Real-world treatment patterns and adverse events in metastatic renal cell carcinoma from a large US claims database.

BACKGROUND: Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC. METHODS: US administrative claims data (Truven Health MarketScan Commercial Databases) were used to assess trends in 1 L treatment initiation in mRCC (2006-2015) and characterize patterns of individual 1 L treatments, baseline characteristics, comorbidities and treatment-related AEs from 2011 through 2015. Outcomes were evaluated by drug class and route of administration. RESULTS: Ten-year trend analysis (n = 4270) showed that TK/VEGF-directed therapy rapidly became more common than mTOR-directed therapy, and oral treatments were favored over intravenous (IV) treatments. Overall, 1992 eligible patients initiated 1 L treatment for mRCC from 2011 through 2015: 1752 (88%) received TK/VEGF-directed agents and 233 (12%) received mTOR-directed agents; 1674 (84%) received oral treatments, and 318 (16%) received IV treatments. The most common 1 L treatment was sunitinib (n = 849), followed by pazopanib (n = 631), temsirolimus (n = 157) and bevacizumab (n = 154). Patient characteristics and comorbidities, including age, diabetes and congestive heart failure, were independent predictors of 1 L mRCC treatment choice. The three most common potentially 1 L treatment-related AEs were nausea/vomiting (128.2 per 100 patient-years [PY]), hypertension (69 per 100 PY) and renal insufficiency (44.6 per 100 PY). A wide variety of agents were used as second-line (2 L) therapy. Substantial latency of onset was observed for several potentially treatment-related toxicities in patients treated with TK/VEGF- or mTOR-directed agents. CONCLUSIONS: In the US, 1 L TK/VEGF inhibitor uptake in recent years appears largely in line with national approvals and guidelines, with varied 2 L agent use. Although retrospective evaluation of claims data cannot assess underlying causality, insights from these real-world RCC treatment and AE patterns will be useful in informing medical and payer decisions.

Vismodegib Use in Clinical Practice: Analysis of a United States Medical Claims Database.

BACKGROUND: Information is limited on the use of vismodegib for treatment of advanced basal cell carcinoma beyond the setting of clinical trials. OBJECTIVE: To investigate the treatment patterns and characteristics of patients treated with vismodegib in clinical practice. METHODS: A longitudinal, retrospective cohort study was undertaken using data from a US commercial insurance claims (Truven Health Analytics MarketScan) database. Eligible patients were ≥18 years of age, with ≥1 claim for vismodegib from January 2012 to December 2015. RESULTS: A total of 321 patients were included in the analysis. Approximately 20% of the patients took 1 or more treatment breaks of ≥ 30 days each before treatment discontinuation. Median duration of vismodegib treatment before the first treatment break and discontinuation was 4.0 and 5.5 months, respectively. Older age ( > 65 years) and absence of Gorlin syndrome were associated with increased risk for treatment interruption or discontinuation. Overall, 47% and 36% of patients underwent surgery or radiotherapy within the 6 months before and after vismodegib initiation, respectively. CONCLUSIONS: Real-world evidence indicates that vismodegib is being used in clinical practice as part of combination treatment strategies. J Drugs Dermatol. 2018;17(2):143-148.

Development of a conceptual model of health-related quality of life among hepatitis C patients: A systematic review of qualitative studies.

AIM: The Food and Drug Administration guidelines emphasize that patient-reported outcome (PRO) instruments used in clinical trials must be developed based on a conceptual model, yet existing PRO instruments currently used in clinical trials of hepatitis C virus (HCV) patients are not based on a predetermined model. The purpose of this study was to identify a comprehensive list of health-related quality of life (HRQoL) themes that may be unique to HCV by reviewing qualitative research articles of HCV patients. The information collected from the review was used to develop a preliminary model of HRQoL in HCV patients. METHODS: Ovid Medline, Ovid Embase, Ovid PsycINFO and PubMed were searched for peer-reviewed journals from 1989 to 2012. Set inclusion/exclusion criteria were utilized with a focus on HRQoL among HCV patients. Eligible articles that met quality assessment criteria were analyzed using meta-synthesis to generate categories and themes to propose a conceptual model. RESULTS: Ten articles that met the inclusion/exclusion criteria and the quality assessment criteria were reviewed. Eleven themes were identified: physical symptoms, physical activities, guilt, stigma, emotional distress, psychological behavior, social relationship, social activities, work function, sexual function and cognitive function. These were further grouped into six HRQoL domains: physical, psychological/emotional, social, work, sexual and cognitive functionality. CONCLUSION: The systematic review and the proposed model represent a useful starting point in the critical appraisal of the conceptual underpinnings of PRO instruments used in HCV patients.

Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use.

BACKGROUND: Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors. METHODS: A retrospective cohort design and US private health care claims data were used. Study subjects received chemotherapy regimens classified as "low" or "intermediate," or unclassified, in terms of FN risk, and were stratified by cancer and regimen. For each subject, the first chemotherapy course, and each cycle and FN episode within the course, were identified. FN incidence proportions were estimated by the presence and number of risk factors and chronic comorbidities. RESULTS: Across the 17 tumor/regimen combinations considered (n=160,304 in total), 74% to 98% of patients had 1 or more risk factor for FN and 41% to 89% had 2 or more. Among patients with 1 or more risk factor, FN incidence ranged from 7.2% to 29.0% across regimens, and the relative risk of FN (vs those without risk factors) ranged from 1.1 (95% CI, 0.8-1.3) to 2.2 (95% CI, 1.5-3.0). FN incidence increased in a graded and monotonic fashion with the number of risk factors and comorbidities. CONCLUSIONS: In this retrospective evaluation of patients with cancer receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, most patients had 1 or more FN risk factor and many had 2 or more. FN incidence was found to be elevated in these patients, especially those with multiple risk factors.

Impact of computerized provider order entry on pharmacist productivity.

PURPOSE: To examine the impact of computerized provider order entry (CPOE) implementation on average time spent on medication order entry and the number of order actions processed. METHODS: An observational time and motion study was conducted from March 1 to March 17, 2011. Two similar community hospital pharmacies were compared: one without CPOE implementation and the other with CPOE implementation. Pharmacists in the central pharmacy department of both hospitals were observed in blocks of 1 hour, with 24 hours of observation in each facility. Time spent by pharmacists on distributive, administrative, clinical, and miscellaneous activities associated with order entry were recorded using time and motion instrument documentation. Information on medication order actions and order entry/verifications was obtained using the pharmacy network system. RESULTS: The mean ± SD time spent by pharmacists per hour in the CPOE pharmacy was significantly less than the non-CPOE pharmacy for distributive activities (43.37 ± 7.75 vs 48.07 ± 8.61) and significantly greater than the non-CPOE pharmacy for administrative (8.58 ± 5.59 vs 5.72 ± 6.99) and clinical (7.38 ± 4.27 vs 4.22 ± 3.26) activities. The CPOE pharmacy was associated with a significantly higher number of order actions per hour (191.00 ± 82.52 vs 111.63 ± 25.66) and significantly less time spent (in minutes per hour) on order entry and order verification combined (28.30 ± 9.25 vs 36.56 ± 9.14) than the non-CPOE pharmacy. CONCLUSION: The implementation of CPOE facilitated pharmacists to allocate more time to clinical and administrative functions and increased the number of order actions processed per hour, thus enhancing workflow efficiency and productivity of the pharmacy department.

Use of and attitude toward complementary and alternative medicine: understanding the role of generational influence.

CONTEXT: The prevalence of the use of complementary and alternative medicine (CAM) is increasing in developed countries, including the United States. Some patients use CAM without informing their physicians, subjecting themselves to potentially dangerous contraindications. Identifying patient populations that have an inclination to use CAM can help physicians provide patient-centered care, ensuring better health outcomes. OBJECTIVE: This study aimed to explore the role of generational influences on the use of and attitudes toward CAM. DESIGN: The research team designed a cross-sectional survey that classified participants into four generational influence categories: (1) category 1-students who recently had left another country to reside in the United States without their parents, (2) category 2-students who had left another country to reside in the United States with their parents, (3) category 3-students born in the United States whose parents were born or immigrated to the United States but whose grandparents were not born in the United States, and (4) category 4-students born in the United States whose parents and grandparents were born in the United States. SETTING: The study took place at the University of Houston in Houston, Texas PARTICIPANTS: Participants were 400 students from the university. OUTCOME MEASURES: Variance was measured using a 6-item, 5-point Likert scale, analyzing differences in attitudes toward CAM. Multiple logistic and linear regressions analyses assessed the influence of generation on use of and attitudes toward CAM, respectively. RESULTS: Participants in category 1 reported the highest CAM use (43.6%) and had the most positive attitude toward CAM, which significantly differed from the other categories. After controlling for covariates, generational influence as categorized was a significant (P < .05) predictor of attitude toward CAM, which in turn was a significant (P < .0001) predictor of CAM use. CONCLUSIONS: Attitudes toward CAM vary significantly by generational influence. Recent immigrants gradually assimilate and change their cultural beliefs about CAM use, and they had the highest use of and the most positive attitude toward CAM. Physicians may want to consider integrating CAM treatments for patients who have recently immigrated to the United States to enhance treatment compliance.

Real-World Progression-Free Survival as an Endpoint in Lung Cancer: Replicating Atezolizumab and Docetaxel Arms of the OAK Trial Using Real-World Data.

Evaluating cancer treatments in real-world data (RWD) requires informative endpoints. This study replicated the atezolizumab and docetaxel arms of the OAK trial using RWD and compared progression-free survival (PFS) outcomes derived from abstracted physician's notes in RWD (rwPFS) against PFS outcomes derived from the clinical trial PFS (ctPFS). Atezolizumab and docetaxel arms of the phase III OAK randomized controlled trial (RCT; NCT02008227) were replicated in a US nationwide real-world database using selected OAK inclusion/exclusion criteria and propensity score-based adjustment for baseline prognostic variables. Concordance of outcomes was assessed using Kaplan-Meier medians and hazard ratios (HRs). The RWD cohorts comprised 133 patients on atezolizumab and 479 patients on docetaxel. After adjustment, prognostic variables were balanced between RCT arms and corresponding RWD cohorts. The rwPFS and ctPFS outcomes showed better concordance for docetaxel (2.99 vs. 3.52 months; HR: 0.99, 95% confidence interval (CI): 0.85-1.15) than for atezolizumab (3.71 vs. 2.76 months; HR: 0.8, 95% CI: 0.61-1.02). Excluding events labeled "pseudo-progression" from both RWD and RCT improved concordance for atezolizumab (4.24 vs. 4.14 months; HR: 0.95, 95% CI: 0.70-1.25). These findings were robust across sensitivity analyses. Replicating RCTs using RWD and comparing outcomes can help characterize RWD endpoints. Similarity of results between rwPFS and ctPFS at the cohort level may depend on drug category, highlighting the need for further studies to verify and understand when the corresponding outcomes can be compared, including within the same patient.

Alpha-Fetoprotein as a Potential Surrogate Biomarker for Atezolizumab + Bevacizumab Treatment of Hepatocellular Carcinoma.

PURPOSE: Atezolizumab + bevacizumab is the new standard of care for systemic treatment-naïve, unresectable hepatocellular carcinoma (HCC). This exploratory study investigated on-treatment alpha-fetoprotein (AFP) response as a potential surrogate biomarker of prognosis for the combination therapy. EXPERIMENTAL DESIGN: Data from Group A of the phase Ib GO30140 study were used to identify the optimal time for AFP measurement and AFP cutoffs to differentiate patients by their best confirmed response per independent review facility-assessed RECIST (IRF-RECIST) version 1.1: responders from nonresponders and patients with disease control from primary progressors. We applied these cutoffs to independent data from the atezolizumab + bevacizumab arm of the phase III IMbrave150 trial to distinguish patients based on (i) overall survival (OS) and progression-free survival (PFS) per IRF-RECIST 1.1 and (ii) best confirmed response per IRF-RECIST 1.1. RESULTS: We derived AFP cutoffs of ≥75% decrease and ≤10% increase from baseline at 6 weeks to identify responders and those who had disease control, respectively. These cutoffs had high sensitivity and specificity in GO30140. In IMbrave150 patients, sensitivity was 0.59 and specificity was 0.86 for the ≥75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the ≤10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR < 0.5; P < 0.01). CONCLUSIONS: AFP response at 6 weeks after initiating treatment is a potential surrogate biomarker of prognosis for patients with HCC receiving atezolizumab + bevacizumab. See related commentary by Cappuyns and Llovet, p. 3405.

Natural History of Human Epidermal Growth Factor Receptor 2-Amplified and Human Epidermal Growth Factor Receptor 2 Wild-Type Refractory Metastatic Colorectal Cancer in US Clinical Practice.

PURPOSE: The molecular heterogeneity of metastatic colorectal cancer (mCRC) presents a therapeutic challenge, with few trials focused on patients with human epidermal growth factor receptor 2 amplification (HER2-Amp). Our limited understanding of real-world patterns and outcomes by HER2 status of treatment-refractory patients leaves treatment decisions with little contextual information. We conducted a retrospective cohort study to describe the natural disease history of patients with refractory mCRC using an electronic health record-derived database with oncogenomic information. METHODS: We included patients with stage IV or recurrent mCRC diagnosed from January 2011 through December 2019 from a deidentified clinicogenomic database. Patients with ≥ 2 documented clinic visits, ≥ 2 lines of therapy (LOT) after mCRC diagnosis, and comprehensive genomic profiling were eligible. Patient records defined by treatment-refractory LOT were allocated to the HER2-Amp or HER2 wild-type (WT) cohort on the basis of comprehensive genomic profiling. Index date was defined as the start of any treatment-refractory LOT (≥ 2 LOT; patients could contribute multiple records). Descriptive statistics included demographic and clinical characteristics, treatments, laboratory values, and biomarkers. Overall survival (OS) was calculated as time (in months) from the index date until death from any cause and analyzed using Kaplan-Meier methodology. Sensitivity analyses were conducted to test the robustness of the primary findings. RESULTS: A total of 576 patients were included (1,339 records); 63 (158 records) were HER2-Amp, and 513 (1,181 records) were HER2-WT. Demographics, clinical characteristics, biomarkers, and laboratory values were comparable between HER2 cohorts. OS was similar, with an unadjusted median OS of 11.2 months (95% CI, 8.6 to 15.1) and 9.9 months (95% CI, 8.3 to 10.9) across LOT for HER2-Amp and HER2-WT cohorts, respectively. CONCLUSION: This study showed considerable treatment heterogeneity and poor outcomes among patients with treatment-refractory mCRC, emphasizing a substantial unmet therapeutic need.

Hybrid-control arm construction using historical trial data for an early-phase, randomized controlled trial in metastatic colorectal cancer.

Background: Treatment for metastatic colorectal cancer patients beyond the second line remains challenging, highlighting the need for early phase trials of combination therapies for patients who had disease progression during or following two prior lines of therapy. Leveraging hybrid control design in these trials may preserve the benefits of randomization while strengthening evidence by integrating historical trial data. Few examples have been established to assess the applicability of such design in supporting early phase metastatic colorectal cancer trials. Methods: MORPHEUS-CRC is an umbrella, multicenter, open-label, phase Ib/II, randomized, controlled trial (NCT03555149), with active experimental arms ongoing. Patients enrolled were assigned to a control arm (regorafenib, 15 patients randomized and 13 analysed) or multiple experimental arms for immunotherapy-based treatment combinations. One experimental arm (atezolizumab + isatuximab, 15 patients randomized and analysed) was completed and included in the hybrid-control study, where the hybrid-control arm was constructed by integrating data from the IMblaze370 phase 3 trial (NCT02788279). To estimate treatment efficacy, Cox and logistic regression models were used in a frequentist framework with standardized mortality ratio weighting or in a Bayesian framework with commensurate priors. The primary endpoint is objective response rate, while disease control rate, progression-free survival, and overall survival were the outcomes assessed in the hybrid-control study. Results: The experimental arm showed no efficacy signal, yet a well-tolerated safety profile in the MORPHEUS-CRC trial. Treatment effects estimated in hybrid control design were comparable to those in the MORPHEUS-CRC trial using either frequentist or Bayesian models. Conclusions: Hybrid control provides comparable treatment-effect estimates with generally improved precision, and thus can be of value to inform early-phase clinical development in metastatic colorectal cancer.

"Real-world" outcomes and prognostic indicators among patients with high-risk muscle-invasive urothelial carcinoma.

INTRODUCTION: There is no current standard of care for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after neoadjuvant chemotherapy and surgical resection or for those who cannot receive or decline cisplatin-based perioperative chemotherapy. Understanding current, real-world treatment patterns may help inform decisions from clinical, research, and population health management perspectives. We examined real-world treatment patterns, survival outcomes, and prognostic factors among Medicare beneficiaries with high-risk MIUC who did not receive adjuvant treatment after surgical resection. METHODS: We identified patients with high-risk MIUC in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who underwent surgical resection (radical cystectomy and/or radical nephroureterectomy). Eligible patients had indicators of high-risk MIUC and surgical resection between 2001 and 2013. Demographic and clinical characteristics, including comorbidities, American Joint Commission on Cancer (AJCC) stage, tumor stage/grade and nodal status, and distribution of neoadjuvant treatment by the year of surgical resection were evaluated. Overall survival (OS) and disease-free survival (DFS) were assessed for the full cohort and by subgroups using Kaplan-Meier survival analysis. Adjusted Cox proportional hazards models were used to evaluate patient demographics and clinical characteristics associated with OS and DFS. RESULTS: A total of 665 patients were included in the analysis, with a mean age of 75.5 years; most were men (61%) and had AJCC stage IIIA disease (69%). Neoadjuvant treatment increased over the entire study period, both overall (from 12% to 46%) and cisplatin based (from 5% to 38%). Median OS for the entire cohort was 23.1 months (95% confidence interval: 18, 27); median DFS was 13.5 months (95% confidence interval: 11.3, 16.8). AJCC stage IIIB/IVA was the most significant predictor of poor prognosis for both OS and DFS, followed by non-white race and comorbidity burden. CONCLUSION: The prognosis for high-risk patients with MIUC remains poor, with significant risk of mortality within 2 years of radical cystectomy despite increasing use of neoadjuvant treatment. Unmet treatment needs persist for this difficult-to-treat patient population despite the increasing use of cisplatin-based neoadjuvant chemotherapy.

Building External Control Arms From Patient-Level Electronic Health Record Data to Replicate the Randomized IMblaze370 Control Arm in Metastatic Colorectal Cancer.

PURPOSE: External control (EC) arms derived from electronic health records (EHRs) can provide appropriate comparison groups when randomized control arms are not feasible, but have not been explored for metastatic colorectal cancer (mCRC) trials. We constructed EC arms from two patient-level EHR-derived databases and evaluated them against the control arm from a phase III, randomized controlled mCRC trial. METHODS: IMblaze370 evaluated atezolizumab with or without cobimetinib versus regorafenib in patients with mCRC. EC arms were constructed from the Flatiron Health (FH) EHR-derived de-identified database and the combined FH/Foundation Medicine Clinico-Genomic Database (CGDB). IMblaze370 eligibility criteria were applied to the EC cohorts. Propensity scores and standardized mortality ratio weighting were used to balance baseline characteristics between the IMblaze370 and EC arms; balance was assessed using standardized mean differences. Kaplan-Meier method estimated median overall survival (OS). Cox proportional hazards models estimated hazard ratios with bootstrapped 95% CIs to compare differences in OS between study arms. RESULTS: The FH EC included 184 patients; the CGDB EC included 108 patients. Most characteristics were well-balanced (standardized mean difference < 0.1) between each EC arm and the IMblaze370 population. Median OS was similar between the IMblaze370 control arm (8.5 months [95% CI, 6.41 to 10.71]) and both EC arms: FH (8.5 months [6.93 to 9.92]) and CGDB (8.8 months [7.85 to 9.92]). OS comparisons between the IMblaze370 experimental arm and the FH EC (hazard ratio, 0.85 [0.64 to 1.14]) and CGDB EC (0.86 [0.65 to 1.18]) yielded similar results as the comparison with the IMblaze370 control arm (1.01 [0.75 to 1.37]). CONCLUSION: EC arms constructed from the FH database and the CGDB closely replicated the control arm from IMblaze370. EHR-derived EC arms can provide meaningful comparators in mCRC trials when recruiting a randomized control arm is not feasible.

Real-world practice patterns in veterans with metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is incurable, with most patients surviving less than 3 years. However, many treatments that extend survival have been approved in the past decade. OBJECTIVE: To describe the patient demographics, disease characteristics, treatment patterns, and outcomes in a cohort of Veterans diagnosed with mCRPC in the Veterans Health Administration. DESIGN: We identified 3,637 Veterans diagnosed with prostate cancer between January 2006 and August 2015 with evidence of mCRPC through December 2016. We described the most commonly used systemic mCRPC treatments according to mCRPC diagnosis era: Epoch 1 (2006-2010) or Epoch 2 (2011-2016). Patient demographics, disease characteristics, and treatment patterns were examined using descriptive statistics. An unadjusted Kaplan-Meier method was used to estimate the median time to biochemical progression and overall survival (OS) with 95% confidence intervals. RESULTS: The median age at initial prostate cancer diagnosis was 68 years. Approximately 67% of patients were non-Hispanic white, 29% were black, and 4% were other/unknown. A high-risk Gleason score (8-10) was reported in 748 (67%) of patients in Epoch 1 and 1578 (63%) of patients in Epoch 2, and the median prostate-specific antigen level at initial prostate cancer diagnosis was higher in Epoch 1 patients than in Epoch 2 patients (68 vs. 35 ng/ml). Following mCRPC diagnosis, the most common first-line therapies in Epoch 1 patients were docetaxel (83%) and abiraterone (9%), whereas Epoch 2 patients mainly received abiraterone (47%), docetaxel (36%), and enzalutamide (15%). In Epoch 1 and Epoch 2 patients, the median time to biochemical progression (unadjusted) was 9 and 13 months, respectively, and the median OS (unadjusted) was 15 and 23 months, respectively. CONCLUSIONS: The introduction of new therapies has resulted in increased use of the noncytotoxic agents abiraterone and enzalutamide as first-line treatment in lieu of docetaxel. Our results suggest that more recently diagnosed patients (Epoch 2) have a delayed time to biochemical progression and longer OS (unadjusted) compared with patients diagnosed earlier (Epoch 1).

Effect of warning placement on the information processing of college students reading an OTC drug facts panel.

OBJECTIVE: To compare three over-the-counter (OTC) Drug Facts panel versions for information processing optimization among college students. PARTICIPANTS: University of Houston students (N = 210) participated in a cross-sectional survey from January to May 2010. METHODS: A current FDA label was compared to two experimental labels developed using the theory of CHREST to test information processing by re-positioning the warning information within the Drug Facts panel. Congruency was defined as placing like information together. Information processing was evaluated using the OTC medication Label Evaluation Process Model (LEPM): label comprehension, ease-of-use, attitude toward the product, product evaluation, and purchase intention. RESULTS: Experimental label with chunked congruent information (uses-directions-other information-warnings) was rated significantly higher than the current FDA label and had the best average scores among the LEPM information processing variables. CONCLUSION: If replications uphold these findings, the FDA label design might be revised to improve information processing.

Assessing a conceptual model of over-the-counter medication misuse, adverse drug events and health-related quality of life in an elderly population.

AIM: The objectives of the present study were to test Spilker's quality of life model in the elderly population consuming over-the-counter (OTC) medications. It was hypothesized that OTC medication misuse increases adverse drug events (ADEs), ADEs as a result of OTC medication misuse decrease health-related quality of life (HRQoL) and the impact of OTC medication misuse on patients' HRQoL is fully medicated by ADEs associated with OTC medications. METHODS: Data were used from a previously carried out cross-sectional study using survey instruments with elderly patients consuming OTC medications in Houston, Texas, USA. The presence/absence of OTC misuse was assessed by an expert panel based on patient reported information on drug use characteristics; ADE was self-reported and HRQoL was measured using the Short Form-12v2, which contains a physical component summary score (PCS) and a mental component summary score (MCS). RESULTS: Of the 154 respondents, 18.2% misused OTC medications and 22.1% reported ADE as a result of OTC medications. The mean ± SD score of PCS and MCS was 40.6 ± 6.8 and 46.4 ± 7, respectively. The hypothesized framework provided a well-fitted solution to the data (χ(2) = 1.387, d.f. = 2, P = 0.49; weighted root mean square residual = 0.317). Misuse of OTC medications significantly increased ADEs associated with OTC medications (ß = 0.298) and increased ADEs significantly decreased patient reported PCS (ß = -0.312), but not MCS (ß = -0.213). OTC medication misuse indirectly decreased PCS and MCS by mediating the effect of an increase in ADE; however, the association was not statistically significant. CONCLUSIONS: Misuse of OTC medications is highly associated with ADEs. ADEs are capable of decreasing the physical health of elderly patients.

Risk of Nondherence to Diabetes Medications Among Medicare Advantage Enrollees: Development of a Validated Risk Prediction Tool.

BACKGROUND: Low adherence to oral antidiabetic drugs (OADs) in the Medicare population can greatly reduce Centers for Medicare & Medicaid Services (CMS) star ratings for managed care organizations (MCOs). OBJECTIVE: To develop and validate a risk assessment tool (Prescription Medication Adherence Prediction Tool for Diabetes Medications [RxAPT-D]) to predict nonadherence to OADs using Medicare claims data. METHODS: In this retrospective observational study, claims data for members enrolled in a Medicare Advantage Prescription Drug (MA-PD) program in Houston, Texas, were used. Data from 2012 (baseline period) were used to identify key variables to predict adherence in 2013 (follow-up period). Members aged 65 years and older with a diabetes diagnosis, at least 1 prescription for OADs (biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or meglitinides), and continuously enrolled for both years were included in the study. Patients with insulin prescriptions were excluded from the cohort. The study outcome, nonadherence in 2013, was defined as proportion of days covered (PDC) < 80%. Multivariable logistic models using 200 bootstrap replications (with replacement) identified factors associated with nonadherence. The final model was tested for discrimination and calibration statistics and internally validated using 10-fold cross-validation. Using weighted beta coefficients of the predictors, the RxAPT-D was created to stratify nonadherence risk and was tested for sensitivity, specificity, positive prediction value, and negative prediction value. The predictive ability of the tool was compared with that of past PDC values using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. RESULTS: Data from 7,028 MA-PD members were used for tool development. Seven predictors (age, total OAD refills, total OAD classes filled, days supply of last filled OAD, pill burden, coverage of last filled OAD, and past adherence) statistically significant in ≥ 50% of the bootstrapped samples were identified from the logistic models. The final model demonstrated good discrimination (c-statistics = 0.75) and calibration (Hosmer-Lemeshow goodness-of-fit P < 0.05) statistics, with good internal validity (area under the curve = 0.73). The RxAPT-D demonstrated adequate sensitivity statistics: sensitivity = 0.73, specificity = 0.63, positive prediction value = 0.74, and negative prediction value = 0.62. Compared with use of past adherence measures, the RxAPT-D had higher prediction ability, relative IDI = 2.09, and user defined NRI = 0.16 with 24% events correctly reclassified. CONCLUSIONS: The RxAPT is an effective tool to identify patients who are likely to become nonadherent to OADs in the follow-up year. Pharmacists in MCOs can use this tool to identify patients expected to be nonadherent to OADs and develop targeted intervention programs to assist in improving MCO CMS star ratings. DISCLOSURES: This study received unrestricted partial funding from the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation Adherence Research Starter Award. Serna is employed by Cigna-HealthSpring. Mhatre is now employed with Genentech. The authors report no other potential conflicts of interest. The material in this study is based on work supported (or supported in part) by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. The abstract for this article was presented at the Academy of Managed Care Pharmacy's 28th Annual Meeting & Expo, April 2016, San Francisco, California, with the title "Development and Validation of a Tool to Predict Nonadherence to Oral Antidiabetic Drugs in Medicare Beneficiaries." Study concept and design were primarily contributed by Sujit Sansgiry and Mhatre, with assistance from the other authors. Mhatre, Serna, and Sujit Sansgiry took the lead in data collection, assisted by the other authors, and data interpretation was performed by Mhatre, Shubhada Sansgiry, and Essien, assisted by the other authors. The manuscript was written by Mhatre and Fleming, assisted by the other authors, and revised primarily by Mhatre, along with Sujit Sansgiry and assisted by the other authors.

Impact of over-the-counter medication use on patients' health-related quality of life: development and psychometric validation of Over-the-Counter Medication Impact Scale.

BACKGROUND AND OBJECTIVE: Over-the-counter (OTC) medication use can impact an individual's health-related quality of life (HRQoL); however, there is no instrument specifically developed to measure the impact of OTC medication use on patients' HRQoL. The aim of the study was to develop an OTC Medication Impact Scale (OTC-MIS), a generic patient-reported outcome measure to assess the impact of OTC medication use on patients' HRQoL. METHODS: Items were generated based on the principles of the HRQoL theory, and were comparable to the domains of the Short-Form version 12 scale (SF-12). The OTC-MIS was tested for construct and criterion validity, internal consistency reliability, and floor and ceiling effects. The psychometric properties of the scale were evaluated in a general elderly population (n = 153), as well as in a disease-specific HIV population (n = 215), to assess generalizability of the scale in different populations. RESULTS: All the items had response rates >95 %; there were no floor or ceiling effects in the scale. Reliability in terms of Cronbach's alpha was >0.9, and exploratory factor analysis indicated unidimensionality of the scale. The instrument showed known-group validity (p < 0.01) among patients with and without OTC medication-associated adverse events, and adequate criterion validity when compared with the SF-12v2 scale (p < 0.05). CONCLUSION: The OTC-MIS is a validated and reliable measure to assess the impact of OTC medication use on patient HRQoL and may prove beneficial in evaluating the role OTC medications play in healthcare processes.