 39.1 (age 60+). The number needed to treat to avoid lifelong thyroid replacement therapy increased with age from 7.8 (age 20-29) to 59.3 (age 60+). The average 10-year cost/treatment for active surveillance and radiofrequency ablation were $6,400 and $11,700, respectively, translating to a cost per progression-avoided of $106,500. CONCLUSION: As an alternative to active surveillance, radiofrequency ablation may have a greater therapeutic impact in younger patients. However, routine implementation may be cost-prohibitive for most patients with papillary thyroid microcarcinomas.

Ability of Caprini and Padua risk-assessment models to predict venous thromboembolism in a nationwide Veterans Affairs study.

OBJECTIVE: Venous thromboembolism (VTE) is a preventable complication of hospitalization. Risk-stratification is the cornerstone of prevention. The Caprini and Padua are two of the most commonly used risk-assessment models (RAMs) to quantify VTE risk. Both models perform well in select, high-risk cohorts. Although VTE RAMs were designed for use in all hospital admissions, they are mostly tested in select, high-risk cohorts. We aim to evaluate the two RAMs in a large, unselected cohort of patients. METHODS: We analyzed consecutive first hospital admissions of 1,252,460 unique surgical and non-surgical patients to 1298 Veterans Affairs facilities nationwide between January 2016 and December 2021. Caprini and Padua scores were generated using the Veterans Affairs' national data repository. We determined the ability of the two RAMs to predict VTE within 90 days of admission. In secondary analyses, we evaluated prediction at 30 and 60 days, in surgical vs non-surgical patients, after excluding patients with upper extremity deep vein thrombosis, in patients hospitalized ≥72 hours, after including all-cause mortality in a composite outcome, and after accounting for prophylaxis in the predictive model. We used area under the receiver operating characteristic curves (AUCs) as the metric of prediction. RESULTS: A total of 330,388 (26.4%) surgical and 922,072 (73.6%) non-surgical consecutively hospitalized patients (total N = 1,252,460) were analyzed. Caprini scores ranged from 0 to 28 (median, 4; interquartile range [IQR], 3-6); Padua scores ranged from 0-13 (median, 1; IQR, 1-3). The RAMs showed good calibration and higher scores were associated with higher VTE rates. VTE developed in 35,557 patients (2.8%) within 90 days of admission. The ability of both models to predict 90-day VTE was low (AUCs: Caprini, 0.56; 95% confidence interval [CI], 0.56-0.56; Padua, 0.59; 95% CI, 0.58-0.59). Prediction remained low for surgical (Caprini, 0.54; 95% CI, 0.53-0.54; Padua, 0.56; 95% CI, 0.56-0.57) and non-surgical patients (Caprini, 0.59; 95% CI, 0.58-0.59; Padua, 0.59; 95% CI, 0.59-0.60). There was no clinically meaningful change in predictive performance in any of the sensitivity analyses. CONCLUSIONS: Caprini and Padua RAM scores have low ability to predict VTE events in a cohort of unselected consecutive hospitalizations. Improved VTE RAMs must be developed before they can be applied to a general hospital population.