Prioritizing Research Informing Antibiotic Prophylaxis Guidelines for Knee Arthroplasty Patients.

INTRODUCTION: Guidelines for routine antibiotic prophylaxis (AP) before dental procedures to prevent periprosthetic joint infection (PJI) have been hampered by the lack of prospective clinical trials. OBJECTIVES: To apply value-of-information (VOI) analysis to quantify the value of conducting further clinical research to reduce decision uncertainty regarding the cost-effectiveness of AP strategies for dental patients undergoing total knee arthroplasty (TKA). METHODS: An updated decision model and probabilistic sensitivity analysis (PSA) evaluated the cost-effectiveness of AP and decision uncertainty for 3 AP strategies: no AP, 2-y AP, and lifetime AP. VOI analyses estimated the value and cost of conducting a randomized controlled trial (RCT) or observational study. We used a linear regression meta-modeling approach to calculate the population expected value of partial perfect information and a Gaussian approximation to calculate population expected value of sample information, and we subtracted the cost for research to obtain the expected net benefit of sampling (ENBS). We determined the optimal trial sample sizes that maximized ENBS. RESULTS: Using a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the PSA found that a no-AP strategy had the highest expected net benefit, with a 60% probability of being cost-effective, and 2-y AP had a 37% probability. The optimal sample size for an RCT to determine AP efficacy and dental-related PJI risk would require approximately 421 patients per arm with an estimated cost of $14.7 million. The optimal sample size for an observational study to inform quality-of-life parameters would require 2,211 patients with an estimated cost of $1.2 million. The 2 trial designs had an ENBS of approximately $25 to $26 million. CONCLUSION: Given the uncertainties associated with AP guidelines for dental patients after TKA, we conclude there is value in conducting further research to inform the risk of PJI, effectiveness of AP, and quality-of-life values. KNOWLEDGE TRANSFER STATEMENT: The results of this value-of-information analysis demonstrate that there is substantial uncertainty around clinical, health status, and economic parameters that may influence the antibiotic prophylaxis guidance for dental patients with total knee arthroplasty. The analysis supports the contention that conducting additional clinical research to reduce decision uncertainty is worth pursuing and will inform the antibiotic prophylaxis debate for clinicians and dental patients with prosthetic joints.

Is Antibiotic Prophylaxis Cost-effective for Dental Patients Following Total Knee Arthroplasty?

INTRODUCTION: Routine antibiotic prophylaxis (AP) to prevent prosthetic joint infection remains controversial. The lack of prophylaxis guideline consensus from the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) contributes to clinician confusion. OBJECTIVES: This cost-effectiveness decision model informs the AP debate and guideline development by comparing the benefits, harms, and costs of alternative prophylaxis strategies. METHODS: A Markov state-transition model was developed comparing lifetime health outcomes and costs of alternative AP strategies for dental patients aged 65 y with a history of total knee arthroplasty (TKA). Based on our interpretation of AP recommendations from the AAOS and ADA, incremental cost-effectiveness ratios were calculated to compare the following strategies: no AP, AP for the first 2 y after a TKA, and lifetime AP. RESULTS: The no-AP strategy had the lowest average lifetime costs ($17,119) and quality-adjusted life years (11.2151). Compared with a no-prophylaxis strategy, the 2-y AP strategy had incremental costs of $56 and 0.0006 QALYs gained and was cost-effective (incremental cost-effectiveness ratio = $95,100) when a willingness-to-pay threshold of $100,000 per quality-adjusted life year was used. Based on the results of 1-way sensitivity analysis, the no-AP strategy was cost-effective when we modestly increased base case amoxicillin adverse event estimates that were substantially lower than estimates reported in previous models. When plausible combinations of important model parameters were varied, model results suggested that there may be clinical scenarios when AP may be appropriate for some medically at-risk patient populations. CONCLUSION: The results of cost-effectiveness decision modeling generally support questioning routine AP for dental patients with TKA. Sensitivity analyses suggest that prophylaxis may be cost-effective for patient populations with a higher medical risk of infection. This finding is consistent with the recommendations of the 2015 ADA practice guideline and the appropriate use criteria jointly developed by the AAOS and the ADA. KNOWLEDGE TRANSFER STATEMENT: The results of this decision modeling research support the contention that routine AP before invasive dental procedures to prevent prosthetic joint infection may not be cost-effective for patients without medical conditions, potentially conferring a higher infection risk. Model sensitivity analyses suggest that there may be clinical situations when medically at-risk patients benefit from AP.

Projecting the clinical benefits of adjuvant radiotherapy versus observation and selective salvage radiotherapy after radical prostatectomy: a decision analysis.

Our purpose was to project and compare clinical and quality-adjusted life year (QALY) outcomes of adjuvant radiotherapy (ART) versus salvage RT (SRT) after radical prostatectomy for men with locally advanced prostate cancer. We constructed a Markov model to simulate the randomized studies of observation versus ART, assuming 75% of observation patients would receive SRT at PSA recurrence. Transition probabilities and utility inputs were drawn from randomized trials of ART and cohort studies of SRT. We projected 10-year PSA recurrence-free survival, metastasis-free survival and overall survival. We found that observation with selective SRT yielded slightly worse outcomes than ART for post-RT PSA recurrence-free survival (47 and 52%), metastasis-free survival (69 and 70%) and overall survival (72 and 73%). Findings were robust to sensitivity analyses. After adjusting for the disutility of RT, observation plus SRT yielded better QALYs at 10 years than ART (6.80 and 6.13 QALYs). Thus, observation plus SRT may be optimal for men likely to comply with surveillance who wish to minimize side effects of the treatment. These findings reflect outcomes for the average patient given the current level of evidence and are meant to help inform current decision-making as we await future clinical studies of comparative effectiveness.

Computed tomography screening for lung cancer in Hodgkin's lymphoma survivors: decision analysis and cost-effectiveness analysis.

BACKGROUND: Hodgkin's lymphoma patients have an elevated risk of developing lung cancer and may be targeted for lung cancer screening. We used a decision-analytic model to estimate the potential clinical benefits and cost-effectiveness of computed tomography (CT) screening for lung cancer in Hodgkin's lymphoma survivors. MATERIALS AND METHODS: We developed a Markov decision-analytic model to compare annual low-dose CT screening versus no screening in a hypothetical cohort of patients diagnosed with stage IA-IIB Hodgkin's lymphoma at age 25, with screening starting 5 years after initial diagnosis. We derived model parameters from published studies and the Surveillance, Epidemiology and End Results (SEER) Program, and assumed that stage-shift produces a survival benefit. RESULTS: Annual CT screening increased survival by 0.64 years for smokers and 0.16 years for non-smokers. The corresponding benefits in quality-adjusted survival were 0.58 quality-adjusted life-years (QALYs) for smokers and 0.14 QALYs for non-smokers. The incremental cost-effectiveness ratios for annual CT screening compared with no screening were $34 100/QALY for smokers and $125 400/QALY for non-smokers. CONCLUSIONS: Our analysis suggests that if early promising results for lung cancer screening hold, CT screening for lung cancer may increase survival and quality-adjusted survival among Hodgkin's lymphoma survivors, with a benefit and incremental cost-effectiveness ratio for smokers comparable to that of other recommended cancer screening strategies.

Cost-effectiveness of low dose corticosteroids versus non-steroidal anti-inflammatory drugs and COX-2 specific inhibitors in the long-term treatment of rheumatoid arthritis.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are used in nearly every patient with rheumatoid arthritis (RA) as part of a comprehensive management programme, but their use can be associated with side-effects. Low dose corticosteroid (<10 mg/day prednisone) in the treatment of RA is controversial. Although it is effective and possibly disease modifying, concerns exist about potential adverse events. We assessed costs and health effects of corticosteroids compared with NSAIDs and cyclo-oxgenase-2 (COX-2) inhibitors. METHODS: Markov (state transition) models were used to simulate a cohort of RA patients taking disease-modifying antirheumatic drugs and either corticosteroids or NSAIDs. The regimens were assumed to be equally effective for the control of RA. Data on incidence, costs and consequences of adverse events from corticosteroids and from NSAIDs were taken from the literature. Costs were measured in 1999 US dollars; health effects expressed as quality-adjusted life years (QALYs). Sensitivity analyses were performed including best-case scenarios (0.5x adverse event rate) and worst-case scenarios (1.5x adverse event rate). RESULTS: In the base-case analysis corticosteroids were superior to NSAIDs. The sensitivity analyses of adverse event rate, using best-case and worst-case scenarios, and age showed that the results were sensitive to each combination of adverse event rate and age. In contrast, the sensitivity analyses of costs and utilities were robust. Using misoprostol or omeprazole prophylaxis with NSAIDs would make corticosteroids cost-effective. Compared with NSAIDs with COX-2 specific inhibition, corticosteroids were still cost-effective. CONCLUSION: Corticosteroids are more cost-effective than NSAIDs and COX-2 inhibitors in the long-term treatment of RA.

Newborns with suspected occult spinal dysraphism: a cost-effectiveness analysis of diagnostic strategies.

OBJECTIVE: To assess the clinical and economic consequences of different diagnostic strategies in newborns with suspected occult spinal dysraphism. METHODS: A decision-analytic model was constructed to project the cost and health outcomes of magnetic resonance imaging (MRI), ultrasound (US), plain radiographs, and no imaging in newborns with suspected occult spinal dysraphism. Morbidity and mortality rates of early versus late diagnosis of dysraphism and the sensitivity and specificity of MRI, US, and plain radiographs were obtained from the literature. Cost estimates were obtained from a hospital cost accounting database and from the Medicaid fee schedule. RESULTS: We found that the choice of imaging strategy depends on the underlying risk of occult spinal dysraphism. In low-risk children with intergluteal dimple or newborns of diabetic mothers (pretest probability: 0.3%-0.34%), US was the most effective strategy with an incremental cost-effectiveness ratio of $55 100 per quality-adjusted life year gained. For children with lumbosacral dimples, who have a higher pretest probability of 3.8%, US was less costly and more effective than the other 3 strategies considered. In intermediate-risk newborns with low anorectal malformation (pretest probability: 27%), US was more effective and less costly than radiographs and no imaging. However, MRI was more effective than US at an incremental cost-effectiveness of $1000 per quality-adjusted life year gained. In the high-risk group that included high anorectal malformation, cloacal malformation, and exstrophy (pretest probability: 44%-46%), MRI was actually cost-saving when compared with the other diagnostic strategies. For the intermediate-risk group, we found our analysis to be sensitive to the costs and diagnostic performances (sensitivity and specificity) of MRI and US. Lower MRI cost or greater MRI diagnostic performance improved the cost-effectiveness of the MRI strategy, whereas lower US cost or greater US diagnostic performance worsened the cost-effectiveness of the MRI strategy. Therefore, individual or institutional expertise with a specific diagnostic modality (MRI versus US) may influence the optimal diagnostic strategy. CONCLUSIONS: In newborns with suspected occult dysraphism, appropriate selection of patients and diagnostic strategy may increase quality-adjusted life expectancy and decrease cost of medical work-up.

Modeling for health care and other policy decisions: uses, roles, and validity.

The role of models to support recommendations on the cost-effective use of medical technologies and pharmaceuticals is controversial. At the heart of the controversy is the degree to which experimental or other empirical evidence should be required prior to model use. The controversy stems in part from a misconception that the role of models is to establish truth rather than to guide clinical and policy decisions. In other domains of public policy that involve human life and health, such as environmental protection and defense strategy, models are generally accepted as decision aids, and many models have been formally incorporated into regulatory processes and governmental decision making. We formulate an analytical framework for evaluating the role of models as aids to decision making. Implications for the implementation of Section 114 of the Food and Drug Administration Modernization Act (FDAMA) are derived from this framework.

Measuring Alzheimer's disease progression with transition probabilities: estimates from CERAD.

OBJECTIVES: To estimate annual transition probabilities (i.e., the likelihood that a patient will move from one disease stage to another in a given time period) for AD progression. Transition probabilities are estimated by disease stages (mild, moderate, severe) and settings of care (community, nursing home), accounting for differences in age, gender, and behavioral symptoms as well as the length of time a patient has been in a disease stage. METHODS: Using data from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the authors employed a modified survival analysis to estimate stage-to-stage and stage-to-nursing home transition probabilities. To account for individual variability, a Cox proportional hazards model was fit to the CERAD data to estimate hazard ratios for gender, age (50 to 64, 65 to 74, and more than 75 years), and level of behavioral symptoms (low/high, according to responses to the Behavioral Rating Scale for Dementia) for each of the key stage-to-stage and stage-to-nursing home transitions. RESULTS: The transition probabilities underscore the rapid progression of patients into more severe disease stages and into nursing homes and the differences among population subgroups. In general, male gender, age under 65, and high level of behavioral symptoms were associated with higher transition probabilities to more severe disease stages. Disease progression is roughly constant as a function of the time a patient has spent in a particular stage. CONCLUSIONS: Transition probabilities provide a useful means of characterizing AD progression. Economic models of interventions for AD should consider the varied course of progression for different population subgroups, particularly those defined by high levels of behavioral symptoms.

Children with headache suspected of having a brain tumor: a cost-effectiveness analysis of diagnostic strategies.

OBJECTIVE: To assess the clinical and economic consequences of 3 diagnostic strategies-magnetic resonance imaging (MRI), computed tomography followed by MRI for positive results (CT-MRI), and no neuroimaging with close clinical follow-up-in the evaluation of children with headache suspected of having a brain tumor. Three risk groups based on clinical variables were evaluated. MATERIALS AND METHODS: A decision-analytic Markov model and cost-effectiveness analysis was performed incorporating the risk group prior probability, MRI and CT sensitivity and specificity, tumor survival, progression rates, and cost per strategy. Outcomes were based on quality-adjusted life year (QALY) gained and incremental cost per QALY gained. RESULTS: For low-risk children with chronic nonmigraine headaches of >6 months' duration as the sole symptom (prior probability of brain tumor 0.01%), no neuroimaging with close clinical follow-up was less costly and more effective than the 2 neuroimaging strategies. For the intermediate-risk children with migraine headache and normal neurologic examination (prior probability of brain tumor 0.4%), CT-MRI was the most effective strategy but cost >$1 million per QALY gained compared with no neuroimaging. For high-risk children with headache of <6 months' duration and other clinical predictors of a brain tumor such as an abnormal neurologic examination (prior probability of brain tumor 4%), the most effective strategy was MRI, with cost-effectiveness ratio of $113 800 per QALY gained compared with no imaging. CONCLUSION: Our analysis suggests that MRI maximizes QALY gained at a reasonable cost-effectiveness ratio in children with headache at high risk of having a brain tumor. Conversely, the strategy of no imaging with close clinical follow-up is cost saving in low-risk children. Although the CT-MRI strategy maximizes QALY gained in the intermediate-risk patients, its additional cost per QALY gained is high. In children with headache, appropriate selection of patients and diagnostic strategy may maximize quality-adjusted life expectancy and decrease costs of medical workup.

Cost effectiveness of human papillomavirus testing to augment cervical cancer screening in women infected with the human immunodeficiency virus.

PURPOSE: To determine the cost effectiveness of incorporating molecular testing for high-risk types of human papillomavirus into a cervical cancer screening program for women infected with the human immunodeficiency virus (HIV). SUBJECTS AND METHODS: We developed a Markov model to simulate the natural history of cervical cancer precursor lesions in HIV-infected women. Probabilities of progression and regression of cervical lesions were conditional on transient or persistent infection with human papillomavirus, as well as stage of HIV and effectiveness of antiretroviral therapy. Incorporating data from prospective cohort studies, national databases, and published literature, the model was used to calculate quality-adjusted life expectancy, life expectancy, lifetime costs, and incremental cost-effectiveness ratios for two main strategies: targeted screening-human papillomavirus testing is added to the initial two cervical cytology smears obtained after an HIV diagnosis and subsequent screening intervals are modified based on the test results; and universal screening-no testing for human papillomavirus is performed, and a single cytology screening interval is applied to all women. RESULTS: In HIV-infected women on anti-retroviral therapy, a targeted screening strategy in which cervical cytology screening was conducted every 6 months for women with detected human papillomavirus DNA, and annually for all others, cost $10,000 to $14,000 per quality-adjusted life year gained compared with no screening. A universal screening strategy consisting of annual cervical cytology for all women was 15% less effective and had a less attractive cost-effectiveness ratio. Targeted screening remained economically attractive in multiple sensitivity analyses, although when the overall incidence of cervical cancer precursor lesions was lowered by 75%, the screening interval for women with detected human papillomavirus DNA could be widened to 1 year. CONCLUSIONS: Adding human papillomavirus testing to the two cervical cytology smears obtained in the year after an HIV diagnosis, and modifying subsequent cytology screening intervals based on the results, appears to be an effective and cost-effective modification to current recommendations for annual cytology screening in HIV-infected women.

Costs and effectiveness of staging and treatment options in early-stage Hodgkin's disease.

PURPOSE: Using a cost-effectiveness analysis, to weigh the costs and benefits of the different staging and treatment options in early-stage Hodgkin's disease. METHODS: We constructed a decision-analytic model for a hypothetical cohort of 25-year-old patients with early-stage Hodgkin's disease. Markov models were used to simulate the lifetime costs and prognosis of each staging and treatment strategy. Baseline probabilities and cost estimates were derived from published studies and bills of relevant patient cohorts. RESULTS: Among the six management strategies considered, the incremental cost-effectiveness ratio of laparotomy and tailored treatment compared with mantle and para-aortic-splenic radiation therapy in all clinical stage I-II patients was $24,100/quality-adjusted life year, while that of the strategy of combined modality therapy in all clinical stage I-II patients compared with laparotomy was $61,700/quality-adjusted life year. All the remaining strategies were dominated by one of these three strategies. Sensitivity analysis showed that the cost-effectiveness ratios were driven predominantly by the effectiveness rather than the cost of each strategy. In particular, the analysis was heavily influenced by the utility of the post-laparotomy health state. CONCLUSIONS: In considering the various alternative management strategies in early-stage Hodgkin's disease, even very small gains in effectiveness were enough to justify the additional costs of more expensive treatment options.

Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels.

BACKGROUND: The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels. METHODS: We performed a cost-effectiveness analysis based on actual clinical, cost, and health-related quality-of-life data from the Cholesterol and Recurrent Events (CARE) trial. Survival and recurrent coronary heart disease events were modeled from trial data in Markov models, with the use of different assumptions regarding the long-term benefit of therapy. RESULTS: Pravastatin therapy increased quality-adjusted life expectancy at an incremental cost of $16,000 to $32,000 per quality-adjusted life-year gained. In subgroup analyses, the cost-effectiveness of pravastatin therapy was more favorable for patients >60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels >125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy. CONCLUSIONS: The cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels compares favorably with other interventions.

The cost-effectiveness of vaccination against Lyme disease.

BACKGROUND: Vaccination against Lyme disease appears to be safe and effective; however, the cost per quality-adjusted life-year (QALY) gained with vaccination is unknown. METHODS: We developed a decision-analytic model to evaluate the cost-effectiveness of vaccination compared with no vaccination in individuals living in endemic areas of Lyme disease. Our analysis encompassed a 10-year time horizon including a 2-year vaccination schedule with an additional year of vaccine effectiveness. The costs and probabilities of vaccination risk, compliance and efficacy, and Lyme disease clinical sequelae and treatment were estimated from the literature. Health-related quality-of-life weights of the various clinical sequelae of Lyme disease infection were obtained from a sample of 105 residents from Nantucket Island, Massachusetts. RESULTS: Vaccinating 10 000 residents living in endemic areas with a probability of Lyme disease per season of 0.01 averted 202 cases of Lyme disease during a 10-year period. The additional cost per QALY gained compared with no vaccination was $62 300. Vaccination cost $12 600/QALY gained for endemic areas with an attack rate of 2.5% per season, and $145 200/QALY gained for an attack rate of 0.5%. Vaccinating individuals over an accelerated 2-month vaccination schedule improved the cost-effectiveness to $53 700/QALY gained. If a yearly booster shot is required for persisting efficacy, the marginal cost-effectiveness ratio increases to $72 700/QALY. The cost-effectiveness of vaccination was most sensitive to the Lyme disease treatment efficacy and assumptions about the persistence of vaccination effect. CONCLUSION: Vaccination against Lyme disease appears only to be economically attractive for individuals who have a seasonal probability of Borrelia burgdorferi infection of greater than 1%.

A comparison of HUI2 and HUI3 utility scores in Alzheimer's disease.

PURPOSE: The Health Utilities Index (HUI) is a generic, multiattribute, preference-based health-status classification system. The HUI Mark 3 (HUI3) differs from the earlier HUI2 by modifying attributes and allowing more flexibility for capturing high levels of impairment. The authors compared HUI2 and HUI3 scores of patients with Alzheimer's disease (AD) and caregivers, and contrasted results of a cost-effectiveness analysis of new drugs for AD using the two systems. METHODS: In a cross-sectional study of 679 AD patient/caregiver pairs, stratified by patient's disease stage (questionable/mild/moderate/severe/profound/terminal) and setting (community/assisted living/nursing home), caregivers completed the combined HUI2/HUI3 questionnaire as proxy respondents for patients and for themselves. RESULTS: Mean (SD) global utility scores for patients were lower on the HUI3 (0.22[0.26]) than on the HUI2 (0.53 [0.21]). Patient HUI3 utility scores ranged from 0.47(0.24) for questionable AD to -0.23 (0.08) for terminal AD, compared with a range of 0.73 (0.15) to 0.14 (0.07) for the HUI2. Among the 203 patients in the severe, profound, and terminal stages, 96 (48%) had negative global HUI3 utility scores, while none had a negative HUI2 score. The utility scores for caregivers were similar on the HUI3 (0.87 [0.14]) and HUI2 (0.87 [0.11]). Cost-effectiveness analysis of a new medication to treat AD showed somewhat more favorable results using the HUI3. CONCLUSIONS: The HUI2 and HUI3 discriminate well across AD stages. Compared with the HUI2, the HUI3 yields lower global utility scores for patients with AD, and more scores for states judged worse than dead. The HUI3 may yield substantially different results from the HUI2, particularly for persons who have serious cognitive impairments such as AD.

A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis.

OBJECTIVE: Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings. METHODS: We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes. RESULTS: In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results. CONCLUSION: Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable.

Cost-effectiveness of screening for colorectal cancer in the general population.

CONTEXT: A recent expert panel recommended that persons at average risk of colorectal cancer (CRC) begin screening for CRC at age 50 years using 1 of several strategies. However, many aspects of different CRC screening strategies remain uncertain. OBJECTIVE: To assess the consequences, costs, and cost-effectiveness of CRC screening in average-risk individuals. DESIGN: Cost-effectiveness analysis from a societal perspective using a Markov model. SUBJECTS: Hypothetical subjects representative of the 50-year-old US population at average risk for CRC. SETTING: Simulated clinical practice in the United States. MAIN OUTCOME MEASURES: Discounted lifetime costs, life expectancy, and incremental cost-effectiveness (CE) ratio, compared used 22 different CRC screening strategies, including those recommended by the expert panel. RESULTS: In 1 base-case analysis, compliance was assumed to be 60% with the initial screen and 80% with follow-up or surveillance colonoscopy. The most effective strategy for white men was annual rehydrated fecal occult blood testing (FOBT) plus sigmoidoscopy (followed by colonoscopy if either a low- or high-risk polyp was found) every 5 years from age 50 to 85 years, which resulted in a 60% reduction in cancer incidence and an 80% reduction in CRC mortality compared with no screening, and an incremental CE ratio of $92,900 per year of life gained compared with annual unrehydrated FOBT plus sigmoidoscopy every 5 years. In a base-case analysis in which compliance with screening and follow-up is assumed to be 100%, screening more often than every 10 years was prohibitively expensive; annual rehydrated FOBT plus sigmoidoscopy every 5 years had an incremental CE ratio of $489,900 per life-year gained compared with the same strategy every 10 years. Other strategies recommended by the expert panel were either less effective or cost more per year of life gained than the alternatives. Colonoscopy every 10 years was less effective than the combination of annual FOBT plus sigmoidoscopy every 5 years. However, a single colonoscopy at age 55 years achieves nearly half of the reduction in CRC mortality obtainable with colonoscopy every 10 years. Because of increased life expectancy among white women and increased cancer mortality among blacks, CRC screening was even more cost-effective in these groups than in white men. CONCLUSIONS: Screening for CRC, even in the setting of imperfect compliance, significantly reduces CRC mortality at costs comparable to other cancer screening procedures. However, compliance rates significantly affect the incremental CE ratios. In this model of CRC, 60% compliance with an every 5-year schedule of screening was roughly equivalent to 100% compliance with an every 10-year schedule. Mathematical modeling used to inform clinical guidelines needs to take into account expected compliance rates. JAMA. 2000;284:1954-1961.

Should postmenopausal women with rheumatoid arthritis who are starting corticosteroid treatment be screened for osteoporosis? A cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of different strategies for preventing corticosteroid-induced osteoporosis. METHODS: Simulated cohorts of postmenopausal women with rheumatoid arthritis (RA) starting corticosteroid treatment were examined. A Markov decision analysis model was developed to compare different management strategies, including watchful waiting, screen and treat, and empirical treatment. Treatment thresholds for the screen and treat strategy were varied from bone mineral density (BMD) T scores <-1.0 to BMD T scores <-4.0. RESULTS: Compared with a watchful waiting approach, the incremental cost-effectiveness ratio for a strategy of screen and treat with alendronate at a BMD T score of <-1.0 was $92,600 per quality-adjusted life year (QALY) gained. This result was sensitive to the cost and efficacy of osteoporosis therapy and, importantly, to the treatment threshold. At a treatment threshold of a BMD T score <-2.5, the incremental cost-effectiveness ratio of screening and treating was $76,100 per QALY. None of these results differed substantially for women taking estrogen replacement therapy. CONCLUSION: The incremental cost-effectiveness ratio of a strategy of screening and treating postmenopausal female RA patients with BMD T scores of < -1.0, compared with watchful waiting, was greater than that of other well-accepted medical interventions. The cost-effectiveness ratios were more acceptable when a T score treatment threshold of <-2.5 was used. These conclusions are limited by the lack of data on fracture and treatment efficacy in corticosteroid-treated patients.

Cost-effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men.

PURPOSE: Homosexual and bisexual men are at an increased risk for human papillomavirus-induced squamous intraepithelial lesions and cancer of the anus. Our objective was to estimate the cost-effectiveness of screening for anal squamous intraepithelial lesions in these high-risk patients. SUBJECTS AND METHODS: A Markov model was developed to evaluate alternative screening strategies using anal cytology in a hypothetical cohort of homosexual and bisexual men. Data were obtained from prospective cohort studies, national databases, Medicare reimbursement rates, and the published literature. Model outcomes included life expectancy, quality-adjusted life expectancy, total lifetime costs, and incremental cost-effectiveness ratios. RESULTS: The undiscounted life expectancy gain associated with anal cytology screening every 3 years was 5.5 months. Compared with no screening, screening every 3 years increased the discounted quality-adjusted life expectancy by 1.8 months and cost $7,000 per quality-adjusted life year (QALY) gained. Screening every 2 years cost $15,100 per QALY gained compared with screening every 3 years. Annual screening provided incremental benefits of less than 0.5 quality-adjusted months and had an incremental cost of $34,800 per QALY gained. Screening every 6 months provided little additional benefit (i.e, 5 days) over that of annual screening and had an incremental cost of $143,500 per QALY gained. CONCLUSION: In homosexual and bisexual men, screening every 2 or 3 years for anal squamous intraepithelial lesions with anal cytology would provide life-expectancy benefits comparable with other accepted preventive health measures, and would be cost-effective.

Cost-effectiveness of fusion with and without instrumentation for patients with degenerative spondylolisthesis and spinal stenosis.

STUDY DESIGN: A cost-effectiveness study was performed from the societal perspective. OBJECTIVE: To evaluate the costs and benefits of laminectomy alone and laminectomy with concomitant lumbar fusion for patients with degenerative lumbar spondylolisthesis and spinal stenosis. SUMMARY OF BACKGROUND DATA: Costs, probabilities, and utilities were estimated from the literature. Short-term risks considered were perioperative complications, the probability of the fusion healing, and the probability that surgery will relieve symptoms. Long-term risks considered were recurrence of symptoms and reoperation. METHODS: The 10-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios (reported as dollars per quality-adjusted year of life gained) were calculated using a Markov model. Sensitivity analysis was performed on all variables using clinically plausible ranges. RESULTS: Laminectomy with noninstrumented fusion costs $56,500 per quality-adjusted year of life versuslaminectomy without fusion. The cost-effectiveness of laminectomy with noninstrumented fusion was most sensitive to the increase in quality-of-life associated with relief of severe stenosis symptoms. The cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion was $3,112,800 per quality-adjusted year of life. However, if the proportion of patients experiencing symptom relief after instrumented fusion was 90% as compared with 80% for patients with noninstrumented fusion, then the cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion would be $82,400 per quality-adjusted year of life. CONCLUSIONS: The cost-effectiveness of laminectomy with noninstrumented fusion compares favorably with other surgical interventions, although it depends greatly on the true effectiveness of these surgeries to alleviatesymptoms and on how patients value the quality-of-life effect of relieving severe stenosis symptoms. Instrumented fusion was very expensive compared with the incremental gain in health outcome. Better data on the effectiveness of these alternative procedures are needed.