Nonparametric Bounds for the Risk Function

Nonparametric bounds for the risk difference are straightforward to calculate and make no untestable assumptions about unmeasured confounding or selection bias due to missing data (e.g., dropout). These bounds are often wide and communicate uncertainty due to possible systemic errors. An illustrative example is provided

Impact of covariate omission and categorization from the Fine–Gray model in randomized-controlled trials

In this paper, we study the statistical issues related to the omission and categorization of important covariates in the context of the Fine–Gray model in randomized-controlled trials with competing risks. We show that the omission of an important covariate from the Fine–Gray model leads to attenuated estimates for treatment effect and loss of proportionality in general. Our simulation studies reveal substantial attenuation in the estimate for treatment effect and the loss of statistical power, while dichotomizing a continuous covariate leads to similar but less pronounced impact. Our results are illustrated using data from a randomized clinical trial of HIV-infected individuals. The relative merits of conducting an adjusted versus an unadjusted analysis of treatment effect in light of both statistical and practical considerations are discussed

Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide

Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor α, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-α all had high areas under the curve of 0.74–0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor α were associated with grade II–IV and III–IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide

Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland

BACKGROUND: Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. METHODS AND FINDINGS: HIV-infected patients aged ≥18 years who started ART 2004-2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. CONCLUSIONS: In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings

The diffusion of financial supervisory governance ideas

Who is watching the financial services industry? Since 1980, there have been multiple waves of thought about whether the ministry of finance, the central bank, a specialized regulator or some combination of these should have supervisory authority. These waves have been associated with the convergence of actual practices. How much and through what channels did internationally promoted ideas about supervisory 'best practice' influence institutional design choices? I use a new dataset of 83 countries and jurisdictions between the 1980s and 2007 to examine the diffusion of supervisory ideas. With this data, I employ Cox Proportional Hazard and Competing Risks Event History Analyses to evaluate the possible causal roles best practice policy ideas might have played. I find that banking crises and certain peer groups can encourage policy convergence on heavily promoted ideas

Modelling competing risks data with missing cause of failure

When competing risks data arise, information on the actual cause of failure for some subjects might be missing. Therefore, a cause-specific proportional hazards model together with multiple imputation (MI) methods have been used to analyze such data. Modelling the cumulative incidence function is also of interest, and thus we investigate the proportional subdistribution hazards model (Fine and Gray model) together with MI methods as a modelling approach for competing risks data with missing cause of failure. Possible strategies for analyzing such data include the complete case analysis as well as an analysis where the missing causes are classified as an additional failure type. These approaches, however, may produce misleading results in clinical settings. In the present work we investigate the bias of the parameter estimates when fitting the Fine and Gray model in the above modelling approaches. We also apply the MI method and evaluate its comparative performance under various missing data scenarios. Results from simulation experiments showed that there is substantial bias in the estimates when fitting the Fine and Gray model with naive techniques for missing data, under missing at random cause of failure. Compared to those techniques the MI-based method gave estimates with much smaller biases and coverage probabilities of 95 per cent confidence intervals closer to the nominal level. All three methods were also applied on real data modelling time to AIDS or non-AIDS cause of death in HIV-1 infected individuals. Copyright © 2010 John Wiley &amp; Sons, Ltd

Subjective risk assessment and perception in the Greek and English bakery industries

Several factors influencing risk perception in the area of occupational health and safety are known, but there is still lack of a full understanding of the ways in which people characterize risk. This study aimed to provide an insight of employee risk assessment and perception in the bakery industry. 87 British and 64 Greek employees in two comparable bakery companies were asked to estimate and evaluate hazards at their workplace. The participants&apos; judgments of 12 hazardsaccording to 7 risk aspectswere collected and analyzed. Subjective assessment on important occupational hazards included handling heavy loads, repetitiveness, high temperatures, high rate of work, stressful deadlines, and noise. Although limited in the population involved, our findings revealed strong cross-national differences in employee risk perception of specific groups of hazards in the bakery industry. Additional interviews revealed evidence that Greek employees&apos; risk perception depends mostly on work experience while British employees were aware of risks due to company health and safety policy, recognizing that safety is the responsibility of both the management and the worker. Cross-national (cultural) factors that influence workforce risk perception and attitudes towards safety have to be taken into account by technical experts and policy makers in the designing of prevention strategies and risk communication. Copyright © 2009 Evangelos C. Alexopoulos et al