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Load and resistance factor design of foundations is done in the offshore industry and is now being done in bridge projects in the United States. Common methods used to establish resistance factors include calibration to assumed factors of safety and reliability analysis using field load test databases. Reliability analyses are the preferred tools for this work but the needed probabilistic information regarding design method uncertainty is difficult to obtain. Furthermore, field load test databases, while relatively attractive for assessing design uncertainty, are not able to discriminate between uncertainties caused by soil variability, test methods, and model design relationships. In contrast to previous efforts, this paper illustrates an approach to uncertainty assessment that seeks to isolate the various sources of uncertainty. Using this approach, reliability analysis is used to develop resistance factors for the design of driven pipe piles in sand. The resistance factor results are used to highlight some of the differences between design methods that are exposed by the proposed uncertainty assessment technique. A brief design example is also given that illustrates the use of the resistance factors. [ABSTRACT FROM AUTHOR]

Quantifying tumor-infiltrating lymphocytes (TILs) in breast cancer tumors is a challenging task for pathologists. With the advent of whole slide imaging that digitizes glass slides, it is possible to apply computational models to quantify TILs for pathologists. Development of computational models requires significant time, expertise, consensus, and investment. To reduce this burden, we are preparing a dataset for developers to validate their models and a proposal to the Medical Device Development Tool (MDDT) program in the Center for Devices and Radiological Health of the U.S. Food and Drug Administration (FDA). If the FDA qualifies the dataset for its submitted context of use, model developers can use it in a regulatory submission within the qualified context of use without additional documentation. Our dataset aims at reducing the regulatory burden placed on developers of models that estimate the density of TILs and will allow head-to-head comparison of multiple computational models on the same data. In this paper, we discuss the MDDT preparation and submission process, including the feedback we received from our initial interactions with the FDA and propose how a qualified MDDT validation dataset could be a mechanism for open, fair, and consistent measures of computational model performance. Our experiences will help the community understand what the FDA considers relevant and appropriate (from the perspective of the submitter), at the early stages of the MDDT submission process, for validating stromal TIL density estimation models and other potential computational models. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: The proposed legislation Verifying Accurate and Leading-edge In vitro clinical test Development (VALID) clarifies the US Food and Drug Administration's authority to regulate laboratory-developed tests. Many stakeholders have pointed out that the lack of direct US Food and Drug Administration oversight has led to erroneous results that have serious patient consequences-in particular for patients with cancer. Technology Certification is a key provision proposed in VALID to navigate the balance between safety, patient access, and innovation; however, the maintenance cost of the proposed framework after implementation is unclear., Methods: On the basis of 2019 retrospective data from a laboratory-developed test-based cancer diagnostics laboratory, we expressed laboratory complexity by the number and complexity of assays and in vitro diagnostic technologies. We estimated the national health care cost increase by modeling three stringencies of complying with the Act. We performed sensitivity analysis of our regulatory stringency model taking into account number of patients tested, materials, submission cost, and labor using extra cost per patient as the output., Results: We estimate the national health care cost increase to range from $33M US dollars (USD) to $1,110M USD or $0.21 USD to $0.70 USD per employed person in the United States. Sensitivity analysis demonstrates that regulatory stringency is the primary driver of extra cost per patient. Cancer testing does not reflect all areas of in vitro diagnostics affected by VALID; nonetheless, concrete cost models are paramount in informing the ongoing legislative negotiations., Conclusion: Our findings show the critical importance of clarity in the legislative language to ensure balance between VALID's goals of assuring high-quality test performance and the burden to laboratories and overall health care cost., Competing Interests: Laura LasiterEmployment: Regulatory and Quality Solutions, AgNovos, Qiagen, Smith & Nephew Bruce QuinnConsulting or Advisory Role: Illumina, Thermo Fisher Scientific, InVitae, Guardant Health, Natera, Adaptive Biotechnologies, Genelex, Eurofins Roberto SalgadoConsulting or Advisory Role: Roche, AstraZeneca, Bristol-Myers SquibbResearch Funding: Merck, Puma Biotechnology, RocheTravel, Accommodations, Expenses: Roche, MerckNo other potential conflicts of interest were reported.

The Centers for Disease Control and Prevention provides trainings to support implementation of five evidence-based HIV prevention interventions (EBIs) for men who have sex with men (MSM): d-up: Defend Yourself!; Many Men, Many Voices; Mpowerment; Personalized Cognitive Counseling; and Popular Opinion Leader. We evaluated trainees' implementation of these EBIs and, using multivariable logistic regression, examined factors associated with implementation. Approximately 43% of trainees had implemented the EBIs for which they received training. Implementation was associated with working in community-based organizations (vs. health departments or other settings); acquiring training for Mpowerment or Popular Opinion Leader (vs. Personalized Cognitive Counseling); having ≥3 funding sources (vs. one); and having (vs. not having) sufficient time and necessary EBI resources. Findings suggest that implementation may vary by trainee characteristics, especially those related to employment setting, EBI training, funding, and perceived implementation barriers. Efforts that address these factors may help to improve EBI implementation among trainees.

Clinical cancer research today often includes testing the value of biomarkers to direct treatment and for drug development. However, the practical challenges of integration of molecular information into clinical trial protocols are increasingly appreciated. Inherent difficulties include evidence gaps in available biomarker data, a paucity of robust assay methods, and the design of appropriate studies within the constraints of feasible trial operations, and finite resources. Scalable and proportionate approaches are needed to systematically cope with these challenges. Therefore, we assembled international experts from three clinical trials organisations to identify the common challenges and common solutions. We present a practical risk-assessment framework allowing targeting of scarce resources to crucial issues coupled with a library of useful resources and a simple actionable checklist of recommendations. We hope that these practical methods will be useful for running biomarker-driven trials and ultimately help to develop biomarkers that are ready for integration in routine practice., (Copyright © 2014 Elsevier Ltd. All rights reserved.)