AHRQ series on complex intervention systematic reviews-paper 5: advanced analytic methods.

BACKGROUND AND OBJECTIVE: Advanced analytic methods for synthesizing evidence about complex interventions continue to be developed. In this paper, we emphasize that the specific research question posed in the review should be used as a guide for choosing the appropriate analytic method. METHODS: We present advanced analytic approaches that address four common questions that guide reviews of complex interventions: (1) How effective is the intervention? (2) For whom does the intervention work and in what contexts? (3) What happens when the intervention is implemented? and (4) What decisions are possible given the results of the synthesis? CONCLUSION: The analytic approaches presented in this paper are particularly useful when each primary study differs in components, mechanisms of action, context, implementation, timing, and many other domains

Value of information analytical methods: Report 2 of the ISPOR value of information analysis emerging good practices task force

The allocation of health care resources among competing priorities requires an assessment of the expected costs and health effects of investing resources in the activities, and on the opportunity cost of the expenditure. To date, much effort has been devoted to assessing the expected costs and health effects, but there remains an important need to also reflect the consequences of uncertainty in resource allocation decisions and the value of further research to reduce uncertainty. Decision-making with uncertainty may turn out to be suboptimal, resulting in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to better inform resource decisions. This value can be quantified using Value of Information (VOI) analysis. This report, from the ISPOR VOI Task Force, describes methods for computing four VOI measures: the Expected Value of Perfect Information (EVPI), Expected Value of Partial Perfect Information (EVPPI), Expected Value of Sample Information (EVSI) and Expected Net Benefit of Sampling (ENBS). Several methods exist for computing EVPPI and EVSI, and this report provides guidance on selecting the most appropriate method based on the features of the decision problem. The report provides a number of recommendations for good practice when planning, undertaking or reviewing VOI analyses. The software needed to compute VOI is discussed, and areas for future research are highlighted

The potential cost-effectiveness of novel cord blood therapies in children with autism spectrum disorder.

ObjectiveTo model the long-term clinical and economic outcomes of potential cord blood therapy in autism spectrum disorder (ASD).Study designMarkov microsimulation of ASD over the lifespan was used to compare two strategies: 1) standard of care (SOC), including behavioral and educational interventions, and 2) novel cord blood (CB) intervention in addition to SOC. Input data reflecting behavioral outcomes included baseline Vineland Adaptive Behavior Scale (VABS-3), monthly VABS-3 changes, and CB intervention efficacy on adaptive behavior based on a randomized, placebo-controlled trial (DukeACT). Quality-adjusted life-years (QALYs) were correlated to VABS-3. Costs for children with ASD ($15,791, ages 2-17 years) and adults with ASD ($56,559, ages 18+ years), and the CB intervention (range $15,000-45,000) were incorporated. Alternative CB efficacy and costs were explored.ResultsWe compared model-projected results to published data on life-expectancy, mean VABS-3 changes, and lifetime costs. Undiscounted lifetime QALYs in the SOC and CB strategies were 40.75 and 40.91. Discounted lifetime costs in the SOC strategy were$1,014,000, and for CB ranged from $1,021,000-$1,058,000 with CB intervention cost ($8,000-$45,000). At $15,000 cost, CB was borderline cost-effective (ICER =$105,000/QALY). In one-way sensitivity analysis, CB cost and efficacy were the most influential parameters on CB ICER. CB intervention was cost-effective at costsConclusionsA modestly effective intervention designed to improve adaptive behavior in autism can be cost-effective under certain circumstances. Intervention cost and efficacy most affected the cost-effectiveness results and should be targeted to increase economic efficiency

Two-way sensitivity analysis on cord blood intervention efficacy and cost.

This figure shows the effect of varying CB intervention efficacy and cost on cost-effectiveness outcomes. CB intervention efficacy on VABS-3 communication subscale score was varied across the Y-axis, from a mean change of 1.0–6.0. CB intervention cost was varied across the X-axis, ranging from $3,000-$33,000. The projected ICER of each combination of efficacy and cost are shown in the Figure and are color coded: green indicates an ICER $150,000/QALY (Legend). The white star indicates the projected cost-effectiveness of DukeACT intervention basecase parameters. CB: cord blood, VABS: Vineland Adaptive Behavior Scale, ICER: incremental cost-effectiveness ratio.</p

Tornado diagram of cost-effectiveness of one-way sensitivity analyses.

This Figure shows the influence of several individual parameters, varied across their plausible ranges, on cost-effectiveness on the CB intervention. Ranges assessed are presented as (base-case value: value that yields lowest ICER—value that yields highest ICER). The four most influential parameters on cost-effectiveness results were CB cost, CB efficacy, child QOL mapping equation beta parameter, and minor toxicity cost. CB: cord blood, ICER: incremental cost-effectiveness ratio, QALY: quality-adjusted life year, QOL: quality of life, VABS-3: Vineland Adaptive Behavior Scale-3.</p

Model input data.

ObjectiveTo model the long-term clinical and economic outcomes of potential cord blood therapy in autism spectrum disorder (ASD).Study designMarkov microsimulation of ASD over the lifespan was used to compare two strategies: 1) standard of care (SOC), including behavioral and educational interventions, and 2) novel cord blood (CB) intervention in addition to SOC. Input data reflecting behavioral outcomes included baseline Vineland Adaptive Behavior Scale (VABS-3), monthly VABS-3 changes, and CB intervention efficacy on adaptive behavior based on a randomized, placebo-controlled trial (DukeACT). Quality-adjusted life-years (QALYs) were correlated to VABS-3. Costs for children with ASD ($15,791, ages 2–17 years) and adults with ASD ($56,559, ages 18+ years), and the CB intervention (range $15,000–45,000) were incorporated. Alternative CB efficacy and costs were explored.ResultsWe compared model-projected results to published data on life-expectancy, mean VABS-3 changes, and lifetime costs. Undiscounted lifetime QALYs in the SOC and CB strategies were 40.75 and 40.91. Discounted lifetime costs in the SOC strategy were$1,014,000, and for CB ranged from $1,021,000-$1,058,000 with CB intervention cost ($8,000-$45,000). At $15,000 cost, CB was borderline cost-effective (ICER =$105,000/QALY). In one-way sensitivity analysis, CB cost and efficacy were the most influential parameters on CB ICER. CB intervention was cost-effective at costsConclusionsA modestly effective intervention designed to improve adaptive behavior in autism can be cost-effective under certain circumstances. Intervention cost and efficacy most affected the cost-effectiveness results and should be targeted to increase economic efficiency.</div

Lifetime societal costs and quality-adjusted life years.

Lifetime societal costs and quality-adjusted life years.</p

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ObjectiveTo model the long-term clinical and economic outcomes of potential cord blood therapy in autism spectrum disorder (ASD).Study designMarkov microsimulation of ASD over the lifespan was used to compare two strategies: 1) standard of care (SOC), including behavioral and educational interventions, and 2) novel cord blood (CB) intervention in addition to SOC. Input data reflecting behavioral outcomes included baseline Vineland Adaptive Behavior Scale (VABS-3), monthly VABS-3 changes, and CB intervention efficacy on adaptive behavior based on a randomized, placebo-controlled trial (DukeACT). Quality-adjusted life-years (QALYs) were correlated to VABS-3. Costs for children with ASD ($15,791, ages 2–17 years) and adults with ASD ($56,559, ages 18+ years), and the CB intervention (range $15,000–45,000) were incorporated. Alternative CB efficacy and costs were explored.ResultsWe compared model-projected results to published data on life-expectancy, mean VABS-3 changes, and lifetime costs. Undiscounted lifetime QALYs in the SOC and CB strategies were 40.75 and 40.91. Discounted lifetime costs in the SOC strategy were$1,014,000, and for CB ranged from $1,021,000-$1,058,000 with CB intervention cost ($8,000-$45,000). At $15,000 cost, CB was borderline cost-effective (ICER =$105,000/QALY). In one-way sensitivity analysis, CB cost and efficacy were the most influential parameters on CB ICER. CB intervention was cost-effective at costsConclusionsA modestly effective intervention designed to improve adaptive behavior in autism can be cost-effective under certain circumstances. Intervention cost and efficacy most affected the cost-effectiveness results and should be targeted to increase economic efficiency.</div

Value of Information Analysis for Research Decisions—An Introduction: Report 1 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force

Healthcare resource allocation decisions made under conditions of uncertainty may turn out to be suboptimal. In a resource constrained system in which there is a fixed budget, these suboptimal decisions will result in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to make better resource allocation decisions. This value can be quantified using a value of information (VOI) analysis. This report, from the ISPOR VOI Task Force, introduces VOI analysis, defines key concepts and terminology, and outlines the role of VOI for supporting decision making, including the steps involved in undertaking and interpreting VOI analyses. The report is specifically aimed at those tasked with making decisions about the adoption of healthcare or the funding of healthcare research. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing the results of VOI analyses

Hydroxychloroquine in the pregnancies of women with lupus: a meta-analysis of individual participant data

ObjectiveMultiple guidelines recommend continuing hydroxychloroquine (HCQ) for SLE during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to identify the potential benefits and harms of HCQ use within lupus pregnancies.MethodsEligible studies included prospectively collected pregnancies in women with lupus. After a systematic literature search, seven datasets meeting inclusion criteria were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset, and results were aggregated to provide a pooled OR.ResultsSeven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a first trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared with pregnancies without HCQ, those with HCQ had lower odds of highly active lupus, but did not have different odds of fetal loss, preterm delivery or pre-eclampsia. Among women with low lupus activity, HCQ reduced the odds of preterm delivery.ConclusionsThis large study of prospectively-collected lupus pregnancies demonstrates a decrease in lupus activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy