Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive fibrosing interstitial lung disease of unknown origin. Recently, nintedanib and pirfenidone demonstrated efficacy in slowing ...disease progression and were approved by the US Food and Drug Administration. Although numerous treatments have been evaluated in IPF, none have shown significant decreases in mortality. The objective of this study was to identify all pharmacologic treatments evaluated for IPF and analyze their efficacy via Bayesian network meta-analysis and pairwise indirect treatment comparisons. This review did not evaluate the effect of steroid therapy.
We searched MEDLINE, Embase, and the Cochrane Library for studies published on or before August 2014. Studies were required to contain a randomized evaluation of nonsteroidal drug therapy for treatment of IPF and be published in English. Key outcomes of interest for this analysis were pulmonary function as measured by FVC as well as all-cause and respiratory-specific death. All outcomes were analyzed via a Bayesian framework.
Our review identified 30 eligible studies that evaluated 16 unique treatments. Under both the fixed-effect and random-effect models for respiratory-specific mortality, no treatments performed better than placebo. For all-cause mortality, pirfenidone and nintedanib had effects approaching significance with credible intervals slightly crossing the null under a fixed-effect model. Notably, for respiratory-specific mortality, all-cause mortality, and decline in percent predicted FVC, nintedanib and pirfenidone were virtually indistinguishable and no clear advantage was detected.
Although two treatments have been approved for IPF on the basis of reduced decline in pulmonary function, neither one has a clear advantage on mortality outcomes.
Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection ...methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 1.90-4.00), overall survival (hazard ratio=2.36 1.73-3.22), and cumulative incidence of relapse (hazard ratio=3.65 2.53-5.27), but not non-relapse mortality (hazard ratio=1.12 0.81-1.55). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than
polymerase chain reaction-based detection (I
=75.1%
<0.1% for leukemia-free survival, 67.8%
<0.1% for overall survival, and 22.1%
<0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.
Abstract Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all ...treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made.
Background Lymphovascular invasion (LVI) is considered a high-risk pathologic feature in resected non-small cell carcinoma (NSCLC). The ability to stratify stage I patients into risk groups may ...permit refinement of adjuvant treatment recommendations. We performed a systematic review and meta-analysis to evaluate whether the presence of LVI is associated with disease outcome in stage I NSCLC patients. Methods A systematic search of the literature was performed (1990 to December 2012 in MEDLINE/EMBASE). Two reviewers independently assessed the quality of the articles and extracted data. Pooled hazard ratios (HRs) and 95% confidence intervals (CI) were estimated with a random effects model. Two end points were independently analyzed: recurrence-free survival (RFS) and overall survival (OS). We analyzed unadjusted and adjusted effect estimates, resulting in four separate meta-analyses. Results We identified 20 published studies that reported the comparative survival of stage I patients with and without LVI. The unadjusted pooled effect of LVI was significantly associated with worse RFS (HR, 3.63; 95% CI, 1.62 to 8.14) and OS (HR, 2.38; 95% CI, 1.72 to 3.30). Adjusting for potential confounders yielded similar results, with RFS (HR, 2.52; 95% CI, 1.73 to 3.65) and OS (HR, 1.81; 95% CI, 1.53 to 2.14) both significantly worse for patients exhibiting LVI. Conclusions The present study indicates that LVI is a strong prognostic indicator for poor outcome for patients with surgically managed stage I lung cancer. Future prospective lung cancer trials with well-defined methods for evaluating LVI are necessary to validate these results.
Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity and mortality and a disproportionate burden on Black communities. Few population-based studies have examined the ...prevalence of comorbidities among persons with SCD. We estimated the prevalence of comorbidities experienced by individuals with SCD enrolled in employer-based health insurance plans in the US over their non-elderly lifetimes (0–64 years of age) with a retrospective cohort design using Truven Health MarketScan commercial claims data from 2007–2018. ICD-9/10 codes were used to identify individuals with SCD using a previously published algorithm. For this cohort, comorbidities associated with SCD were identified across 3 age categories (<18, 18–45, 46–64 years-old), based on the CMS Chronic Comorbidities Warehouse or SCD-specific diagnosis codes, when applicable. The total number of SCD patients available for analysis in each age category was 7,502 (<18 years), 10,183 (18–45 years) and 4,459 (46–64 years). Across all ages, vaso-occlusive pain, infections (non-specific), and fever were the most common comorbidities. Vaso-occlusive pain and infection were the most prevalent conditions for persons age <18- and 18–45-year-olds, while in the 46–54-year-old age group, infection and cardiovascular including pulmonary hypertension were most prevalent. Compared to persons <18 years old, the prevalence of vaso-occlusive pain, fever, and acute chest syndrome claims declined in older populations. The comorbidity burden of SCD is significant across all age groups. SCD patients experience comorbidities of age such as chronic pain, cardio-vascular conditions including pulmonary hypertension and renal disease at far higher rates than the general population. Novel disease modifying therapies in development have the potential to significantly reduce the comorbidity burden of SCD.
Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity and mortality and a disproportionate burden on Black communities. Few population-based studies have examined the ...prevalence of comorbidities among persons with SCD. We estimated the prevalence of comorbidities experienced by individuals with SCD enrolled in employer-based health insurance plans in the US over their non-elderly lifetimes (0-64 years of age) with a retrospective cohort design using Truven Health MarketScan commercial claims data from 2007-2018. ICD-9/10 codes were used to identify individuals with SCD using a previously published algorithm. For this cohort, comorbidities associated with SCD were identified across 3 age categories (<18, 18-45, 46-64 years-old), based on the CMS Chronic Comorbidities Warehouse or SCD-specific diagnosis codes, when applicable. The total number of SCD patients available for analysis in each age category was 7,502 (<18 years), 10,183 (18-45 years) and 4,459 (46-64 years). Across all ages, vaso-occlusive pain, infections (non-specific), and fever were the most common comorbidities. Vaso-occlusive pain and infection were the most prevalent conditions for persons age <18- and 18-45-year-olds, while in the 46-54-year-old age group, infection and cardiovascular including pulmonary hypertension were most prevalent. Compared to persons <18 years old, the prevalence of vaso-occlusive pain, fever, and acute chest syndrome claims declined in older populations. The comorbidity burden of SCD is significant across all age groups. SCD patients experience comorbidities of age such as chronic pain, cardio-vascular conditions including pulmonary hypertension and renal disease at far higher rates than the general population. Novel disease modifying therapies in development have the potential to significantly reduce the comorbidity burden of SCD.
Women’s underperformance in MBA programs has been the subject of recent debate and policy interventions, despite a lack of rigorous evidence documenting when and why it occurs. The current studies ...document a performance gap, specifying its contours and contributing factors. Two behaviors by female students that may factor into the gap are public conformity and private internalization. We predicted that women conform to the norm associating maleness with technical prowess by minimizing their public assertiveness in class discussions and meetings, but that they do not internalize the norm by reducing private effort. Data from multiple cohorts of a top-ranked MBA program reveal female underperformance occurred in technical subjects (e.g., accounting), but not social subjects (e.g., marketing). As predicted, the gender effect ran not through private effort but through public assertiveness, even controlling for gender differences in interests and aptitudes. These findings support some current policy interventions while casting doubt on others.
Sickle cell disease (SCD) is a clinically heterogeneous disease with many acute and chronic complications driven by ongoing vaso-occlusion and hemolysis. It causes a disproportionate burden on Black ...and Hispanic communities. Our objective was to follow the SMDM/ISPOR Task Force recommendations for good practices and create a conceptual model of the progression of SCD under current clinical practice to inform cost-effectiveness analyses (CEA) of promising curative therapies in the pipeline over a lifetime horizon.
We used consultations with experts, providers, and patients to identify acute events and chronic conditions in the conceptual model. We compared our model structure to previous CEA models of interventions for SCD, assessed the prevalence of the identified disease attributes in Medicaid and Medicare claims databases, and identified relevant outcomes following the 2nd Panel in CEA. We determined an appropriate modeling technique and relevant data sources for parameterizing the model.
The conceptual model structure included four dimensions of disease: chronic pain, acute events, chronic conditions, and treatment complications, spanning 26 disease attributes with significant impacts on health-related quality of life and resource. We modeled chronic pain separately to reflect its importance to patients and interaction with all other disease attributes. We identified additional data sources for health state utilities and non-medical costs and benefits of SCD. We will use a microsimulation model with age- and sex-specific transitions between health states predicted by patient demographic characteristics and disease history.
Developing the model structure through an explicit process of model conceptualization can increase the transparency and accuracy of results. We will populate the conceptual model with the data sources described and evaluate the cost-effectiveness of curative therapies.
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