Publications by authors named "J Peter Campbell"

7,332 Publications

Systematic design, generation, and application of synthetic datasets for flow cytometry.

PDA J Pharm Sci Technol 2022 Jan 14. Epub 2022 Jan 14.

Loughborough University.

Application of synthetic datasets in training and validation of analysis tools have led to improvements in many decision-making tasks in a range of domains from computer vision to digital pathology. Synthetic datasets overcome the constraints of real-world datasets, namely difficulties in collection and labelling, expense, time and privacy concerns. In flow cytometry, real cell-based datasets are limited by properties such as size, number of parameters, distance between cell populations and distributions, and are often focused on a narrow range of disease or cell types. Researchers in some cases have designed these desired properties into synthetic datasets, however operators have implemented them in inconsistent approaches and there is a scarcity of publicly available, high-quality synthetic datasets. In this research, we propose a method to systematically design and generate flow cytometry synthetic datasets with highly controlled characteristics. We demonstrate the generation of two-cluster synthetic datasets with specific degrees of separation between cell populations, and of non-normal distributions with increasing levels of skewness and orientations of skew pairs. We apply our synthetic datasets to test the performance of a popular automated cell populations identification software, SPADE3, and define the region where the software performance decreases as the clusters get closer together. Application of the synthetic skewed dataset suggests the software is capable of processing non-normal data. We calculate the classification accuracy of SPADE3 with robustness not achievable with real-world datasets. Our approach aims to advance research towards generation of high-quality synthetic flow cytometry datasets, and to increase their awareness among the community. The synthetic datasets can be utilised in benchmarking studies that critically evaluate cell population identification tools and help illustrate potential digital platform inconsistencies. These datasets have the potential to improve cell characterisation workflows that integrate automated analysis in clinical diagnostics and cell therapy manufacturing.
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http://dx.doi.org/10.5731/pdajpst.2021.012659DOI Listing
January 2022

Levofloxacin prophylaxis for pediatric leukemia patients: Longitudinal follow-up for impact on health care-associated infections.

Pediatr Blood Cancer 2022 Jan 14:e29525. Epub 2022 Jan 14.

Department of Infection Control and Prevention, Texas Children's Hospital, Houston, Texas, USA.

Background: Bloodstream infections (BSIs) cause morbidity and mortality in pediatric patients with leukemia. Antibiotic prophylaxis during periods of chemotherapy-induced neutropenia may reduce the incidence of BSIs.

Procedure: A levofloxacin prophylaxis guideline was implemented for pediatric patients with acute myeloid leukemia and relapsed acute lymphoblastic leukemia. We conducted a retrospective cohort study over 4 years (2 years pre and 2 years post implementation) of the practice guideline to assess the impact on central line-associated bloodstream infections (CLABSI) and BSI events. Secondary outcomes included incidence of Clostridioides difficile-associated diarrhea, bacteremia due to multidrug-resistant organisms (MDRO), and bacteremia due to levofloxacin nonsusceptible organisms. STATA was used for data analysis.

Results: Sixty-three and 72 patients met inclusion criteria for the pre- and postimplementation cohorts, respectively. Demographics were similar between the groups. We observed 60 BSI events in the pre-group versus 49 events in the post-group (p = .1). Bacteremia due to Gram-negative rods (risk ratio [RR] 0.37 [0.21, 0.66], p < .001) and National Healthcare Safety Network (NHSN) CLABSIs (RR 0.62 [0.44, 0.89], p = .01) were significantly reduced in the postimplementation group. The incidences of C. difficile-associated diarrhea and MDRO bacteremia were similar between groups. However, we observed an increase in the incidence of BSI due to Gram-negative rods that were nonsusceptible to levofloxacin (RR 3.38 [0.72, 6.65], p < .001).

Conclusion: Following implementation of a levofloxacin prophylaxis guideline, we observed a significant decrease in BSIs due to Gram-negative rods and NHSN CLABSIs. Vigilant monitoring of outcomes post guideline implementation is critical to track emergence of resistant organisms.
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http://dx.doi.org/10.1002/pbc.29525DOI Listing
January 2022

Analysis of the components of cancer risk perception and links with intention and behaviour: A UK-based study.

PLoS One 2022 13;17(1):e0262197. Epub 2022 Jan 13.

Department of Public Health and Primary Care, Prevention Group, Primary Care Unit, University of Cambridge Clinical School, Cambridge, United Kingdom.

Risk perception refers to how individuals interpret their susceptibility to threats, and has been hypothesised as an important predictor of intentions and behaviour in many theories of health behaviour change. However, its components, optimal measurement, and effects are not yet fully understood. The TRIRISK model, developed in the US, conceptualises risk perception as deliberative, affective and experiential components. In this study, we aimed to assess the replicability of the TRIRISK model in a UK sample by confirmatory factor analysis (CFA), explore the inherent factor structure of risk perception in the UK sample by exploratory factor analysis (EFA), and assess the associations of EFA-based factors with intentions to change behaviour and subsequent behaviour change. Data were derived from an online randomised controlled trial assessing cancer risk perception using the TRIRISK instrument and intention and lifestyle measures before and after communication of cancer risk. In the CFA analysis, the TRIRISK model of risk perception did not provide a good fit for the UK data. A revised model developed using EFA consisted of two separate "numerical" and "self-reflective" factors of deliberative risk perception, and a third factor combining affective with a subset of experiential items. This model provided a better fit to the data when cross-validated. Using multivariable regression analysis, we found that the self-reflective and affective-experiential factors of the model identified in this study were reliable predictors of intentions to prevent cancer. There were no associations of any of the risk perception factors with behaviour change. This study confirms that risk perception is clearly a multidimensional construct, having identified self-reflective risk perception as a new distinct component with predictive validity for intention. Furthermore, we highlight the practical implications of our findings for the design of interventions incorporating risk perception aimed at behaviour change in the context of cancer prevention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262197PLOS
January 2022

Performing Cost-Effectiveness Analyses to Support Policy Making: Key Lessons From the Assessment of Aducanumab.

Neurology 2022 Jan 12. Epub 2022 Jan 12.

Institute for Clinical and Economic Review, Boston, MA.

The purpose of this paper is to describe the process and the methods of cost-effectiveness analysis for clinicians interested in joining or leading aspects of this branch of evidence-based research. Cost-effectiveness is a useful tool for policymakers and is considered a starting point for discussions of fair pricing. Clinicians are important members of teams conducting cost-effectiveness analyses, particularly as it relates to integrating their clinical expertise into the decisions around the design and conduct of the analysis. Their input is essential in assuring that models adequately reflect clinical practice and are informed by expert judgments of how existing data can best be interpreted to build a comprehensive analysis of the clinical and economic outcomes of different treatment options. We illustrate specific contributions that clinicians are well positioned to make in these teams using a recent cost-effectiveness analysis of aducanumab that was conducted to support fair drug pricing. While discussing these contributions, we explain key components of a cost-effectiveness analysis, such as time horizon, health states, and perspective, to support the understanding of the methods of cost-effectiveness by the clinical researchers and to promote a common dialogue among these multidisciplinary teams.
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http://dx.doi.org/10.1212/WNL.0000000000013313DOI Listing
January 2022

Cost-Effectiveness and Value-Based Pricing of Aducanumab for Patients With Early Alzheimer Disease.

Neurology 2022 Jan 12. Epub 2022 Jan 12.

Institute For Clinical and Economic Review, Boston, MA.

Introduction: Aducanumab was granted accelerated approval with a conflicting evidence base, near-unanimous FDA Advisory Committee vote to reject approval, and a widely criticized launch price of $56,000 per year. The objective of this analysis was to estimate its cost-effectiveness.

Methods: We developed a Markov model to compare aducanumab in addition to supportive care to supportive care alone over a lifetime horizon. Results were presented from both the health system and modified societal perspective. The model tracked the severity of disease and the care setting. Incremental cost-effectiveness ratios were calculated, and a threshold analysis was conducted to estimate at what price aducanumab would meet commonly used cost-effectiveness thresholds.

Results: Using estimates of effectiveness based on pooling of data from both pivotal trials, patients treated with aducanumab spent four more months in earlier stages of AD. Over the lifetime time horizon, treating a patient with aducanumab results in 0.154 more QALYs gained per patient and 0.201 evLYGs per patient from the health care system perspective, with additional costs of approximately $204,000 per patient. The incremental outcomes were similar for the modified societal perspective. At the list price of $56,000 per year, the cost-effectiveness ranged from $1.02 million per evLYG to $1.33 million per QALY gained from the health care system perspective; and from $938,000 per evLYG to $1.27 million per QALY gained in the modified societal perspective. The annual price to meet commonly used cost-effectiveness thresholds ranged from $2,950 to $8,360, which represents a discount of 85-95% off from the annual launch price set by the manufacturer. Using estimates of effectiveness based only on the trial that suggested a benefit, the mean incremental cost was greater than $400,000 per QALY gained.

Discussion: Patients treated with aducanumab received minimal improvements in health outcomes at considerable cost. This resulted in incremental cost-effectiveness ratios that far exceeded commonly used value thresholds, even under optimistic treatment effectiveness assumptions. These findings are subject to the substantial uncertainty regarding whether aducanumab provides any true net health benefit, but evidence available currently suggests that an annual price of aducanumab of $56,000 is not in reasonable alignment with its clinical benefits.
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http://dx.doi.org/10.1212/WNL.0000000000013314DOI Listing
January 2022
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