Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

OBJECTIVES: To assess, from a Swedish societal perspective, the cost effectiveness of interferon ß-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). METHODS: A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. RESULTS: In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. CONCLUSION: Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs.

Potential health care cost savings associated with early treatment of multiple sclerosis using disease-modifying therapy.

BACKGROUND: Clinical trials have shown that treatment with disease-modifying therapies (DMTs), such as interferon, at the time of clinically isolated syndrome can delay the onset of multiple sclerosis (MS). OBJECTIVES: The objective of this study was to assess health care utilization and expenditures associated with treating patients early with DMTs rather than delaying until patients meet the full diagnostic criteria of MS. METHODS: A retrospective study used insurance claims data (2000-2008) of enrolled patients before documented MS (1 inpatient or 2 outpatient claims with International Classification of Diseases, 9th Revision, Clinical Modification 340 coding). Treatment cohorts were early DMT (DMT claim before the first documented MS; N = 227) and delayed DMT (DMT started after documented MS; N = 3724). Comparisons during 1 year of follow-up were adjusted for confounding using multivariate methods. RESULTS: Adjusted annual per-patient expenditures (including patient out of pocket) for early versus delayed were as follows: total ($28,280 vs $29,102; P = 0.44), excluding DMT cost ($15,214 vs $17,630; P < 0.01), and MS-related ($9365 vs $13,661; P < 0.01). Hospitalizations were 10.1% versus 16.5% (adjusted odds ratio [OR] = 0.51; 95% CI, 0.32-0.81). CONCLUSIONS: Analysis indicated that early DMT treatment was associated with fewer hospitalizations than delayed treatment, and there was no statistically significant difference in annual health care expenditures. This suggests that the drug costs of early therapy were offset by savings in other medical expenditures.

Economic evaluation of sorafenib in unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: A double-blind, randomized phase III trial of sorafenib in advanced hepatocellular carcinoma demonstrated that sorafenib significantly prolonged overall survival compared to placebo (median overall survival = 10.7 months vs 7.9 months, P < 0.001). Sorafenib is the first and only systemic agent demonstrating survival benefit in these patients. The aim of this study was to assess the cost-effectiveness of sorafenib versus best supportive care in the treatment of advanced hepatocellular carcinoma in the USA. METHODS: A Markov model was developed following time-to-progression and survival using phase III trial data. Health effects are expressed as life-years gained. Resource utilization included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs, expressed in 2007 $US, came from diagnosis-related groupings, fee schedules, and the Red Book. Costs and effects were evaluated over a patient's lifetime and discounted at 3%. RESULTS: Results are presented as incremental cost/life-year gained. Deterministic and probabilistic sensitivity analyses were conducted. Life-years gained were increased for sorafenib compared to best supportive care (mean ± standard deviation: 1.58 ± 0.17 vs 1.05 ± 0.10 life-years gained/sorafenib patient and best supportive care, respectively). Lifetime total costs were $US40,639 ± $US3052 for sorafenib and $US7, 804 ± $US1349 for best supportive care. The incremental cost-effectiveness ratio was $US62,473/life-year gained. CONCLUSIONS: The economic evaluation indicates that sorafenib is cost-effective compared to best supportive care, with a cost-effectiveness ratio within the established threshold that US society is willing to pay (i.e. $US50,000-$US100,000) and significantly lower than alternative thresholds suggested in recent years ($US183,000-$US264,000/life-year gained, or $US300,000/quality-adjusted life-year) in oncology.

The burden of illness associated with hepatocellular carcinoma in the United States.

BACKGROUND/AIMS: Despite the rising prevalence of hepatocellular carcinoma (HCC), data on its economic consequences are limited. This study was undertaken to estimate the aggregate annual financial burden associated with HCC in the United States, including healthcare costs and the value of lost productivity. METHODS: Annual prevalence of HCC and incidence and survival were estimated using SEER data. The linked SEER-Medicare database was used to estimate distributions of healthcare utilization, quantities of treatment, and unit costs among 392 HCC patients. An age- and sex-matched cohort of non-cancer controls was used to estimate background non-cancer-related resource use and costs. RESULTS: We determined the annual cost of HCC in the United States to be $454.9 million, with per-patient costs of $32,907. Healthcare costs and lost productivity accounted for 89.2% and 10.8% of total cost, respectively. Costs associated with localized HCC accounted for the highest portion (44.5%) of the total cost of illness, at $202.5 million. Regional, distant, and unstaged HCC accounted for 31.0%, 13.9%, and 10.6%, respectively. CONCLUSIONS: Our results exhibit a considerable economic impact of HCC and substantial national spending on this disease.

The identification of benefit in medical intervention: an overview and suggestions for process.

Benefit and risk assessments are not only important to regulatory authorities but also important to the providers, patients, pharmaceutical industry, and payers. In order for patients and providers to continue to have access to new innovative medicines, which have some level of inherent risk, it is critical to have a systematic and balanced focus on understanding the safety risks and benefits to the patient during drug development, at the time of approval and postmarketing. There has been a significant amount of activity around efforts to improve the ability to assess risks in the postmarketing environment. However, there is no widely accepted, systematic approach or process for the ongoing evaluation of benefit. This article introduces 4 critical components in the process of identifying and assessing benefit with a goal of providing a framework that is transparent, comprehensive, applicable to various perspectives, and simple to communicate and implement. We propose the development of a catalog applied to a particular disease to identify the optimal data sources and methods to address the interests of a given perspective. Two key resources will need to be developed to support the catalog development: (1) a summary of benefit measures and preferences by disease and from various perspectives and (2) an investment in a simple visual communication mechanism with minimal statistical language. As the emphasis is on transparency, relevance, applicability, and communication, this approach to assessing benefit should maximize the impact of these data to all stakeholders and decision makers.

Current status of patient-reported outcomes in industry-sponsored oncology clinical trials and product labels.

Assessing patient-reported outcomes (PROs) in clinical trials is of interest to clinicians, patients, regulators, and industry. The use and impact of PROs is a growing area of methodologic research, particularly as they relate to tumor types, biomarkers, and various patient populations and cultures. Both the US Food and Drug Administration (FDA) and European Agency for the Evaluation of Medicinal Products in recent guidance have acknowledged the need to account for treatment-related impact on patient symptoms and/or health-related quality of life (HRQOL). Clinical research likely reflects the informative value of PROs. A search of www.clinicaltrials.gov, the FDA Web site, and product package inserts was conducted to assess the inclusion of symptom assessment and HRQOL within industry-sponsored clinical trials in cancer and approved cancer therapies and their respective product labels. Overall, there were 2,704 industry-sponsored oncology trials, of which 322 (12%) included a PRO measure. Of the 70 FDA new or revised labels, only six package inserts include PRO data. Symptoms were assessed uniformly across the phases of clinical trials, whereas HRQOL assessment increased in the later phases of clinical trials. Collecting PRO data can enhance our understanding of cancer burden and the impact of interventions on patients' lives.

Patient-reported outcomes assessment in cancer trials: taking stock, moving forward.

To evaluate and improve the use of cancer trial end points that reflect the patient's own perspective, the National Cancer Institute organized an international conference, Patient-Reported Outcomes Assessment in Cancer Trials (PROACT), in 2006. The 13 preceding articles in this special issue of the Journal were commissioned in preparation for or in response to the PROACT conference, which was cosponsored by the American Cancer Society. Drawing from these articles and also commentary from the conference itself, this concluding report takes stock of what has been learned to date about the successes and challenges in patient-reported outcome (PRO) assessment in phase III, phase II, and symptom management trials in cancer and identifies ways to improve the scientific soundness, feasibility, and policy relevance of PROs in trials. Building on this synthesis of lessons learned, this article discusses specific administrative policies and management procedures to improve PRO data collection, analysis, and dissemination of findings; opportunities afforded by recent methodologic and technologic advances in PRO data collection and analysis to enhance the scientific soundness and cost efficiency of PRO use in trials; and the importance of better understanding the usefulness of PRO data to the full spectrum of cancer decision makers, including patients and families, health providers, public and private payers, regulatory agencies, and standards-setting organizations.

The burden of illness associated with renal cell carcinoma in the United States.

BACKGROUND: There were over 36,000 new cases of kidney cancer reported in the United States in 2004, the most common type being renal cell carcinoma (RCC). Available treatments for localized RCC frequently lead to cure; however RCC patients with advanced disease have limited treatment options and low survival rates. Data on the economic burden of RCC are limited. METHODS: A prevalence-based model was used to estimate the aggregate annual societal cost burden of RCC in the U.S., including costs of treatment and lost productivity. Key parameters in the model include: the annual number of patients treated for RCC by age group and cancer stage; utilization of cancer treatments; unit costs; work-days missed; and wage rates. Multiplying stratum-specific distributions of treatment by annual quantities of treatments and unit costs yields estimates of RCC-related health-care costs. Multiplying stratum-specific estimates of annual workdays missed by average wage rates yields estimates of RCC-related lost productivity. RESULTS: The annual prevalence of RCC in the U.S. was estimated to be 109,500 cases. The associated annual burden (inflated to 2005 U.S.$) was approximately $4.4 billion ($40,176 per patient). Health-care costs and lost productivity accounted for 92.4% ($4.1 billion) and 7.6% ($334 million), respectively. Reflecting its higher prevalence, the total cost associated with localized RCC accounted for the greatest share (78.2%), followed by regional, distant, and unstaged RCC, at 18.3%, 2.8%, and 0.7%, respectively. CONCLUSIONS: The economic burden of RCC in the U.S. is substantial. Interventions to reduce the prevalence of RCC have the potential to yield considerable economic benefits.

Development and validation of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI).

The Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index (FKSI) was developed and validated to enhance treatment decision-making, practice guidelines, symptom management, and treatment efficacy for kidney cancer patients. Thirty-four symptoms related to the disease were identified and tested. An equal weighting of patient and clinician ratings of the relative importance of each of these items led to production of a 15-item index (FKSI-15) and a 10-item abbreviated option (FKSI-10). To assess psychometric properties, patients completed the FKSI, Functional Assessment of Cancer Therapy-General (FACT-G), Eastern Cooperative Oncology Group-Performance Status Rating (ECOG-PSR), and a Global Rating of Change Scale (GRCS). Patient responses to the FKSI were analyzed for internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness to change in clinical status. The FKSI-10 showed high internal consistency; correlations between both FKSI-10 and the physical and functional well being domains of the FACT-G were high. The FKSI-10 differentiated patients grouped by ECOG-PSR (all P < 0.001) and discriminated patients based on their GRCS rating. The minimally important difference (MID) range estimate for the FKSI-10 was 2-4 points; the psychometric properties of the FKSI-15 were very similar (MID range, 3-5 points).Thus, the FKSI-15 and FKSI-10 are reliable and valid symptom indices for evaluating kidney cancer patients.

Validation of a patient-administered questionnaire to measure the severity and bothersomeness of lower urinary tract symptoms in uncomplicated urinary tract infection (UTI): the UTI Symptom Assessment questionnaire.

OBJECTIVE: To develop and validate a self-administered questionnaire to assess the 'severity' and 'bothersomeness' of the most frequently reported signs and symptoms of uncomplicated urinary tract infection (uUTI). SUBJECTS AND METHODS: The UTI Symptoms Assessment questionnaire (UTISA) is a 14-item instrument asking about the severity and bothersomeness of seven key uUTI symptoms. It was developed after comprehensive literature and data review and administration in draft form to a sample of 30 women with uUTI. The final questionnaire was completed by 276 women with uUTI who participated in a noncomparative clinical trial of ciprofloxacin. The women completed the questionnaire in electronic format at baseline (before the first dose of ciprofloxacin once-daily), at 3-h and 8-h intervals until all UTI symptoms were resolved, and at the test-of-cure visit. Baseline scores on the King's Health Questionnaire (KHQ) were used to assess convergent and divergent validity; responses to the Global Rating of Change (GRC) were used to assess both responsiveness and the 'minimally important difference'. Discriminant validity and responsiveness were assessed by comparing UTISA scores with a clinical evaluation of UTI symptoms performed by the investigator at baseline and at the test-of-cure visit. RESULTS: The UTISA was found to comprise three four-item domains named 'urination regularity', 'problems with urination', and 'pain associated with UTI'. Two questions asking about haematuria loaded on a fourth factor. The three domains were homogeneous (with high inter-item correlations) and internally consistent. Convergent validity was shown by high correlations between similar UTISA and KHQ domains (all r(s) > 0.40), and divergent validity by small correlations between unlike domains (all r(s) < 0.15). In general, the UTISA domains showed excellent discriminant validity, with scores on selected domains discriminating between women with different clinical evaluations. The responsiveness of the UTISA was also excellent, with high correlations between changes in domain scores and the clinical evaluation and GRC items. Symptom improvement was highest in the first 3 h, leading to greater responsiveness and minimally important difference during this period. However, the UTISA could detect even small subsequent changes. CONCLUSION: The three-domain UTISA has excellent psychometric properties and it is likely to prove an excellent tool for assessing uUTI outcome from a patient's perspective, both in research and clinical settings.

Validation of a patient-administered questionnaire to measure the activity impairment experienced by women with uncomplicated urinary tract infection: the Activity Impairment Assessment (AIA).

BACKGROUND: To validate a questionnaire to assess the activity impairment associated with uncomplicated urinary tract infection (uUTI). METHODS: The Activity Impairment Assessment (AIA) assesses the amount of time an individual's work or regular activities have been impaired as a result of their UTI. The measure was completed by 276 women with uUTI who had participated in a prospective, open-label, non-comparative multi-centre clinical trial of CIPRO XR (extended-release ciprofloxacin). Baseline scores on the King's Health Questionnaire (KHQ) and clinical symptom evaluations were collected for validation purposes. RESULTS: An exploratory factor analysis showed that all items loaded > 0.84 on a single component. This uni-dimensional structure was supported by Rasch analysis. The AIA was found to have excellent levels of internal consistency (Cronbach's alpha = 0.93), convergent validity (all rs > .70) and divergent validity (rs = .078). The AIA displayed excellent discriminant validity in relation to clinical evaluations, and was found to be responsive to change across all clinical evaluations. CONCLUSION: The unidimensional AIA shows high levels of internal reliability, convergent and divergent validity, discriminant validity and responsiveness. It is an excellent tool for measuring activity impairment in UTI.

The treatment satisfaction scale: a multidimensional instrument for the assessment of treatment satisfaction for erectile dysfunction patients and their partners.

BACKGROUND: The development of the Treatment Satisfaction Scale (TSS) was previously reported (Kubin et al., 2004). OBJECTIVE: This article describes the psychometric validation process and psychometric properties (e.g., reliability, validity, and responsiveness) of TSS. METHODS: Initial patient and partner questionnaires were administered in a multi-national clinical trial. On the basis of exploratory analyses, iterative psychometric testing, and consideration of face validity and interpretability, the number of items was reduced, and six scales were constructed: "Satisfaction with Medication," "Ease with Erection," "Satisfaction with Erectile Function," "Pleasure from Sexual Activity," "Satisfaction with Orgasm," and either "Sexual Confidence" (for patients) or "Confidence in Completion" (for partners). RESULTS: Multi-item scales had good internal consistency reliability and concurrent validity with the IIEF. All patient scales and most partner scales were valid in relation to clinical criteria, and all tested scales were responsive to change over time. CONCLUSION: The TSS is brief, culturally valid, and the most comprehensive multidimensional measure of satisfaction with ED treatment for patients and their partners, and addresses some of the shortcomings of existing measures.

Costs of broad-spectrum antibiotic use for acute sinusitis, chronic bronchitis, and pneumonia in a managed care population.

Respiratory infections place a heavy burden on patients, providers, employers, and health care systems. The prescribing of antibiotics is common, despite the fact that many respiratory conditions are caused by viruses. The economic effect of treating respiratory tract infections with broad-spectrum antibiotics was retrospectively analyzed by means of health care claims data from six managed care health plans affiliated with a large national insurer. A regression model was used to adjust for factors that can influence treatment costs, such as age, baseline cost, retreatment, and drug cost. The costs of treating chronic bronchitis, pneumonia, and acute sinusitis with moxifloxacin, gatifloxacin and nonfluoroquinolone broad-spectrum agents were significantly lower than the costs associated with levofloxacin treatment.

Escherichia coli resistance in uncomplicated urinary tract infection: a model for determining when to change first-line empirical antibiotic choice.

Escherichia coli is typically the causative organism in uncomplicated urinary tract infection (UTI). Resistance rates of E. coli to trimethoprim/sulfamethoxazole (TMP/SMX) are increasing, exceeding 10% in many communities. Guidelines recommend using alternative treatments in these areas. Providers must reevaluate policies to include considerations for E. coli resistance. A model was developed, with cases for illustration, to help organizations determine the resistance rate threshold, where TMP/SMX is no longer first-line therapy. Using published data, a 19% to 21% threshold was derived, supporting a previous report of 22%. The model can aid decision makers updating internal policies to conform with guidelines for the treatment of uncomplicated UTI and to improve care.