Sensitivity analysis for correlated survival models

In this thesis we introduce a model for informative censoring. We assume that the joint distribution of the failure and the censored times depends on a parameter δ, which is actually a measure of the possible dependence, and a bias function B(t,θ). Knowledge of δ means that the joint distribution is fully specified, while B(t,θ) can be any function of the failure times. Being unable to draw inferences about δ, we perform a sensitivity analysis on the parameters of interest for small values of δ, based on a first order approximation. This will give us an idea of how robust our estimates are in the presence of small dependencies, and whether the ignorability assumption can lead to misleading results. Initially we propose the model for the general parametric case. This is the simplest possible case and we explore the different choices for the standardized bias function. After choosing a suitable function for B(t,θ) we explore the potential interpretation of δ through it's relation to the correlation between quantities of the failure and the censoring processes. Generalizing our parametric model we propose a proportional hazards structure, allowing the presence of covariates. At this stage we present a data set from a leukemia study in which the knowledge, under some certain assumptions, of the censored and the death times of a number of patients allows us to explore the impact of informative censoring to our estimates. Following the analysis of the above data we introduce an extension to Cox's partial likelihood, which will call "modified Cox's partial likelihood", based on the assumptions that censored times do contribute information about the parameters of interest. Finally we perform parametric bootstraps to assess the validity of our model and to explore up to what values of parameter δ our approximation holds

Does preservation of the sub-valvular apparatus during mitral valve replacement affect long-term survival and quality of life? A Microsimulation Study

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Techniques to preserve the sub-valvular apparatus in order to reduce morbidity and mortality following mitral valve replacement have been frequently reported. However, it is uncertain what impact sub-valvular apparatus preservation techniques have on long-term outcomes following mitral valve replacement. This study investigated the effect of sub-valvular apparatus preservation on long-term survival and quality of life following mitral valve replacement. Methods A microsimulation model was used to compare long-term survival and quality-adjusted life years following mitral valve replacement after conventional valve replacement and sub-valvular apparatus preservation. Probabilistic sensitivity analysis and alternative analysis were performed to investigate uncertainty associated with the results. Results Our Analysis suggests that patients survive longer if the sub-valvular apparatus are preserved (65.7% SD 1.5%, compared with 58.1% SD 1.6% at 10 years). The quality adjusted life years gained over a 10 year period where also greater after sub-valvular apparatus preservation. (6.54 QALY SD 0.07 QALY, compared with 5.61 QALY, SD 0.07 QALY). The superiority of preservation techniques was insensitive to patient age, parameter or model uncertainty. Conclusion This study suggests that long-term outcomes may be improved when the sub-valvular apparatus are preserved. Given the lack of empirical data further research is needed to investigate health-related quality of life after mitral valve replacement, and to establish whether outcomes differ between preservation techniques.Published versio

A case-study in the clinical epidemiology of psoriatic arthritis: multistate models and causal arguments.

In psoriatic arthritis, permanent joint damage characterizes disease progression and represents a major debilitating aspect of the disease. Understanding the process of joint damage will assist in the treatment and disease management of patients. Multistate models provide a means to examine patterns of disease, such as symmetric joint damage. Additionally, the link between damage and the dynamic course of disease activity (represented by joint swelling and stress pain) at both the individual joint level and otherwise can be represented within a correlated multistate model framework. Correlation is reflected through the use of random effects for progressive models and robust variance estimation for non-progressive models. Such analyses, undertaken with data from a large psoriatic arthritis cohort, are discussed and the extent to which they permit causal reasoning is considered. For this, emphasis is given to the use of the Bradford Hill criteria for causation in observational studies and the concept of local (in)dependence to capture the dynamic nature of the relationships

The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods

<p>Abstract</p> <p>Background</p> <p>The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors.</p> <p>Methods</p> <p>The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis.</p> <p>Conclusions</p> <p>ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.</p

Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: Results from an international inception cohort study

To examine the association between neuropsychiatric (NP) events with antiphospholipid antibodies (lupus anticoagulant, anticardiolipin), anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies in an international inception cohort

Sensitivity analysis for multiple right censoring processes: Investigating mortality in psoriatic arthritis

In a mortality study in psoriatic arthritis (PsA), censored observations are generated from the fact that patients fail to attend their scheduled appointments at the clinic. As a result, more than one types of right-censored observations are available. In survival analysis, the treatment of censored observations remains a concern. The assumption of ignorable censoring, although in many cases justified, is an important assumption made often for convenience rather than any other reason. In this paper we discuss a semi-parametric model for the analysis of survival data, where sensitivity analysis on quantities of interest can be performed when small levels of association between the failure and the censoring processes are assumed. Extension of the model allows for the presence of more than one censoring processes, where one may be characterized as ignorable and the other not. This model will be used to analyze the PsA mortality data, where a sensitivity analysis on parameters can be done under the assumption of non-ignorable censoring. Sensitivity analysis will also be performed in the presence of two censoring processes, one of which will be classified as non-ignorable. Copyright © 2010 John Wiley &amp; Sons, Ltd

Optical coherence tomography angiography for monitoring the treatment of neovascular age-related macular degeneration

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:. To determine the diagnostic accuracy of OCT-A (index test) compared to the combination of SD-OCT and FFA (reference standard) for the monitoring of active CNVMs, to decide on the need for retreatment in people with nAMD who have already received antiangiogenic therapy. By definition an OCT-A is the combination of SD-OCT and OCT-A, as a SD-OCT scan is always produced by the OCT-A machines at the time of the angiogram. Should OCT-A prove to be as sensitive and specific as the combined use of SD-OCT and FFA, it could replace the latter in daily clinical practice, since it is easier, faster and safer to perform. In current clinical practice FFA is not performed at every visit due to its inherent drawbacks. For the purpose of this review we will examine studies comparing OCT-A to SD-OCT alone or with FFA, in a multi modal imaging setting. As per clinical practice not all patients receive FFA, we therefore plan to conduct subgroup analyses for studies that always use FFA compared with studies that sometimes use FFA. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd