Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves

<p>Abstract</p> <p>Background</p> <p>The results of Randomized Controlled Trials (RCTs) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated.</p> <p>Methods</p> <p>We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios) with statistics based on repeated reconstructions by multiple observers.</p> <p>Results</p> <p>The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported.</p> <p>Conclusion</p> <p>The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.</p

The LSST Dark Energy Science Collaboration (DESC) Science Requirements Document

The Large Synoptic Survey Telescope (LSST) Dark Energy Science Collaboration (DESC) will use five cosmological probes: galaxy clusters, large scale structure, supernovae, strong lensing, and weak lensing. This Science Requirements Document (SRD) quantifies the expected dark energy constraining power of these probes individually and together, with conservative assumptions about analysis methodology and follow-up observational resources based on our current understanding and the expected evolution within the field in the coming years. We then define requirements on analysis pipelines that will enable us to achieve our goal of carrying out a dark energy analysis consistent with the Dark Energy Task Force definition of a Stage IV dark energy experiment. This is achieved through a forecasting process that incorporates the flowdown to detailed requirements on multiple sources of systematic uncertainty. Future versions of this document will include evolution in our software capabilities and analysis plans along with updates to the LSST survey strategy.Comment: 32 pages + 60 pages of appendices. This is v1 of the DESC SRD, an internal collaboration document that is being made public and is not planned for submission to a journal. Data products for reproducing key plots are available at the LSST DESC Zenodo community, https://zenodo.org/communities/lsst-desc; see "Executive Summary and User Guide" for instructions on how to use and cite those product

Surface Sampling of a Dry Aerosol Deposited Ricin

Sampling of small molecules from both porous and non-porous surfaces poses a significant challenge across biological agents. Particle sizes of toxins are smaller than living organisms and can be extremely toxic at low level concentrations. A small number of studies evaluating sampling efficiencies of commercial off the shelf (COTS) materials have been performed with toxins and proteins. However, they have been limited to non-ricin stimulants with drastically different physical properties than their native counterparts. We have identified a commercially available non-toxic recombinant ricin, complete with both A and B subunits present, which can be recognized by antibodies commonly used to assay native ricin. In evaluating recovery efficiency, we deposited the recombinant ricin by both liquid deposition, and as a dry aerosol. Our studies demonstrated a significant difference in recovery efficiencies from liquid deposited ricin, ranging between 30% and 70%, than from an aerosol generated deposition ranging from below detectable levels to 22%, depending on the contaminated surface and swab material being used. This study demonstrates the necessity for accurate dissemination techniques of sampling technologies for the consideration of use in an environment where suspected toxin contamination is being evaluated

Surface Sampling of Spores in Dry-Deposition Aerosols▿

The ability to reliably and reproducibly sample surfaces contaminated with a biological agent is a critical step in measuring the extent of contamination and determining if decontamination steps have been successful. The recovery operations following the 2001 attacks with Bacillus anthracis spores were complicated by the fact that no standard sample collection format or decontamination procedures were established. Recovery efficiencies traditionally have been calculated based upon biological agents which were applied to test surfaces in a liquid format and then allowed to dry prior to sampling tests, which may not be best suited for a real-world event with aerosolized biological agents. In order to ascertain if differences existed between air-dried liquid deposition and biological spores which were allowed to settle on a surface in a dried format, a study was undertaken to determine if differences existed in surface sampling recovery efficiencies for four representative surfaces. Studies were then undertaken to compare sampling efficiencies between liquid spore deposition and aerosolized spores which were allowed to gradually settle under gravity on four different test coupon types. Tests with both types of deposition compared efficiencies of four unique swabbing materials applied to four surfaces with various surface properties. Our studies demonstrate that recovery of liquid-deposited spores differs significantly from recovery of dry aerosol-deposited spores in most instances. Whether the recovery of liquid-deposited spores is overexaggerated or underrepresented with respect to that of aerosol-deposited spores depends upon the surface material being tested