Design of Experiments and Sample Surveys Commons^™

Protocol For A National Probability Survey Using Home Specimen Collection Methods To Assess Prevalence And Incidence Of Sars-Cov-2 Infection And Antibody Response, Aaron J. Siegler, Patrick S. Sullivan, Travis Sanchez, Ben Lopman, Mansour Fahimi, Charles Sailey, Martin Frankel, Richard Rothenberg, Colleen F. Kelley, Heather Bradley

Publications and Research

Purpose: The U.S. response to the SARS-CoV-2 epidemic has been hampered by early and ongoing delays in testing for infection; without data on where infections were occurring and the magnitude of the epidemic, early public health responses were not data-driven. Understanding the prevalence of SARSCoV- 2 infections and immune response is critical to developing and implementing effective public health responses. Most serological surveys have been limited to localities that opted to conduct them and/or were based on convenience samples. Moreover, results of antibody testing might be subject to high false positive rates in the setting of low prevalence of immune …

Trends And Disparities In Self-Reported And Measured Osteoporosis Among Us Adults, 2007-2014., Qing Wu, Yingke Xu, Ge Lin

Environmental & Occupational Health Faculty Publications

(1) Background: Studies examining osteoporosis trends among US adults by different socioeconomic status (SES) are limited. The prevalence of self-reported osteoporosis in the US is rarely reported. (2) Methods: Data from the National Health and Nutritional Examination Survey (NHANES) between 2007–2008 and 2013–2014 cycles were analyzed. Age-adjusted prevalence of self-reported and that of measured osteoporosis were calculated overall and by sex, race/ethnicity, education attainment, and SES. (3) Results: The prevalence of self-reported osteoporosis was higher than that of measured osteoporosis in all three survey cycles for women, and in 2007–2008 and 2009–2010 for men. Participants with high school/GED or higher …

I Spy With My Little Eye … A Knee About To Go 'Pop'? Can Coaches And Sports Medicine Professionals Predict Who Is At Greater Risk Of Acl Rupture?, Anne Inger Mørtvedt, Tron Krosshaug, Roald Bahr, Erich Petushek

Michigan Tech Publications

BACKGROUND: The vertical drop jump (VDJ) test is widely used for clinical assessment of ACL injury risk, but it is not clear whether such assessments are valid.

AIM: To examine if sports medicine professionals and coaches are able to identify players at risk of sustaining an ACL injury by visually assessing player performance during a VDJ test.

METHODS: 102 video clips of elite female handball and football players performing a baseline VDJ test were randomly extracted from a 738-person prospective cohort study that tracked ACL injuries. Of the sample, 20 of 102 went on to suffer an ACL injury. These …

Recent Developments In Alternatives To Animal Testing, Katy Taylor

Application of Alternative Methods Collection

Methods that replace techniques that use live animals, or methods of testing substances without live animal use, are known as alternatives, replacements or non-animal methods. Some prefer the term advanced technologies given the fact that they often rely on more sophisticated technology and are more human- relevant than the animal test they replace (see Langley et al., 2015). There have been efforts to replace animal tests since the 1960s. Significant progress initially came in replacing animals used to diagnose human disease; to produce biological drugs (such as vaccines); and to safety test batches of these drugs as they were produced. …

The Changing Paradigm In Preclinical Toxicology: In Vitro And In Silico Methods In Liver Toxicity Evaluations, Fozia Noor

Application of Alternative Methods Collection

In vitro methods, based on human primary cells, cell lines, and genetically modified reporter cell lines, have greatly expanded the scope of in vitro toxicology. Other significant progress in the area of human-induced pluripotent stem cells (hiPSCs) (Asgari et al., 2010; Schwartz et al., 2014; Shinde et al., 2016; Shtrichman, Germanguz and Itskovitz-Eldor, 2013) is allowing the application of patient and disease-specific hiPSCs (Ghodsizadeh et al., 2010; McCracken et al., 2014; Siller et al., 2013). Moreover, the tools of precise genome editing with engineered nucleases, such as the zinc finger nucleases (zfns), the transcription activator-like effecter nucleases (talens) and, more …

How To Evaluate The Science Of Non-Human Animal Use In Biomedical Research And Testing: A Proposed Format For Debate, Ray Greek, Lisa A. Kramer

Validation of Alternative Methods Collection

Over time, the interpretation of science has occasionally been corrupted by vested interest groups, be they financially motivated or ego driven. Scientific consensus and widespread public beliefs usually catch up with the evidence, but this can take a very long time and often costs lives. The use of non-human animals in biomedical research and testing is a scientific endeavor and, as such, can and should be evaluated in light of the best science currently available. But facts that have been accepted in all areas of science are routinely ignored or called into question by well-funded, vested interest groups, compromising the …

How Can The Final Goal Of Completely Replacing Animal Procedures Successfully Be Achieved?, Christiane Baumgartl-Simons, Christiane Hohense

Validation of Alternative Methods Collection

Article 23 of European Union (EU) Directive 86/609/EEC required that Member States promote the development and validation of alternative technologies and stated that the European Commission (EC) “shall report before the end of 1987 on the possibility of modifying tests and guidelines” (European Parliament, 1986, Article 23). This Directive was replaced by Directive 2010/63/EU on the protection of animals used for scientific purposes, which now requires that Member States develop and validate alternative approaches much more precisely and specifies that the ultimate objective is the “full replacement of procedures on live animals for scientific and educational purposes, as soon as …

Replacing Animal Tests To Improve Safety For Humans, Kathy Archibald, Robert Coleman, Tamara Drake

Application of Alternative Methods Collection

In this chapter, we propose a new, pragmatic approach that could accelerate the replacement of most, if not all, regulatory animal tests with superior tests based on human biology. We also propose that changes to the requirements for safety testing, issued by the us Food and Drug Administration (fda), must be made in order to enable the use of superior new tests, which are currently disadvantaged by the outdated language of the regulations. But first, it is imperative to establish some level of understanding of the efficacy of existing animal-based methods in order to know whether any possible replacement is …

A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed …

When Is A Randomised Controlled Trial Health Equity Relevant? Development And Validation Of A Conceptual Framework, J. Jull, M. Whitehead, M. Petticrew, E. Kristjansson, D. Gough, Sarah Baird, +Several Additional Authors

Global Health Faculty Publications

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials.

Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials.

Results A randomised trial can …

"It Makes You Feel Like Someone Cares" Acceptability Of A Financial Incentive Intervention For Hiv Viral Suppression In The Hptn 065 (Tlc-Plus) Study., Elizabeth Greene, Allison Pack, Jill Stanton, Victoria Shelus, Elizabeth E Tolley, Jamilah Taylor, Wafaa M El Sadr, Bernard M Branson, Jason Leider, Natella Rakhmanina, Theresa Gamble

Pediatrics Faculty Publications

BACKGROUND: HPTN 065 (TLC-Plus) evaluated the feasibility and effectiveness of providing quarterly $70 gift card financial incentives to HIV-infected patients on antiretroviral therapy (ART) to encourage ART adherence and viral suppression, and represents the largest study to-date of a financial incentive intervention for HIV viral suppression. A post-trial qualitative substudy was undertaken to examine acceptability of the financial incentives among those receiving and implementing the intervention.

METHODS: Between July and October 2013, semi-structured interviews were conducted with 72 patients and 12 investigators from 14 sites; three focus groups were conducted with 12 staff from 10 sites. Qualitative data collection elicited …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing, Elin Törnqvist, Anita Annas, Britta Granath, Elisabeth Jalkesten, Ian Cotgreave, Mattias Öberg

Application of Alternative Methods Collection

The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. …

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …

Inflammatory Findings On Species Extrapolations: Humans Are Definitely No 70-Kg Mice, Marcel Leist, Thomas Hartung

Validation of Alternative Methods Collection

Modern toxicology has embraced in vitro methods, and major hopes are based on the Omics technologies and systems biology approaches they bring along (Hartung and McBride in ALTEX 28(2):83–93, 2011; Hartung et al. in ALTEX 29(2):119–28, 2012). A culture of stringent validation has been developed for such approaches (Leist et al. in ALTEX 27(4):309–317, 2010; ALTEX 29(4):373–88, 2012a; Toxicol Res 1:8–22, 2012b), while the quality and usefulness of animal experiments have been little scrutinized. A new study (Seok et al. 2013) now shows the low predictivity of animal responses in the field of inflammation. These findings corroborate earlier findings from …

Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens

Experimentation Collection

Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …

Lot Quality Assurance Sampling (Lqas) And The Mozambique Malaria Indicator Surveys, Caitlin Biedron, Marcello Pagano, Bethany L. Hedt, Albert Kilian, Amy Ratcliffe, Samuel Mabunda, Joseph J. Valadez

Harvard University Biostatistics Working Paper Series

No abstract provided.

Barriers Encountered During Enrollment In An Internet-Mediated Randomized Controlled Trial, Lorraine R. Buis, Adrienne W. Janney, Michael L. Hess, Silas A. Culver, Caroline R. Richardson

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Online technology is a promising resource for conducting clinical research. While the internet may improve a study's reach, as well as the efficiency of data collection, it may also introduce a number of challenges for participants and investigators. The objective of this research was to determine the challenges that potential participants faced during the enrollment phase of a randomized controlled intervention trial of Stepping Up to Health, an internet-mediated walking program that utilized a multi-step online enrollment process.

Methods

We conducted a quantitative content analysis of 623 help tickets logged in a participant management database during the enrollment …

Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley

Application of Alternative Methods Collection

In this report, we argue specifically that acute toxicity data should not be sought from animal tests. The underlying principle of such tests on rats and mice is that the results can be effectively extrapolated to humans. In fact, after nearly 80 years of use of these tests, the predictivity of rodent data for human acute toxic effects has been disputed but never proven.

Referent Selection Strategies In Case-Crossover Analyses Of Air Pollution Exposure Data: Implications For Bias, Holly Janes, Lianne Sheppard, Thomas Lumley

UW Biostatistics Working Paper Series

The case-crossover design has been widely used to study the association between short term air pollution exposure and the risk of an acute adverse health event. The design uses cases only, and, for each individual, compares exposure just prior to the event with exposure at other control, or “referent” times. By making within-subject comparisons, time invariant confounders are controlled by design. Even more important in the air pollution setting is that, by matching referents to the index time, time varying confounders can also be controlled by design. Yet, the referent selection strategy is important for reasons other than control of …

Non-Parametric Estimation Of Roc Curves In The Absence Of A Gold Standard, Xiao-Hua Zhou, Pete Castelluccio, Chuan Zhou

UW Biostatistics Working Paper Series

In evaluation of diagnostic accuracy of tests, a gold standard on the disease status is required. However, in many complex diseases, it is impossible or unethical to obtain such the gold standard. If an imperfect standard is used as if it were a gold standard, the estimated accuracy of the tests would be biased. This type of bias is called imperfect gold standard bias. In this paper we develop a maximum likelihood (ML) method for estimating ROC curves and their areas of ordinal-scale tests in the absence of a gold standard. Our simulation study shows the proposed estimates for the …

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

The University of Michigan Department of Biostatistics Working Paper Series

Randomized allocation of treatments is a cornerstone of experimental design, but has drawbacks when a limited set of individuals are willing to be randomized, or the act of randomization undermines the success of the treatment. Choice-based experimental designs allow a subset of the participants to choose their treatments. We discuss here causal inferences for experimental designs where some participants are randomly allocated to treatments and others receive their treatment preference. This paper was motivated by the “Women Take Pride” (WTP) study (Janevic et al., 2001), a doubly randomized preference trail (DRPT) to assess behavioral interventions for women with heart disease. …

Overlap Bias In The Case-Crossover Design, With Application To Air Pollution Exposures, Holly Janes, Lianne Sheppard, Thomas Lumley

UW Biostatistics Working Paper Series

The case-crossover design uses cases only, and compares exposures just prior to the event times to exposures at comparable control, or “referent” times, in order to assess the effect of short-term exposure on the risk of a rare event. It has commonly been used to study the effect of air pollution on the risk of various adverse health events. Proper selection of referents is crucial, especially with air pollution exposures, which are shared, highly seasonal, and often have a long term time trend. Hence, careful referent selection is important to control for time-varying confounders, and in order to ensure that …

Cross-Modal Enhancement Of Perceived Brightness: Sensory Interaction Versus Response Bias, Yoav Arieh, Lawrence E. Marks, Eric C. Odgaard

Department of Psychology Faculty Scholarship and Creative Works

Stein, London, Wilkinson, and Price (1996) reported the presence of cross-modal enhancement of perceived visual intensity: Participants tended to rate weak lights as brighter when accompanied by a concurrent pulse of white noise than when presented alone. In the present study, two methods were used to determine whether the enhancement reflects an early-stage sensory process or a later-stage decisional process, such as a response bias. First, the enhancement was eliminated when the noise accompanied the light on only 25% versus 50% of the trials. Second, the enhancement was absent when tested with a paired-comparison method. These findings are consistent with …

Anatomy And Three-Dimensional Reconstructions Of The Brain Of A Bottlenose Dolphin (Tursiops Truncatus) From Magnetic Resonance Images, Lori Marino, Keith D. Sudheimer, Timothy L. Murphy, Kristina K. Davis, D. Ann Pabst, William A. Mclellan, James K. Rilling, John I. Johnson

Veterinary Science and Medicine Collection

Cetacean (dolphin, whale, and porpoise) brains are among the least studied mammalian brains because of the formidability of collecting and histologically preparing such relatively rare and large specimens. Magnetic resonance imaging offers a means of observing the internal structure of the brain when traditional histological procedures are not practical. Furthermore, internal structures can be analyzed in their precise anatomic positions, which is difficult to accomplish after the spatial distortions often accompanying histological processing. In this study, images of the brain of an adult bottlenose dolphin, Tursiops truncatus, were scanned in the coronal plane at 148 antero-posterior levels. From these scans …

Magnetic Resonance Imaging And Three-Dimensional Reconstructions Of The Brain Of A Fetal Common Dolphin, Delphinus Delphis, Lori Marino, Timothy L. Murphy, Lyad Gozal, John I. Johnson

Veterinary Science and Medicine Collection

To demonstrate the kinds of data that can be obtained non-destructively and non-invasively from preserved museum specimens using modern imaging technology the head region of a whole body fetal specimen of the common dolphin, Delphinus delphis, aged 8–9 months post-conception, was scanned using Magnetic Resonance Imaging (MRI). Series of scans were obtained in coronal, sagittal and horizontal planes. A digital three-dimensional reconstruction of the whole brain was prepared from the coronal series of scans. Sectional areas and three-dimensional volumes were obtained of the cerebral hemispheres and of the brainstemplus-cerebellum. Neuroanatomical features identified in the scans include the major sulci of …

Assessing The Accuracy Of A New Diagnostic Test When A Gold Standard Does Not Exist, Todd A. Alonzo, Margaret S. Pepe

UW Biostatistics Working Paper Series

Often the accuracy of a new diagnostic test must be assessed when a perfect gold standard does not exist. Use of an imperfect test biases the accuracy estimates of the new test. This paper reviews existing approaches to this problem including discrepant resolution and latent class analysis. Deficiencies with these approaches are identified. A new approach is proposed that combines the results of several imperfect reference tests to define a better reference standard. We call this the composite reference standard (CRS). Using the CRS, accuracy can be assessed using multistage sampling designs. Maximum likelihood estimates of accuracy and expressions for …

Methodological And Substantive Issues In Substance Abuse Prevention Research, C. Anderson Johnson, John W. Farquhar, Steve Sussman

CGU Faculty Publications and Research

This article summarizes current issues in drug abuse prevention research through integration of other articles in this journal and by heeding historical trends in prevention science. Recommendations are made for future research directions. For prevention to advance, iterative processes are needed involving both quasi-experimental and experimental designs and involving both small, simple units and large, complex, interactive units. Accuracy of measurement and replication are of paramount importance.

The Significance Of Alternative Techniques In Biomedical Research: An Analysis Of Nobel Prize Awards, Martin Stephens

Experimentation Collection

No abstract provided.

Protection Of Animals And Animal Experimentation: A Survey Of Scientific Experts, Norbert Lagoni, Joachim Fiebelkorn, Hans-Joachim Wormuth

Experimentation Collection

This article summarizes information from a survey of biomedical scientists, specifically pharmacologists and toxicologists, on the use of laboratory animals and the potential for replacing their use with alternative methods for the development and evaluation of pharmaceutical substances. The majority of those surveyed felt that the alternatives could supplement or complement animal tests, but not replace the tests altogether. However, most favored the use of nonsentient material in safety tests.