Assessing the transition from intravenous to subcutaneous delivery of rituximab: Benefits for payers, health care professionals, and patients with lymphoma.

Subcutaneous (SC) administration of rituximab provides an opportunity for reduced patient treatment burden and increased healthcare efficiencies as an alternative to intravenous (IV) rituximab. There is minimal evidence comparing costs associated with SC and IV rituximab in a US setting. This research assessed the impact of transitioning patients from IV to SC rituximab for treatment of non-Hodgkin's lymphoma (NHL) from the US payer, provider, and patient perspective. We developed a model to estimate cost differences for transitioning 20% of a patient cohort from IV to SC rituximab. We included patients with incident diffuse large B-cell lymphoma, incident and recurrent follicular lymphoma, and incident and recurrent chronic lymphocytic leukemia. In the model, each patient received the same number of doses and that there was no difference in discontinuation between cohorts due to non-inferior efficacy and a similar safety profile. Model inputs were collected from published literature and publicly available data. Scenario analyses tested the impact of availability of low-cost biosimilars. In the base case (1,000,000 covered lives), we estimated a total of 157 patients, with 769 total drug administrations. A transition of 20% of patients from IV to SC was projected to generate $153,000 in payer savings, increase provider capacity by 270 hours, and free 470 hours of patient time. Scenario analyses suggest SC administration will be cost saving for payers even with a market where biosimilars approach 50% market share. A 20% transition to SC rituximab in a single cohort of patients has the potential to generate significant US health system value in the form of payer savings, increased practice capacity, and patient time.

Health care resource utilization and costs among adult patients with hemophilia A on factor VIII prophylaxis: an administrative claims analysis.

BACKGROUND: Standard of care for bleed prevention in patients with severe congenital hemophilia A is continuous prophylaxis with factor VIII (FVIII), typically administered intravenously 2-3 times per week in the home setting. Nonfactor prophylaxis and gene therapy are emerging novel prophylaxis strategies for hemophilia A, and it is important to compare their health economics with that of FVIII prophylaxis. Current data on resource utilization and costs in the adult hemophilia A prophylaxis population are limited, and a structured approach to analyze annual costs in these patients using administrative claims data has not been previously reported. OBJECTIVE: To assess health care resource utilization and costs of continuous FVIII prophylaxis in commercially insured adults with hemophilia A without inhibitors. METHODS: Administrative claims records from beneficiaries covered by major selfinsured companies in the United States from January 1999 through March 2017 (OptumHealth Care Solutions) were queried, and records for adult patients (aged 18-64 years) diagnosed with hemophilia A who received FVIII were extracted. Three criteria were defined to distinguish patients most likely to be managed with continuous FVIII prophylaxis from those on episodic treatment based on the frequency and timing of FVIII claims over a 12-month period of continuous enrollment: (1) having ≥ 4 FVIII claims, (2) having ≥ 6 FVIII claims, or (3) having no gaps > 60 days between FVIII claims. Patients with evidence of bypassing agent use were excluded. Health care resource utilization and costs were assessed for all patients with any FVIII use and for patients defined as being managed with continuous FVIII prophylaxis based on each criterion. RESULTS: The analysis included 189 patients with a diagnosis code for hemophilia A (ICD 9-CM code 286.0; ICD-10-CM code D66) from January 1999 through March 2017 who had at least 12 months of continuous enrollment and at least 1 noninpatient/nonemergency department claim for FVIII concentrate (any type) during their last 12 months of continuous enrollment (overall cohort). Within the overall cohort, 118, 94, and 61 patients met the criteria for FVIII prophylaxis based on the first, second, and third definitions, respectively. Per patient mean (SD) total health care costs for the overall cohort was $287,055 (306,933). For patients meeting criteria 1 through 3, per patient costs ranged from $407,752 (321,036) to $551,645 (302,841). FVIII concentrate accounted for over 90% of costs, with mean (SD) annual FVIII costs of $264,777 (292,423) in the overall cohort and $384,197 (303,826), $433,029 (313,711), and $531,098 (297,142) among patients meeting the respective definitions for prophylaxis. CONCLUSIONS: This analysis highlights the substantial economic burden associated with managing adults with hemophilia A on FVIII prophylaxis, where per patient mean total annual health care costs ranged from $407,752 to $551,645. Over 90% of such costs were attributable to FVIII concentrate dispensed. DISCLOSURES: This study was funded by BioMarin Pharmaceutical, which was involved in protocol development, analysis plan development, data interpretation, manuscript preparation, and publication decisions. All authors contributed to protocol development, analysis plan development, data interpretation, and manuscript development. All authors maintained control over the final content. Sammon, Solari, Kim, and Hinds are employees and shareholders of BioMarin Pharmaceutical. Cook, Sheikh, and Chawla are employees of Analysis Group, a consulting company that was contracted by BioMarin Pharmaceutical to conduct this study and develop the manuscript. Croteau has received professional fees from BioMarin Pharmaceutical, Bayer, CSL Behring, Genentech, and Pfizer. Thornberg has received professional fees from BioMarin Pharmaceutical, Genentech, Novo Nordisk, Sanofi, and Spark Therapeutics, as well as research funding from Novo Nordisk and Sanofi.

Budget Impact Analysis of Comprehensive Genomic Profiling in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: This study assessed the economic impact of increased use of comprehensive genomic profiling (CGP) versus conventional testing strategies among patients with advanced non-small-cell lung cancer (aNSCLC) from a US commercial health plan perspective. METHODS: A decision analytic model was developed to estimate the incremental benefits and costs across testing methodologies (CGP v non-CGP), as well as across sample types (tissue-based and liquid-based), for patients with newly diagnosed aNSCLC. Model outcomes included total direct costs, testing costs, and per member per month budget impact. Secondary model outcomes included the number of patients needed to test with CGP to add 1 life-year, and the number of patients needed to test with CGP to treat one individual with a biomarker-matched therapy. RESULTS: In a hypothetical 2,000,000-member health plan, 790 members were estimated to have incident aNSCLC; 609 underwent molecular diagnostic testing with 122 (20%) tested with CGP (109 tissue-based and 13 liquid) in the base-case. An increase in CGP from 20% to 30% (an additional 61 patients tested with CGP) was associated with 3.11 additional life-years gained and a $0.01 in US dollars per member per month budget impact. Approximately 19.6 patients would need to be tested with CGP versus non-CGP to add one life-year and 5.9 patients would need to be tested with CGP to treat at least one patient with a biomarker-matched therapy. CONCLUSION: An increase in CGP from 20% to 30% among patients with aNSCLC undergoing molecular diagnostic testing was associated with modest budget impact, most of which was attributable to prolonged survival associated with increased use of more effective treatments.

The Budget Impact of Including Rucaparib on a US Payer Formulary for the Treatment of Patients with Metastatic Ovarian Cancer.

OBJECTIVE: A budget impact model was constructed to assess the incremental budget impact that rucaparib availability would have on a US health plan. METHODS: An incremental budget impact was estimated over a 3-year horizon as the difference in total annual cost of treatment, with and without rucaparib available, for second-line maintenance, third-line treatment, and the combined maintenance and treatment settings. The hypothetical health plan includes one million covered lives, and commercial and Medicare lines of business. Alternative products included in the model were based on the National Comprehensive Cancer Network guidelines. The eligible patient population was estimated using an incidence-based approach. Modeled costs include drug acquisition, intravenous drug administration, required laboratory testing, and medical management of adverse events. RESULTS: In the maintenance setting, average total expenditures over 3 years were estimated to be US$1,465,043 with rucaparib versus US$1,461,350 without it as a treatment option; the average incremental budget impact was US$3693 (US$0.0003 per member per month [PMPM]). In the treatment setting, average total expenditures were estimated to be US$1,320,718 with rucaparib versus US$1,313,736 without it; the average incremental budget impact was US$6982 (US$0.0006 PMPM). Budget impact is smaller in commercial plans than Medicare because of the higher incidence of ovarian cancer in the over-65 population. CONCLUSION: The budget impact of adding rucaparib to the formulary for a health plan adds negligible PMPM costs of < US$0.001 in all tested settings and scenarios due to the small population eligible for therapy.

Healthcare resource utilization and costs associated with postpartum depression among commercially insured households.

OBJECTIVE: To quantify the economic burden of postpartum depression (PPD) that accrues to commercially insured households in the year following childbirth. METHODS: Administrative claims data from OptumHealth Care Solutions (2009-2016) were used to identify households that included women identified with PPD per the algorithm and propensity score-matched comparison households of women who were not identified with PPD or a history of depression after childbirth. Study outcomes included direct total all-cause medical and pharmaceutical costs during the first year following childbirth and number of outpatient visits at the household level stratified by household member. RESULTS: Households affected by PPD as identified by the algorithm (N = 7769) incurred 22% higher mean total all-cause medical and pharmaceutical spending than unaffected matched controls (N = 41,308) during the first year following childbirth ($36,049 versus $29,448, p < 0.01) and an average of 16 more outpatient visits than unaffected households (p < .01). Costs accrued by mothers comprised the largest share (>50%) of total all-cause spending. Mothers identified with PPD had significantly higher annual mean direct total all-cause medical and pharmaceutical spending than their matched controls without PPD ($19,611 versus $15,410, p < .01), driven primarily by an average of 11 more outpatient visits than unaffected mothers (p < .01). CONCLUSIONS: Households affected by PPD as identified by the algorithm incurred higher mean total all-cause medical and pharmaceutical spending during the first year following childbirth than did their matched controls identified without PPD, but not all costs were attributable to maternal treatment for PPD. These findings contribute to a better understanding of the potential economic burden associated with PPD and demonstrated costs may extend beyond the mother to members of the household.

Assessing the potential cost-effectiveness of a gene therapy for the treatment of hemophilia A.

Aim: Hemophilia A is a genetic, chronic disorder classified by deficient or defective coagulation factor VIII (FVIII) that puts those affected at risk for spontaneous bleeding episodes, which lead to joint damage and chronic pain over time. Currently, most severe hemophilia A patients are treated with prophylactic FVIII, which requires costly and frequent infusions and life-long adherence to medication. A gene therapy (valoctocogene roxaparvovec) is currently in development for the treatment of severe hemophilia A. This model assessed the potential cost-effectiveness of treating patients with valoctocogene roxaparvovec rather than prophylactic therapy.Materials and methods: We developed an individual-based, state-transition microsimulation model for assessing the likely cost-effectiveness of valoctocogene roxaparvovec compared to prophylactic FVIII. Men aged 30 with severe hemophilia A were modeled over a lifetime horizon, and costs were reported from the perspective of the United States health care system. Through microsimulation, patient-level heterogeneity was captured in starting weight, starting Pettersson score (PS), durability of valoctocogene roxaparvovec, and annual bleed rate (ABR).Results: The model projects that treatment with single-administration valoctocogene roxaparvovec would be cost-saving to people with hemophilia A at a price point comparable to other currently available gene therapy products due to its potential to reduce FVIII utilization, direct medical costs, lifetime bleeds, and accumulated joint damage.Limitations: The model relies upon evidence-based assumptions for clinical inputs due to limited data availability. Such uncertainty was mitigated by modeling heterogeneity across the population, specifically with regards to long-term gene therapy durability, lifetime bleed rates, and joint damage progression.Conclusion: Valoctocogene roxaparvovec was found to be cost-saving-on average by about $6.8 million per patient-and more effective than prophylactic therapy for treatment of hemophilia A. The comparative benefit of gene therapy was observed across a broad range of simulated patients that were representative of the real-world severe hemophilia A population.

US care pathways: continued focus on oncology and outstanding challenges.

OBJECTIVES: To update an ongoing assessment of care pathway development, implementation, and evaluation, and to evaluate the emerging relationship between care pathways and other components of value-based care. STUDY DESIGN: Targeted literature review followed by an online survey and in-depth interviews. METHODS: The PubMed/Cochrane databases and gray literature were searched for publications on care pathways (January 1, 2014, to March 3, 2017); a supplemental targeted search was completed in October 2017. Qualitative data were collected via an online survey and semistructured, in-depth interviews with payers, providers, pathway vendors, and opinion leaders. RESULTS: A total of 112 articles or posters were identified in recently published research. The survey and interviews included 32 and 19 respondents, respectively. Care pathways are increasingly driven by providers and provider networks. Overall, we found increased awareness of and adherence to codified best practices or standards, and prioritization of high-quality evidence during development. Research findings suggest stronger links between outcomes-based measures and both physician reimbursement and care pathway evaluation. Integration with other value-based care initiatives, including alternative payment models, is also gradually emerging. CONCLUSIONS: This study identified growing use of high standards of evidence and adoption of other best practices in the development, implementation, and evaluation of care pathways. As the influence of care pathways on patient care continues to expand, additional efforts are needed to increase transparency, disclose conflicts of interest, engage with patients, effectively align care pathways with improvements in patient outcomes, and integrate efficiently with other value-based care initiatives.

Budget impact analysis of comprehensive genomic profiling in patients with advanced non-small cell lung cancer.

AIMS: Broad molecular profiling of patients with advanced non-small cell lung cancer (NSCLC) is strongly advised to optimize genomic matching with available targeted treatment options or investigational agents. Unlike conventional molecular diagnostic testing, or smaller hotspot panels, comprehensive genomic profiling (CGP) identifies genomic alterations across hundreds of clinically relevant cancer genes from a single tissue specimen. The present study sought to estimate the budget impact of increased use of CGP using a 324-gene panel (FoundationOne) vs non-CGP (represented by a mix of conventional molecular diagnostic testing and smaller NGS hotspot panels) and the number needed to test with CGP to gain 1 life year. MATERIALS AND METHODS: A decision analytic model was developed to assess the budget impact of increased CGP in advanced NSCLC from a US private payer perspective. Model inputs were based on published literature (epidemiology and treatment outcomes), real-world data (testing and rates, medical service costs), list prices for CGP and anti-cancer drugs, and assumptions for clinical trial participation. RESULTS: Among 2 million covered lives, 532 had advanced NSCLC; 266 underwent molecular diagnostic testing. An increase in CGP among those tested, from 2% to 10%, was associated with $0.02 per member per month budget impact, of which $0.013 was attributable to costs of prolonged drug treatment and survival and $0.005 to testing cost. Approximately 12 patients would need to be tested with CGP to add 1 life year. LIMITATIONS: The model incorporated certain assumptions to account for inputs with a limited evidence profile and simplify the possible post-CGP treatments. CONCLUSIONS: An increase in CGP utilization from 2% to 10% among patients with advanced NSCLC undergoing molecular diagnostic testing was associated with a modest budget impact, most of which was attributable to increased use of more effective treatments and prolonged survival.

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers.

AIMS: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. METHODS: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010-2014). RESULTS: Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1-22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). LIMITATIONS: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. CONCLUSIONS: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.

Estimated Cost of Anticancer Therapy Directed by Comprehensive Genomic Profiling in a Single-Center Study.

PURPOSE: Comprehensive genomic profiling (CGP) detects several classes of genomic alterations across numerous genes simultaneously and can match more patients with genomically targeted therapies than conventional molecular profiling. The current study estimated the costs of anticancer drugs and overall survival (OS) for patients who were treated with matched and unmatched therapy. METHODS: Costs were estimated for patients with complete data (188 of 500 patients) from a prospective, nonrandomized study of patients with diverse refractory cancers who underwent CGP and were treated with matched or unmatched therapy. We assessed mean time to treatment failure (TTF) and mean observed OS. Patient-specific drug and administration costs were imputed for the first regimen after CGP on the basis of drug classes, unit costs, and time on treatment. RESULTS: Patients on matched (n = 122) versus unmatched (n = 66) therapy had longer mean TTF (+1.5 months) and observed OS (+2.4 months) and higher drug costs (+$38,065; all P < .01). Increased drug costs were largely attributable to the longer duration of therapy associated with extended TTF (66.3%) rather than higher monthly drug costs (33.7%). Incremental increases in TTF (+1.9 months v +1.2 months) and observed OS (+2.5 months v +2.1 months) between matched and unmatched therapies were larger for those who underwent CGP in earlier- versus later-line therapy. Incremental increases in drug costs between matched and unmatched therapies were lower for earlier- compared with later-line therapy (+$27,000 v +$43,000, respectively). CONCLUSION: Matched therapy was associated with longer TTF, increased OS, and manageable incremental cost increases compared with unmatched therapy. Most of these increased costs were a result of the longer duration of therapy rather than higher monthly drug costs. The benefits of matching were numerically greater in earlier versus later lines of therapy, which is consistent with the value of early use of CGP.

Utility values associated with advanced or metastatic non-small cell lung cancer: data needs for economic modeling.

INTRODUCTION: Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

The Expected Net Present Value of Developing Weight Management Drugs in the Context of Drug Safety Litigation.

BACKGROUND: Following withdrawals, failures, and significant litigation settlements, drug product launches in the anti-obesity category slowed despite a large and growing unmet need. Litigation concerns, a more risk-averse regulatory policy, and the difficulty of developing a product with a compelling risk-benefit profile in this category may have limited innovators' expected return on investment and restricted investment in this therapeutic area. OBJECTIVE: The objective of the study was to estimate perceived manufacturer risk associated with product safety litigation and increased development costs vs. revenue expectations on anticipated return on investment and to determine which scenarios might change a manufacturer's investment decision. METHODS: Expected net present value of a weight-management drug entering pre-clinical trials was calculated for a range of scenarios representing evolving expectations of development costs, revenue, and litigation risk over the past 25 years. These three factors were based on published estimates, historical data, and analogs from other therapeutic areas. RESULTS: The main driver in expected net present value calculations is expected revenue, particularly if one assumes that litigation risk and demand are positively correlated. Changes in development costs associated with increased regulatory concern with potential safety issues for the past 25 years likely did not impact investment decisions. CONCLUSIONS: Regulatory policy and litigation risk both played a role in anti-obesity drug development; however, product revenue-reflecting efficacy at acceptable levels of safety-was by far the most important factor. To date, relatively modest sales associated with recent product introductions suggest that developing a product that is sufficiently efficacious with an acceptable level of safety continues to be the primary challenge in this market.

Estimating the incremental net health benefit of requirements for cardiovascular risk evaluation for diabetes therapies.

PURPOSE: To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. METHODS: We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. RESULTS: The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was -1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18 million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. CONCLUSION: The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or for gone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result.

A systematic review of the economic and humanistic burden of illness in irritable bowel syndrome and chronic constipation.

BACKGROUND: Irritable bowel syndrome (IBS) and chronic constipation (CC) are common functional gastrointestinal disorders affecting 14% and 20% of the U.S. population, respectively. Reviews of the evidence on the burden of illness associated with IBS and CC have not been comprehensive in scope and have not provided an assessment of the distribution of health care costs across categories of resource use. OBJECTIVES: To (a) identify studies from any geographic region or country perspective that measure the economic burden of the disease; (b) analyze the direct (medical, drug, and other components) and indirect costs of illness; and (c) assess published evidence of the humanistic burden as measured by quality of life (QOL). METHODS: An electronic literature search was conducted using journal databases, including MEDLINE, The Cochrane Library, EconLit, CINAHL, and Digestive Disease Week meeting abstracts. Specific search terms used were "irritable bowel syndrome" and "chronic constipation." In databases that accommodated Boolean searches, terms related to economic and quality of life outcomes were incorporated. Studies were included if they evaluated patients with an IBS or CC diagnosis and quantitatively measured the economic or humanistic burden of disease. Results were descriptively analyzed. RESULTS: The search identified a total of 882 unique publications. Thirty-five articles and abstracts met the inclusion criteria. Studies included 1,706 IBS-C, 2,264 IBS-D, 2,892 IBS-A, 15,830 IBS unclassified, and 1,278 CC patients. Nineteen of 35 studies assessed cost-of-illness endpoints, and from the U.S. perspective, the direct cost per-patient for IBS ranged from $1,562 to $7,547 per year, while direct costs of CC ranged from $1,912 to $7,522 per year. From the U.S. perspective, the indirect costs of IBS ranged from $791 to $7,737 per year, and no study assessed the indirect costs of CC. For IBS, data on the distribution of costs attributable to categories of resource use varied widely, particularly outpatient costs (12.7% to > 50% of total costs), inpatient costs (6.2% to 40.8%), and pharmacy or drug costs (5.9% to 46.6%). Comparable data on CC were not identified. Nineteen studies of IBS patients measured the humanistic burden of disease; 14 studies utilized SF-36; and within-study domain scores were significantly lower in IBS patients compared with non-IBS controls. Only 1 study of CC patients reported humanistic burden of disease. CONCLUSIONS: The studies identified in the systematic review varied in the method used to identify patients with IBS and CC. Results were not typically reported by IBS subtype. We observed a large variation in attributable direct and indirect costs and drivers of these costs. Future research should refine burden of illness estimates to subtypes so that estimates associated with IBS-C and CC are differentiated.

Biologic disease-modifying drug treatment patterns and associated costs for patients with rheumatoid Arthritis.

OBJECTIVE: To assess the influence of biologic treatment patterns on healthcare costs for patients with rheumatoid arthritis (RA) initiating tumor necrosis factor-α (TNF-α) antagonist therapy. METHODS: Patients with 2 RA diagnoses (International Classification of Diseases, 9th ed, 714.xx), and without psoriasis or Crohn's disease, were identified in a US employer-based insurance claims database. A sample of 2545 was constructed based on an index event of initiating TNF-α antagonist therapy and 30 months of continuous enrollment. Baseline characteristics were assessed in the 6-month pre-index period and treatment patterns were determined during the 12-month post-index period. Medical service and prescription drug costs were analyzed for Months 13-24 using multivariate regression analysis to control for baseline characteristics and time-varying confounding associated with treatment and disease severity. RESULTS: In the first year after TNF-α initiation, 89% used a single TNF-α antagonist; only 9% and 2% had switched TNF-α antagonists or received non-TNF biologic disease-modifying antirheumatic drugs, respectively. Descriptive analyses revealed pairwise differences between groups (p < 0.05) in baseline characteristics (comorbidities, RA-related procedure use, and prescription drug use). Controlling for observed baseline characteristics, costs were greater for those treated with multiple vs single TNF-α antagonists: annual RA-related prescription drug costs ($8,340 vs $7,058; p = 0.012), RA-related healthcare costs ($15,048 vs $13,312; p = 0.008), and total healthcare costs ($26,697 vs $21,381; p < 0.001). CONCLUSION: In this sample, the majority of patients with RA were treated with a single TNF-α antagonist over the first year on therapy. For those who switched therapy, Year 2 RA-related and total direct healthcare costs were higher, adjusting for claims-based measures of RA disease severity.

Good research practices for cost-effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA Task Force report.

OBJECTIVES: A growing number of prospective clinical trials include economic end points. Recognizing the variation in methodology and reporting of these studies, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) chartered the Task Force on Good Research Practices: Randomized Clinical Trials-Cost-Effectiveness Analysis. Its goal was to develop a guidance document for designing, conducting, and reporting cost-effectiveness analyses conducted as a part of clinical trials. METHODS: Task force cochairs were selected by the ISPOR Board of Directors. Cochairs invited panel members to participate. Panel members included representatives from academia, the pharmaceutical industry, and health insurance plans. An outline and a draft report developed by the panel were presented at the 2004 International and European ISPOR meetings, respectively. The manuscript was then submitted to a reference group for review and comment. RESULTS: The report addresses issues related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members agreed that trials should be designed to evaluate effectiveness (rather than efficacy), should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. Analyses should be guided by an analysis plan and hypotheses. An incremental analysis should be conducted with an intention-to-treat approach. Uncertainty should be characterized. Manuscripts should adhere to established standards for reporting results of cost-effectiveness analyses. CONCLUSIONS: Trial-based cost-effectiveness studies have appeal because of their high internal validity and timeliness. Improving the quality and uniformity of these studies will increase their value to decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions.

Premenstrual dysphoric disorder: is there an economic burden of illness?

OBJECTIVE: To quantify the economic burden associated with premenstrual dysphoric disorder (PMDD) by assessing health care service use and related expenditures, work loss, role limitation, and productivity. METHODS: Women ages 21 to 45, randomly selected from membership of a northern California HMO (n = 1,194), provided prospective daily symptom ratings and survey data on health care use and productivity for two menstrual cycles. Summary measures of 12-month utilization and expenditures based on HMO encounter data also were constructed. Based on daily symptom ratings, we classified women as having minimal (n = 186), moderate (n = 801), and severe (n = 151) premenstrual symptoms, or PMDD (n = 56) and compared health care use and expenditures, predicted values of productivity and work loss, and marginal effects of symptom severity on outcome measures. RESULTS: Women with PMDD had higher degrees of luteal phase (premenstrual) productivity impairment than those with minimal symptoms. Compared with the minimal and moderate symptom groups, women with PMDD continued to report lower productivity (P <0.01) in the 5 to 10 days after onset of menses (follicular phase). We found little evidence that women spent more time in bed, reduced time at work, or decreased activities at home or school as a result of premenstrual symptoms. As symptom severity increased, the likelihood of health care service use increased only for an emergency department, obstetrician/gynecologist, or alternative medicine provider visit. There were no significant differences in health care expenditures across the symptom groups. CONCLUSION: The economic burden associated with PMDD manifests itself primarily in reported productivity decrements rather than health care utilization or costs associated with time away from work.

Severity of premenstrual symptoms in a health maintenance organization population.

OBJECTIVE: To describe severity of emotional and physical symptoms in a large diverse sample; to examine demographic, health status, and behavioral correlates of symptom severity; and to describe use of medications and alternative remedies for premenstrual symptoms. METHODS: A total of 1194 women, ages 21-45, selected from members of a large northern California health maintenance organization, completed daily ratings of symptom severity for two menstrual cycles. An empirically derived algorithm defined symptom severity groups as minimal (n = 186), moderate (n = 801), severe (n = 151), or premenstrual dysphoric disorder (n = 56). Symptom severity as a continuous variable was defined by the two-cycle mean symptom ratings in the luteal phase. Demographic, health status, and behavioral factors and use of treatments for premenstrual symptoms were assessed by self-report. RESULTS: Luteal phase symptom-specific ratings were generally significantly greater in the premenstrual dysphoric disorder group than in the other groups (P <.001). Symptom severity score increased with each comorbidity and decreased with each year of age. Symptom severity was also inversely associated with oral contraceptive use (emotional symptoms) and better perceived health (physical symptoms). Hispanics reported greater severity of symptoms, and Asians less, relative to whites. Use of herbal and nutritional supplements for premenstrual symptoms steadily increased from 10.8% in the minimal group to 30.4% in the premenstrual dysphoric disorder group (P <.01). CONCLUSION: The degree of premenstrual symptom severity varies in the population, is relatively constant within each woman over two consecutive cycles, particularly for emotional symptoms, and is influenced by age, race/ethnicity, and health status.

Cost-effectiveness of antidepressant medications.

BACKGROUND: Antidepressant medications have been shown to effectively relieve symptoms, improve interpersonal and occupational functioning and reduce disability from coexisting medical conditions. Although the newer selective serotonin reuptake inhibitors (SSRIs) have improved tolerability, are easier to take and are associated with longer lengths of therapy when compared with the tricyclic antidepressants (TCAs), the relative cost-effectiveness of alternative antidepressants remains unclear. AIMS OF THE STUDY: This study seeks to determine (i) the probability that relapse or recurrence of depression can be prevented by appropriate antidepressant choice, (ii) the cost associated with relapse or recurrence of depression and (iii) the relative cost-effectiveness of alternative antidepressants. METHODS: We use a quasi-experimental design to compare claims from a state Medicaid plan for TCA and SSRIs users. RESULTS: Premature discontinuation of antidepressant medication is the strongest predictor of relapse and recurrence. Antidepressant choice was not an independent predictor of relapse or recurrence. The effect of relapse and recurrence on expenditures is complex, with a non-significant trend toward lower expenditures for those who had longer periods between episodes of depression two years after initiation of treatment for the first episode. We were unable to replicate prior research results regarding the impact of SSRIs on duration of therapy in this Medicaid plan. CONCLUSIONS: Premature discontinuation of antidepressant treatment is associated with a high probability of relapse and recurrence. Health care expenditures are not altered by preventing relapse and recurrence. We suggest that antidepressant medications associated with reduced probability of premature discontinuation should be considered cost-effective. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: There are very few variables which health care providers can use to improve the outcomes and associated economic consequences of depression. Among these factors, treatment choice and adherence to the prescribed treatment are likely candidates. In this paper, we suggest that adherence to antidepressant medication results in substantial improvement in the time to relapse or recurrence of depression. Choice of an SSRI may thus improve treatment outcome by lengthening remission. In addition, this choice is not associated with higher costs. IMPLICATIONS FOR HEALTH POLICY FORMULATION: Depressive illnesses are associated with high rates of health service use and functional impairment. Thus, the societal burden is quite high. This paper furthers the debate regarding the relative cost-effectiveness of antidepressant medications, and our findings suggest several ways that policy makers can improve the care of depressed individuals at little additional cost. Specifically our findings highlight the importance of adherence to current recommendations regarding the length of antidepressant treatment and suggest several methods for improving this important outcome. IMPLICATIONS FOR FURTHER RESEARCH: The relative cost-effectiveness of alternative antidepressant medications continues to be an important and unsolved issue. We suggest the need for future research in this area using a variety of research designs appropriate to the question. The quasi-experimental approach outlined here seems promising in this regard.