Identification and mapping of worldwide sources of generic real-world data.

PURPOSE: The demand for real-world data as supportive evidence to traditional clinical studies has increased in the past few years. The present study aimed to identify worldwide generic sources of real-world data and to assess completeness and suitability of selected real-world evidence (RWE) data sources to conduct prespecified research. METHODS: A systematic literature review was conducted to identify generic (non-disease specific) sources of real-world data in Medline and Embase from January 1, 2010 to September 8, 2015. Data sources used in observational studies were identified and summarized based on their geographical distribution and the type of data. In the next step, the selected data sources were critically evaluated for their completeness. RESULTS: A total of 10,069 identified publications were screened, leading to 2635 unique data sources across 102 countries. Europe had the maximum number of data sources (n = 1163) followed by United States (n = 578), and Asia, Middle East, and African Countries (n = 374). The most common type of identified data sources across all countries was structured data sources, ie, administrative databases and registries. Of the identified data sources, 300 were selected for further investigation. From the selected databases, ~50% had confirmed information on over 60% of the investigated variables, ~61% were suitable for epidemiological research, and 60% had possibility of linkage. CONCLUSIONS: The present study applied a systematic literature review approach and identified available generic sources of real-world data worldwide, in addition to the United States and Europe, which are suitable for conducting pre-defined researches and support future RWE studies.

Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma.

PURPOSE: To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study. DESIGN: Database study. PARTICIPANTS: In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence. METHODS: Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed. MAIN OUTCOME MEASURES: Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG. RESULTS: The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3 × 10-5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64-0.76; P = 1.0 × 10-15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57-0.77; P = 1.2 × 10-7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18-1.35; P = 1.8 × 10-11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18-1.37; P = 5.9 × 10-10). CONCLUSIONS: We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.

A unified framework for classification of methods for benefit-risk assessment.

BACKGROUND: Patients, physicians, and other decision makers make implicit but inevitable trade-offs among risks and benefits of treatments. Many methods have been proposed to promote transparent and rigorous benefit-risk analysis (BRA). OBJECTIVE: To propose a framework for classifying BRA methods on the basis of key factors that matter most for patients by using a common mathematical notation and compare their results using a hypothetical example. METHODS: We classified the available BRA methods into three categories: 1) unweighted metrics, which use only probabilities of benefits and risks; 2) metrics that incorporate preference weights and that account for the impact and duration of benefits and risks; and 3) metrics that incorporate weights based on decision makers' opinions. We used two hypothetical antiplatelet drugs (a and b) to compare the BRA methods within our proposed framework. RESULTS: Unweighted metrics include the number needed to treat and the number needed to harm. Metrics that incorporate preference weights include those that use maximum acceptable risk, those that use relative-value-adjusted life-years, and those that use quality-adjusted life-years. Metrics that use decision makers' weights include the multicriteria decision analysis, the benefit-less-risk analysis, Boers' 3 by 3 table, the Gail/NCI method, and the transparent uniform risk benefit overview. Most BRA methods can be derived as a special case of a generalized formula in which some are mathematically identical. Numerical comparison of methods highlights potential differences in BRA results and their interpretation. CONCLUSIONS: The proposed framework provides a unified, patient-centered approach to BRA methods classification based on the types of weights that are used across existing methods, a key differentiating feature.

Comparison of Benefit-Risk Assessment Methods for Prospective Monitoring of Newly Marketed Drugs: A Simulation Study.

OBJECTIVES: To compare benefit-risk assessment (BRA) methods for determining whether and when sufficient evidence exists to indicate that one drug is favorable over another in prospective monitoring. METHODS: We simulated prospective monitoring of a new drug (A) versus an alternative drug (B) with respect to two beneficial and three harmful outcomes. We generated data for 1000 iterations of six scenarios and applied four BRA metrics: number needed to treat and number needed to harm (NNT|NNH), incremental net benefit (INB) with maximum acceptable risk, INB with relative-value-adjusted life-years, and INB with quality-adjusted life-years. We determined the proportion of iterations in which the 99% confidence interval for each metric included and excluded the null and we calculated mean time to alerting. RESULTS: With no true difference in any outcome between drugs A and B, the proportion of iterations including the null was lowest for INB with relative-value-adjusted life-years (64%) and highest for INB with quality-adjusted life-years (76%). When drug A was more effective and the drugs were equally safe, all metrics indicated net favorability of A in more than 70% of the iterations. When drug A was safer than drug B, NNT|NNH had the highest proportion of iterations indicating net favorability of drug A (65%). Mean time to alerting was similar among methods across the six scenarios. CONCLUSIONS: BRA metrics can be useful for identifying net favorability when applied to prospective monitoring of a new drug versus an alternative drug. INB-based approaches similarly outperform unweighted NNT|NNH approaches. Time to alerting was similar across approaches.

Prospective Benefit-Risk Monitoring of New Drugs for Rapid Assessment of Net Favorability in Electronic Health Care Data.

BACKGROUND: Benefit-risk assessment (BRA) methods can combine measures of benefits and risks into a single value. OBJECTIVES: To examine BRA metrics for prospective monitoring of new drugs in electronic health care data. METHODS: Using two electronic health care databases, we emulated prospective monitoring of three drugs (rofecoxib vs. nonselective nonsteroidal anti-inflammatory drugs, prasugrel vs. clopidogrel, and denosumab vs. bisphosphonates) using a sequential propensity score-matched cohort design. We applied four BRA metrics: number needed to treat and number needed to harm; incremental net benefit (INB) with maximum acceptable risk; INB with relative-value-adjusted life-years; and INB with quality-adjusted life-years (QALYs). We determined whether and when the bootstrapped 99% confidence interval (CI) for each metric excluded zero, indicating net favorability of one drug over the other. RESULTS: For rofecoxib, all four metrics yielded a negative value, suggesting net favorability of nonselective nonsteroidal anti-inflammatory drugs over rofecoxib, and the 99% CI for all but the number needed to treat and number needed to harm excluded the null during follow-up. For prasugrel, only the 99% CI for INB-QALY excluded the null, but trends in values over time were similar across the four metrics, suggesting overall net favorability of prasugrel versus clopidogrel. The 99% CI for INB-relative-value-adjusted life-years and INB-QALY excluded the null in the denosumab example, suggesting net favorability of denosumab over bisphosphonates. CONCLUSIONS: Prospective benefit-risk monitoring can be used to determine net favorability of a new drug in electronic health care data. In three examples, existing BRA metrics produced qualitatively similar results but differed with respect to alert generation.

A questionnaire to assess the relevance and credibility of observational studies to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report.

Evidence-based health care decisions are best informed by comparisons of all relevant interventions used to treat conditions in specific patient populations. Observational studies are being performed to help fill evidence gaps. Widespread adoption of evidence from observational studies, however, has been limited because of various factors, including the lack of consensus regarding accepted principles for their evaluation and interpretation. Two task forces were formed to develop questionnaires to assist decision makers in evaluating observational studies, with one Task Force addressing retrospective research and the other Task Force addressing prospective research. The intent was to promote a structured approach to reduce the potential for subjective interpretation of evidence and drive consistency in decision making. Separately developed questionnaires were combined into a single questionnaire consisting of 33 items. These were divided into two domains: relevance and credibility. Relevance addresses the extent to which findings, if accurate, apply to the setting of interest to the decision maker. Credibility addresses the extent to which the study findings accurately answer the study question. The questionnaire provides a guide for assessing the degree of confidence that should be placed from observational studies and promotes awareness of the subtleties involved in evaluating those.

Economic burden associated with extrapyramidal symptoms in a medicaid population with schizophrenia.

No studies have assessed the economic impact of extrapyramidal symptoms due to atypical antipsychotics in schizophrenia. To assess healthcare resource use and medical costs associated with extrapyramidal symptoms in patients with schizophrenia. A retrospective analysis of Marketscan(®) Medicaid Multi-State Database (2004-2009) was conducted. Patients with schizophrenia and newly initiated on an AAP were included. Patients with and without extrapyramidal symptoms were matched using propensity-score matching. Healthcare utilization and costs were assessed in the 12-month follow-up period using logistic and two-part (gamma) regression models. Of 4,621 patients, 583 (12.6 %) had extrapyramidal symptoms. Patients with extrapyramidal symptoms had significantly more schizophrenia-related and all-cause hospitalizations and schizophrenia-related emergency room visits, as well as significantly higher schizophrenia-specific and all-cause total healthcare, inpatient, and prescription drug costs compared to patients without extrapyramidal symptoms. Extrapyramidal symptoms in patients with schizophrenia is associated with increased healthcare resource utilization and higher medical costs.

Treatment dynamics of newly marketed drugs and implications for comparative effectiveness research.

OBJECTIVES: Clinicians and payers require rapid comparative effectiveness (CE) evidence generation to inform decisions for new drugs. We empirically assessed treatment dynamics of newly marked drugs and their implications for conducting CE research. METHODS: We used claims data to evaluate five drug-outcome pairs: 1) raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin + ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs. nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We examined utilization dynamics in the early marketing period, including evolving utilization patterns, outcome risk among those treated with new versus established drugs, and prior treatment patterns that may indicate treatment resistance or intolerance. We addressed these challenges by replicating active CE monitoring with sequential matched cohort analysis. RESULTS: Patients initiating new drugs were more likely to have used other drugs for the same indication in the past, but the majority of patients in all new drug cohorts were treatment naive (82.0% overall). Patients initiating rofecoxib had higher predicted baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs. Patients initiating risedronate and alendronate had similar predicted baseline risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe had lower risks of outcomes of interest relative to their comparators. Prospective monitoring yielded results consistent with expectation for each example. CONCLUSIONS: Many challenges to assessing the CE of new drugs are borne out in empirical data. Attention to these challenges can yield valid CE results.

Patient adherence to transdermal rivastigmine after switching from oral donepezil: a retrospective claims database study.

OBJECTIVE: To examine patient adherence before and after switching from donepezil to the rivastigmine patch. METHODS: This retrospective cohort study used the MarketScan Commercial and Medicare data sets (2004 to 2009). Patients with a diagnosis of Alzheimer disease who were new donepezil users and were subsequently switched to the rivastigmine patch were included. The proportion of days covered (PDC) and PDC difference between donepezil and the rivastigmine patch were calculated from the time of initiation to the switch, capped at 1 year after the first respective claim. PDC was calculated as the number of days with drugs available divided by the number of days in the respective follow-up periods. RESULTS: The sample included 772 patients (mean age 77 y; 58% female). The mean time between switching from donepezil to the rivastigmine patch was 579 (SD=317.3) days. The mean PDC for the rivastigmine patch was highest among patients who switched within 3 months (80.4% vs. 90.7%; P=0.04) and within 7 to 9 months (61.3% vs. 71.0%; P=0.05) of initiating donepezil. When adherence was analyzed in increments of 1 year, patients who switched to the rivastigmine patch within the first year of treatment had significantly greater adherence to rivastigmine compared with those who were on donepezil (PDC 69.3% vs. 60.6%; P=0.0004). CONCLUSIONS: Switching from donepezil to the rivastigmine patch seems to be associated with increased adherence, especially in patients who switched within the first year of initiating donepezil.

Health care utilization and costs among patients with AD with and without dysphagia.

OBJECTIVE: To assess health care utilization and associated costs among patients with Alzheimer disease (AD), with and without dysphagia. METHODS: MarketScan Commercial and Medicare databases were analyzed. Patients with a diagnosis of AD with and without dysphagia between October 2006 and September 2010 were included. Acetylcholinesterase inhibitor usage, the number of outpatient and emergency room (ER) visits and hospitalizations, and associated health care costs were assessed. All variables were measured 1 year after the initial diagnosis of AD at the patient level. Patients with dysphagia were matched to patients without dysphagia using propensity score-matching (PSM) methods. Regression models were conducted to compare utilization and costs between the 2 groups. RESULTS: A total of 485 patients with dysphagia and 8492 patients without dysphagia were included. Before matching, patients with dysphagia were older (81.1 vs. 79.8 y), and had higher Charlson Comorbidity Index scores (2.4 vs. 1.7). After matching, all baseline covariates were not statistically different between the 2 groups. Multivariate regression results showed that patients with dysphagia had a higher likelihood of all-cause hospitalizations [odds ratio (OR)=2.26, 95% confidence interval (CI)=1.70-2.99, P=0.001] and all-cause ER visits (OR=1.45, 95% CI=1.12-1.87, P=0.007) compared with patients without dysphagia; they also had a higher likelihood for AD-related hospitalizations and ER visits. The difference in all-cause total health care, ER, and hospitalization costs between patients with and without dysphagia were $3620 (95% CI=$2863-$4375), $258 (95% CI=$241-$274), and $3547 (95% CI=$3325-$3770), respectively. CONCLUSIONS: This study suggests that patients with AD and dysphagia have higher health care utilization and costs compared with patients without dysphagia.

Resource utilization, costs and treatment patterns of switching and discontinuing treatment of MS patients with high relapse activity.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease that affects mainly adults in the prime of their lives. However, few studies report the impact of high annual relapse rates on outcomes. The purpose of this study was to identify high relapse activity (HRA) in patients with MS, comparing differences in outcomes between patients with and without HRA. METHODS: A retrospective longitudinal study was conducted using the MarketScan® Commercial Claims and Encounters and Medicare Supplemental Database. Patients had to have at least one ICD-9 for MS (340.XX) in 2009 and one in 2008, be older than 18 years, and have continuous enrolment in the years 2009-2010. HRA was defined as having ≥2 relapses in 2009. Multivariate analyses compared all-cause and MS-specific emergency room (ER) visits, hospitalizations, and all-cause costs, excluding disease modifying therapy (DMT) costs, in 2010 between patients with and without HRA, controlling for baseline characteristics. A subgroup analysis using treatment exposure was also performed. RESULTS: 19,219 patients were included: 5.3% (n=1,017) had ≥2 relapses in 2009. Patients with HRA were more likely to have all-cause and MS-specific resource utilization than patients without HRA. Mean total all-cause non DMT costs were $12,057 higher for the HRA group. In the subgroup analysis, HRA treatment-naïve patients were more likely to start treatment, and HRA treatment-experienced patients were more likely to discontinue or switch index DMT (P<0.01). CONCLUSIONS: Patients with ≥2 relapses annually have higher resource utilization and costs. The difference in cost was over twice as large in treatment-naïve patients versus treatment-experienced patients. HRA was also associated with an increased likelihood of starting DMT treatment (treatment-naïve patients), and switching or discontinuing DMT therapy (treatment-experienced patients).

Compliance, persistence, healthcare resource use, and treatment costs associated with aliskiren plus ARB versus ACE inhibitor plus ARB combination therapy: in US patients with hypertension.

BACKGROUND: Evidence is currently equivocal on the added benefits of dual blockade of the renin-angiotensin-aldosterone system with the combination of either an ACE inhibitor (ACEI) plus an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) or aliskiren, the first-in-class direct renin inhibitor, plus an ARB. OBJECTIVE: To compare the compliance, persistence, healthcare resource utilization, and healthcare costs associated with aliskiren plus ARB versus ACEI plus ARB combination therapies among adult patients diagnosed with hypertension. METHODS: Patients (aged ≥18 years) initiated on either combination therapy were identified in the MarketScan Commercial and Medicare Supplemental Databases (1 July 2007 to 30 June 2008). The ARB components considered were candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan. The ACEI components included benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. Outcomes measured during the 6-month study period included the proportion of days covered (PDC), treatment discontinuation, healthcare resource utilization, and changes in healthcare costs (study period minus 6-month baseline values). Risk-adjusted differences in outcomes between treatments and associated 95% confidence intervals (CIs) were estimated using multivariate regression models, controlling for demographics, region, co-morbidities, prescription drug use, and resource utilization during the baseline period. RESULTS: Adjusting for baseline characteristics, aliskiren plus ARB patients (n = 1395) demonstrated a significantly higher PDC (67.0% vs 54.3%; difference 12.7%; 95% CI 10.6, 14.7) and a significantly lower discontinuation rate (50.4% vs 68.6%; odds ratio 0.46; 95% CI 0.40, 0.54) than ACEI plus ARB patients (n = 16 507). Aliskiren plus ARB patients had significantly fewer all-cause hospitalizations (adjusted incidence rate ratio [IRR] 0.73; 95% CI 0.61, 0.86) and significantly fewer all-cause emergency room (ER) visits (adjusted IRR 0.72; 95% CI 0.61, 0.85) than ACEI plus ARB patients. Compared with ACEI plus ARB therapy, aliskiren plus ARB therapy was associated with significantly larger increases in prescription costs by $US264 post therapy initiation (95% CI 153, 375), but with non-significantly greater reductions in total healthcare costs by -$583 (95% CI -2409, 1242).[2008 values]. CONCLUSION: In adult hypertensive patients, treatment with aliskiren plus ARB was associated with significantly better compliance/persistence and fewer hospitalizations and ER visits compared with ACEI plus ARB therapy. Reductions in total healthcare costs were non-significantly different between patients treated with aliskiren plus ARB versus ACEI plus ARB, despite the increased prescription costs associated with aliskiren plus ARB therapy.

Cardiovascular morbidity, heart rates and use of antimuscarinics in patients with overactive bladder.

OBJECTIVE: To determine if cardiovascular (CV) comorbidity and treatment-associated antimuscarinic effects differ between patients with and without overactive bladder (OAB), and between treated and untreated patients with OAB, as OAB, CV disorders and exposure to medications with antimuscarinic effects are common in older patients. PATIENTS AND METHODS: Adults from the HealthCore Integrated Research Database with a diagnosis of OAB (International Classification of Diseases-9 codes; from 1 January 2000 to 31 December 2006) or a pharmacy claim for an antimuscarinic OAB medication, formed the OAB cohort, further stratified as treated and untreated. A random sample of patients with neither a diagnosis for OAB nor any urinary bladder dysfunction, nor a pharmacy claim for antimuscarinics, formed the non-OAB cohort. CV comorbidities and use of medications with antimuscarinic effects were assessed for the 12 months before OAB diagnosis/treatment. Information on heart rate (HR) on the day of the first OAB drug prescription was obtained from the GE Healthcare dataset. HR was assessed for patients aged > or =18 years with a diagnosis of OAB who were prescribed antimuscarinics (oxybutynin or tolterodine) at any dose or oral formulation between January 1995 and November 2006. RESULTS: The 6607 patients with OAB, with a substantial proportion with elevated HR at baseline, were more likely to have CV comorbidities (39% vs 21%; P < 0.001) and previous exposure to medications with antimuscarinic effects (33% vs 17%; P < 0.001) than the non-OAB patients. Rate of CV comorbidities (40% vs 38%; P = 0.326) did not differ between treated and untreated patients with OAB. However, there was a difference in previous exposure to medications with antimuscarinic effects (37% vs 29%; P < 0.001); 39.1% of patients with OAB had a HR of >80 beats/min before starting antimuscarinic treatment. CONCLUSION: In this study, the prevalence of CV comorbidities was significantly higher in patients with than without OAB; previous exposure to medications with antimuscarinic effects was also higher in patients with OAB. There was no difference in pre-existing CV comorbidities between the treated and untreated patients with OAB, but the high use of medications with antimuscarinic effects among these patients suggests that the presence of CV comorbidity might not be considered before using antimuscarinic agents for OAB.

Results of a retrospective, observational pilot study using electronic medical records to assess the prevalence and characteristics of patients with resistant hypertension in an ambulatory care setting.

BACKGROUND: Resistant hypertension, or failure to attain blood pressure (BP) goals while treated with > or = 3 antihypertensives (including a diuretic), occurred in 15% to 18% of patients in prospective cohort trials. OBJECTIVES: The aims of this work were to identify the prevalence of resistant hypertension in an ambulatory care setting and to describe the characteristics of patients with resistant hypertension. METHODS: Adults with hypertension were retrospectively identified in a US electronic medical record from November 1, 2002, through November 30, 2005. Antihypertensive treatment and BP values were assessed to identify those with BP > or = 140/90 mm Hg (>130/80 mm Hg for those with diabetes mellitus or kidney disease). Patients treated with > or = 3 agents (including a thiazide) who had > or = 1 BP level above target were classified as having resistant hypertension. Baseline characteristics were compared between those with and those without resistant hypertension. RESULTS: Of 29,474 study patients aged > or = 18 years, 21,460 (72.8%) had > or = 1 prescription order for an antihypertensive and 19,202 (65.1%) had a follow-up BP level above target. The analysis found that 2670 patients (9.1% overall or 12.4% of those who were treated) were classified as having resistant hypertension. Relative to those without resistant hypertension, a greater proportion of those with resistant hypertension were female (65.6% vs 60.5%), were older (66.2 vs 63.0 years), had a higher body mass index (31.6 vs 30.4 kg/m(2)), had higher baseline BP levels (148/81 vs 138/80 mm Hg), and had higher rates of diabetes mellitus (35.2% vs 20.1%) or kidney disease (4.9% vs 2.7%) than those without resistant hypertension (all comparisons, P < 0.001). CONCLUSIONS: This retrospective, observational pilot study of usual community practice supports the findings from prospective trials that resistant hypertension is an important clinical problem. More effective management is needed to enable patients with, or at risk for, resistant hypertension to achieve BP goals.

Psychometric validation of the overactive bladder satisfaction with treatment questionnaire (OAB-SAT-q).

AIMS: Valid and reliable questionnaires must be used to accurately assess patients' satisfaction with overactive bladder (OAB) treatment. This study evaluated the reliability and validity of the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q). METHODS: This was a secondary analysis of clinical study data of patients randomized to darifenacin or darifenacin plus Behavioral Modification Program. Patients completed the Overactive Bladder Questionnaire (OAB-q) and a 3-day bladder diary at Baseline and Week 12 and the OAB-SAT-q at Week 12. Internal consistency reliability was assessed by Cronbach's alpha. Concurrent validity was assessed through correlations with OAB-q change scores and adverse events (AEs). Discriminant validity was assessed among subgroups using general linear models. RESULTS: Analyses utilized a per-protocol population (completion of OAB-q at Baseline and OAB-q and OAB-SAT-q at Week 12) (n = 375). Exploratory factor analysis of the OAB-SAT-q revealed three 3-item subscales (Satisfaction, Side Effects, Endorsement) and two single items (Convenience, Preference). Cronbach's alphas = 0.84-0.95. Subscale-to-subscale correlations = 0.10-0.67 (all P < 0.01 except Side Effects and Convenience). The Side Effects subscale significantly correlated with number of treatment-related AEs (r = 0.27; P < 0.01) and discriminated between patients with/without dry mouth and patients with/without constipation. The Satisfaction and Endorsement subscales discriminated between patients who worsened or had no change in micturition frequency and urinary urgency and patients who had a reduction of >3 episodes (all P < 0.001). The OAB-SAT-q does not appear to discriminate by incontinence episodes. CONCLUSION: The OAB-SAT-q demonstrated good psychometric properties in this initial evaluation-including internal consistency reliability and concurrent and discriminant validity-and appears to be a useful assessment of OAB treatment satisfaction. Neurourol. Urodynam. 28:416-422, 2009. (c) 2008 Wiley-Liss, Inc.

Patient decision to initiate therapy for osteoporosis: the influence of knowledge and beliefs.

BACKGROUND: There are effective treatments to prevent osteoporotic fractures, but these treatments are underutilized. OBJECTIVE: To evaluate the influence of patient characteristics, perceptions, knowledge and beliefs about osteoporosis on the decision to initiate osteoporotic treatment. PARTICIPANTS: We identified female members of a managed care plan who had a dual energy x-ray absorptiometry (DXA) bone density test and fulfilled World Health Organization criteria for osteoporosis. Patients were excluded if they received osteoporotic medications in the prior 6 months. MEASUREMENTS: Patients were sent a questionnaire that included items assessing satisfaction with physician-patient communication, trust in the physician, osteoporosis knowledge and beliefs, beliefs about prescription medications, and perceptions of barriers to medication use. Administrative electronic health records were used to identify prescription drug use and health care utilization. RESULTS: Two hundred and thirty-six women returned surveys and research authorization forms out of 465 contacted for participation. One hundred and thirty-five (57.2%) filled a prescription for an osteoporotic drug in the first 3 months after the DXA exam. The largest differences between initiators and non-initiators were in beliefs in the benefits of medications, and distrust of medications, with initiators believing more strongly in the benefits and effectiveness of medications (p < .001), and non-initiators reporting more distrust of medications (p < .001). Osteoporosis knowledge and the belief that osteoporosis is a serious disease were also related to therapy initiation in bivariate analysis. CONCLUSIONS: Only 57% of patients initiated osteoporotic medication within 3 months of diagnosis. The decision to start osteoporosis treatment appeared to be related to a patient's beliefs in the effectiveness of osteoporosis medications and distrust of medications.

Does the route of administration for estrogen hormone therapy impact the risk of venous thromboembolism? Estradiol transdermal system versus oral estrogen-only hormone therapy.

OBJECTIVE: The aim of this study was to quantify the magnitude of risk reduction for venous thromboembolism events associated with an estradiol transdermal system relative to oral estrogen-only hormone therapy agents. METHODS: A claims analysis was conducted using the Thomson Reuters MarketScan database from January 2002 to October 2009. Participants 35 years or older who were newly using an estradiol transdermal system or an oral estrogen-only hormone therapy with two or more dispensings were analyzed. Venous thromboembolism was defined as one or more diagnosis codes for deep vein thrombosis or pulmonary embolism. Cohorts of estradiol transdermal system and oral estrogen-only hormone therapy were matched 1:1 based on both exact factor and propensity score matching, and an incidence rate ratio was used to compare the rates of venous thromboembolism between the matched cohorts. Remaining baseline imbalances from matching were included as covariates in multivariate adjustments. RESULTS: Among the matched estradiol transdermal system and oral estrogen-only hormone therapy users (27,018 women in each group), the mean age of the cohorts was 48.9 years; in each cohort, 6,044 (22.4%) and 1,788 (6.6%) participants had a hysterectomy and an oophorectomy at baseline, respectively. A total of 115 estradiol transdermal system users developed venous thromboembolism, compared with 164 women in the estrogen-only hormone therapy cohort (unadjusted incidence rate ratio, 0.72; 95% CI, 0.57-0.91; P = 0.006). After adjustment for confounding factors, the incidence of venous thromboembolism remained significantly lower for estradiol transdermal system users than for estrogen-only hormone therapy users. CONCLUSIONS: This large population-based study suggests that participants receiving an estradiol transdermal system have a significantly lower incidence of venous thromboembolism than do participants receiving oral estrogen-only hormone therapy.

Use of health care resources and cost of care for adults with constipation.

BACKGROUND & AIMS: Constipation is a multisymptom disorder that frequently compromises quality of life and leads patients to seek medical advice. To evaluate the clinical and fiscal effects of constipation, we assessed health care resource use by patients with constipation enrolled in a large state Medicaid program. METHODS: We identified 105,130 patients older than age 18 who saw a physician at least once for constipation and were enrolled in the California Medicaid program (Medi-Cal). We then studied health care resource use and costs (reimbursed by Medi-Cal) in 76,854 patients without supplementary insurance. The 15-month analysis period encompassed 3 months before and 12 months after the first visit. The prevalence of comorbid conditions was assessed in the sample of 105,130 patients. RESULTS: During the study period, 106,555 physician visits were for constipation; the total associated cost was $3,016,017 ($39/patient). The total cost for gastrointestinal procedures and laboratory testing was $14,052,503 ($183/patient). There were 41,723 over-the-counter and 1665 prescription drug purchases; the total cost was $388,780 ($5/patient). Approximately 0.6% of patients (n = 479) were admitted to the hospital for constipation; the total cost was $1,433,708 ($2993/admission). The total direct health care costs for patients with constipation in the Medi-Cal system for the 15-month period was $18,891,008 ($246/patient). Within 12 months of the first physician visit for constipation, 5657 of 105,130 patients had hemorrhoids and 2288 had intestinal impaction or obstruction. CONCLUSIONS: Adults seeking treatment for constipation account for significant health care resource use and often have comorbid conditions. The clinical and fiscal burden of constipation in US adults cannot be disregarded or trivialized.

Consequences of poor compliance with bisphosphonates.

BACKGROUND: Prior research on the ability of bisphosphonates to prevent fractures and related health care utilization has been based on high levels of compliance achievable in clinical trial settings. This study was undertaken to assess rates of osteoporotic fractures and health care utilization as a function of bisphosphonate compliance in usual clinical practice. METHODS: This retrospective cohort study used 2000-2004 pharmacy and medical claims data from 45 large U.S. employers. Our sample included persons diagnosed with osteoporosis, aged 40 years or older, and who initiated use of either alendronate or risedronate. Main outcome measures were medication compliance, rates of osteoporotic fracture, and costs for inpatient care, outpatient services, and prescription drugs. RESULTS: We identified 17,988 new users of bisphosphonate therapy. After 1 to 3 years of follow-up, only 30.6% to 42.9% of patients could achieve high compliance (80%-100%), 17.4%-23.0% moderate compliance (79%-40%), and 33.8%-52.0% had low compliance (0%-39%). Multivariate models of fracture risk showed benefits (p<10) with compliance levels of at least 60%, after which no risk benefit could be detected. Multivariate models of health care costs showed statistically significant (p<.05) total costs savings of $859 to $366 per year with high to moderate compliance levels. However, individuals achieving less than 40% compliance had no detectable decrease in inpatient or outpatient costs to offset the increase in drug costs. CONCLUSIONS: Reductions in fracture risk and overall health costs can be detected in individuals achieving as little as 60% to 40% compliance with bisphosphonates. However, as many as 34% of patients in the first year of therapy and 52% by the third year will not reach even the minimal compliance levels required to receive benefits.