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Introduction: Pruritus is the primary symptom of atopic dermatitis (AD). The objective of this study was to develop a patient-reported outcome (PRO) instrument for daily administration in clinical trials to measure AD-related itch in adolescents and adults that would meet the standards described in the US Food and Drug Administration’s (FDA’s) PRO Guidance. Materials and methods: Six focus groups were conducted with 49 patients with AD (32 adults; 17 adolescents). Three iterative rounds of cognitive debriefing interviews were conducted in 26 patients with AD (17 adults; 9 adolescents) to pretest and refine the instrument. Results: AD-related itching was considered the most bothersome AD symptom by nearly two-thirds of the focus group participants. The items in the initial version of the instrument, named the Atopic Dermatitis Itch Scale (ADIS), were developed to reflect concepts most relevant to the assessment of itching as described during the focus groups. Based on results of the cognitive debriefing interviews, an 8-item final version of the ADIS was created. Conclusion: The ADIS is a content valid PRO instrument addressing the concepts critical to the measurement of AD-related itching. To our knowledge, it is the first instrument developed to assess AD-related itch in patients as young as 12 years following the recommendations of the PRO Guidance.

This trial was conducted to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4 R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect.

Mantle cell lymphoma (MCL) is a rare, aggressive, incurable B-cell malignancy. Ibrutinib has been shown to be highly active for patients with relapsed/refractory (R/R) MCL. The RAY trial (MCL3001) was a phase 3, randomized, open-label, multicenter study that compared ibrutinib with temsirolimus in patients with R/R MCL. Active disease is frequently associated with impaired functional status and reduced well-being. Therefore, the current study employed two patient-reported outcome instruments, the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EQ-5D-5L, to assess symptoms, well-being, health status, and health-related quality of life of patients on treatment within the RAY trial. We found that patients on ibrutinib had substantial improvement in FACT-Lym subscale and total scores, and had improvement in EQ-5D-5L utility and VAS scores compared with temsirolimus patients, indicating a superior well-being. These improvements in well-being correlated with clinical response, indicating that better health-related quality of life was associated with decreased disease burden.

Summary Background The risk of case-fatality following hospitalisation for asthma has not been well characterised. We describe trends in 30 day case-fatality following hospitalisation for asthma in adults in Scotland from 1981 to 2009. Methods Using the Scottish Morbidity Record Scheme (SMR01) with all asthma hospitalisations for adults (≥18 years) with ICD9 493 and ICD10 J45–J46 in the principal diagnostic position at discharge (1981–2009). These data were linked to mortality data from the General Register Office for Scotland (GROS), with asthma case-fatality defined as death within 30 days of asthma admission (in or out of hospital). Logistic regression was used to explore the impact of age, sex, previous asthma admission (in the 12 months prior to hospitalisation), socioeconomic deprivation, year of admission and co-morbidity on 30-day case-fatality. Results There were a total of 116 457 asthma hospitalisations; a total of 1000 (0.9%) hospitalisations resulted in a post-admission death (within 30 days of admission). Odds ratios for unadjusted and adjusted case-fatality showed a decreased risk of case-fatality from the mid-1990s onwards when compared to case-fatality in 1981. Advancing age and co-morbid diagnoses of respiratory failure, cancer, renal failure, cor pulmonale, coronary heart disease and respiratory infection were associated with increased likelihood of death. Conclusions 30 day case-fatality has declined over the last three decades, comparable to case-fatality reported in other parts of the UK. This decline may be in part due to improved guidelines, protocols and disease management for asthma over the last 30 years. The likelihood of death 30 days following an asthma admission increased with age group and was associated with respiratory failure, renal failure and cancer.

To develop and assess content validity of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome (PRO) measure of psoriasis symptoms.Following initial literature exploration and input from experts, concept elicitation was conducted in two rounds (focus groups and individual interviews) with 59 subjects with mild to severe psoriasis. Transcripts were coded to identify symptom concepts and develop a conceptual framework using ATLAS.ti software. Qualitative content analysis and clinical expert input supported item generation and development of a draft measure. Two rounds of face-to-face cognitive interviews with 40 subjects with moderate to severe psoriasis were conducted to test subject comprehension and content coverage.Concepts of itching, scaling, flaking, tearing/cracking, burning, stinging, pain, bleeding and color of appearance were the most common symptom-related expressions. Saturation of concept was demonstrated. Severity was identified as the most meaningful attribute of psoriasis symptoms. A final 8-item measure was developed to assess patient-perceived symptom severity for itch, pain, burning, stinging, cracking, scaling, flaking and redness. Twenty-four-hour recall and 7-day recall versions were prepared for future quantitative assessment of measurement properties.The PSI is a short, low burden, patient-reported measure of psoriasis symptom severity with documented evidence of content validity.

OBJECTIVES: To empirically identify groupings of strength, physical performance, adiposity, and lean mass and test how such groupings of these interrelated measures may relate to disability risk. DESIGN: Prospective Health, Aging and Body Composition Study. SETTING: Two U.S. clinical centers. PARTICIPANTS: One thousand two hundred sixty-three women and 1,221 men. MEASUREMENTS: Weight, strength (knee extension, grip); walking speed, chair stands, dual X-ray absorptiometry (fat and lean mass for total body, arm, and leg; percent fat), and thigh computed tomography scans (muscle area, muscle density). Analyses were stratified according to sex. Factor analysis reduced these variables into a smaller number of components, and proportional hazards models assessed risk of major disability for the components identified. RESULTS: In both sexes, factor analysis reduced the 14 individual variables into three components that explained 76% to 77% of the data variance: Factor 1, an adiposity component, with strong loading by fat mass, weight, and muscle density; Factor 2, a strength and lean body size component with strong loading by lean mass, weight, and strength; Factor 3, a physical performance component with positive loading by walking speed and chair stand performance. Factor 1 (adiposity) and Factor 3 (performance) but not Factor 2 (strength and lean body size) were associated with disability over 6.1±2.6 years. CONCLUSION: The adiposity and physical performance constructs but not the strength and lean body size construct were associated with disability risk, suggesting that adiposity and performance should be considered as risk factors for disability.

Objective The objective of this study was to develop a patient-reported outcome (PRO) to assess reduced muscle strength in sarcopenia. Design Qualitative research study. Setting University of Arkansas for Medical Sciences. Participants Subjects with sarcopenia. Measurements Adults aged 55 years and older with sarcopenia (n = 12) attended open-ended, concept elicitation interviews to characterize the functional effects of reduced muscle strength on their lives. The resulting qualitative data were analyzed using a qualitative analysis software program (Atlas.ti [Atlas.ti GmbH, Berlin, Germany]) and a common set of codes was developed to summarize the data. Subsequently, the initial PRO measure was drafted. Cognitive interviews were then conducted with additional sarcopenia subjects (n = 12) to refine the measure. Results Qualitative interviews identified key concepts (eg, impacts) in the areas of activities of daily living, emotions, social activities, energy, balance, coordination, sleep, and strength. Based on data from the cognitive debriefing interviews (eg, understandability, relevance, suggestions to reword items), the PRO measure development team came to consensus on which items or parts of the instructions to retain, revise, or delete. The final measure included 14 items. Conclusion The final PRO measure, the Age-Related Muscle Loss Questionnaire, can be used in both clinical practice and clinical trial settings to assess functional impacts of reduced muscle strength in sarcopenia.

Background Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial. Objective To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation. Methods This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma. At baseline, patients had an ACQ score ≥1.5. Exacerbations were defined as requirement for systemic corticosteroids. A Cox proportional hazards model was used, with ACQ score as the time-dependent covariate. The analysis was repeated for individual components of the ACQ. Results Each 1-point increase in ACQ was associated with a 50% increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the following 2-week period. Evaluation of individual ACQ components also demonstrated a similar trend, though each to a lesser degree than the full composite ACQ. Conclusion Although based on a retrospective analysis, with small number of exacerbations, these findings support the utility of the composite ACQ score measurement to predict risk of future exacerbation in clinical trials and clinical practice. The composite ACQ score measurement was found to be a better predictor of future risk than individual ACQ components.

The severity of anemia at which to initiate erythropoiesis-stimulating agent (ESA) treatment in nondialysis chronic kidney disease (CKD) patients is unclear. Risk of mortality, hospitalizations, and blood transfusion were compared among nondialysis CKD patients with "early" versus "delayed" ESA initiation.A retrospective cohort study was conducted on CKD (estimated GFR60 ml/min/1.73m(2)) outpatients in the national Veterans Administration who were initiated on ESAs. Patients with ESRD, gastrointestinal bleeding, chemotherapy, or hematologic malignancy were excluded. Patients were characterized as having early [hemoglobin (Hb) 10.0 to 11.0 g/dl] or delayed (Hb 8.0 to 9.9 g/dl) ESA initiation. A propensity score comprising demographic, clinical, and laboratory variables was used to select a 1:1 matched cohort. Cox survival and negative binomial regression were used to compare the matched groups for all-cause mortality, hospitalizations, and blood transfusions.Of 1837 patients who met inclusion criteria, 1410 (77%) were successfully matched. The groups did not differ significantly in 31 characteristics reflecting sociodemographics, comorbidity, healthcare utilization, and renal function. There was no significant difference in mortality with early initiation. Those initiated early had a 17% lower risk of initial hospitalization and a 29% lower risk of transfusion compared with delayed initiation patients. Results did not differ between those with and without pre-ESA transfusion or hospitalization.In nondialysis CKD, ESA initiation at Hb 10.0 to 11.0 g/dl compared with 8.0 to 9.9 g/dl is associated with reduced risk of blood transfusion and initial hospitalization.

Objectives To examine the association between strength, function, lean mass, muscle density and risk of hospitalization.

Objective The 24-week Etanercept Assessment of Safety and Effectiveness (EASE) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis. The objective of this analysis was to assess patient-reported outcomes (PROs) and health-care resource utilization (HRU) data from the EASE study. Methods Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted (single round of discontinuation and re-treatment with etanercept) etanercept 50 mg once weekly for the second 12 weeks. PROs included the following: 1) the patient global assessments of psoriasis, joint pain, and itching scores; 2) the Dermatology Life Quality Index; 3) the Medical Outcomes Study Short Form 36 vitality domain; 4) the Beck Depression Inventory; 5) the European Quality-of-Life Group Feeling Thermometer; and 6) a patient satisfactionsurvey. HRU was evaluated using the Economic Implications of Psoriasis patient questionnaire. Results Continuous treatment with etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks produced sustained and clinically important improvements in PROs and reductions in HRU. Reductions in some outcome measures after treatment discontinuation at week 12 were observed in the interrupted group; however, most changes did not revert to baseline levels, consistent with some residual clinical effect, and re-treatment produced improvements similar to week 12 levels. Conclusions Continuous etanercept treatment provided greater sustained improvements in PROs than interrupted therapy; however, interrupting etanercept therapy, if needed, has predictable and manageable effects.

Objective We sought to assess whether patients with psoriasis with moderate or severe disease are being treated with systemic therapy. Methods Participants were identified from a random sample of the National Psoriasis Foundation contact database who were 18 years and older, with severe psoriasis (>10% body surface area) and moderate psoriasis (3%-10% body surface area); respondents with psoriatic arthritis were excluded. Results In all, 1657 respondents with psoriasis completed the survey (28% severe, 41% moderate). A total of 39% of respondents with severe psoriasis and 37% with moderate psoriasis were not currently receiving any treatment. Among respondents currently receiving therapy, only 43% of respondents with severe psoriasis received either traditional systemic therapy, biologic therapy, or phototherapy. Limitations Respondents were from the National Psoriasis Foundation contact database and reported their current severity, which may be affected by their treatment. Body surface area as a measure of patient-reported severity has not been validated but has been used in several published studies. Conclusions Almost 40% of respondents with psoriasis were currently not receiving treatment. For respondents with severe psoriasis, 26% were treated with systemic therapy, phototherapy, or both; 39% were not in treatment; and 35% were treated with topical therapy alone.

Chiun-Fang Chiou,1 Bruce CM Wang,2 Ronald Caldwell,3 Wesley Furnback,2 Jung-Sun Lee,4 Nathan Kothandaraman,5 SunKyoung Lee,6 Jin Wang,7 Fan Zhang8 1Regional Market Access, Janssen Asia-Pacific, Singapore; 2Elysia Group, LLC, Taipei, Taiwan; 3Department of Economics, University of Michigan, Ann Arbor, MI, USA; 4Department of Psychiatry, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea; 5Government Affairs, Johnson & Johnson Sdn Bhd, Selangor, Malaysia; 6Market Access, Janssen Korea Ltd, Seoul, Korea; 7Strategy and Development, Xian Janssen Pharmaceutical Co, Ltd, 8Medical Affairs, Xian Janssen Pharmaceutical Co, Ltd, Beijing, People’s Republic of China Background: Schizophrenia results in substantial health care utilization costs. Much of these costs can be attributed to health care use resulting from nonadherence to treatment, relapse, and hospitalization.Aims of the study: The objective of this research is to further estimate the health care resource utilization costs of patients with schizophrenia in the People’s Republic of China, Korea, and Malaysia with a specific focus on the reduction in hospitalization costs associated with the use of long-acting, injectable paliperidone palmitate (PP) relative to alternative treatment medications.Methods: The study focuses exclusively on the estimated reduction in hospitalization days following treatment with PP and the potential associated cost savings. Cost analysis was done using a payer’s perspective and only includes direct health care costs associated with hospitalization. Localized cost data were taken from published sources, and health care utilization was estimated based on a clinical study conducted in countries in the Asia-Pacific region. People’s Republic of China, Korea, and Malaysia had the highest number of patients enrolled in the clinical study, and thus were chosen for this research. Analysis looked at 12-month and 18-month periods following initial treatment with PP relative to a retrospective 12-month period utilizing alternative treatment medications.Results: Results suggest that reductions in hospital utilization cost over 12months may occur through the use of PP relative to alternatives – ranging from $1,991 for the People’s Republic of China to $6,698 for Korea and $6,716 for Malaysia.Conclusion: Given the substantial costs associated with the treatment of schizophrenia both worldwide and in Asia, it is important to fully understand the costs and outcomes associated with various treatment options. In this research, we have specifically analyzed the direct health care cost savings associated with hospital utilization for patients taking PP relative to alternative treatment methods. The results suggest that reductions in hospital utilization cost were associated with PP treatment, likely largely due to increased adherence to treatment. Keywords: schizophrenia, antipsychotic treatment, health economics, cost savings&nbsp

Treatment options for the management of rheumatoid arthritis (RA) have expanded from the traditional disease-modifying antirheumatic drugs (DMARDs) to include the biologic DMARDs that inhibit tumor necrosis factoralpha (TNF-a).To assess the medical literature for studies of the economic value of biologic DMARDs, specifically the 3 TNF-a inhibitors (adalimumab, etanercept, and infliximab) used for the management of RA, compared with the traditional DMARDs such as sulfasalazine, antimalarials, penicillamine, gold, methotrexate, azathioprine, leflunomide, and cyclophosphamide.A comprehensive search of the MEDLINE and HealthSTAR databases was conducted to identify cost-efficacy, cost-effectiveness, or cost-utility studies published in the English language (from 1966 through November 2004). The search terms and/or MeSH (medical subject headings) titles were cost-benefit analysis, rheumatoid arthritis, antirheumatic agents, antineoplastic and immunosuppressive agents. Studies were critically reviewed and quality was assessed using the Quality of Health Economic Studies instrument. Most studies evaluated the use of biologics among RA patients resistant to DMARDs. Studies were assessed with regard to comparators evaluated, measures of efficacy, perspectives, model duration, treatment duration, and discount rate.From 180 titles identified, 155 were excluded for the following reasons: 89 because they did not consider the drugs of interest, 15 because the population was not RA, 19 because of having the wrong drugs and population, 22 because they were review articles, and 10 because they were general articles. Twentyfive abstracts were accepted for further review. Of these, 13 abstracts were subsequently selected for full-text review. One of the authors identified a study not indexed in MEDLINE. Ultimately, 2 cost-effectiveness and 6 cost-utility studies were selected for this critical review. One study over 6 months reported that triple therapy with DMARDs (methotrexate-hydroxychloroquine-sulfasalazine) was cost effective for methotrexate-resistant patients, which is consistent with American College of Rheumatology (ACR) guidelines that support the use of triple therapy prior to biologics. The incremental cost-effectiveness ratio (ICER) was $1,500 per patient to achieve an ACR20 response for this triple therapy compared with no second-line agent. Overall, biologic therapies cost considerably more than traditional DMARDs but produced more quality-adjusted life-years (QALYs). Despite differences in design and assumptions, published economic models consistently reported ICERs50,000 dollars per QALY gained for biologics compared with traditional DMARDs, although ICERs of100,000 dollars were reported from sensitivity analyses.Clinical guidelines currently recommend the use of biologics as step therapy after failure of traditional DMARDs. Reported ICERs comparing biologics with traditional DMARDs are within a range that is comparable with other accepted medical interventions. The worth of the additional expenditure will ultimately be judged by formulary and policy decision makers because no maximum cost has been defined. Models can be used to inform decision makers, but they must be interpreted and applied carefully. More research is also needed to differentiate the relative economic value of the various biologic agents by therapeutic indication.

Objective. To develop a multi-attribute outcome measure for children with asthma that allows for the calculation of quality-adjusted life years in cost-effectiveness studies and can also be used to assign preference weights to asthma-symptom-free days. Study design. A literature review and two interviewer-administered surveys. Setting. Homes or community centers of participants in Seattle, United States. Main measures. Visual analog scale (VAS), standard gamble (SG), and relative risk attitude equation techniques were used to estimate two sets of preference weights for 10 health states. The PAHOM was used to record health states of pediatric asthma patients. Results. A total of 94 subjects provided complete responses without any illogical ratings to VAS questions and 101 provided the same to SG questions. The VAS preference weights of the health states range from a maximum of 1 for perfect health to a minimum of 0.03 for severe asthma symptoms, emotional problems, and activity limitations. Those based on the relative risk attitude equation constructed with both VAS and SG preference weights range from 1 to 0.06. The mean PAHOM scores of pediatric asthma patients based on VAS and converted SG preference weights were 0.70 and 0.83, respectively. Conclusions. The PAHOM calendar can be used to identify asthma patients’ health outcomes, to calculate the preference weights of asthma patients’ health states, and to estimate the number of symptom-free days. These factors make the PAHOM a promising instrument for use in effectiveness and cost-effectiveness studies in children with asthma.

Objective To appraise the cost-effectiveness of competing therapeutic strategies in patient cohorts eligible for aspirin prophylaxis with varying degrees of gastrointestinal (GI) and cardiovascular risk. Methods Cost-effectiveness and cost-utility analyses were performed to evaluate 3 competing strategies for the management of chronic arthritis: 1) a generic nonselective nonsteroidal antiinflammatory drug (NSAIDNS) alone; 2) NSAIDNS plus a proton pump inhibitor (PPI); and 3) a cyclooxygenase 2-selective inhibitor (coxib) alone. Cost estimates were from a third-party payer perspective. The outcomes were incremental cost per ulcer complication avoided and incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was performed to evaluate the impact of varying patient GI risks and aspirin use. Results In average-risk patients, the NSAIDNS + PPI strategy costs an incremental $45,350 per additional ulcer complication avoided and $309,666 per QALY gained compared with the NSAIDNS strategy. The coxib strategy was less effective and more expensive than the NSAIDNS + PPI strategy. Sensitivity analysis revealed that the NSAIDNS + PPI strategy became the dominant approach in patients at high risk for an NSAID adverse event (i.e., patients taking aspirin with ≥1 risk factor for a GI complication). Conclusion Generic nonselective NSAIDs are most cost-effective in patients at low risk for an adverse event. However, the addition of a PPI to a nonselective NSAID may be the preferred strategy in patients taking aspirin or otherwise at high risk for a GI or cardiovascular adverse event.

Background & Aims: Health economic analyses are increasingly common in the digestive diseases literature and often are cited to frame practice guidelines. Although clinical trials are subjected routinely to critical appraisal, there has been no attempt to appraise the quality of health economic analyses with a validated instrument. We sought to appraise the quality of health economic analyses in digestive diseases, and to identify predictors of study quality. Methods: We performed a systematic review to identify digestive disease health economic analyses published since 1980. We assessed these studies using the Quality of Health Economic Studies (QHES), a validated quality-scoring instrument (score range 0 –100; >75 high quality). We conducted regression analysis to identify predictors of high quality. Results: Of 186 identified analyses, 29% were high quality, 71% failed to address potential model biases, 52% failed to disclose conflicts of interest, and 74% failed to describe methods for deriving the model assumptions. Four factors predicted high quality in logistic regression: (1) one or more authors had an advanced degree in health services or a related field (odds ratio for high quality, 5.0; 95% confidence interval, 2.6 –9.3); (2) the study used decision-analysis software package (odds ratio, 2.4; 95% confidence interval, 1.2– 4.7); (3) the study was federally funded (odds ratio, 2.2; 95% confidence interval, 1.2– 4.1); and (4) the study cited the National Panel on Cost Effectiveness guidelines (odds ratio, 2.1; 95% confidence interval, 1.1– 4.2). Conclusions: Less than one third of health economic analyses in digestive diseases meet criteria for high quality. Study quality is limited by factors that potentially can be remedied. These data may be used to focus the attention of journal editors and peer reviewers to ensure the future high quality of health economic analyses in digestive diseases.

Objective To examine from the health care services payer perspective the economic consequences of contraceptives available to women in the United States. Methods A Markov model was constructed to compare effectiveness and costs among nine contraceptive methods (including 3-month injectable, oral contraceptives, intrauterine device (IUD), intrauterine system (IUS), barrier methods and surgical methods). Primary health states included initial/continued use, method failure and method discontinuation with transitions every year for 5 years. Plan disenrollment was also incorporated in the model. Estimates for probabilities of events, resource used, and costs for the base-case were derived from a comprehensive literature review, average wholesale drug prices, the 2000 Medicare Reimbursement Fee Schedule and MEDSTAT’s 2000 DRG Guide, in conjunction with expert opinion. Sensitivity analyses were performed on all variables. Results Aside from vasectomy, which was outside the scope of this study, the most effective methods were tubal ligation, levonorgestrel (LNG)-20 IUS and copper T 380A IUD. The least expensive methods (accounting for all costs) were LNG-20 IUS, copper T 380A IUD and 3-month injectable; the 5-year cost/person were $1646, $1678 and $2195, respectively. Conclusion From a third-party payer perspective, LNG-20 IUS and copper T 380A IUD dominated all reviewed methods, except for tubal ligation. However, the small increase in contraceptive efficacy with tubal ligation has a high cost. IUD and IUS device costs have a significant impact on the relative cost-effectiveness of these two methods.

Objective We performed an evaluation of patient symptoms, health care use, and costs to define the burden of illness of irritable bowel syndrome (IBS) and the relation to the severity of abdominal pain/discomfort in a large health maintenance organization. Methods All 6500 adult health maintenance organization members who had undergone flexible sigmoidoscopy in the year 2000 were mailed a questionnaire that elicited Rome I symptom criteria and severity ratings for abdominal pain/discomfort. Multiple health care use measures were obtained from various administrative databases. IBS patients were compared with a control group of non-IBS subjects, and analyses were adjusted for age and sex. Results We received 2613 (40.2%) responses. Compared with non-IBS subjects over 2 yr, IBS patients had more outpatient visits (medical, surgery, and emergency, p < 0.05), were hospitalized more often (p < 0.05), and had more total outpatient prescriptions (p < 0.05) and IBS-related prescriptions (p < 0.05). Over 1 yr, total costs were 51% higher in IBS patients, who also had higher costs for outpatient visits, drugs, and radiology and laboratory tests (p < 0.05). Total costs were increased by 35%, 52%, and 59% in IBS patients with mild, moderate, and severe symptoms of abdominal pain/discomfort compared with non-IBS subjects (p < 0.05). Conclusions Using Rome I symptom criteria, we found that IBS is associated with a broad pattern of increased health care use and costs. The severity of abdominal pain/discomfort is a significant predictor of health care use and costs for patients with IBS compared with non-IBS subjects.

OBJECTIVE: Several strategies exist for the prevention of recurrent ulcer-related hemorrhage, yet the cost-effectiveness has not been evaluated and remains uncertain. The aim of this study was to compare the cost-effectiveness of competing management strategies considering both nonsteroidal anti-inflammatory drugs status and the accuracy of Helicobacter pylori (H. pylori) testing. METHODS: Decision analysis was used to compare the cost-per-recurrent hemorrhage prevented for 11 strategies over 1 yr. Clinical and costs estimates were derived from a systematic review of the medical literature and the Medicare Fee Schedule and Drug Topics Redbook. Sensitivity analyses were performed for important variables. RESULTS: The test/retest eradication strategy with maintenance proton pump inhibitor therapy for H. pylori-negative patients was most effective (prevention of recurrence in 96.0%). The test/retest eradication strategy with maintenance histamine-2 receptor antagonist therapy for H. pylori-negative patients was least costly ($1070). The test/retest strategies were dominant with average cost-effectiveness ratios of $1118–1310/recurrent hemorrhage prevented with maintenance antisecretory therapy. The average cost-effectiveness ratios for “selective” H. pylori eradication strategies with maintenance antisecretory therapy were $1263–1673. The model was robust to varying estimates over prespecified ranges. CONCLUSIONS: Test/retest strategies for H. pylori are cost-effective for the prevention of recurrent ulcer-related hemorrhage because they maximize H. pylori detection and eradication, resulting in fewer recurrent hemorrhages and fewer patients requiring antisecretory therapy.

To empirically identify groupings of strength, physical performance, adiposity, and lean mass and test how such groupings of these interrelated measures may relate to disability risk.Prospective Health, Aging and Body Composition Study.Two U.S. clinical centers.One thousand two hundred sixty-three women and 1,221 men.Weight, strength (knee extension, grip); walking speed, chair stands, dual X-ray absorptiometry (fat and lean mass for total body, arm, and leg; percent fat), and thigh computed tomography scans (muscle area, muscle density). Analyses were stratified according to sex. Factor analysis reduced these variables into a smaller number of components, and proportional hazards models assessed risk of major disability for the components identified.In both sexes, factor analysis reduced the 14 individual variables into three components that explained 76% to 77% of the data variance: Factor 1, an adiposity component, with strong loading by fat mass, weight, and muscle density; Factor 2, a strength and lean body size component with strong loading by lean mass, weight, and strength; Factor 3, a physical performance component with positive loading by walking speed and chair stand performance. Factor 1 (adiposity) and Factor 3 (performance) but not Factor 2 (strength and lean body size) were associated with disability over 6.1 ± 2.6 years.The adiposity and physical performance constructs but not the strength and lean body size construct were associated with disability risk, suggesting that adiposity and performance should be considered as risk factors for disability.

In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated.To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe plaque psoriasis.A total of 912 patients received 50 mg subcutaneous etanercept once weekly (OW) for the first 12 weeks of this extension study. Thereafter, eligible patients could maintain the 50 mg QW dose (n = 321) or escalate to 50 mg twice weekly (BIW; n = 591) anytime thereafter based on one of three predetermined criteria.Etanercept was well tolerated during 1056 patient-years of exposure; no difference was observed between the 50 mg QW and 50 mg BIW dosages in rates of adverse events and infections. Improvement in skin disease was maintained throughout the study. Patients who stopped and then restarted etanercept also showed improvement in psoriasis.Psoriatic patients continued to benefit from open-label etanercept treatment, both continuous and interrupted therapy, which was generally well tolerated after a combined 2.5 years of experience.

Objective.To evaluate the effects of etanercept treatment on patient-reported outcomes (PRO) in patients with psoriatic arthritis (PsA).Methods.A 24-week double-blind comparison to placebo was followed by a 48-week open-label phase in which all eligible patients received etanercept. PRO were measured using the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), the Medical Outcomes Study Short-Form (SF-36), the EQ-5D visual analog scale (VAS), and the American College of Rheumatology (ACR) patient pain assessment.Results.Beginning at Week 4 and continuing through Week 24 of double-blind treatment, patients treated with etanercept had significantly higher mean percentage improvement in HAQ-DI relative to baseline than patients given placebo (53.6% vs 6.4% at Week 24; p < 0.001). After 48 weeks of open-label treatment with etanercept, the mean percentage change from study baseline was 52.8% for the original etanercept group and 46.9% for the original placebo group, with 41.2% of patients overall achieving a HAQ-DI of 0. Mean changes relative to baseline for SF-36 physical component summary scores, EQ-5D VAS, and ACR pain assessment were also significant in the double-blind period for etanercept compared with placebo (p < 0.001 for all 3 measures). Patients taking placebo achieved similar improvements once they began treatment with etanercept in the open-label period.Conclusion.Patients with PsA treated with etanercept reported significant improvements in physical function that were almost 10 times the improvement seen with placebo and were maintained for up to 2 years. Almost half of patients treated with etanercept reported no disability by the end of the study.

Although insulin is the most effective diabetes medication for lowering blood glucose, how insulin is used in clinical practice and how well patients respond to insulin therapy over the course of several years has not been documented. Our objective was to describe glycemic control, side-effects and dose titration over 7 years among persons starting insulin in a health plan that has long used a treatment algorithm similar to the current American Diabetes Association/European Association for the Study of Diabetes (ADA-EASD) algorithm for the management of hyperglycemia.Patients (n = 2417) who initiated insulin therapy between 1 January 1999 and 31 December 2004 were followed for a mean of 49.5 months until 30 June 2007, death, or health plan termination. Mean hemoglobin A1C, number of units of insulin purchased and body weight were assessed on a quarterly basis. The proportion experiencing edema or hypoglycemia was assessed annually.Mean population A1C declined from 9.3 to 7.8% following insulin initiation and remained at that level for 7 years. However, A1C remained above 8% for 40% of patients, half of whom remained above 9.0%. The mean individual coefficient of variation in A1C was 0.12 (inter-quartile range 0.072-0.143). Mean daily insulin dosage started at 55 units and increased to approximately 100 units. Patients gained a mean of 6 lb (2.7 kg) during the first year then gained weight more gradually thereafter. Physicians diagnosed edema in 8-9% of patients annually. Hypoglycemia occurred in fewer than 2% of patients in any given year, with no cases requiring hospitalization.Insulin lowered mean A1C by about 1.5 percentage points to stable levels, but this required ongoing dosage increases. Nevertheless, many patients remained in poor control. Insulin is effective when used per ADA-EASD guidelines but health plans wishing to optimize diabetes care may need to intensify insulin therapy or consider the use of adjunct therapies in the years after initiation. This study was limited by its observational descriptive design, and its reliance on insulin purchases rather than actual consumption.

This review compares the cost-effectiveness of four biologics - adalimumab (Humira, Abbott Laboratories), anakinra (Kineret, Amgen Inc.), etanercept (Enbrel, Wyeth) and infliximab (Remicade, Schering-Plough) - used in the treatment of rheumatoid arthritis. A decision analytic model was constructed to estimate the costs and effectiveness of these biologics used alone or in combination with methotrexate during 1 year, from the perspective of a managed care organization. The direct costs consisted of drugs and healthcare resources. Effectiveness was measured by quality-adjusted life years based on preference weights and health states in which patients achieved one out of four levels of response according to the American College of Rheumatology (ACR) response criteria (No ACR, ACR20, ACR50 and ACR70), and experienced one of the four levels of adverse events (e.g., no, mild, moderate and severe) due to their treatments. Results were sensitive to changes in treatment costs and probabilities of health states in directions as predicted. For monotherapy and combination therapy regimens, anakinra was the least expensive option while etanercept dominated other treatments.

Clinical trials of biologic agents have established the efficacy of these agents in improving outcomes among individuals with moderate to severe rheumatoid arthritis (1–3). Results of these trials are usually based on ACR 20/50/70 responder criteria or EULAR improvement criteria, which include some patient-reported outcomes, but patient-reported outcomes have not traditionally been the primary focus of clinical trials. More recently, some studies have begun to focus on patient-reported outcomes such as joint pain, pain severity, fatigue, and function (4–6). A limited number of these trials have evaluated results beyond one year. For example, of the trials evaluated by Chen and colleagues for a systematic review of the effectiveness of various biologic agents, only 2 of 11 trials of etanercept extended beyond 12 months, and the longest noted trials of infliximab were 54 weeks (for 4 of 9 trials)(1). Similarly, Gartlehner noted in another systematic review of 26 trials of biologic agents that the longest trial was 52 weeks (7). In addition, patients enrolled in clinical trials are selected based on very strict inclusion and exclusion criteria and treatment is defined by the clinical trial protocol. Patients are assigned to treatments randomly to assess the efficacy of the treatment being studied accurately and to minimize differences between treatment groups. However, in community practice, treatment assignment is not random and care is not as strictly controlled, so effectiveness may differ from the efficacy seen in clinical trials. In 1998, two biologic agents, etanercept and infliximab were approved for the first time for the treatment of individuals with moderate to severe RA. Given the high cost of these agents, it is important to assess how treatment is being allocated and whether individuals on treatment long-term are receiving meaningful benefits from treatment. Some community-based studies suggest that patients who receive biologic agents have worse function and pain than those who do not (6). The purpose of this analysis was to examine self-reported symptoms and functioning of persons with RA treated by community rheumatologists who initiated biologic agents, and changes in symptoms and function after up to two years of use, compared to a group of individuals from the same cohort who did not use biologic agents.

Moderate to severe psoriasis is a significant inflammatory disease that frequently requires systemic therapies to effectively treat the underlying disorder. Etanercept and narrow-band ultraviolet light B (NB-UVB) are widely used to treat this disease.To evaluate the effectiveness, tolerability, and patient-reported outcomes of combination etanercept plus NB-UVB phototherapy in moderate to severe plaque psoriasis.This 12-week, single-arm, open-label study evaluated the combination of etanercept 50 mg twice weekly and NB-UVB thrice weekly in 86 patients. The primary outcome measure wasor =75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75). Other measures included PASI 90, PASI 100, and the Dermatology Life Quality Index (DLQI).At week 12, 26.0% achieved PASI 100, 58.1% achieved PASI 90, and 84.9% of patients achieved PASI 75. Mean improvement from baseline in DLQI was 84.4%. No unexpected, untoward adverse events were noted.A 12-week course of etanercept plus NB-UVB phototherapy was well tolerated and produced clinically meaningful improvements in signs and symptoms of moderate to severe plaque psoriasis and in patient-reported outcomes. Further investigation of the safety and efficacy of the use of such combination for this indication in controlled clinical trials would be of interest.

To examine the longterm effect of etanercept (ETN) therapy on health-related quality of life (HRQOL) and utility in patients with ankylosing spondylitis.Patients completing a 24-week placebo-controlled trial were continued on ETN in a 72-week open-label extension study. Short Form-36 (SF-36), EuroQOL-5D (EQ-5D), and EuroQOL visual analog scale (EQ-VAS) scores were collected at open-label baseline and every 12 weeks thereafter. Mental and physical component scores (MCS and PCS) of the SF-36, EQ-5D and SF-6D utility scores, and quality-adjusted life-years (QALY) were calculated.257 patients [129 previous placebo (PLA) and 128 ETN recipients] enrolled in this open-label extension study, and 85% completed the 72-week followup. PCS, EQ-5D and SF-6D utilities, and EQ-VAS were significantly lower at open-label baseline in the previous PLA group (PLA/ETN group) than in the previous ETN group (ETN/ETN group; all p0.001). At week 12, PCS and MCS, EQ-5D and SF-6D utility scores, and EQ-VAS were similar in the PLA/ETN and ETN/ETN groups. As expected, mean change in EQ-5D in the PLA/ETN group was significantly greater than that for SF-6D (0.18 vs 0.06; p0.0001). HRQOL and utility improvements were maintained in both groups for up to 72 weeks. The average 72-week QALY gain per person in the PLA/ETN group was 0.24 and 0.10 for EQ-5D and SF-6D, respectively.Patients continuing ETN therapy sustained HRQOL and utility improvements attained during the original PLA-controlled trial. Patients previously taking PLA showed rapid and sustained improvements in HRQOL and utility and substantial QALY gain with ETN therapy.

Experience Diagnosing, Understanding Care, and Treatment With Etanercept (EDUCATE) is a multicenter, phase 4, 24-week, open-label study of the safety and efficacy of etanercept therapy in patients with psoriatic arthritis (PsA) in routine dermatologic practice. We present data on patient-reported outcomes (PROs) from EDUCATE, which demonstrate that subjects with PsA achieved clinically meaningful improvements in both skin- and joint-related PROs after 24 weeks of treatment.

The Experience Diagnosing, Understanding Care, and Treatment with Enbrel (EDUCATE) trial is a phase IV, 24-week, multicenter, open-label study of etanercept 50 mg weekly in the treatment of psoriatic arthritis (PsA) in community dermatology clinics. In this study, patients with active PsA and moderate to severe plaque psoriasis have measurable uses of healthcare resources at baseline, reflecting a burden of illness. Etanercept significantly reduced healthcare resource utilization, absenteeism, and caregiver assistance in PsA patients after 24 weeks of treatment. These results could translate into savings on both direct and indirect costs and improvements in health-related quality of life for patients with PsA.

Fan Zhang,1 Tianmei Si,2,3 Chiun-Fang Chiou,4 Anthony WF Harris,5 Chang Yoon Kim,6 Padmashree Jahagirdar,7 Steve Ascher8 1Xian Janssen Pharmaceuticals, Beijing, People’s Republic of China; 2Department of Clinical Psychopharmacology, Peking University Institute of Mental Health, Beijing, People’s Republic of China; 3Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, People’s Republic of China; 4Janssen Asia-Pacific, Singapore; 5Discipline of Psychiatry, Sydney Medical School, University of Sydney, Australia and Brian Dynamics Center, Westmead Millennium Institute for Medical Research, Westmead, NSW, Australia; 6Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 7Theorem Clinical Research, Bangalore, India; 8Janssen Research and Development, LLC, Titusville, NJ, USA Objective: To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics.Methods: In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18–50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50–150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods.Results: A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18 (mean [standard deviation, SD] change: -11.3 [21.38], P

Objective To improve accuracy and content coverage of the original 33-item Cedars-Sinai Health-Related Quality of Life for Rheumatoid Arthritis Instrument (CSHQ-RA). Methods A total of 312 RA patients from 55 sites were screened in a 24-week trial. Patients completed an expanded 48-item version of the CSHQ-RA, Medical Outcomes Study Short Form 36 (MOS SF-36), and Stanford Health Assessment Questionnaire (HAQ) Disability Index at 5 visits. The revised CSHQ-RA was created based on response frequencies and distributions, item-to-item correlation, factor and Rasch analysis, and input from experts. Psychometric evaluation included internal consistency, test–retest reliability, convergent and discriminant validity, and responsiveness. Minimum clinically important difference (MCID) was also measured. Results Response rates were 93% at baseline and 71% at 12 weeks. Eighty-one percent of respondents at baseline were women, mean ± SD age was 52 ± 12 years, and mean ± SD duration of RA was 10.8 ± 10.4 years. The revised CSHQ-RA included 36 items measuring 7 domains (4 original and 3 new). All Cronbach's alpha coefficients were >0.8, indicating good internal consistency. Test–retest reliability measured intraclass correlation coefficients, which ranged from 0.86 to 0.95. All 7 domains correlated significantly with the MOS SF-36 and HAQ, indicating good convergent validity. Analysis of variance of disability group scores showed good discriminant validity (P < 0.0001). The MCIDs ranged from 6.2 for social well-being to 14.8 for pain/discomfort. Conclusion The revised CSHQ-RA was validated using a broader RA patient population. It captures 3 additional domains (social well-being, pain/discomfort, and fatigue), which allow for measuring all important aspects of health-related quality of life.

To develop and validate multiattribute measures for patients with rheumatoid arthritis (RA) to report health states and estimate preference weights.Survey materials were mailed to 748 patients. Factor analysis, an item response theory-based model, and an internal consistency test were used to identify attributes and evaluate items. Two multiattribute preference weight functions (MAPWF) were constructed. Construct validity of the new measures was then tested.Four hundred eighty-seven patients returned the survey; 24 items on 6 health attributes were selected to form the new outcomes measure. Two MAPWF were derived with preference weights measured with time tradeoff and visual analog scales as dependent variables. All validity test results were statistically significant.Our results reveal that the new measures are reliable and valid in assessing health states and associated preference weights of patients with RA.

In an effort to assess the burden associated with psoriasis, the MEDLINE database and bibliographies of articles published from 1975 through 2004 were searched, emphasizing patients with moderate-to-severe disease, to summarize the current understanding on various aspects of disease burden. The clinical burden of psoriasis is both well documented and significant. The disease is debilitating: Sufficient disease severity interferes with patients' work and day-to-day living. Perhaps even more damaging is the psychosocial toll psoriasis exacts on the afflicted. Numerous studies document the extent of mental and emotional anguish, features not often revealed through objective measures. Successful treatment must focus on improving a patient's quality of life as well as reducing the clinical features of psoriasis. The economic burden is also significant, though far fewer studies of the associated indirect costs have been published in the literature.

Background Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment is limited by the lack of validated instruments. We developed and validated a new treatment-specific patient satisfaction instrument: the Patient Satisfaction Questionnaire for Anemia Treatment (PSQ-An). Treatment burden and overall satisfaction scales were designed for ease of use in clinical practice. Methods 312 cancer patients (141 breast, 69 gynecological, and 102 non-small cell lung) were targeted to complete the PSQ-An at 4 week intervals. Data from weeks 5 and 9 were analyzed. Patients also completed the MOS SF-36 Global Health assessment and questions concerning resources devoted to anemia treatment. Item reduction used endorsement rates, floor/ceiling effects, and item-item correlations. Factor analysis identified meaningful subscales. Test-retest reliability was assessed. Construct validity was tested, using Pearson's correlations, by comparing subscale scores to Global Health, hemoglobin levels, and resources devoted to anemia treatment. Results The overall response rate was 92.9% (264/284) at week 5. Most (84.2%) of the patients were female, and the mean (SD) age was 60.2 (± 11.8) years. Two distinct subscales were identified measuring treatment burden (7 items) and overall satisfaction (2 items). Test-retest reliability was examined (ICC: 0.45–0.67); both were internally consistent (alpha = 0.83). Both subscales exhibited convergent and divergent validity with independent measures of health. ANOVA results indicated that the PSQ-An Satisfaction subscale discriminated between 5 levels of MOS SF-36 Global Health (P = 0.006). Conclusion The PSQ-An is a validated, treatment-specific instrument for measuring satisfaction with anemia treatment for cancer patients. PSQ-An subscales reflect the burden of injection anemia treatment on cancer patients and their assessment of the overall treatment value.

To assess the psychometric characteristics of the original 33-item Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis Questionnaire (O-CSHQ-RA) and 11-item CSHQ-RA Short Form (SF) using a representative population of patients with rheumatoid arthritis (RA) from 55 sites across the United States.Data were from a 24-week multicenter, open-label, single-arm study of 312 RA patients receiving anakinra. Cronbach's alpha coefficient was used to indicate the internal consistency. Test-retest reliability was assessed by establishing the intraclass correlation coefficient (ICC) for screening and baseline visit responses. Convergent validity was tested with the Pearson correlation coefficient. Analysis of variance was performed to determine discriminant validity. A Wilcoxon signed-rank test and analysis of covariance were used to assess the responsiveness. A discriminant function was generated to determine the clinically meaningful change.Test-retest reliability was demonstrated for both versions of the CSHQ-RA, with ICC ranging from 0.82 to 0.94. Cronbach's alpha coefficients wereor = 0.9, indicating good internal consistency. Pearson correlations between health-related quality of life instruments and CSHQ-RA measures ranged from -0.33 to -0.73 and 0.39 to 0.76, demonstrating good convergent validity. Scores on both versions of the CSHQ-RA differed significantly (p0.0001) for patients with different levels of physical disability as measured by the Stanford Health Assessment Questionnaire. Both instruments were responsive to differences in patient health as measured by the general health question (p0.0001). Clinically meaningful changes were calculated for all 5 domains of the O-CSHQ-RA (6.9-14.0) and the overall O-CSHQ-RA SF (12.7).These results support the validity and reliability of both the original CSHQ-RA and the 11-item CSHQ-RA SF when tested in a representative patient population.

To estimate weights for health states comprising American College of Rheumatology (ACR) response and different levels of adverse events associated with rheumatoid arthritis (RA) treatments.A survey was mailed to 748 patients with RA from southern California. In addition to several questionnaires commonly used for patients with RA, patients were instructed to evaluate 10 hypothetical health states, in which they could have an ACR response and/or adverse events due to new treatments, with a visual analog scale (VAS). Patients also evaluated their current health with a VAS question and a time tradeoff (TTO) question. Linear extrapolation was used to derive 6 more health states. The Pearson correlation coefficient was used to validate VAS and TTO results.A total of 487 (65%) patients returned the survey. Among the 10 health states evaluated with VAS directly, the health state in which a patient has ACR70 with no adverse events had the highest VAS weight (0.84), followed by the one having an ACR50 response with no adverse events (0.80). Correlation coefficients ranged from 0.63 for the correlation between VAS and physical component summary to -0.18 between TTO and pain and tender joint count; the correlation coefficients were all statistically significant, indicating there was convergent validity of the VAS and that VAS functioned differently from TTO in how it measured weights.VAS weights for 16 ACR response health states of patients with RA were derived. These weights could be used for cost-utility analyses of interventions for patients with RA.

Background & Aims: Treatment-induced anemia undermines the efficacy of antiviral therapy in hepatitis C by mandating ribavirin dose reduction and diminishing adherence to therapy. Erythropoietic growth factors (EGFs) may correct treatment-induced anemia, facilitate maintenance of full-dose therapy, and improve rates of sustained virologic response (SVR). We sought to determine the cost effectiveness of adjunctive treatment with an EGF vs standard care in the treatment of hepatitis C. Methods: We used a decision analysis to calculate the cost effectiveness of 2 treatment strategies for a patient cohort with chronic hepatitis C, increased transaminase levels, and no cirrhosis who were receiving pegylated-interferon and ribavirin (RBV): (1) RBV dose-reduction for anemia, followed by discontinuation of therapy if anemia persisted (standard care strategy), (2) adjunctive treatment with EGF therapy for anemia, with RBV dose reduction reserved for persistent anemia despite EGF therapy (EGF strategy). We conducted cost-effectiveness and cost-utility analyses to compare short- and long-term outcomes between the strategies. Results: The percentage achieving SVR was 52.3% in the standard care strategy and 59.5% in the EGF strategy. Compared with standard care, the EGF strategy cost an incremental $36,568 per unadjusted life-year gained and $16,443 per quality-adjusted life-year gained. In a sensitivity analysis, if a third-party payer was willing to pay $50,000 per quality-adjusted life-year gained for the use of an EGF, then 86.1% of patients would be within the budget. Conclusions: Compared with standard care, adjunctive therapy with an EGF for the management of treatment-induced anemia may increase the probability of achieving SVR, increase unadjusted lifespan, and increase quality-adjusted lifespan at an acceptable cost.

To quantify the economic impact of premenstrual syndrome (PMS) on the employer.Data were collected from 374 women aged 18-45 with regular menses. Direct costs were quantified using administrative claims of these patients and the Medicare Fee Schedule. Indirect costs were quantified by both self-reported days of work missed and lost productivity at work. Regression analyses were used to develop a model to project PMS-related direct and indirect costs.A total of 29.6% (n = 111) of the participants were diagnosed with PMS. A PMS diagnosis was associated with an average annual increase of $59 in direct costs (P0.026) and $4333 in indirect costs per patient (P0.0001) compared with patients without PMS.A PMS diagnosis correlated with a modest increase in direct medical costs and a large increase in indirect costs.

To develop an abridged version of the 33-item Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis instrument (CSHQ-RA) and test the validity and reliability of the abridged instrument.Items from the original 33-item, 5-domain CSHQ-RA were assessed using psychometric and regression analyses of survey responses from 274 patients with rheumatoid arthritis. Items were retained in the final instrument based on statistical analysis and evaluation by an expert panel. Test-retest reliability, internal consistency, convergent and discriminant validity, and ceiling and floor effects were examined for the shortened CSHQ-RA.Statistical analysis and expert assessment yielded an 11-item instrument including questions in 4 domains. Test-retest reliability and internal consistency were high and the instrument showed good convergent and discriminant validity.The abridged CSHQ-RA short form is a valid and reliable instrument that can be used to examine the impact of RA on patients' health-related quality of life. Prospective validation in clinical trial settings is warranted.

The relationship between the severity of abdominal discomfort/pain and generic and disease-specific quality of life (QoL) was explored in patients with irritable bowel syndrome in an MCO. Subjects were stratified into four symptom-severity groups. Descriptive and multivariate analyses were used to examine the relationship of QoL to severity of abdominal discomfort/pain. Generic and disease-specific QoL scores declined as severity of abdominal discomfort/pain increased. The lowest 36-Item Short-Form Health Survey scores for respondents with the most severe abdominal discomfort/pain were for role physical (24.2 +/- 35.4) and vitality (33.7 +/- 19.2). In multivariate regression models controlling for age, sex, work status and education, severity of abdominal discomfort/pain was a significant independent predictor of QoL.

Objective To test the validity and reliability of a newly developed disease-specific multidimensional quality of life instrument: the Cedars-Sinai Health-Related Quality of Life Instrument (CSHQ-RA). Methods A total of 350 rheumatoid arthritis (RA) patients were asked to complete the CSHQ-RA at 2 time points (4 weeks apart). Patients also completed the Medical Outcomes Study Short Form 36 (SF-36) and the Stanford Health Assessment Questionnaire (HAQ) Disability Index (DI) at the second time point. Construct validity was tested, using Pearson's correlations, by comparing subscale scores on the CSHQ-RA to those obtained from the mental component summary (MCS) and physical component summary (PCS) of the SF-36. HAQ DI scores were used to assess the discriminant validity of the CSHQ-RA. Intraclass correlation coefficients (ICCs) were used to assess test–retest reliability. Results Response rates for the first and second survey were 83% (291) and 93% (276), respectively; 84% of respondents were women, and mean age was 57 years. Mean scores ± SDs on instruments were: HAQ 0.73 ± 0.69; MCS 49 ± 12; and PCS 33 ± 11. Pearson's correlations between the CSHQ-RA subscale scores and the SF-36 scores ranged from 0.55 to 0.76 (P < 0.001). Analysis of variance indicate that scores on the CSHQ-RA discriminated between levels of physical disability as measured by the HAQ (P < 0.001). Test–retest reliability was demonstrated in the instrument's subscale scores (ICC 0.70–0.90). Conclusion These results support the construct validity, discriminant validity, and reliability of the CSHQ-RA as a measure that captures the impact of RA on patients' health-related quality of life.

OBJECTIVE: To examine the increasing use of health economic studies and practical implications of evaluating their quality utilizing the Quality of Health Economic Studies (QHES) instrument. METHODS: We first reviewed secondary references to examine ways in which health economic analyses are used in different health care settings, the manner in which these data are appraised and evaluated, and their relevance and value in decision making. The QHES, a new instrument designed to support fast, accurate initial assessments of study quality, was then introduced and validated. A case study was performed using the QHES to score the quality of 30 cost-effectiveness studies in gastroesophageal reflux disease (GERD) published since 1985. Areas where additional research could guide efforts to identify and enhance the use of higher-quality cost-effectiveness studies were suggested. RESULTS: Results from the published validation study of the QHES demonstrated the validity of this new instrument. The resulting QHES scores in the case study of GERD papers ranged from 43 to 91 with a mean of 63.6 (SD=14.7). Approximately 27% of the studies rated had scores less than 50, and 27% had scores above or equal to 75. All 30 studies made conclusions and recommendations and justified them based on their study results. Most studies used appropriate cost and health outcome measures. Very few studies stated the perspective of their analysis and reasons for its selection. The majority of the studies did not perform incremental analysis. CONCLUSION: An examination of the QHES validation study and the case study in GERD suggests that there is a rationale and potential utility to use a quality scoring system for cost-effectiveness studies. The QHES may play an important role in discriminating higher-quality cost-effectiveness information to enhance decision making. The QHES can also serve as a guideline for conducting and reporting future cost-effectiveness studies, as an aid in the editorial process, and for stratification in systematic reviews. Complex decisions regarding resource allocation rarely rely solely on economic considerations but do increasingly use health economic analyses. To the extent that such analyses are used, the QHES may help ensure that higher-quality analyses receive more analytic attention and greater weight in the decision-making process.

[corrected] Promoting the adoption of medical evidence into clinical practice has been advocated as one approach to improving healthcare quality and reducing medical errors. Data describing the effectiveness of different strategies to achieve this goal in real-world settings are limited.To determine the effectiveness of selected interventions on the adoption of medical evidence into clinical practice.A cross-sectional survey of a random sample of physicians selected from the American Medical Association's Physician Master File.We examined the perceived effectiveness of 7 strategies (represented by 27 individual interventions) and 5 general approaches for promoting the adoption of medical evidence into clinical practice in 1100 practicing physicians. Respondent exposure to interventions was also determined. Regression analyses were performed to identify factors that affected effectiveness ratings. Analysis of variance was used to test the hypothesis of equal mean scores across different comparison groups.Of 1,100 surveys mailed, 63 (5.7%) were excluded and 431 were completed (response rate = 41.6%). Mean +/- SD effectiveness scores for the 27 individual interventions on a 5-point Likert scale ranged from 2.0 +/- 0.9 (literature received from insurance companies and managed care organizations) to 4.2 +/- 0.8 (one-on-one communication with respected colleagues). Ranges for the 7 strategies were 2.6 +/- 1.0 (patient-mediated interventions) to 3.6 +/- 0.9 (educational meetings) and for the 5 general approaches were 1.98 +/- 0.9 (administrative interventions) to 3.3 +/- 0.8 (provider education). The hypothesis of equal mean effectiveness scores was rejected for all comparisons (P.001). Frequency of exposure was the only variable to predict effectiveness (P.001 for all regression models).From the perspective of practicing physicians, the frequency of exposure to strategies for promoting the adoption of medical evidence into clinical practice strongly affects their perceived effectiveness.

To evaluate the effect of the oral contraceptive Yasmin (drospirenone, 3 mg, and ethinyl estradiol, 30 micrograms) (Berlex Laboratories, Wayne, New Jersey) on premenstrual symptomatology and health-related quality of life (HRQoL).Participating health care providers received 11,260 self-administered surveys for distribution to women initiating use of Yasmin. Of these, 1,932 (17.2%) baseline surveys and 1,104 follow-up surveys (57.1%) were returned, with 858 (44.4%) of the returns evaluated as suitable for analysis.Premenstrual symptomatology, as measured with the negative affect and water retention domains of the Moos Menstrual Distress Questionnaire (MDQ), significantly improved from baseline in all phases of the menstrual cycle (P = .000). All individual MDQ items improved significantly in the late luteal phase and during menses (P = .000), and the majority (76.9%) improved significantly in the remainder of the cycle (P.05). Improvements were also observed in general sense of well-being (P.05), impairment in usual activities due to premenstrual symptomatology (P.05) and Mental Component Summary scale (P = .000) but not the Physical Component Summary scale of the Short Form-12 generic HRQoL instrument.These data support the effectiveness of Yasmin in reducing premenstrual symptomatology and improving HRQoL and general sense of well-being.

Objective To update and complement existing instruments, we developed a multidimensional disease-specific instrument, intended to reflect the impact of rheumatoid arthritis (RA) with modern treatment options on patient's Health-Related Quality of Life (HRQOL). Methods Items were developed from a systematic review of published HRQOL measures and transcripts of RA patient focus groups. Items were refined by an expert panel and administered to 350 patients for psychometric testing. Results The systematic review identified 228 potential items, and the focus group transcripts identified 96 additional items. Expert review and pilot testing resulted in an initial 58-item instrument. Twenty-six items were excluded due to floor/ceiling effects, poor response rates, or high item-item correlations. Factor analysis identified a 5-factor structure (eigenvalues ≥1). Multi-trait scaling performed on both completed surveys confirmed the 5 sub-scale structure (Cronbach's > 0.87). Conclusion The CSHQ-RA consists of 33 items that address 5 HRQOL domains, each with high internal consistency. Additional testing will assess the instrument's validity and responsiveness.

To provide a practical quantitative tool for appraising the quality of cost-effectiveness (CE) studies.A committee comprising [corrected] of health economists selected a set of criteria for the instrument from an item pool. Data collected with a conjoint analysis survey on 120 international health economists were used to estimate weights for each criterion with a random effects regression model. To validate the grading system, a survey was sent to 60 individuals with health economics expertise. Participants first rated the quality of three CE studies on a visual analogue scale, and then evaluated each study using the grading system. Spearman rho and Wilcoxon tests were used to detect convergent validity and analysis of covariance (ANCOVA) for discriminant validity. Agreement between the global rating by experts and the grading system was also examined.Sixteen criteria were selected. Their coefficient estimates ranged from 1.2 to 8.9, with a sum of 93.5 on a 100-point scale. The only insignificant criterion was "use of subgroup analyses." Both convergent validity and discriminant validity of the grading system were shown by the results of the Spearman rho (correlation coefficient = 0.78, P0.0001), Wilcoxon test (P = 0.53), and ANCOVA (F(3,146) = 5.97, p = 0.001). The grading system had good agreement with global rating by experts.The instrument appears to be simple, internally consistent, and valid for measuring the perceived quality of CE studies. Applicability for use in clinical and resource allocation decision-making deserves further study.