Aim Haemophilia A (HA) is a male-predominant disorder, yet women and girls can have factor VIII (FVIII) deficiency with bleeding events requiring treatment. This study aimed to identify and characterize female patients with HA. Methods Administrative claims dated 01 January 2012-31 July 2016 were accessed for patients with 18 months' coverage by commercial or Medicare Advantage with Part D insurance. Patients were included by HA diagnoses or treatments and/or bleeding-related diagnoses or procedures, and excluded by haemophilia B or qualitative platelet disorder diagnoses. A sample of charts was examined for bleeding history, HA therapies and bleeding treatments. All-cause healthcare utilization and costs were also described. Results Among 353 patients meeting initial inclusion criteria, 86 charts were procured, with 8 patients identified as having HA. Their mean age was 60 +/- 17 years and most were Medicare-insured. The mean Charlson Comorbidity Index score was 2.50 +/- 2.56; the most prevalent comorbid conditions involved coagulation/haemorrhage, fluid/electrolyte balance and non-traumatic joint disorders. Over 18 months, a mean of 54 ambulatory visits and 120 pharmacy fills were observed; mean medical costs were $86 694 and pharmacy costs were $25 396. Conclusions Identifying females with HA is challenging using healthcare claims, because diagnostic nomenclature is unclear for female patients treated for bleeding events. Although chart abstraction enhanced claims data, very few female patients were identified with HA. Nevertheless, even in a small sample, sizeable burden in comorbidity and healthcare use was observed. Improved nomenclature and coding for HA diagnoses for women and girls is key to improving research and treatment.

Background Excess adiposity, which affects 69% of US adults, increases coronary heart disease ( CHD ) risk in an association that manifests below conventional obesity cut points. The population‐level impact on CHD risk that is attainable through modest adiposity reductions in populations is not well characterized. We estimated the effect of hypothetical reductions in both body mass index ( BMI ) and waist circumference ( WC ) on CHD incidence. Methods and Results The study population included 13 610 ARIC (Atherosclerosis Risk in Communities) participants. Our hypothetical reduction in BMI or WC was applied relative to the temporal trend, with no hypothetical reduction among those with BMI >24 or WC >88 cm, respectively. This threshold for hypothetical reduction is near the clinical guidelines for excess adiposity. CHD risk differences compared the hypothetical reduction with no reduction. Sensitivity analysis was conducted to estimate the effect of applying the hypothetical BMI reduction at the established overweight cut point of 25. Cumulative 12‐year CHD incidence with no intervention was 6.3% (95% CI, 5.9–6.8%). Risk differences following the hypothetical BMI and WC reductions were −0.6% (95% CI, −1.0% to −0.1%) and −1.0% (95% CI, −1.4% to −0.5%), respectively. These results were robust for the sensitivity analyses. Consequently, we estimated that this hypothetical reduction of 5% in BMI and WC, respectively, could have prevented 9% and 16%, respectively, of the CHD events occurring in this study population over 12 years, after adjustment for established CHD risk factors. Conclusions Meaningful CHD risk reductions could derive from modest reductions in adiposity attainable through lifestyle modification.

180 Background: Radium-223 (RA-223) is the first FDA approved targeted alpha therapy that significantly improves overall survival (OS) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) with symptomatic bone metastases. There is limited real world data describing RA-223 current use. Methods: A retrospective patient chart review was done of men who received at least 1 cycle of Ra-223 for mCRPC in 10 centers throughout the US (4 academic, 6 private practices). All pts had a minimum follow-up of 4 months, or placed in hospice or death. Descriptive analyses for clinical characteristics and treatment outcomes were performed. Results: Among the 200 pts (mean age-73.6 years, mean Charlson comorbidity index-6.9) RA-223 was initiated on average 1.6 years from mCRPC diagnosis (first line use (1L)=38.5%, 2L=31.5% and ≥3L=30%). 78% completed 5-6 cycles of RA-223 with mean therapy duration of 4.2 months. Among all pts, 43% received RA-223 as monotherapy (no overlap with other mCRPC therapies) while 57% had combination therapy with either abiraterone or enzalutamide. Median OS following RA-223 initiation was 21.2 months (95% CI 19.6- 29.2). Table provides the RA-223 utilization by type of clinical practice. Conclusions: Utilization of RA-223 in this real world data set was distinct from clinical trial data. Most patients received RA-223 in combination with abiraterone or enzalutamide, therapies that were unavailable when the pilot trial was conducted. Median survival was 21.2 months. Real world use of RA-223 has evolved as newer agents have become FDA approved in bone-metastatic CRPC. Academic and community patterns of practice were more similar than distinct. [Table: see text]

Haemophilia A is characterised by factor VIII deficiency resulting in uncontrolled bleeding if untreated. The gold standard of management is prophylactic intravenous factor VIII replacement. Standard half-life products (SHL) are typically infused three times weekly. Currently marketed extended half-life products (EHL) aim to reduce the frequency of dosing, while optimising protection against bleeding. However, little evidence is available to describe how these products are used in actual clinical practice. Our primary objective was to describe real world utilization of SHL and EHL in Europe. A descriptive analysis was conducted, utilizing data from the CHESS Paediatrics study, a cross-sectional survey and chart review study in 2017-2018, replicating the methodology of a previous adult studya. Males aged less than 18 years, who have moderate or severe hemophilia A, are treated with factor VIII, and reside in France, Germany, Italy, Spain or the UK were included in the analysis. At the data cut off in May 2018, 555 patients were included, 307 aged 1-11 years, and 248 aged 12-17 years. 404 were receiving SHL, 86 were receiving EHL, and in 65 the treatment was unspecified. In patients receiving regular prophylaxis, weekly infusion frequency was lower with EHL (median 2 vs 3 with SHL), while median weekly factor utilization (IU/kg) was not statistically different. Furthermore, the EHL patients had a trend towards more severe disease (in terms of age, severity, chronic joint damage, and history of inhibitors to factor VIII). There is not a statistically significant difference in weekly factor utilization between currently marketed SHL and EHL products. Comparison of factor utilization should be interpreted with caution, in the context of the heterogeneous haemophilia A patient population, potential for channelling of new drugs towards more severe patients, and tailoring of treatment to optimise patient health. aO'Hara et al. Orphanet(2017)12:106

OBJECTIVES:The rapid spread of infections due to antibiotic-resistant, Gram-negative bacteria in Europe and surrounding regions requires a heightened level of awareness among physicians within their practice settings.METHODS:We surveyed 800 physicians who treat these infections across France, Germany, Spain, Italy, and Russia to assess their awareness of best management approaches.RESULTS:We found that more than two-thirds do not consider themselves highly aware of best management practices. The respondents are facing these resistant infections as evidenced by the antibiotics they report using and their stated interest in newer agents. Respondents indicated that precious time is lost waiting for culture results, but also said they will need more information about accuracy, use, and costs for adopting rapid molecular testing.CONCLUSIONS:The survey further identified the need for treatment guidelines and clinical decision support tools that can be applied at the bedside.

Excess adiposity, which affects 30% of the world’s population, is associated with risk of coronary heart disease (CHD), yet the potential reductions in CHD burden attainable through shifts in the population distributions of adiposity are unclear. Risk of CHD conveyed by excess adiposity is mostly mediated by the associated metabolic dysregulation, with manifestations such as hypertension and diabetes. Considering these metabolic pathways, we estimated the effect of hypothetical population reductions in general adiposity [body mass index (BMI)] or visceral adiposity [indexed by waist circumference (WC)], each consistent with lifestyle modification, on the risk of incident CHD in a US-based biracial population. The study population included 13,610 ARIC study participants aged 45-64 years, after excluding those with CHD (667) or chronic conditions associated with weight change (969) at baseline. Our hypothetical intervention reduced general adiposity (BMI) or waist circumference (WC) by 5% relative to the temporal trend observed under no intervention; the intervention was applied only among those with BMI > 24 kg/m2 (or WC>88 cm). For example, an individual who increased from a BMI of 25.2 to 27 over the study period under no intervention would increase from 24 to 25.7 following the intervention. Incident CHD was ascertained from 1987 to 2001. CHD risk differences were estimated comparing the intervention to no intervention. Over the follow-up time, 736 (BMI analysis) and 712 (WC analysis) incident CHD events occurred. For the BMI analysis, the median BMI (kg/m2) at the end of follow-up was 28.2 under no intervention and 25.6 under the hypothetical intervention. The cumulative 12-year incidence of CHD and 95% CI under no intervention was 6.3% (5.9, 6. 8%) and the risk difference following the hypothetical BMI change was -0.6% (-1.0, -0.1%). For the WC analysis, the median WC (cm) at the end of follow-up was 100.6 under no intervention and 98.3 under the hypothetical intervention. The cumulative 12-year incidence of CHD and 95% CI was 6.2% (5.8, 6. 7%) under no intervention and the risk difference following the hypothetical WC change was -1.0% (-1.4, -0.5%). Hence, 9% and 16% of CHD events occurring in this study population over 12 years could have been prevented by an annual 5% shift in BMI and WC, respectively. We estimated that meaningful reductions in CHD risk could result from modest reductions in adiposity that are consistent with what might be observed under public health efforts aimed at lifestyle modification. CHD risk reduction was larger under a hypothetical WC reduction compared to a BMI reduction, consistent with metabolic dysregulation associated with visceral adiposity. Public health messages and clinical recommendations that promote modification in WC, perhaps with reference to clothing size, would offer more concrete targets than similar messages for composite measures such as BMI.

Introduction: Shifting the population distribution of common risk factors has considerable potential to reduce disease burden. Peripheral artery disease (PAD) is a disabling, often life-threatening condition affecting 8.5 million U.S. adults, yet the potential impact of feasible shifts in the population distribution of adiposity on the associated burden of PAD has not been reported. Methods: From the population-based, biracial ARIC cohort, 13,604 individuals (54% female; 27% African American; and mean age: 54 years) were examined after excluding 969 participants who at baseline had chronic conditions associated with weight change and 632 with prevalent PAD. Exposure [body mass index (BMI)] and covariates (smoking, hypertension, and diabetes) were ascertained at each of 4 triennial study visits. Incident PAD events were identified from active surveillance of hospitalizations and ICD-9-CM discharge codes. Diabetes and hypertension are time-varying covariates that may lie on the causal pathway between BMI and PAD, and are in turn affected by previous BMI. Using the parametric g-formula, we assessed the hypothesis that a reduction in the cumulative incidence of PAD would be observed following a hypothetical 5% yearly BMI reduction down to 24 kg/m2 for all individuals under 65 years of age with a BMI> 24 kg/m2. This approach allows for control of time-varying confounding by covariates that may act as both mediators and confounders, provided that we have longitudinal measures of those covariates. Participants were followed until the first incident PAD event (2%), study dropout (27%), death (7%), or end of follow-up (64%). Results: During a median 12 years of follow-up, we identified 231 participants with incident PAD (31% female; 17% African American; 51% smokers; 45% with diabetes; and 77% with hypertension). The 12-year cumulative incidence of PAD was 1.89% (95%CI: 1.62, 2.17%) under the natural course, and 1.72% (95%CI: 1.46, 2.08%) following a 5% yearly reduction in BMI. Thus, we predicted a -0.17% (95%CI: -0.38, 0.13) change in the risk of PAD. The cumulative incidence of PAD following hypothetical shifts of various magnitude down to a BMI of 24 kg/m2 followed an expected dose response curve, although all estimates were within the 95% confidence limits of our study’s estimated cumulative incidence. Conclusion: We observed an estimated reduction of small magnitude in the risk of PAD attributed to a feasible shift in the population distribution of BMI, consistent with the larger impact of PAD risk factors that are not influenced by BMI, such as cigarette smoking and age. There is need for characterization of the effect of reducing mid-life BMI on PAD with extended follow-up time, and to older ages when PAD risk is highest. Our results suggest that 9% of PAD cases occurring in this study population over the 12 years of follow-up could have been prevented by a 5% shift in the population distribution of BMI.

OBJECTIVE Adults with diabetes typically take multiple medications for hyperglycemia, diabetes-associated conditions, and other comorbidities. Medication adherence is associated with improved outcomes, including reduced health care costs, hospitalization, and mortality. We conducted a retrospective analysis of a large pharmacy claims database to examine patient, medication, and prescriber factors associated with adherence to antidiabetic medications. RESEARCH DESIGN AND METHODS We extracted data on a cohort of >200,000 patients who were treated for diabetes with noninsulin medications in the second half of 2010 and had continuous prescription benefits eligibility through 2011. Adherence was defined as a medication possession ratio ≥0.8. We used a modified adherence measure that accounted for switching therapies. Logistic regression analysis was performed to determine factors independently associated with adherence. RESULTS Sixty-nine percent of patients were adherent. Adherence was independently associated with older age, male sex, higher education, higher income, use of mail order versus retail pharmacies, primary care versus nonendocrinology specialist prescribers, higher daily total pill burden, and lower out-of-pocket costs. Patients who were new to diabetes therapy were significantly less likely to be adherent. CONCLUSIONS Several demographic, clinical, and potentially modifiable system-level factors were associated with adherence to antidiabetic medications. Patients typically perceived to be healthy (those who are younger, new to diabetes, and on few other medications) may be at risk for nonadherence. For all patients, efforts to reduce out-of-pocket costs and encourage use of mail order pharmacies may result in higher adherence.

6602 Background: US health care spending continues to exceed that of other industrialized countries, in part because there is insufficient transparency as to the relative value (benefit-cost) of different treatment options. Comparing drug regimens based on their overall value would help create a common set of metrics to enable better drug therapy decision-making and help improve quality and reduce costs of care. Methods: We developed a methodology to review, synthesize and assess the evidence of a drug's performance across three major domains of clinical efficacy, safety & use and economics, and to combine those assessments to determine overall value of a drug regimen. We then incorporated multi-attribute decision analysis and our evidence methodology into an interactive web-based tool to compare the relative value of all relevant drug regimens in an indication. The tool uses an explicit and transparent methodology and uses a total of 30 elements within the three domains. Results: Using the interactive web-based tool, we compared 3 adjuvant chemotherapy regimens in HER2+, ER-/ PR- breast cancer: 1) doxorubicin + cyclophosphamide then paclitaxel (AC-T), 2) doxorubicin + cyclophosphamide then paclitaxel + trastuzumab (AC-TH), and 3) carboplatin + docetaxel + trastuzumab (TCH). We assessed the relative value of the regimens based on weighted scores within the 3 domains. Higher scores are better. In this case study, AC-TH and TCH had similar efficacy and safety scores; AC-TH scored highest overall because of better economics. (See table.) Scores can be modified by the end user to reflect patient-specific factors such as unique toxicity concerns (e.g., history of heart failure). Conclusions: A transparent, personalizable interactive tool created to compare the relative value of drug regimens can be used to support treatment decisions for HER2+, ER-/PR- breast cancer incorporating clinical and economic considerations. Next steps will include validation using network meta-analysis and extension to other related areas of cancer care. Weighted domain scores by drug regimen. DOMAIN (Weighting) AC-T AC-TH TCH Efficacy (70%) 189 320 320 Safety & Use (20%) 58.1 56.6 58.6 Economic (10%) 70.5 63.2 45.7 TOTAL SCORE 318 440 424

While opioids have become a standard treatment option for those experiencing moderate to severe chronic pain, side effects of constipation and related symptoms have interfered with their usage in as many as 40-50% of treated patients. Prior research has elucidated the range of these symptoms, but no study has determined which of these symptoms patients most desire improving or whether improving constipation itself by as little as one more bowel movement per week is deemed an important change.We conducted an online patient survey of 513 participants residing in one of six countries who reported having chronic pain, were taking opioids, and experiencing opioid-induced constipation (OIC) to address these questions.Respondents rank ordered their preferences and the following eight symptoms generated >80% endorsement as important to improve: improvement in having bowel movements without rectal pain, soft stools that are not loose or watery, regular bowel movements, a reduction in rectal straining, relief from feeling bloated, feeling less fear about having OIC when following their opioid medication regime, a desire to worry less overall about having a bowel movement, and with less 'stomach' area pain. When asked 'how important is it you to have 1 more bowel movement per week", over 90% endorsed it was 'somewhat', 'very', or 'extremely important' with nearly 70% (n = 354) endorsing the 'extremely' or 'very important' response options. In multivariate models, being in more overall pain or reporting fewer than 3 bowel movements per week were found to be independent predictors of the importance.These results highlight the notable range of OIC symptoms most desired by patients to improve and demonstrate that bowel movements of only one more per week were important to register a meaningful improvement. The latter is particularly helpful for those assessing the minimal clinically important difference in treating this condition.

Objectives: To evaluate the impact of specialty pharmacy management on medication adherence, medical utilization, and medical costs for patients with rheumatoid arthritis (RA).Study Design: Retrospective cohort design.Methods: We compared outcomes for RA patients who filled prescriptions through a specialty pharmacy and patients who only received their medications through retail pharmacies. Medical and drug utilization data over a 3-year period were extracted from de-identified administrative claims. Patients were identified by RA diagnosis and by prescriptions for etanercept or adalimumab. Primary outcome measures were RA medication adherence; occurrence of office visit, hospitalization, or emergency department (ED) visit; drug costs; and medical costs. Differences between specialty and retail patient groups were evaluated using regression analysis, adjusting for age, sex, region, comorbidity, and concomitant medication use.Results: Specialty pharmacy patients had significantly higher rates of medication adherence than retail pharmacy patients (P <. 0001 for each year). Specialty pharmacy patients were less likely to have an office visit in years 2 and 3 of the study. Differences in hospitalization risk were not significant, but ED risk was lower for specialty pharmacy patients in year 3. Medical costs were significantly lower for specialty pharmacy patients in all 3 years of the study. Pharmacy costs were higher for specialty pharmacy patients due to the higher rate of medication adherence.Conclusions: Specialty pharmacy management can increase adherence to RA medication therapy, reduce medical resource use, and reduce medical costs. Savings in indirect costs may help offset the increased drug costs associated with better adherence.

Improving adherence to medication offers the possibility of both reducing costs and improving care for patients with chronic illness. We examined a national sample of diabetes patients from 2005 to 2008 and found that improved adherence to diabetes medications was associated with 13 percent lower odds of subsequent hospitalizations or emergency department visits. Similarly, losing adherence was associated with 15 percent higher odds of these outcomes. Based on these and other effects, we project that improved adherence to diabetes medication could avert 699,000 emergency department visits and 341,000 hospitalizations annually, for a saving of $4.7 billion. Eliminating the loss of adherence (which occurred in one out of every four patients in our sample) would lead to another $3.6 billion in savings, for a combined potential savings of $8.3 billion. These benefits were particularly pronounced among poor and minority patients. Our analysis suggests that improved adherence among patients with diabetes should be a key goal for the health care system and policy makers. Strategies might include reducing copayments for certain medications or providing feedback about adherence to patients and providers through electronic health records.

To develop a benchmark measure of US physicians' level of knowledge and extent of use of pharmacogenomic testing, we conducted an anonymous, cross-sectional, fax-based, national survey. Of 397,832 physicians receiving the survey questionnaire, 10,303 (3%) completed and returned it; the respondents were representative of the overall US physician population. The factors associated with the decision to test were evaluated using χ(2) and multivariate logistic regression. Overall, 97.6% of responding physicians agreed that genetic variations may influence drug response, but only 10.3% felt adequately informed about pharmacogenomic testing. Only 12.9% of physicians had ordered a test in the previous 6 months, and 26.4% anticipated ordering a test in the next 6 months. Early and future adopters of testing were more likely to have received training in pharmacogenomics, but only 29.0% of physicians overall had received any education in the field. Our findings highlight the need for more effective physician education on the clinical value, availability, and interpretation of pharmacogenomic tests.

There is a rapidly growing overweight and obesity epidemic in the US, and a high demand for long-term safe and effective weight-loss agents. While 3 new antiobesity therapies underwent FDA review in 2010, little is known about the utilization of available weight-loss drugs. The objective of this analysis is to describe the real-world prescription patterns, adherence, and persistence of weight-loss pharmacotherapy in the United States. A retrospective cohort analysis was conducted using Medco's integrated claims database to evaluate adult patients initiating weight-loss pharmacotherapy between May 2007-October 2010. Eligibility criteria included new weight-loss drug prescription claims (no weight-loss therapy prescriptions 6 months prior to index claim date) and continuous eligibility for 6 months pre- and 14 months post-index claim date. Patients on drugs with >1000 distinct patient counts were analyzed for adherence (annual Medication Possession Ratio; MPR), persistency (allowing a 45 day gap), and concomitant therapy. Analyses included 91,160 patients receiving five drugs: phentermine (N=67434), sibutramine (N=13438), orlistat (N=8047), phendimetrazine (N=4631), and, diethylpropion (N= 4350). Mean±SD age was 44±12 years (96%, 18-64 y/o), 82% were female, 46% resided in the South, and 91% filled prescriptions at retail only. Among obesity drug prescribers with known specialty, 71% were family/internal medicine practitioners. Patients received a mean of 3±3 concomitant chronic medications, with 38%, 31%, 22%, and 11% on antihypertensive, antidepressant, dyslipidemia, or oral antidiabetic therapy, respectively. The mean adherence ranged from MPR=0.20 (phendimetrazine) to MPR=0.26 (phentermine). Persistence at 3, 6, and 12 months ranged respectively from 26%-38% (low-phendimetrazine, high-phentermine), 9%-16% (low-phendimetrazine, high-sibutramine), and 3%-6% (low-phendimetrazine, high-sibutramine). Weight-loss pharmacotherapies in the United States were prescribed by primary care physicians to predominantly younger, female patients on concomitant therapy for common obesity-related conditions. Adherence and persistence to therapy is low, even over short-term exposure, although treatment duration may extend beyond recommendations in some cases (e.g., phentermine).

To measure the comparative direct medical care costs between incident warfarin patients who did or did not experience genotyping to guide dosing. We reanalyzed the previously published MM-WES in which we demonstrated that genotyping reduces the risk of hospitalization for bleeding and thromboembolism in patients who initiate warfarin treatment in typical outpatient practice settings. We used a cost consequence analysis to estimate the 6-month costs and consequences of warfarin genotyping. The intervention group (IG) comprised 896 patients and a comparison group was constructed from 2688 historical controls (HC). The direct medical care costs were estimated for inpatient, office visits and laboratory utilization (including cost of genotyping) and summed to a total cost per patient. A boot-strapping method was performed to estimate confidence limits around the difference in mean cost per patient to assess statistical significance. Over the 6-month monitoring period, the all cause–related per patient costs for the genotyped IG patient was $4127 compared to $5040 for HC. The all-cause difference of -$913 per patient reached statistical significance, 95% CI (-$895, -$930). Various subgroup analyses including warfarin-related costs will be presented. Our analysis suggests that providing results of warfarin genotyping to treating physicians in typical outpatient settings produces cost-savings within six months of initiating warfarin therapy. These estimates are likely conservative as they do not include ancillary costs such as rehabilitation or indirect costs, nor do they estimate costs beyond six months.

9149 Background: Sunitinib (SUN) and sorafenib (SOR) are oral tyrosine kinase inhibitors approved for renal cell carcinoma and gastrointestinal stromal tumors (SUN) and hepatocellular carcinoma (SOR). Sporadic reports of thyroid dysfunction and hypertension (HTN) have been made with these agents. Determination of the true side effect incidence will allow for more efficient monitoring and treatment recommendations. Methods: An observational cohort study was performed using de-identified pharmacy claims data from 2006 to 2009 to evaluate patients (pts) who were prescribed SUN, SOR or capecitabine (CAP). The primary outcome was time to first prescription for thyroid replacement (TR) or HTN treatment. CAP was used as a comparison group for drug-induced hypothyroidism or HTN. Pts were included if they had at least 2 consecutive prescriptions or 45 days of consecutive therapy. Exclusion criteria included presence of concurrent prescriptions for other oral cancer therapies or active prescriptions for TR or HTN t...