Short-Term Calcium Intervention Studies, In Animals snd Humans, Using Epithelial Proliferation as Biomarker of Response. The Initiation of a Calcium Intervention Trial in Adenoma Patients

Many lifestyle intervention trials depend on collecting self-reported outcomes, such as dietary intake, to assess the intervention’s effectiveness. Self-reported outcomes are subject to measurement error, which impacts treatment effect estimation. External validation studies measure both self-reported outcomes and accompanying biomarkers, and can be used to account for measurement error. However, in order to account for measurement error using an external validation sample, an assumption must be made that the inferences are transportable from the validation sample to the intervention trial of interest. This assumption does not always hold. In this paper, we propose an approach that adjusts the validation sample to better resemble the trial sample, and we also formally investigate when bias due to poor transportability may arise. Lastly, we examine the performance of the methods using simulation, and illustrate them using PREMIER, a lifestyle intervention trial measuring self-reported sodium intake as an outcome, and OPEN, a validation study measuring both self-reported diet and urinary biomarkers.

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Randomization of subjects to study-arms of a parallel study in the presence of multiple covariates

10.21203/rs.3.rs-24266/v1 ◽

2020 ◽

Author(s):

Eric Schoen ◽

Suzan Wopereis

Keyword(s):

Body Mass Index ◽

Healthy Volunteers ◽

Statistical Models ◽

Intervention Studies ◽

Parallel Study ◽

Intervention Trial ◽

Statistical Software ◽

Clear Cut ◽

Clinical Center ◽

Multiple Covariates

Abstract Background: Parallel intervention studies involving healthy volunteers usually require a procedure to allocate the subjects to study-arms. Statistical models to evaluate the different outcomes of the study-arms will include study-arm as a factor along with any covariate that might affect the results. To ensure that the effects of the covariates are confounded to the least possible extent with the effects of the arms, strained randomization can be applied. However, there is at present no clear-cut procedure when there are multiple covariates. Methods: We propose a D-optimal blocking procedure to allocate subjects with known values of the covariates to the study arms. We prove that the procedure minimizes the variances of the baseline differences between the arms corrected for the covariates. The procedure uses standard statistical software. Results: We demonstrate the potential of the method by an application to a human parallel intervention trial with three arms and 162 healthy volunteers. The covariates were gender, age, body mass index, an initial composite health score, and a categorical indicator called _rst-visit group, defining groups of volunteers who visit the clinical center on the same day (17 groups). Volunteers were allocated equally to the study-arms by the D-optimal blocking procedure. The D-efficiency of the model connecting an outcome with the study-arms and correcting for the covariates equals 99.2%. We simulated 10,000 random allocations of subjects to arms either unstratified or stratified by first-visit group. Intervals covering the middle 95% of the D-efficiencies for these allocations were [82.0, 92.0] and [93.2, 98.4], respectively. Conclusions: Allocation of volunteers to study-arms with a D-optimal blocking procedure with the values of the covariates as inputs substantially improves the efficiency of the statistical model that connects the response with the study arms and corrects for the covariates.

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Short-Term Malnutrition in Neonatal Rabbits: Effect on Gastrointestinal Epithelial Proliferation

Journal of Nutrition ◽

10.1093/jn/119.5.785 ◽

1989 ◽

Vol 119 (5) ◽

pp. 785-789 ◽

Cited By ~ 1

Author(s):

Susan S. Baker ◽

Cara Campbell

Keyword(s):

Epithelial Proliferation ◽

Short Term

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Antioxidant Actions of Polyphenols in Humans

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.2.112 ◽

2003 ◽

Vol 73 (2) ◽

pp. 112-119 ◽

Cited By ~ 66

Author(s):

Dragsted

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Intervention Studies ◽

Molecular Structures ◽

Model Systems ◽

Short Term ◽

Consistent Finding ◽

Antioxidative Defence ◽

Present Text ◽

Specific Health

Many polyphenols are potent antioxidants in foods and model systems and they have therefore very naturally been linked with the hypothesis that their redox activities may confer them with specific health benefits. Their prevalence in plant derived foods, which are generally accepted as healthy has supported this view and inspired researchers to conduct human intervention trails with polyphenol rich food items in order to investigate their ability to counteract oxidative stress. Several biomarkers have gained widespread use to assess oxidative damage and antioxidative defence capabilities in humans. These markers pioneer our knowledge about factors related to oxidative stress in proteins, lipids and DNA and present results indicate that oxidative damage may be very localised and that refined markers may be necessary in order to disentangle the complex local factors which determine the extent of oxidative damage in different molecular structures. The present text reviews the human short-term intervention studies with polyphenol-rich foods, which address their impact on biomarkers of oxidative damage and antioxidative defence. None of the oxidative damage markers seem to be consistently affected by polyphenol-rich foods or to be consistently related to one another. The most consistent finding regarding antioxidative defence markers is a postprandial effect on plasma antioxidative capacity after ingestion of foods rich in catechins and complex procyanidins.

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