Discussion of: Statistical and Regulatory Issues with the Application of Propensity Score Analysis to Nonrandomized Medical Device Clinical Studies

In this paper, the original up-and-down method, modified up-and-down method, the Robbins-Monro method, and a fixed-sample Spearman-Kärber method are compared for the point estimator as well as the confidence interval of LD₅₀. In particular, three different designs of the modified up-and-down approach based on the combination of experiments on one test space and reduced test space are investigated. The standard normal distribution and chi-square distribution are used as tolerance distributions. Simulation results indicate that the modified up-and-down method tends to be some-what better than the original up-and-down method in terms of the mean squared error under normal tolerance distribution. In case of chi-square distribution, the modified method is shown to be substantially better when the test space is wide and the initial dose is further away from the LD₅₀.     

In or out? Methodological considerations for including and excluding findings from a meta‐analysis of predictors of antiretroviral adherence in HIV‐positive women

AIM: This paper is a discussion detailing the decisions concerning whether to include or exclude findings from a meta-analysis of report of quantitative studies of antiretroviral adherence in HIV-positive women. BACKGROUND: Publication constraints and the absence of reflexivity as a criterion for validity in, and reporting of, quantitative research preclude detailing the many judgements made in the course of a meta-analysis. Yet, such an accounting would assist researchers better to address the unique challenges to meta-analysis presented by the bodies of research they have targeted for review, and to show the subjectivity, albeit disciplined, that characterizes the meta-analytic process. DATA SOURCES: Data were 29 published and unpublished studies on antiretroviral adherence in HIV-positive women of any race/ethnicity, class, or nationality living in the United States of America. The studies were retrieved between June 2005 and January 2006 using 40 databases. REVIEW METHODS: Findings were included if they met the statistical assumptions of meta-analysis, including: (1) normal distribution of observations; (2) homogeneity of variances; and (3) independence of observations. RESULTS: Relevant studies and findings were excluded because of issues related to differences in study design, different operationalizations of dependent and independent variables, multiple cuts from common longitudinal data sets, and presentation of unadjusted and adjusted findings. These reasons led to the exclusion of 73% of unadjusted relationships and 87% of adjusted relationships from our data set, leaving few findings to synthesize. CONCLUSION: Decisions made during research synthesis studies may result in more information losses than gains, thereby obliging researchers to find ways to preserve findings that are potentially valuable for practice.     

Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review

PURPOSE: To evaluate the accuracy of conventional and new methods of Papanicolaou (Pap) testing when used to detect cervical cancer and its precursors. DATA SOURCES: Systematic search of English-language literature through October 1999 using MEDLINE, EMBASE, other computerized databases, and hand searching. STUDY SELECTION: All studies that compared Pap testing (conventional methods, computer screening or rescreening, or monolayer cytology) with a concurrent reference standard (histologic examination, colposcopy, or cytology). DATA EXTRACTION: Two reviewers independently reviewed selection criteria and completed 2 x 2 tables for each study. DATA SYNTHESIS: 94 studies of the conventional Pap test and three studies of monolayer cytology met inclusion criteria. No studies of computerized screening were included. Data were organized by cytologic and histologic thresholds used to define disease. For conventional Pap tests, estimates of sensitivity and specificity varied greatly in individual studies. Methodologic quality and frequency of histologic abnormalities also varied greatly between studies. In the 12 studies with the least biased estimates, sensitivity ranged from 30% to 87% and specificity ranged from 86% to 100%. CONCLUSIONS: Insufficient high-quality data exist to estimate test operating characteristics of new cytologic methods for cervical screening. Future studies of these technologies should apply adequate reference standards. Most studies of the conventional Pap test are severely biased: The best estimates suggest that it is only moderately accurate and does not achieve concurrently high sensitivity and specificity. Cost-effectiveness models of cervical cancer screening should use more conservative estimates of Pap test sensitivity.     

Effectiveness of disease management programs in depression: a systematic review

OBJECTIVE: The authors systematically evaluated the published evidence to assess the effectiveness of disease management programs in depression. METHOD: English-language articles on depression were identified through a MEDLINE search for the period from January 1987 to June 2001. Two reviewers evaluated 16,952 published titles, identified 24 depression disease management programs that met explicit inclusion criteria, and extracted data on study characteristics, interventions used, and outcome measures. Pooled effect sizes were calculated by using a random-effects model. RESULTS: Pooled results for disease management program effects on symptoms of depression showed statistically significant improvements (effect size=0.33, N=24). Programs also had statistically significant effects on patients' satisfaction with treatment (effect size=0.51, N=6), patients' compliance with the recommended treatment regimen (effect size=0.36, N=7), and adequacy of prescribed treatment (effect size=0.44, N=11). One program with an explicit screening component showed significant improvement in the rate of detection of depression by primary care physicians (effect size=0.66); two other programs lacking a screening component showed small nonsignificant improvements in the detection rate (effect size=0.18). Disease management programs increased health care utilization (effect size=-0.10, N=8), treatment costs (effect size=-1.03, N=3), and hospitalization (effect size=-0.20, N=2). CONCLUSIONS: Disease management appears to improve the detection and care of patients with depression. Further research is needed to assess the cost-effectiveness of disease management in depression, and consideration should be given to more widespread implementation of these programs.     

Prognostic value of isolated troponin elevation across the spectrum of chest pain syndromes

The risk of death or recurrent myocardial infarction (MI) in patients with chest pain and baseline isolated troponin elevation is unclear. To determine the early and short-term risk of death or MI associated with isolated troponin elevation across a spectrum of chest pain syndromes, we used baseline creatine kinase (CK)-MB and troponin data from the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) B troponin substudy, the Global Utilization of Strategies To Open Occluded Coronary Arteries (GUSTO) IIa troponin substudy, and the Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) study. Patients were grouped into 1 of 4 categories based on marker status (troponin-positive/CK-MB-positive, troponin-positive/CK-MB-negative, troponin-negative/CK-MB-positive, or troponin-negative/CK-MB-negative). The adjusted odds of death or MI occurring at 24 hours and 30 days was assessed by baseline marker status using multivariable logistic regression, with the group negative for both markers used as the reference. Patients who were positive for both markers had the highest odds of the 24-hour and 30-day end point. The adjusted odds of the 30-day end point for patients with isolated troponin elevation were 1.3 (95% confidence interval 0.7 to 2.3) and 4.8 (95% confidence interval 1.4 to 16.0) for high- and low-risk patients, respectively. The risk for 24-hour and 30-day death or MI with isolated positive CK-MB results was lower than with isolated positive troponin results, and it was not significantly greater than if the 2 markers were negative. For patients with high- and low-risk chest pain, baseline troponin elevation without CK-MB elevation was associated with increased risk for early and short-term adverse outcomes. This suggests that these patients should be admitted to the hospital and monitored in either an intensive care or step-down unit.