The utility of the life-course framework to address disparities in child health is based on its ability to integrate the science of child development with the requirements of effective and just public policy. I argue that the life-course framework is best assessed in a historical context and through 4 essential observations. First, early genetic and environmental interactions are complex and influence outcomes in different settings in very different ways. Second, these early-life interactions are themselves subject to considerable later influences and, therefore, may not be highly predictive of later outcomes. Third, the etiologic nature or timing of early-life interactions does not, per se, determine if their life-course effects are amenable to later interventions. Fourth, a highly deterministic view of early-life interactions is not supported by the science and can generate counterproductive approaches to research and policy development. Finally, an alternative approach is proposed on the basis of a "human-capacity" model of the life course that connects the search for underlying basic mechanisms with a policy-based examination of the comparative effectiveness of influences at different developmental stages. This approach suggests an expanded research and policy agenda that might be more capable of generating urgently needed strategies for reducing disparities in child health. Such an approach could ultimately define more comprehensively the power and limits of life-course effects in shaping the social distribution of health outcomes in the real world.

BACKGROUND AND AIMS:: The cost-effectiveness of alternative approaches to the diagnosis of small-bowel Crohn's disease is unknown. This study evaluates whether CT-Enterography (CTE) is a cost-effective alternative to small bowel follow-through (SBFT) and whether capsule endoscopy is a cost-effective third test in patients in whom a high suspicion of disease remains after two previous negative tests.

METHODS:: A decision-analytic model was developed to compare the lifetime costs and benefits of each diagnostic strategy. Patients were considered with low (20%) and high (75%) pretest probability of small-bowel Crohn's disease. Effectiveness was measured in quality-adjusted life-years (QALYs) gained. Parameter assumptions were tested with sensitivity analyses. RESULTS:: With a moderate to high pretest probability of small-bowel Crohn's disease, and higher likelihood of isolated jejunal disease, follow-up with CTE has an incremental cost-effectiveness ratio of less than $54,000/QALY-gained compared to SBFT. The addition of capsule endoscopy after ileocolonoscopy and negative CTE or SBFT costs greater than $500,000 per QALY-gained in all scenarios. Results were not sensitive to costs of tests or complications and were sensitive to test accuracies.

CONCLUSIONS:: The cost-effectiveness of strategies depends critically on the pretest probability of Crohn's disease and if the terminal ileum is examined at ileocolonoscopy. CTE is a cost-effective alternative to SBFT in patients with moderate to high suspicion of small-bowel Crohn's disease. The addition of capsule endoscopy as a third test is not a cost-effective third test even in patients with high pretest probability of disease.

Background. Helicobacter pylori vaccines are under development to prevent infection. We quantified the cost‐effectiveness of such a vaccine in the United States, using a dynamic transmission model.

Methods. We compartmentalized the population by age, infection status, and clinical disease state and measured effectiveness in quality‐adjusted life years (QALYs). We simulated no intervention, vaccination of infants, and vaccination of school‐age children. Variables included costs of vaccine, vaccine administration, and gastric cancer treatment (in 2007 US dollars), vaccine efficacy, quality adjustment due to gastric cancer, and discount rate. We evaluated possible outcomes for periods of 10-75 years.

Results. H. pylori vaccination of infants would cost $2.9 billion over 10 years; savings from cancer prevention would be realized decades later. Over a long time horizon (75 years), incremental costs of H. pylori vaccination would be $1.8 billion, and incremental QALYs would be 0.5 million, yielding a cost‐effectiveness ratio of $3871/QALY. With school‐age vaccination, the cost‐effectiveness ratio would be $22,137/QALY. With time limited to <40 years, the cost‐effectiveness ratio exceeded $50,000/QALY.

Conclusion. When evaluated with a time horizon beyond 40 years, the use of a prophylactic H. pylori vaccine was cost‐effective in the United States, especially with infant vaccination.

New technologies, including prescription drugs and medical devices, are a major driver of increases in U.S. health care expenditures, which have grown by an estimated 71% since 2000.1 The U.S. market for drugs and devices is regulated by the Food and Drug Administration (FDA), which scrutinizes clinical trial data for evidence of safety and efficacy. Although the FDA has been criticized for missteps and inefficiencies in its approval process, these are not the causes of increasing health care expenditures. More relevant is FDA oversight of the labeling and promotion of medical products.

Objective

To evaluate the cost effectiveness of laparoscopy for unexplained infertility.

Design

We performed a cost-effectiveness analysis using a computer-generated decision analysis tree. Data used to construct the mathematical model were extracted from the literature or obtained from our practice. We compared outcomes following four treatment strategies: [1] no treatment, [2] standard infertility treatment algorithm (SITA), [3] laparoscopy with expectant management (LSC/EM), and [4] laparoscopy with infertility therapy (LSC/IT). The incremental cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analyses assessed the impact of varying base-case estimates.

Setting

Academic in vitro fertilization practice.

Patient(s)

Computer-simulated patients assigned to one of four treatments.

Intervention(s)

Fertility treatment or laparoscopy.

Main Outcome Measure(s)

Incremental cost-effectiveness ratios.

Result(s)

Using base-case assumptions, LSC/EM was preferred (ICER =$128,400 per live-birth in U.S. dollars). Changing the following did not alter results: rates and costs of multiple gestations, penalty for high-order multiples, infertility treatment costs, and endometriosis prevalence. Outcomes were most affected by patient dropout from infertility treatments-SITA was preferred when dropout was less than 9% per cycle. Less important factors included surgical costs, acceptability of twins, and the effects of untreated endometriosis on fecundity.

Conclusion(s)

Laparoscopy is cost effective in the initial management of young women with infertility, particularly when infertility treatment dropout rates exceed 9% per cycle.

Objective

To establish guidance on grading strength of evidence for the Evidence-based Practice Center (EPC) program of the U.S. Agency for Healthcare Research and Quality.

Study Design and Setting

Authors reviewed authoritative systems for grading strength of evidence, identified domains and methods that should be considered when grading bodies of evidence in systematic reviews, considered public comments on an earlier draft, and discussed the approach with representatives of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group.

Results

The EPC approach is conceptually similar to the GRADE system of evidence rating; it requires assessment of four domains: risk of bias, consistency, directness, and precision. Additional domains to be used when appropriate include dose-response association, presence of confounders that would diminish an observed effect, strength of association, and publication bias. Strength of evidence receives a single grade: high, moderate, low, or insufficient. We give definitions, examples, mechanisms for scoring domains, and an approach for assigning strength of evidence.

Conclusion

EPCs should grade strength of evidence separately for each major outcome and, for comparative effectiveness reviews, all major comparisons. We will collaborate with the GRADE group to address ongoing challenges in assessing the strength of evidence.

Estimating the potential health benefits and expenditures of a partially effective HIV vaccine is an important consideration in the debate about whether HIV vaccine research should continue. We developed an epidemic model to estimate HIV prevalence, new infections, and the cost-effectiveness of vaccination strategies in the U.S. Vaccines with modest efficacy could prevent 300,000-700,000 HIV infections and save $30 billion in healthcare expenditures over 20 years. Targeted vaccination of high-risk individuals is economically efficient, but difficulty in reaching these groups may mitigate these benefits. Universal vaccination is cost-effective for vaccines with 50% efficacy and price similar to other infectious disease vaccines.