Two-way sensitivity analysis results for MRI sensitivity and specificity (for identifying stroke onset time of <4.5 hours), assuming willingness-to-pay for health of $100,000/QALY.

<p>The MRI-based strategy is optimal in the blue region, which includes the base-case result (marked by an “X”); the no treatment strategy is optimal in the red region given some other combinations of MRI sensitivity and specificity. The line separating the blue and red regions has an angle <45 degrees, which indicates that the results are more influenced by specificity than sensitivity.</p

Lifetime per-person mRS0-1 outcomes, stroke onset time outcomes, inappropriately treated outcomes, quality-adjusted life years (QALYs), costs (),andincrementalcost−effectivenessratios(), and incremental cost-effectiveness ratios (/QALY) for acute wakeup stroke patients.

<p>Lifetime per-person mRS0-1 outcomes, stroke onset time outcomes, inappropriately treated outcomes, quality-adjusted life years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY) for acute wakeup stroke patients.</p

One-way sensitivity analysis results (ICERs for MRI-based strategy vs. no treatment).

<p>Tornado diagram summarizing one-way sensitivity analyses for the MRI-based strategy compared to the no treatment strategy for the base-case analysis. Most incremental cost-effectiveness ratios (ICERs) were close to the base-case result ($88,000/QALY) as model parameters were varied through plausible ranges, with the exceptions of the odds ratio of mRS0-1 with treatment for patients with stroke onset time 271–360 minutes, utility values for mRS5 and mRS4 health states, age in years, and MRI specificity. Parameters are shown in descending order of influence on model results.</p

Time sequence from sleep start to tissue-type plasminogen activator (tPA) initiation for acute wakeup stroke patients in the micro-simulation model.

<p>*Door-to-needle time includes additional 30 minutes for performing and interpreting MRI. **Base-case assumption for true stroke onset during sleep is based on a uniform probability between 0–8 hours. Sleep durations of 4 and 6 hours, and alternative skewed beta distributions used in sensitivity analyses.</p

Cost-effectiveness acceptability curve from probabilistic sensitivity analysis.

<p>The probability of the MRI-based strategy and no treatment strategy being cost-effective plotted against the cost-effectiveness threshold. The probability of a strategy being cost-effective was based on the probabilistic sensitivity analysis, which incorporates the uncertainty of all model parameters.</p

Projected incremental cost effectiveness ratios of potential interventions to improve HCV follow-up.

<p>QALY = Quality-adjusted life year; ICER = incremental cost-effectiveness ratio.</p><p>Costs and QALYs are lifetime and discounted at an annual rate of 3%. Costs are in 2011 U.S.$and rounded to the nearest$100. All QALYs are rounded to the nearest hundredth.</p>a<p>The ICER of linkage compared to standard of care is $26,500/QALY gained; linkage is extended dominated.</p>b<p>The ICER of treatment initiation compared to standard of care is$19,200/QALY gained; treatment initiation is extended dominated.</p>c<p>The ICER of peer navigators compared to standard of care is $20,000/QALY gained.</p

Model input parameters for a Monte Carlo simulation of HCV.

<p>S.D. = standard deviation; PY = person-year; PEG = pegylated interferon; RBV = ribavirin; TPV = telaprevir; SVR = sustained virologic response; ICM = integrated case management; IFN = interferon.</p>a<p>The lifetime probability of linking to HCV care upon receipt of a positive antibody result is 66%.</p>b<p>In the interferon-free scenario, we assumed that 54% of those linked to care would initiate therapy.</p>c<p>Costs varied as a function of age and sex.</p>d<p>Includes the cost of a RNA confirmatory test and a nursing visit.</p>e<p>ntervention costs are presented on a per participant basis, assuming that the participant completes the entire intervention. During the simulation, participants accrued costs on a monthly basis. If the participant was lost to follow-up, or otherwise withdrew from care before the end of the intervention, then that patient stopped accruing intervention costs at the time of being lost (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097317#pone.0097317.s001" target="_blank">Appendix S1</a> for details).</p>f<p>Treatment visit costs are higher in the first month compared to other months.</p>g<p>13% of patients received a reduced weekly dose of 135 mcg in response to non-treatment ending neutropenia <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097317#pone.0097317-Food1" target="_blank">[45]</a>.</p>h<p>RBV dose was a function of genotype (genotype 1 = 1,200 mg/day; genotype 2 or 3 = 800 mg/day). In addition, 36% of patients on triple therapy and 17% on dual therapy were treated with reduced dose RBV = 600 mg/day in response to non-treatment ending anemia <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097317#pone.0097317-Food1" target="_blank">[45]</a>.</p>i<p>Only patients with genotype 1 receive TPV for treatment months 1–3.</p>j<p>13% of patients developed non-treatment ending neutropenia (absolute neutrophil count <750/ml) and received filgrastim 300 mcg/two times weekly <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097317#pone.0097317-Food1" target="_blank">[45]</a>.</p>k<p>Only patients with genotype 1 treated with PEG/RBV/TPV therapy received 150g/month for treating mild rash (28% during the first 3 months of therapy) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097317#pone.0097317-Food1" target="_blank">[45]</a>.</p>l<p>The range reflects the fact that some patients were treated for 6 months, while those without rapid virologic response were treated for 12 months.</p>m<p>Reflects lower quality of life for individuals with HCV risk-factors such as substance use.</p>n<p>This utility weight was multiplied by an individual’s health state utility during the months that a patient was receiving HCV therapy without major toxicity. For example, a patient with HCV and mild to moderate fibrosis who underwent HCV treatment had a utility = 0.801 (0.90×0.89) during the months that (s)he was on medications.</p>o<p>This utility “toll” was subtracted from a patient’s health state utility during the month of a major toxicity event.</p

Intervention clinical outcomes.

<p>The bar graph illustrates the percent of the cohort attaining clinical outcomes along the HCV cascade of care. Each bar shading represents a specific intervention scenario.</p

Unit costs.

a<p>Cost of radiograph and reading by radiologist conducted off-site.</p>b<p>Additional costs were incurred at initial study visit (US$5.42), study visits that included physician administration of an adherence and quality-of-life questionnaire (US$2.71) and physician visits that included initiation of ART for standard group (US$2.71).</p>c<p>MD costs were reduced by one-half beyond 2 mo postdelivery.</p>d<p>One dilation and curettage (US$185.32), one hospital birth (US$247.10), one appendectomy (US$420.06), one inguinal hernia repair (US$420.06), one leg repair (US$420.06), one cervical lymph node biopsy (US$494.19), one removal of uterine fibroids (US$1,235.48).</p

Cost-effectiveness acceptability curves for earlier initiation of ART after a maximum of 3 y including and excluding protocol-driven costs.

<p>Curves were constructed from 100 bootstrap simulations including protocol-driven costs and 100 bootstrap simulations excluding protocol-driven costs.</p