Thrombopoietin receptor agonist discontinuation rates and reasons among patients with immune thrombocytopenia: a study of administrative claims linked with medical chart review.

Administrative claims provide a rich data source for retrospective studies of real-world clinical practice, yet some important data may be inconsistent or unavailable. This study explored factors influencing discontinuation of thrombopoietin receptor agonists (TPO-RAs) among patients with immune thrombocytopenia (ITP), by adding medical chart abstraction for additional details. Adult (≥ 18 years) patients with continuous commercial or Medicare Advantage with Part D health insurance coverage were included. Inclusion criteria were ≥ 1 claim for eltrombopag or romiplostim and ≥ 2 diagnoses of ITP between December 31, 2017, and January 1, 2020. Providers were asked to provide access to medical charts for abstraction. The analyses included only patients who discontinued TPO-RA and described patient characteristics, treatment patterns, platelet values, and reasons for discontinuation. Among 207 ITP patients treated with a TPO-RA, 137 (66%) discontinued treatment during the observation period. The mean TPO-RA treatment duration was 185 days. Mean platelet count at the time of discontinuation was 197 × 109/L. The most common reason for discontinuation was improvement of the patient's condition (42%). Other reasons included worsening of ITP/lack of response (12%), adverse events (12%), and cost-related or social reasons (23%). No reason was reported for 10%. Notably 26% of patients who discontinued remained off all ITP therapy for the remainder of the study, with a mean treatment-free period of 262 days. These results emphasize that some patients with ITP are able to discontinue TPO-RA therapy and achieve durable treatment-free periods.

Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation.

OBJECTIVES: To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. METHODS: 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. RESULTS: The mean time to absolute neutrophil count engraftment was 8.72 ± 2.38 days for the prospective pegfilgrastim group and 9.87 ± 3.13 days for the retrospective filgrastim group (P = 0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P = 0.000). The mean cost of filgrastim was $617.22 ± 37.87, compared with $525.78 for pegfilgrastim (P = 0.032). DISCUSSION: Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. CONCLUSION: Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.

Biosimilar Uptake in Academic and Veterans Health Administration Settings: Influence of Institutional Incentives.

OBJECTIVE: To compare uptake in the ordering of biosimilars at a Veterans Affairs Medical Center (VAMC) to that at an academic medical center, where institutional incentives for infused medications differ. METHODS: We performed a cross-sectional study of medical record data and estimated institutional financial incentives at 2 medical centers in Philadelphia: 1) the University of Pennsylvania Health System (UPHS), and 2) the local VAMC. All ordering events for filgrastim or infliximab products were quantified over time and stratified according to product (biosimilar versus reference product) and center. Financial incentives to the institutions over time were determined based on actual drug costs for the VAMC and average sales prices (ASPs) and Medicare Part B reimbursement rates for UPHS. RESULTS: There were 15,761 infusions of infliximab at UPHS, of which 99% were for the reference product. There was a sharper decline in the use of reference products at the VAMC; 62% of the 446 infliximab infusions ordered at the VAMC were for the reference product. ASPs were consistently lower for biosimilar infliximab products, but the estimated institutional financial incentives remained similar over time for biosimilar and reference infliximab at UPHS. At the VAMC, the costs for 100-mg vials of reference infliximab and infliximab-abda were $623.48 and $115.58, respectively: a $507.90 (81%) savings per vial. CONCLUSION: The uptake of infliximab biosimilars has been slow at an academic medical center compared to a nearby VAMC, where financial savings are realized by the institution from its use. Slow adoption of biosimilar medications may impact the rates of decline in costs.

Tbo-filgrastim versus filgrastim for stem cell mobilization and engraftment in autologous hematopoietic stem cell transplant patients: A retrospective review.

INTRODUCTION: Filgrastim, a granulocyte colony-stimulating factor, is commonly used in autologous hematopoietic stem cell transplants (HSCTs) to assist with peripheral blood progenitor cell (PBPC) collection and to support stem cell engraftment. In the United States, tbo-filgrastim is approved under its own Biologic License Application and is limited to a single indication excluding the HSCT population. METHODS: Approximately one year after a system-wide formulary change to tbo-filgrastim for all on- and off-label indications, our institution conducted an IRB-approved retrospective comparison of tbo-filgrastim to filgrastim in the autologous HSCT setting. The study included 71 patients who received an autologous HSCT from 1 January 2013 to 31 December 2016 with a documented administration of tbo-filgrastim or filgrastim. RESULTS: There were no statistically significant differences noted on CD34 + counts during stem cell mobilization, neutrophil engraftment, infection rates during the engraftment phase, nor duration of hospitalization during the engraftment phase. More patients in the tbo-filgrastim group received plerixafor per protocol resulting in more patients meeting their PBPC collection goal in one day with fewer collection days overall, a result potentially confounded by institutional protocol changes. Utilizing tbo-filgrastim offered an average cost savings per patient of $2664.26 ($1907.33 for PBPC mobilization and $756.93 for stem cell engraftment) when comparing dollars spent on granulocyte colony-stimulating factor products only. CONCLUSION: Tbo-filgrastim demonstrates comparable efficacy with a cost savings benefit compared to filgrastim for autologous PBPC mobilization and stem cell engraftment.

The evolution of value with filgrastim in oncology.

The recombinant G-CSF filgrastim was first approved in 1991, and its value has been evolving ever since. Initial health technology assessments suggested low value due to high drug cost and no evidence for significant gain in overall survival. However, more recent meta-analyses of placebo-controlled randomized trial data show falling costs due to biosimilar competition and absolute overall survival gains of 3.2% (95% CI: 2.1-4.2%) from filgrastim support of cytotoxic chemotherapy. The launch of biosimilar alternatives merits a re-evaluation of decisions by health technology assessments and explains the first inclusion of filgrastim in the WHO Essential Drug List for cancer >20 years after its original approval in 1991, thus demonstrating the power of biosimilar medicines in transforming healthcare.

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada.

Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%-40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the "rebate trap" with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. IMPLICATIONS FOR PRACTICE: We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing "rebate traps" where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

Healthcare costs among patients with hemophilia A treated with factor replacement or bypassing agents.

Objective: To assess real-world costs for patients with hemophilia A treated with bypassing agents versus factor VIII (FVIII) replacement. Methods: Claims data from a large US health insurer during 1 January 2006-30 September 2014 were used for analysis. Treated patients with hemophilia A were identified based on ≥1 medical claim with a diagnosis code for hemophilia A (ICD-9-CM 286.0) and ≥1 medical or pharmacy claim for bypassing therapy and/or FVIII replacement during 1 January 2007-31 August 2014. The bypassing therapy cohort comprised patients with ≥1 claim for bypassing therapy; all others were assigned to the factor replacement therapy cohort. Post-index hemophilia-related costs were computed as combined health plan plus patient paid amounts for medical claims with hemophilia A diagnosis code or hemophilia therapy procedure code (bypassing therapy, FVIII replacement therapy, desmopressin, antifibrinolytic therapy), as well as pharmacy claims for hemophilia therapy. Results: The study sample represented 580 patients: 50 (8.6%) in the bypassing therapy cohort (mean age: 38.5 years; mean post-index period: 2.1 years) and 530 (91.4%) in the factor replacement therapy cohort (mean age: 29.3 years; mean post-index period: 2.7 years). Compared with the factor replacement therapy cohort, mean per-patient-per-month hemophilia-related total costs were 4.8-fold higher in the bypassing therapy cohort ($57,232 vs. $11,899), comprising 4.4-fold higher medical costs ($45,911 vs. $10,352) and 7.3-fold higher outpatient pharmacy costs ($11,321 vs. $1547). Conclusions: Patients with hemophilia A treated with bypassing agents between 2007 and 2014 incurred substantially higher monthly hemophilia-related medical and pharmacy costs than patients treated only with FVIII replacement.

Patient-Administered Biologic and Biosimilar Filgrastim May Offer More Affordable Options for Patients with Nonmyeloid Malignancies Receiving Chemotherapy in the United States: A Budget Impact Analysis from the Payer Perspective.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) are often administered to reduce the incidence, severity, and duration of febrile neutropenia (FN) in chemotherapy patients. Tbo-filgrastim and filgrastim-sndz represent a follow-on biologic and a biosimilar version, respectively, of the short-acting G-CSF filgrastim with comparable efficacy and safety. OBJECTIVE: To estimate the budget impact of increasing use of patient-(home-) administered tbo-filgrastim and filgrastim-sndz from a U.S. payer perspective. METHODS: An interactive budget impact model was developed to estimate the changes in drug cost associated with projected increases in the market share of tbo-filgrastim from 5% to 10% and of filgrastim-sndz from 10% to 12% (with a corresponding decrease in filgrastim market share from 85% to 78%) for a 1 million-member health plan among patients with nonmyeloid malignancies receiving chemotherapy with a high risk of FN. Patient self-administration at home was assumed for 20% of patients receiving short-acting G-CSF treatment; all products were purchased through the patient's pharmacy benefit and were assumed to have tier 3 formulary status with a patient copay of $54 per prescription. Base-case data were derived from publicly available resources. The total plan budget impact was calculated using a 1-year time horizon, along with the differences in per member per month and per member per year (PMPY) costs between the current and future scenarios. RESULTS: The effective annual per-patient drug cost to the plan totaled between $16,961 and $27,199, depending on dosage and packaging, for tbo-filgrastim; between $16,216 and $26,015 for filgrastim-sndz; and between $19,134 and $30,663 for filgrastim. The estimated total annual plan cost associated with patient-administered short-acting G-CSFs was $53,298,217 (PMPY = $53.30) in the current scenario and $52,828,832 (PMPY = $52.82) in the future scenario. Cost savings totaled $469,385 (PMPY = $0.48). The model was most sensitive to changes in the percentage of patients self-administering G-CSF at home and to the wholesale acquisition cost for filgrastim. CONCLUSIONS: The effective annual plan per-patient drug costs for tbo-filgrastim and filgrastim-sndz were 11% and 15% lower than filgrastim, respectively. The present analysis estimated an annual U.S. health plan cost savings approaching $0.5 million following increases in market shares of approximately 5% for tbo-filgrastim and 2% for filgrastim-sndz. DISCLOSURES: This study was sponsored by Teva Branded Pharmaceutical Products R & D, which participated in the study design, data interpretation and analysis, the writing of the report, and the decision to submit. Aventine Consulting received consulting fees from Teva Pharmaceuticals and developed the cost model and provided data analysis support. Trautman and James are employed by Aventine Consulting. Szabo and Tang are employed by Teva Pharmaceuticals.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.

Evaluation of Postmarketing Reports from Industry-Sponsored Programs in Drug Safety Surveillance.

INTRODUCTION AND OBJECTIVE: Adverse event reports from industry-sponsored programs, such as patient support programs, have contributed to a rise in the number of individual case safety reports in the US Food and Drug Administration Adverse Event Reporting System database. This study aimed to characterize individual case safety reports from industry-sponsored program and non-industry-sponsored program sources and compare their usefulness in safety signal detection. METHODS: Individual case safety reports of six drug and biological products were identified in the Food and Drug Administration Adverse Event Reporting System database between the date of Food and Drug Administration product approval and the first quarter of 2017. A random subset of industry-sponsored program and non-industry-sponsored program individual case safety reports were then compared to identify differences in reporters, outcomes, data completeness, and usefulness. The 'usefulness' of individual case safety reports was assessed by manually reviewing the availability of key information in the narrative (e.g., temporality, comorbidities). RESULTS: Compared with non-industry-sponsored program reports, more industry-sponsored program reports were associated with a serious outcome (51.4% vs. 58.8%, p = 0.02) and were reported by consumers (35.5% vs. 50.4%, p < 0.01). Industry-sponsored program reports tended to contain more data elements than non-industry-sponsored program reports (i.e., age, sex, indication for use), but completeness was variable across products. No significant difference in usefulness was identified between non-industry-sponsored program and industry-sponsored program individual case safety reports (30.6% vs. 28.5%, p = 0.42). Useful reports that contained at least one serious, unlabeled adverse event represented only 4% and 6.2% of the non-industry-sponsored program and industry-sponsored program report cohorts, respectively. CONCLUSIONS: Our study suggests that reports obtained from industry-sponsored programs in the Food and Drug Administration Adverse Event Reporting System database contain more data elements but are similar to non-industry-sponsored program reports with regard to 'usefulness' in signal detection.

Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz.

AIM: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. METHODS: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. RESULTS: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). CONCLUSION: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial.

OBJECTIVES: To determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. METHODS: A three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. RESULTS: The model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97-$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. CONCLUSIONS: Dose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262.

Comparison of transplant outcomes and economic costs between biosimilar and originator filgrastim in allogeneic hematopoietic stem cell transplantation.

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT; 13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT; 17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF.

Cost-effectiveness of stroke treatments and secondary preventions.

INTRODUCTION: Stroke is one of the leading causes of morbidity and mortality worldwide. It imposes a significant burden in terms of costs, premature death, long-term disability, restricted social functioning and reduction in patient's quality of life. Effective interventions in stroke treatment and prevention have long-term clinical and economic consequences. AREAS COVERED: This review focuses on the cost-effective evaluations regarding the medical treatments of acute stroke and long-term secondary prevention of stroke. A comprehensive electronic search for economic evaluations in this area was conducted. Different economic modeling approaches, evidence considered in the evaluations and the key findings are all reviewed and discussed. EXPERT OPINION: Intravenous thrombolysis is consistently shown to be the most cost-effective option for acute stroke treatment. Clopidogrel, statin, warfarin and dabigatran are considered as the most cost-effective treatments for secondary stroke prevention. However, lack of long-term outcome data and long-term resource use data adds tremendous uncertainty to the cost-effectiveness stories of these treatments. Economic studies that are updated with more recent clinical findings and studies that seek to identify the cost-effective combinations of different types of treatments are warranted. Also, few of the published economic evaluations considered the economic impact of these treatments on subgroups and individuals with different risks.

Retrospective comparison of the effects of filgrastim and pegfilgrastim on the pace of engraftment in auto-SCT patients.

The high doses of chemotherapy used for the preparatory regimens before autologous blood or marrow stem cell transplantation leave patients at risk for neutropenic complications. The administration of filgrastim post transplant reduces the time to neutrophil recovery and therefore has become a standard practice at many institutions. In 2006, we implemented a practice change from filgrastim to pegfilgrastim. We present data on 164 consecutive patients (82 patients who received filgrastim compared with 82 patients who received pegfilgrastim) who received an auto-SCT between January 2006 and November 2007. Patients who received pegfilgrastim had faster engraftment (9.6 days compared with 10.9 days, P<0.0001), a lower incidence of febrile neutropenia (59% compared with 78%, P=0.015), as well as shorter hospital stay, fewer days of treatment with i.v. antibiotics (6.3 days compared with 9.6 days, P=0.006), and fewer radiographic tests, which translated to an estimated total cost savings of over $8000 per patient. Overall, there were no differences in toxicity with these two agents. We conclude that a single dose of pegfilgrastim is a safe and efficacious alternative to daily injections of filgrastim and can be a cost-effective approach in auto-SCT patients.

Physicians' preferences towards coagulation factor concentrates in the treatment of Haemophilia with inhibitors: a discrete choice experiment.

This study sought to identify attributes of treatment important to haematologists in making their decisions regarding optimal care for inhibitor patients in the United States. A conjoint analysis using a discrete choice experiment was conducted to elicit factors that are most important to haematologists. Twelve product attributes were chosen based on published literature and expert opinion: risk of human viral infections, possibility that the titre of the inhibitor may rise, reduction in the likelihood of dose-related thromboembolic events, the number of infusions required to stop haemorrhage, infusion preparation time, infusion time, infusion volume, time required to stop bleeding, time required to alleviate pain, prophylaxis use, ability to undergo major surgery and cost of medications. Thirty haematologists completed the questionnaires via face-to-face interviews at a scientific meeting in April 2006. Data were analysed using a multinomial logit model to obtain the relative importance of each attribute. Responding haematologists had considerable experience in treating haemophilia patients with inhibitors (average : 13 +/- 9 years). 'Time required to stop bleeding' was the most important factor affecting treatment decisions [relative importance (RI) = 16.3%]. Physicians also preferred treatments that resulted in quick pain relief [RI = 12.9%], reduced the possibility that the titre of inhibitor may rise [RI = 12.8%], required fewer number of infusions to stop a haemorrhage [RI = 12.7%] and reduced the risk of human viral infection [RI = 10.8%]. This study revealed that certain clinical outcomes attributes are the most preferred and important. These findings can assist decision makers in their assessments of optimal first-line care.

Association between bleeding, blood transfusion, and costs among patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Bleeding and blood transfusion are associated with increased morbidity and mortality among patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, the economic consequences of these complications are not well defined. We sought to determine the relationship between bleeding, blood transfusion, and measures of costs among patients with non-ST-segment elevation ACS. METHODS: We analyzed data from the economic substudy of the GUSTO IIb trial (n = 1235) to determine the relationship between bleeding; transfusion; and hospital costs, physician costs, total costs, and length of stay. Linear regression models were developed to determine the cost implications of each bleeding and transfusion event. RESULTS: Of the patients in the economic substudy of GUSTO IIb, 36.8% (n = 455) experienced a bleeding event. As bleeding severity increased, there was a stepwise increase in length of stay (no bleeding 5.4 days, mild bleeding 6.9 days, moderate bleeding 15.0 days, severe bleeding 16.4 days; P < .01) and unadjusted total costs (no bleeding $14,282, mild $21,674, moderate $45,798, severe $66,564; P < .01). After adjustment for baseline differences among patients, each moderate or severe bleeding event increased costs by $3770 and each transfusion event increased costs by $2080. Further modeling demonstrated that the increase in costs was driven by increases in length of stay. CONCLUSIONS: Bleeding and transfusion are associated with increased resource use among patients with NSTE ACS. These data suggest that strategies that reduce both ischemia and the risk for bleeding have the potential to produce important reductions in the costs of care for patients with NSTE ACS.