Cost-effectiveness of the tubeless automated insulin delivery system vs standard of care in the management of type 1 diabetes in the United States.

BACKGROUND: A tubeless, on-body automated insulin delivery (AID) system (Omnipod 5 Automated Insulin Delivery System) demonstrated improved glycated hemoglobin A1c levels and increased time in range (70 mg/dL to 180 mg/dL) for both adults and children with type 1 diabetes in a 13-week multicenter, single-arm study. OBJECTIVE: To assess the cost-effectiveness of the tubeless AID system compared with standard of care (SoC) in the management of type 1 diabetes (T1D) in the United States. METHODS: Cost-effectiveness analyses were conducted from a US payer's perspective, using the IQVIA Core Diabetes Model (version 9.5), with a time horizon of 60 years and an annual discount of 3.0% on both costs and effects. Simulated patients received either tubeless AID or SoC, the latter being defined as either continuous subcutaneous insulin infusion (86% of patients) or multiple daily injections. Two cohorts (children: <18 years; adults: ≥18 years) of patients with T1D and 2 thresholds for nonsevere hypoglycemia (nonsevere hypoglycemia event [NSHE] <54 mg/dL and <70 mg/dL) were considered. Baseline cohort characteristics and treatment effects of different risk factors for tubeless AID were sourced from the clinical trial. Utilities and cost of diabetes-related complications were obtained from published sources. Treatment costs were derived from US national database sources. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Treating children with T1D with tubeless AID, considering an NSHE threshold of less than 54 mg/dL, brings incremental life-years (1.375) and quality-adjusted life-years (QALYs) (1.521) at an incremental cost of $15,099 compared with SoC, resulting in an incremental cost-effectiveness ratio of $9,927 per QALY gained. Similar results were obtained for adults with T1D assuming an NSHE threshold of less than 54 mg/dL (incremental cost-effectiveness ratio = $10,310 per QALY gained). Furthermore, tubeless AID is a dominant treatment option for children and adults with T1D assuming an NSHE threshold of less than 70 mg/dL compared with SoC. The probabilistic sensitivity analyses results showed that compared with SoC, in both children and adults with T1D, tubeless AID was cost-effective in more than 90% of simulations, assuming a willingness-to-pay threshold of $100,000 per QALY gained. The key drivers of the model were the cost of ketoacidosis, duration of treatment effect, threshold of NSHE, and definition of severe hypoglycemia. CONCLUSIONS: The current analyses suggest that the tubeless AID system can be considered a cost-effective treatment compared with SoC in people with T1D from a US payer's perspective. DISCLOSURES: This research was funded by Insulet. Mr Hopley, Ms Boyd, and Mr Swift are full-time Insulet employees and own stock in Insulet Corporation. IQVIA, the employer of Ms Ramos and Dr Lamotte, received consulting fees for this work. Dr Biskupiak is receiving research support and consulting fees from Insulet. Dr Brixner has received consulting fees from Insulet. The University of Utah has received research funding from Insulet. Dr Levy is a consultant with Dexcom and Eli Lilly and has received grant/research support from Insulet, Tandem, Dexcom, and Abbott Diabetes. Dr Forlenza conducted research sponsored by Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. He has been speaker/consultant/advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly.

Cancer incidence in immunocompromised patients: a single-center cohort study.

BACKGROUND: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. METHODS: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. RESULTS: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively. CONCLUSION: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

The Rise of Prescription Digital Therapeutics in Behavioral Health.

Medicine is evolving to incorporate digital technologies of all kinds-technologies that may improve patient health, reduce clinician workload, lower costs, reduce health disparities, and expand access to needed treatments. Prescription digital therapeutics (PDTs) are an emerging technology with particular potential. These are software-based treatments delivered on mobile devices that address the behavioral dimensions of many diseases and conditions. Unlike health and wellness apps, PDTs are rigorously evaluated for safety and effectiveness and are authorized by the US Food and Drug Administration (FDA). Nine PDTs are currently authorized to treat conditions such as substance use disorders, attention-deficit disorder, and chronic insomnia. The findings reported in two recent research papers published by Advances in Therapy related to use of PDTs for substance use disorder and opioid use disorder provide real-world evidence of clinical and cost effectiveness, strengthening the evidence base for these technologies and suggesting a role for these technologies in the efforts to help patients recover from these often-chronic and deadly conditions.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

BACKGROUND: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. METHODS: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). RESULTS: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. CONCLUSIONS: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. IMPACT: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Predicting Optimal Hypertension Treatment Pathways Using Recurrent Neural Networks.

BACKGROUND: In ambulatory care settings, physicians largely rely on clinical guidelines and guideline-based clinical decision support (CDS) systems to make decisions on hypertension treatment. However, current clinical evidence, which is the knowledge base of clinical guidelines, is insufficient to support definitive optimal treatment. OBJECTIVE: The goal of this study is to test the feasibility of using deep learning predictive models to identify optimal hypertension treatment pathways for individual patients, based on empirical data available from an electronic health record database. MATERIALS AND METHODS: This study used data on 245,499 unique patients who were initially diagnosed with essential hypertension and received anti-hypertensive treatment from January 1, 2001 to December 31, 2010 in ambulatory care settings. We used recurrent neural networks (RNN), including long short-term memory (LSTM) and bi-directional LSTM, to create risk-adapted models to predict the probability of reaching the BP control targets associated with different BP treatment regimens. The ratios for the training set, the validation set, and the test set were 6:2:2. The samples for each set were independently randomly drawn from individual years with corresponding proportions. RESULTS: The LSTM models achieved high accuracy when predicting individual probability of reaching BP goals on different treatments: for systolic BP (<140 mmHg), diastolic BP (<90 mmHg), and both systolic BP and diastolic BP (<140/90 mmHg), F1-scores were 0.928, 0.960, and 0.913, respectively. CONCLUSIONS: The results demonstrated the potential of using predictive models to select optimal hypertension treatment pathways. Along with clinical guidelines and guideline-based CDS systems, the LSTM models could be used as a powerful decision-support tool to form risk-adapted, personalized strategies for hypertension treatment plans, especially for difficult-to-treat patients.

Longitudinal changes in glycated haemoglobin following treatment intensification after inadequate response to two oral antidiabetic agents in patients with type 2 diabetes.

AIMS: To identify change in glycated haemoglobin (HbA1c) for 1 year after treatment intensification in patients with HbA1c >53 mmol/mol (7.0%) while on two classes of oral antidiabetic drugs (OADs). MATERIAL AND METHODS: A retrospective cohort study was conducted using a regional health plan claims database for the period January 1, 2010 to March 31, 2017. Patients with type 2 diabetes (T2DM) whose treatment was intensified with insulin, a glucagon-like peptide-1 receptor agonist or a third OAD within 365 days of having HbA1c ≥53 mmol/mol (7.0%) on two OADs were included. The HbA1c trajectory for 1 year after intensification was estimated using a mixed-effects regression model. RESULTS: The analysis included 1226 patients with a mean ± SD HbA1c at treatment intensification of 74.2 ± 18.7 mmol/mol (8.93 ± 1.7%). HbA1c was higher in the insulin group (74.2 mmol/mol) than in the non-insulin group (70.6 mmol/mol), as was the HbA1c decrease (P < 0.01) over the 1-year follow-up, particularly in patients with baseline HbA1c >9%. After intensification, insulin- and non-insulin-treated patients achieved an average change by month in HbA1c of -4.7 mmol/mol and -2.6 mmol/mol points, respectively. The analysis predicted HbA1c to be the lowest at 6 to 10 months post intensification, depending on intensification treatment and HbA1c at intensification; however, on average, HbA1c remained above 64.0 mmol/mol (8.0%). CONCLUSION: In patients with T2DM, intensification following an HbA1c value ≥53 mmol/mol (7.0%) while on two OADs was associated with a significant improvement in glycaemic control. Patients intensified with insulin had a higher baseline HbA1c but greater HbA1c reduction than those intensified with a non-insulin agent. However, HbA1c remained above 64 mmol/mol (8.0%) overall. Additional opportunity exists to further intensify therapy to improve glycaemic control.

Cost-effectiveness of early cancer surveillance for patients with Li-Fraumeni syndrome.

INTRODUCTION: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome [LFS]) are at extremely high lifetime risk of developing cancer. Recent data suggest that tumor surveillance for patients with LFS may improve survival through early cancer detection. The objective of this study was to assess the cost-effectiveness of a cancer surveillance strategy for patients with LFS compared with those whose tumors present clinically. METHODS: A Markov decision analytic model was developed from a third-party payer perspective to estimate cost-effectiveness of routine cancer surveillance over a patient's lifetime. The model consisted of four possible health states: no cancer, cancer, post-cancer survivorship, and death. Model outcomes were costs (2015 United States Dollars [USD]), effectiveness (life years [LY] gained), and incremental cost-effectiveness ratio (ICER; change in cost/LY gained). One-way sensitivity analyses and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: The model showed a mean cost of $46 496 and $117 102 and yielded 23 and 27 LY for the nonsurveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $17 125 per additional LY gained. At the commonly accepted willingness to pay threshold of $100 000/life-year gained, surveillance had a 98% probability of being the most cost-effective strategy for early cancer detection in this high-risk population. CONCLUSIONS: Presymptomatic cancer surveillance is cost-effective for patients with germline pathogenic variants in TP53. Lack of insurance coverage or reimbursement in this population may have significant consequences and leads to undetected cancers presenting in later stages of disease with worse clinical outcomes.

Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center.

New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients' and providers' perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.

Clinical Utility of Pharmacogenetic Testing and a Clinical Decision Support Tool to Enhance the Identification of Drug Therapy Problems Through Medication Therapy Management in Polypharmacy Patients.

BACKGROUND: In polypharmacy patients, medication therapy management (MTM) services provide a comprehensive review of current medications and future treatment goals. Pharmacogenetics (PGx) may further optimize the identification of potential drug therapy problems (DTPs); however, the clinical utility of PGx information with a clinical decision support tool (CDST) in an MTM setting in identifying DTPs has not been systematically assessed. OBJECTIVE: To assess the clinical utility of an MTM service enhanced by pharmacogenetic test results and a clinical decision support tool. METHODS: This study was a post hoc analysis of the data obtained from an open-label, randomized, observational trial. Polypharmacy patients eligible for MTM service were randomly assigned to 3 intervention arms: standard MTM (SMTM), MTM incorporating CDST (CMTM), and CMTM further enhanced by PGx test results of CYP450 and VKORC1 enzymes (PGxMTM). Allocation for this post hoc analysis was based on patient adherence to the research protocol and completion of a PGx test. The number of DTPs per patient was compared across the 3 arms using analysis of variance. In addition, the frequency of serious DTPs as a categorical variable (grade 3 or above vs. lower grade) was compared across the 3 arms between PGx driven and non-PGx driven DTP recommendations. Statistical significance was tested using the chi-square test. The level of agreement between the DTP seriousness and the acceptance made by prescribers was presented as Cohen's kappa coefficient. RESULTS: Numbers of patients after cohort reallocation based on completion of PGx testing were 104, 180, and 58 for the SMTM, CMTM, and PGxMTM arms, respectively. On average, 3.08 DTPs were identified for each patient, which was nearly identical across all 3 arms. Blinded clinical pharmacists considered seriousness (grade 3 or 4) in 31% of the PGx-related DTPs in comparison with 4.9% of the non-PGx DTPs (P < 0.001). The more serious (i.e., grade 3 or above) DTP recommendations were more likely to be accepted by prescribers with the odds ratios of 1.95 (P = 0.05) and 2.39 (P = 0.15), when the analysis was performed for all DTPs and DTPs from the PGxMTM arm only, respectively. CONCLUSIONS: MTM enhanced by PGx testing and the clinical decision support tool did not increase the number of DTPs identified. However, PGx testing and the decision support software helps pharmacists determine more serious DTPs, and resulting subsequent recommendations were more readily accepted by a prescriber. Future study of the patient safety outcomes and overall health care costs associated with the utility of the decision support is warranted. DISCLOSURES: No funding was received for conducting the post hoc analysis presented in this study. Magness is employed by Magellan Health, which received funding from Genelex for costs to administrate the medication management program. The open-label randomized trial was sponsored by Genelex (Clinicaltrials.gov ID number NCT02428660). PGx tests were provided and laboratory analysis was performed by Genelex. Valerie Baron is an employee of YouScript, which created the clinical decision support tool used in this study and formerly was part of Genelex. The other authors have nothing to disclose.

The potential impact of monitoring disease activity biomarkers on rheumatoid arthritis outcomes and costs.

Rheumatoid arthritis (RA) management requires monitoring of disease activity to determine course of treatment. Global assessments are used in clinical practice to determine RA disease activity. Monitoring disease activity via biomarkers may also help providers optimize biologic and nonbiologic drug use while decreasing overall drug spend by delaying use of expensive biologic therapies. By testing multiple biologic domains at the same time, a multibiomarker disease activity test may have utility in RA patient management, through improved intra- and inter-rater reliability. This report provides a comprehensive review of studies of objective measures, single biomarkers and multibiomarker disease activity tests as disease activity measures to decrease uncertainty in treatment decisions, and of biomarkers' potential impact on economic and clinical outcomes of treatment choices.

Impact of a genetic counseling requirement prior to genetic testing.

BACKGROUND: Genetic counseling by a Genetic Counselor (GC) is a requirement prior to genetic testing for cancer susceptibility genes (GC-mandate policy) for some insurers. This study evaluated the impact of this policy from the patient perspective. METHODS: Surveys were sent to individuals for whom their insurer ordered genetic testing for the cancer susceptibility genes BCRA1 and BRCA2 over a 1 year time period that spanned the introduction of a GC-mandate policy. Responses were assessed by time period (before/after policy introduction) and genetic test completion. RESULTS: The surveys were completed by 1247/4950 (25.7%) eligible individuals. After policy introduction, there was no change in the proportion of respondents who completed genetic testing (p = 0.13) or had a mutation (p = 0.55). Overall decisional conflict (uncertainty or feeling uninformed) around genetic testing did not change after policy introduction (p = 0.16), but was significantly higher among respondents who did not complete genetic testing (p < 0.01). Although a larger proportion of respondents saw a GC after policy introduction (p < 0.01), fewer did so to better understand their test results (p < 0.01). The proportion of respondents who did not see a GC due to insurance issues/requirements and time restraints was higher among those tested after policy introduction or who did not complete genetic testing (p < 0.01). In multivariate analysis, respondents with a household income of $25,000 or greater were 3-times more likely to complete testing. CONCLUSIONS: A GC-mandate policy did not improve decisional conflict or increase the number of deleterious mutations identified and low-income respondents were less likely to complete testing. On the contrary, insurance requirements and time constraints may be preventing individuals at risk from receiving appropriate testing.

Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation.

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term 'patient-centered outcomes research' (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR.

Identification of Patients with Statin Intolerance in a Managed Care Plan: A Comparison of 2 Claims-Based Algorithms.

BACKGROUND: While statins are safe and efficacious, some patients may experience statin intolerance or treatment-limiting adverse events. Identifying patients with statin intolerance may allow optimal management of cardiovascular event risk through other strategies. Recently, an administrative claims data (ACD) algorithm was developed to identify patients with statin intolerance and validated against electronic medical records. However, how this algorithm compared with perceptions of statin intolerance by integrated delivery networks remains largely unknown. OBJECTIVE: To determine the concurrent validity of an algorithm developed by a regional integrated delivery network multidisciplinary panel (MP) and a published ACD algorithm in identifying patients with statin intolerance. METHODS: The MP consisted of 3 physicians and 2 pharmacists with expertise in cardiology, internal medicine, and formulary management. The MP algorithm used pharmacy and medical claims to identify patients with statin intolerance, classifying them as having statin intolerance if they met any of the following criteria: (a) medical claim for rhabdomyolysis, (b) medical claim for muscle weakness, (c) an outpatient medical claim for creatinine kinase assay, (d) fills for ≥ 2 different statins excluding dose increases, (e) decrease in statin dose, or (f) discontinuation of a statin with a subsequent fill for a nonstatin lipid-lowering therapy. The validated ACD algorithm identified statin intolerance as absolute intolerance with rhabdomyolysis; absolute intolerance without rhabdomyolysis (i.e., other adverse events); or as dose titration intolerance. Adult patients (aged ≥ 18 years) from the integrated delivery network with at least 1 prescription fill for a statin between January 1, 2011, and December 31, 2012 (first fill defined the index date) were identified. Patients with ≥ 1 year pre- and ≥ 2 years post-index continuous enrollment and no statin prescription fills in the pre-index period were included. The MP and ACD algorithms were applied to the population, and concordance was examined using individual (i.e., sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) and overall performance measures (i.e., accuracy, Cohen's kappa coefficient, balanced accuracy, F-1 score, and phi coefficient). RESULTS: After applying the inclusion criteria, 7,490 patients were evaluated for statin intolerance. The mean (SD) age of the population was 51.1 (8.5) years, and 55.7% were male. The MP and ACD algorithms classified 11.3% and 5.4% of patients as having statin intolerance, respectively. The concordance of the MP algorithm was mixed, with negative classification of statin intolerance measures having high concordance (specificity 0.91, NPV 0.97) and positive classification of statin intolerance measures having poor concordance (sensitivity 0.45, PPV 0.21). Overall performance measures showed mixed agreement between the algorithms. CONCLUSIONS: Both algorithms used a mix of pharmacy and medical claims and may be useful for organizations interested in identifying patients with statin intolerance. By identifying patients with statin intolerance, organizations may consider a variety of options, including using nonstatin lipid-lowering therapies, to manage cardiovascular event risk in these patients. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals and Sanofi US. Boklage is employed by, and owns stock in, Regeneron, and Charland is employed by Sanofi. Bellows has received fees from Avenir for advisory board membership and grants from Myriad Genetics, Biogen, Janssen, and National Institutes of Health. Brixner reports advisory board and consultancy fees and grants from Sanofi. Mitchell reports consultancy fees from Sanofi. Study concept and design were contributed by Bellows, Boklage, Charland, and Brixner. Bellows, Sainski-Nguyen, and Olsen took the lead in data collection, along with Mitchell. Data interpretation was performed by Mitchell, along with the other authors. The manuscript was written by Bellows, Sainski-Nguyen, and Olsen and revised by all the authors.

BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.

BACKGROUND: Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer. METHODS: This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively. RESULTS: Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001). CONCLUSIONS: BRCAwt patients had similar outcomes to BRCAm patients, potentially owing to similar age at diagnosis, representing a BRCA testing channeling bias. Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested. BRCA tested patients had a lower risk of death.

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. MATERIALS AND METHODS: Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. CONCLUSION: The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. IMPLICATIONS FOR PRACTICE: Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests.

Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer.

CONTEXT: Determining human epidermal growth factor receptor 2 (HER2) status is critical for the management of early-stage breast cancer (ESBC). An understanding of HER2 testing practices can provide insight into how test results influence the use of HER2-directed therapy. OBJECTIVE: To assess HER2 testing, HER2+ disease, and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and after the 2007 American Society of Clinical Oncology and College of American Pathologist (ASCO/CAP) guidelines on HER2 testing were published. METHODS: Patients were identified from an institutional tumor registry. HER2 testing patterns and results were examined using a chart review of pathology and clinical notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+ retested by fluorescence in situ hybridization [FISH]) was also evaluated. RESULTS: A total of 1,459 women were included (mean age: 57 years). The rate of HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+ (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most patients with HER2+ ESBC received HER2-targeted therapy (N=185). CONCLUSION: The HER2+ rate was 17% and within the range of the reported rates in the literature. Reflex testing identified additional HER2+ tumors by approximately 10%, and should be considered a potential quality indicator. ASCO/CAP HER2 testing guidelines in 2007 appeared to impact the interpretation and classification of HER2+ tumors.

Response monitoring, tolerability, and effectiveness of imatinib treatment for chronic myeloid leukemia in a retrospective research database.

Retrospective review of imatinib monitoring through electronic health records (EHR) can provide valuable insight into the current management of chronic myelogenous leukemia (CML). This study retrospectively reviewed EHRs from 2001 to 2010 of patients with chronic phase CML (CP-CML) treated with first-line imatinib. Chart evaluations included a review of cytogenetic and molecular testing, overall survival, adverse drug events (ADEs), and therapy modifications. A total of 54 patients with CP-CML were treated with first-line imatinib and had either cytogenetic or molecular testing within 18 months of imatinib initiation. Within the first 18 months of treatment, 33 of 45 patients (73%) undergoing cytogenetic testing experienced a complete cytogenetic response (median, 241 days; range, 110-542 days) and 24 of 48 patients (50%) receiving molecular testing achieved at least a major molecular response (median, 253 days; range, 99-546 days). The average number of cytogenetic and molecular tests conducted within the first 18 months was 2.5 and 3.8, respectively. Nineteen of 54 (35%) had a dose increase of imatinib (>400 mg; median, 329 days; range, 21-1968 days). The 5-year estimated overall survival rate was 88.5%. Between 2006 and 2010 (n=30; 56%), 7 patients (23%) transitioned to dasatinib or nilotinib (median, 399 days from diagnosis; range, 180-1046 days) because of suboptimal response or treatment failure (n=5) and imatinib ADEs (n=2). Forty-six imatinib-associated ADEs occurred in 31 patients (57%), of which 10 (32%) received dose reductions (median, 52 days) and 6 (19%) had discontinuations (median, 139 days). Closely monitored patients with CML treated with imatinib at an NCCN Member Institution experienced outcomes comparable to those reported in key clinical trials.