Comparative effectiveness research
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Background
Multidrug-resistant tuberculosis (MDR-TB) is an important global health problem, and a
control strategy known as DOTS-Plus has existed since 1999. However, evidence regarding the feasibility, effectiveness, cost, and cost-effectiveness of DOTS-Plus is still limited.


Methodology/Principal Findings
We evaluated the feasibility, effectiveness, cost, and cost-effectiveness of a DOTS-Plus pilot project established at Makati Medical Center in Manila, the Philippines, in 1999. Patients with MDR-TB are treated with regimens, including first- and second-line drugs, tailored to their drug susceptibility pattern (i.e., individualised treatment). We considered the cohort enrolled between April 1999 and March 2002. During this three-year period, 118 patients were enrolled in the project; 117 were considered in the analysis. Seventy-one patients (61%) were cured, 12 (10%) failed treatment, 18 (15%) died, and 16 (14%) defaulted. The average cost per patient treated was US$3,355 from the perspective of the health system, of which US$1,557 was for drugs, and US$837 from the perspective of patients. The mean cost per disability-adjusted life year (DALY) gained by the DOTS-Plus project was US$242 (range US$85 to US$426).


Conclusions
Treatment of patients with MDR-TB using the DOTS-Plus strategy and individualised drug
regimens can be feasible, comparatively effective, and cost-effective in low- and middle-income countries.

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PLoS Medicine
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A critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. The objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. We modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. We found that mortality was highly dependent on the local dispensing capacity, the number of individuals requiring prophylaxis, adherence to prophylactic antibiotics, and delays in attack detection. For an attack exposing 250,000 people and requiring the prophylaxis of 5 million people, expected mortality fell from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to 420,000 individuals per day. At low dispensing capacities (14,000 individuals per day), nearly all exposed individuals died, regardless of the rate of adherence to prophylaxis, delays in attack detection, or availability of local inventories. No benefit was achieved by doubling local inventories at low dispensing capacities; however, at higher dispensing capacities, the cost-effectiveness of doubling local inventories fell from $100,000 to $20,000/life year gained as the annual probability of an attack increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid availability of regional inventories, the critical determinant of mortality following anthrax bioterrorism is local dispensing capacity. Bioterrorism preparedness efforts directed at improving local dispensing capacity are required before benefits can be reaped from enhancing local inventories.

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Biosecurity and Bioterrorism
Authors
Margaret L. Brandeau
Douglas K. Owens
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Several factors are changing the landscape of cervical cancer control, including a better understanding of the natural history of human papillomavirus (HPV), reliable assays for detecting high-risk HPV infections, and a soon to be available HPV-16/18 vaccine. There are important differences in the relevant policy questions for different settings. By synthesizing and integrating the best available data, the use of modeling in a decision analytic framework can identify those factors most likely to influence outcomes, can guide the design of future clinical studies and operational research, can provide insight into the cost-effectiveness of different strategies, and can assist in early decision-making when considered with criteria such as equity, public preferences, and political and cultural constraints

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Vaccine
Authors
Jeremy Goldhaber-Fiebert
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BACKGROUND: Cost-effectiveness analyses (CEAs) can provide useful information to policymakers concerned with the broad allocation of resources as well as to local decision makers choosing between different options for reducing the burden from a single disease. For the latter, it is important to use country-specific data when possible and to represent cost differences between countries that might make one strategy more or less attractive than another strategy locally. As part of a CEA of cervical cancer screening in five developing countries, we supplemented limited primary cost data by developing other estimation techniques for direct medical and non-medical costs associated with alternative screening approaches using one of three initial screening tests: simple visual screening, HPV DNA testing, and cervical cytology. Here, we report estimation methods and results for three cost areas in which data were lacking. METHODS: To supplement direct medical costs, including staff, supplies, and equipment depreciation using country-specific data, we used alternative techniques to quantify cervical cytology and HPV DNA laboratory sample processing costs. We used a detailed quantity and price approach whose face validity was compared to an adaptation of a US laboratory estimation methodology. This methodology was also used to project annual sample processing capacities for each laboratory type. The cost of sample transport from the clinic to the laboratory was estimated using spatial models. A plausible range of the cost of patient time spent seeking and receiving screening was estimated using only formal sector employment and wages as well as using both formal and informal sector participation and country-specific minimum wages. Data sources included primary data from country-specific studies, international databases, international prices, and expert opinion. Costs were standardized to year 2000 international dollars using inflation adjustment and purchasing power parity. RESULTS: Cervical cytology laboratory processing costs were I$1.57-3.37 using the quantity and price method compared to I$1.58-3.02 from the face validation method. HPV DNA processing costs were I$6.07-6.59. Rural laboratory transport costs for cytology were I$0.12-0.64 and I$0.14-0.74 for HPV DNA laboratories. Under assumptions of lower resource efficiency, these estimates increased to I$0.42-0.83 and I$0.54-1.06. Estimates of the value of an hour of patient time using only formal sector participation were I$0.07-4.16, increasing to I$0.30-4.80 when informal and unpaid labor was also included. The value of patient time for traveling, waiting, and attending a screening visit was I$0.68-17.74. With the total cost of screening for cytology and HPV DNA testing ranging from I$4.85-40.54 and I$11.30-48.77 respectively, the cost of the laboratory transport, processing, and patient time accounted for 26-66% and 33-65% of the total costs. From a payer perspective, laboratory transport and processing accounted for 18-48% and 25-60% of total direct medical costs of I$4.11-19.96 and I$10.57-28.18 respectively. CONCLUSION: Cost estimates of laboratory processing, sample transport, and patient time account for a significant proportion of total cervical cancer screening costs in five developing countries and provide important inputs for CEAs of alternative screening modalities.

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Cost Effectiveness and Resource Allocation
Authors
Jeremy Goldhaber-Fiebert
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Background: Teriparatide is a promising new agent for the treatment of osteoporosis.

Methods: The objective of this study was to evaluate the cost-effectiveness of teriparatide-based strategies compared with alendronate sodium for the first-line treatment of high-risk osteoporotic women. We developed a microsimulation with a societal perspective. Key data sources include the Study of Osteoporotic Fractures, the Fracture Intervention Trial, and the Fracture Prevention Trial. We evaluated postmenopausal white women with low bone density and prevalent vertebral fracture. The interventions were usual care (UC) (calcium or vitamin D supplementation) compared with 3 strategies: 5 years of alendronate therapy, 2 years of teriparatide therapy, and 2 years of teriparatide therapy followed by 5 years of alendronate therapy (sequential teriparatide/alendronate). The main outcome measure was cost per quality-adjusted life-year (QALY).

Results: For the base-case analysis, the cost of alendronate treatment was $11 600 per QALY compared with UC. The cost of sequential teriparatide/alendronate therapy was $156 500 per QALY compared with alendronate. Teriparatide treatment alone was more expensive and produced a smaller increase in QALYs than alendronate. For sensitivity analysis, teriparatide alone was less cost-effective than alendronate even if its efficacy lasted 15 years after treatment cessation. Sequential teriparatide/alendronate therapy was less cost-effective than alendronate even if fractures were eliminated during the alendronate phase, although its cost-effectiveness was less than $50 000 per QALY if the price of teriparatide decreased 60%, if used in elderly women with T scores of -4.0 or less, or if 6 months of teriparatide therapy had comparable efficacy to 2 years of treatment.

Conclusions: Alendronate compares favorably to interventions accepted as cost-effective. Therapy with teriparatide alone is more expensive and produces a smaller increase in QALYs than therapy with alendronate. Sequential teriparatide/alendronate therapy appear expensive but could become more cost-effective with reductions in teriparatide price, with restriction to use in exceptionally high-risk women, or if short courses of treatment have comparable efficacy to that observed in clinical trials.

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Archives of Internal Medicine
Authors
Douglas K. Owens
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Context:

Women with inherited BRCA1/2 mutations are at high risk for breast cancer, which mammography often misses. Screening with contrast-enhanced breast magnetic resonance imaging (MRI) detects cancer earlier but increases costs and results in more false-positive scans.

Objective:

To evaluate the cost-effectiveness of screening BRCA1/2 mutation carriers with mammography plus breast MRI compared with mammography alone.

Design, Setting, and Patients:

A computer model that simulates the life histories of individual BRCA1/2 mutation carriers, incorporating the effects of mammographic and MRI screening was used. The accuracy of mammography and breast MRI was estimated from published data in high-risk women. Breast cancer survival in the absence of screening was based on the Surveillance, Epidemiology and End Results database of breast cancer patients diagnosed in the prescreening period (1975-1981), adjusted for the current use of adjuvant therapy. Utilization rates and costs of diagnostic and treatment interventions were based on a combination of published literature and Medicare payments for 2005.

Main Outcome Measures:

The survival benefit, incremental costs, and cost-effectiveness of MRI screening strategies, which varied by ages of starting and stopping MRI screening, were computed separately for BRCA1 and BRCA2 mutation carriers.

Results:

Screening strategies that incorporate annual MRI as well as annual mammography have a cost per quality-adjusted life-year (QALY) gained ranging from less than $45 000 to more than $700 000, depending on the ages selected for MRI screening and the specific BRCA mutation. Relative to screening with mammography alone, the cost per QALY gained by adding MRI from ages 35 to 54 years is $55 420 for BRCA1 mutation carriers, $130 695 for BRCA2 mutation carriers, and $98 454 for BRCA2 mutation carriers who have mammographically dense breasts.

Conclusions:

Breast MRI screening is more cost-effective for BRCA1 than BRCA2 mutation carriers. The cost-effectiveness of adding MRI to mammography varies greatly by age.

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Journal of the American Medical Association
Authors
Sylvia K. Plevritis
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