No abstract

The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node –, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. High RS patients were significantly more likely to follow the treatment suggested by ODX versus low RS patients RR: 1.07 (1.01–1.14). The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.

Purpose Evaluation of genomic tests is often challenging because of the lack of direct evidence of clinical benefit compared to usual care and unclear evidence requirements. To address these issues, this study presents a risk-benefit framework for assessing the health-related utility of genomic tests. Methods We incorporated approaches from a variety of established fields, including decision science, outcomes research, and health technology assessment to develop the framework. Additionally, we considered genomic test stakeholder perspectives and case studies. Results We developed a 3-tiered framework: first, we use decision-analytic modeling techniques to synthesize data, project incidence of clinical events, and assess uncertainty. Second, we define the health-related utility of genomic tests as improvement in health outcomes as measured by clinical event rates, life expectancy, and quality-adjusted life-years (QALYs). Finally, we display results using a risk-benefit policy matrix to facilitate the interpretation and implementation of findings from these analyses. Conclusion A formal risk-benefit framework may accelerate the utilization and practice-based evidence development of genomic tests that pose low risk and offer plausible clinical benefit, while discouraging premature use of tests that provide little benefit or pose significant health risks compared to usual care

Importance Prostate-specific antigen (PSA) screening for prostate cancer is controversial. Experts have suggested more personalized or more conservative strategies to improve benefit-risk tradeoffs, but the value of these strategies—particularly when combined with increased conservative management for low-risk cases—is uncertain. Objective To evaluate the potential cost-effectiveness of plausible PSA screening strategies, and to assess the value added by increased use of conservative management among low-risk screen-detected cases. Design Micro-simulation model of prostate cancer incidence and mortality under alternative PSA screening strategies and either (1) “contemporary” treatment practices based on age, stage, and grade observed in the Surveillance, Epidemiology, and End Results program in 2010 or (2) “selective” treatment practices where cases with Gleason sum <7 and clinical T-stage ≤T2a are treated only after clinical progression and all others are treated according to “contemporary” treatment practices. Setting National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, mortality, health-related quality of life, and direct medical expenditure. Participants A simulated contemporary cohort of U.S. men beginning at 40 years of age. Interventions 18 screening strategies that vary by start and stop age, screening interval, and criteria for biopsy referral; “contemporary” or “selective” treatment practices. Main Outcome Measures Life years (LYs), quality-adjusted life years (QALYs), direct medical expenditure, and cost per LY and QALY gained. Results All screening strategies increased LYs (range 0.03–0.06) and costs ($300–$1,400) vs. no screening with cost per LY ranging from $7,300 to $21,600. With “contemporary” treatment, only strategies with biopsy referral when PSA >10.0 µg/L or age-dependent thresholds increased QALYs (0.002–0.004), and only quadrennial screening of ages 55–69 was potentially cost-effective in terms of cost per QALY (ICER=$92,400). With “selective” treatment, all strategies increased QALYs (0.002–0.004) and several strategies were potentially cost-effective in terms of cost per QALY (ICER=$70,800–$136,300). Conclusions For PSA screening to be cost effective it needs to be used conservatively and ideally in combination with a conservative management approach for low-risk disease.

The relentless need for the discovery and development of new agrochemicals continues as a result of driving forces such as loss of existing products through the development of resistance, the necessity for products with more favorable environmental and toxicological profiles, shifting pest spectra, and the changing agricultural needs and practices of the farming community. These new challenges underscore the demand for novel, high-quality starting points to accelerate the discovery of new agrochemicals that address market challenges. This article discusses the efforts to identify the optimum ranges of physicochemical properties of agrochemicals through analysis of modern commercial products. Specifically, we reviewed literature studies examining physicochemical property effects and analyzed the properties typical of successful fungicides, herbicides, and insecticides (chewing and sap-feeding pests). From the analysis, a new set of physicochemical property guidelines for each discipline, as well as building block class, are proposed. These new guidelines should significantly aid in the discovery of next-generation agrochemicals. © 2018 Society of Chemical Industry.

The participants in our study provided insight into why some patients make the decision to opt out of low-dose computed tomography screening, which provides knowledge that can inform intervention development to enhance shared decision-making processes between long-term smokers and their providers and decrease decisional conflict about screening.

Background Computerized provider order entry (CPOE) is the process of entering physician orders directly into an electronic health record. Although CPOE has been shown to improve medication safety and reduce health care costs, these improvements have been demonstrated largely in the inpatient setting; the cost-effectiveness in the ambulatory setting remains uncertain. Objective The objective was to estimate the cost-effectiveness of CPOE in reducing medication errors and adverse drug events (ADEs) in the ambulatory setting. Methods We created a decision-analytic model to estimate the cost-effectiveness of CPOE in a midsized (400 providers) multidisciplinary medical group over a 5-year time horizon— 2010 to 2014— the time frame during which health systems are implementing CPOE to meet Meaningful Use criteria. We adopted the medical group’s perspective and utilized their costs, changes in efficiency, and actual number of medication errors and ADEs. One-way and probabilistic sensitivity analyses were conducted. Scenario analyses were explored. Results In the base case, CPOE dominated paper prescribing, that is, CPOE cost $18 million less than paper prescribing, and was associated with 1.5 million and 14,500 fewer medication errors and ADEs, respectively, over 5 years. In the scenario that reflected a practice group of five providers, CPOE cost $265,000 less than paper prescribing, was associated with 3875 and 39 fewer medication errors and ADEs, respectively, over 5 years, and was dominant in 80% of the simulations. Conclusions Our model suggests that the adoption of CPOE in the ambulatory setting provides excellent value for the investment, and is a cost-effective strategy to improve medication safety over a wide range of practice sizes.

560 Background: Many studies have evaluated the Oncotype Dx Breast Cancer Assay (ODX) and its impact on adjuvant chemotherapy (ACT) treatment decisions. However, it can be difficult for clinicians and other stakeholders to interpret the collective findings of these studies, as they were conducted in diverse settings and have limited sample sizes. To address this issue, we conducted a systematic review and meta-analysis to synthesize ODX results and provide insights about the utility of ODX in actual clinical practice. Methods: We performed a systematic review of ODX studies using PubMed, Embase, ASCO, and SABCS. Studies were included if patients had ER +, node -, early stage breast cancer, reported use of ODX to inform actual ACT decisions, and reported outcomes of interest, including: 1) distribution of ODX recurrence scores (RS); 2) impact of ODX on ACT recommendations; 3) impact of ODX on ACT use; and 4) proportion of patients following the treatment suggested by the ODX RS. Results: A total of 28 studies met inclusion criteria. The distribution of RS categories was 48.8% low, 39.0% intermediate, and 12.2% high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4% of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT was: 28.2% overall, 5.8% low, 37.4% intermediate, and 83.4% high. High RS patients were significantly more likely to follow the treatment suggested by ODX vs. low RS patients RR: 1.07 (1.01–1.14). Conclusions: The pooled results for the impact of ODX on ACT recommendations are consistent with most individual studies to date. However, the proportion of intermediate RS results is nearly 2-fold higher than reported in the ODX development studies by Paik et al., which may have implications for the clinical utility and cost impacts of testing. Also, high RS vs. low RS patients were more likely to follow the ODX results, suggesting a tendency toward aggressive treatment despite a low ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use vs. standard approaches, suggesting additional studies are warranted. [Table: see text]