Maximum likelihood and pseudo score approaches for parametric time-to-event analysis with informative entry times

We develop a maximum likelihood estimating approach for time-to-event Weibull regression models with outcome-dependent sampling, where sampling of subjects is dependent on the residual fraction of the time left to developing the event of interest. Additionally, we propose a two-stage approach which proceeds by iteratively estimating, through a pseudo score, the Weibull parameters of interest (i.e., the regression parameters) conditional on the inverse probability of sampling weights; and then re-estimating these weights (given the updated Weibull parameter estimates) through the profiled full likelihood. With these two new methods, both the estimated sampling mechanism parameters and the Weibull parameters are consistently estimated under correct specification of the conditional referral distribution. Standard errors for the regression parameters are obtained directly from inverting the observed information matrix in the full likelihood specification and by either calculating bootstrap or robust standard errors for the hybrid pseudo score/profiled likelihood approach. Loss of efficiency with the latter approach is considered. Robustness of the proposed methods to misspecification of the referral mechanism and the time-to-event distribution is also briefly examined. Further, we show how to extend our methods to the family of parametric time-to-event distributions characterized by the generalized gamma distribution. The motivation for these two approaches came from data on time to cirrhosis from hepatitis C viral infection in patients referred to the Edinburgh liver clinic. We analyze these data here.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS725 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Learning From Coalitions' Efforts to Promote Equity and Justice.

Coalitions and collaboratives are working to address many of the most pressing contemporary health and social issues. The articles in this special issue provide numerous insights into these complex collaborative processes across different contexts and focal issues. All emphasize and scrutinize the strategies that groups are using in their work. These strategies seek to navigate not only conventional notions of effectiveness but also the challenges of pursuing greater equity and justice. In this concluding article, we distill some of the key insights from these articles as a collective. This special issue on collaborating for equity and justice can serve as a launching point for new efforts by coalitions and researchers pursuing policy, systems, and structural changes, particularly those intent on addressing root causes of health and social disparities

A structured decision approach for integrating and analyzing community perspectives in re-use planning of vacant properties in Cleveland, Ohio

An integrated GIS-based, multi-attribute decision model deployed in a web-based platform is presented enabling an iterative, spatially explicit and collaborative analysis of relevant and available information for repurposing vacant land. The process incorporated traditional and novel aspects of decision science, beginning with an analysis of alternatives, building on this analysis with a workshop to elucidate opinions and concerns from key decision-makers relevant to the problem at hand, then expanded by extracting and compiling fundamental objectives from existing planning efforts and previously published long-term goals. The model was then constructed as an open-source, web-based software platform for use as a process for exploring, evaluating, comparing, and optimizing fundamental, strategic, and means objectives. The resulting beta model, MURL-CLE, is intended to allow all interested parties, from stakeholders to decision makers, to consider alternative options for reuse of vacant land in a neighborhood in Cleveland, OH and to do so in a deliberative, transparent, and defensible process. The beta model is intended to be a platform for growth as a decision science tool and to provide a reproducible mechanism for considering any complex decision that attempts to incorporate multiple competing objectives and to allow an iterative process, as opposed to a prescribed solution or ranking of alternatives, for community decision making

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques