Perspective: US Documentation and Regulation of Human Nutrition Randomized Controlled Trials

ABSTRACT Training to ensure good documentation practices and adherence to regulatory requirements in human nutrition randomized controlled trials has not been given sufficient attention. Furthermore, it is difficult to find this information conveniently organized or in a form relevant to nutrition protocols. Current gaps in training and research surveillance exist in clinical nutrition research because training modules emphasize drugs and devices, promote reliance on monitoring boards, and lack nutrition expertise on human nutrition research teams. Additionally, because eating is essential, ongoing, and highly individualized, it is difficult to distinguish risks associated with interventions from eating under free-living conditions. Controlled-feeding trials provide an option to gain more experimental control over food consumed, but at a price of less external validity, and may pose human behavior issues that are unrelated to the intervention. This paper covers many of the expected practices for documentation and regulation that may be encountered in planning and conducting nutrition intervention trials with examples and references that should be useful to clinical nutrition researchers, funders of research, and research institutions. Included are definitions and guidance on clinical nutrition research oversight (institutional review boards, data safety and monitoring boards, US FDA); participant safety; standard operating procedures; training of investigators, staff, and students; and local culture and reporting requirements relevant to diet-related clinical research conduct and documentation.

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Perspective: Laboratory Considerations and Clinical Data Management for Human Nutrition Randomized Controlled Trials: Guidance for Ensuring Quality and Integrity

Advances in Nutrition ◽

10.1093/advances/nmaa088 ◽

2020 ◽

Cited By ~ 2

Author(s):

Kevin C Maki ◽

Joshua W Miller ◽

George P McCabe ◽

Gowri Raman ◽

Penny M Kris-Etherton

Keyword(s):

Data Collection ◽

Data Management ◽

Randomized Controlled Trials ◽

Clinical Data ◽

Human Nutrition ◽

Controlled Trials ◽

Quality Of Data ◽

Randomized Controlled ◽

Nutrition Research ◽

Human Nutrition Research

ABSTRACT In human nutrition randomized controlled trials (RCTs), planning, and careful execution of clinical data collection and management are vital for producing valid and reliable results. In this article, we provide an overview of best practices for biospecimen collection and analyses, and for the fundamentals of clinical data management, including preparation and study startup; data collection, entry, cleaning, and authentication; and database lock. The reader is also referred to additional resources for information to assist in the planning and conduct of human RCTs. The tools and strategies described are expected to improve the quality of data produced in human nutrition research that can, therefore, be used to support food and nutrition policies.

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Perspective: Guidelines Needed for the Conduct of Human Nutrition Randomized Controlled Trials

Advances in Nutrition ◽

10.1093/advances/nmaa083 ◽

2020 ◽

Author(s):

Connie M Weaver ◽

Alice H Lichtenstein ◽

Penny M Kris-Etherton

Keyword(s):

Randomized Controlled Trials ◽

Human Nutrition ◽

Controlled Trials ◽

Trial Management ◽

Scientific Rigor ◽

Randomized Controlled ◽

Nutrition Research ◽

Human Nutrition Research ◽

Optimal Health ◽

Clinical Trial Management

ABSTRACT Guidelines for designing, conducting, documenting, and reporting human nutrition randomized controlled trials (RCTs) have as yet to be developed and disseminated as reference for investigators, funders, regulators, institutions, assessors, trainees, and others involved in human nutrition research. Diet-related interventions can include diet and/or behavioral manipulation, provision of foods or entire meals, or delivery of dietary components in individual food items or supplements. This Perspective introduces a series of papers that outline core principles for the design and conduct of human nutrition RCTs, documentation and reporting of all aspects of clinical trial management, and data analysis and reporting of results. Human nutrition RCTs have unique considerations delineated in these papers. Conducting them with the highest scientific rigor is essential to the development of evidence-based dietary guidance for promoting optimal health and advancing health care.

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Perspective: Design and Conduct of Human Nutrition Randomized Controlled Trials

Advances in Nutrition ◽

10.1093/advances/nmaa109 ◽

2020 ◽

Cited By ~ 1

Author(s):

Alice H Lichtenstein ◽

Kristina Petersen ◽

Kathryn Barger ◽

Karen E Hansen ◽

Cheryl A M Anderson ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Outcome Measures ◽

Research Question ◽

Human Nutrition ◽

Quality Data ◽

Scientific Integrity ◽

Institutional Review Boards ◽

Controlled Trials ◽

Randomized Controlled ◽

Study Results

ABSTRACT In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

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Estimands: improving inference in randomized controlled trials in clinical nutrition in the presence of missing values

European Journal of Clinical Nutrition ◽

10.1038/s41430-018-0207-x ◽

2018 ◽

Vol 72 (9) ◽

pp. 1291-1295 ◽

Cited By ~ 1

Author(s):

Christian Ritz ◽

Birgitte Rønn

Keyword(s):

Randomized Controlled Trials ◽

Missing Values ◽

Clinical Nutrition ◽

Controlled Trials ◽

Randomized Controlled

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Some Questions of Ethics in RCTs

10.31235/osf.io/fgxun ◽

2021 ◽

Author(s):

Reetika Khera

Keyword(s):

Adverse Events ◽

Randomized Controlled Trials ◽

Ethical Issues ◽

Human Subjects ◽

Belmont Report ◽

Institutional Review Boards ◽

Controlled Trials ◽

Randomized Controlled ◽

Institutional Review ◽

Areas Of Concern

Questions of ethics in Randomized Controlled Trials (RCTs) in development economics need greater attention and a wider perspective. RCTs are meant to be governed by the three principles laid out in the Belmont Report, but often violated them, e.g. when local laws are flouted. In other cases, the framework of the Belmont Report itself has proved inadequate: for instance, when there are unintended outcomes or adverse events for which no-one is held accountable. Primarily using RCTs conducted in India, this paper highlights eight areas of concern. RCTs also have a disproportionate influence on shaping research agendas and on policy. Though ethical issues have been raised, there has been little engagement from the RCT community – a manifestation of its power in the profession. As current safeguards (such as oversight by Institutional Review Boards) have failed to protect human subjects, the concluding section discusses possible ways to resolve these issues.

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Pork consumption and its relationship to human nutrition and health: a scoping review

Meat and Muscle Biology ◽

10.22175/mmb.12953 ◽

2021 ◽

Author(s):

Laura Paige Penkert ◽

Ruogu Li ◽

Jing Huang ◽

Anil Gurcan ◽

Mei Chun Chung ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Scoping Review ◽

Case Control ◽

Human Nutrition ◽

Controlled Trials ◽

Case Control Studies ◽

Nutrition And Health ◽

Randomized Controlled ◽

Scoping Reviews ◽

Pork Consumption

Pork is a frequently consumed red meat that provides substantial amounts of energy, macronutrients, and micronutrients to the diet. Its role in human nutrition and health is controversial and a plethora of data exist in the peer-reviewed scientific literature. Therefore, we conducted a scoping review of clinical and population-based studies to assess the effects of pork consumption on human nutrition and health. Results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Data were extracted from 86 studies, including 16 randomized controlled trials, 1 uncontrolled trial, 7 cohort studies, 4 nonrandomized controlled trials, 4 case-cohort and nested case-control studies, 33 case-control studies, and 21 cross-sectional studies. Intervention studies were conducted in healthy individuals and were short to moderate in duration. The effect of pork intake on patients’ nutrient status was the most commonly assessed outcome. The majority of observational studies assessed the effect of pork on cancer incidence, but no studies assessed the effects of pork on inflammation or oxidative stress. No interventional studies explored diabetes mellitus risk, and only one study assessed cancer risk associated with pork consumption. Several micronutrients in pork, including zinc, iron, selenium, choline, thiamin, and vitamins B6 and vitamin B12, are thought to influence cognitive function and may prove to be a unique area of research. To date, there is a dearth of high-quality randomized controlled trials assessing the effects of pork intake on disease risk factors and outcomes. This review helps highlight the many research gaps that future studies should be designed to address.

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Designing, Conducting, and Documenting Human Nutrition Plant-Derived Intervention Trials

Frontiers in Nutrition ◽

10.3389/fnut.2021.782703 ◽

2021 ◽

Vol 8 ◽

Author(s):

Connie M. Weaver ◽

J. Kalina Hodges

Keyword(s):

Best Practices ◽

Randomized Controlled Trials ◽

Evidence Base ◽

Human Nutrition ◽

Controlled Trials ◽

Dietary Recommendations ◽

Regulatory Policies ◽

Randomized Controlled ◽

Carry Over ◽

Intervention Trials

Best practices for designing, conducting, documenting, and reporting human nutrition randomized controlled trials were developed and published in Advances in Nutrition. Through an example of the randomized clinical trial on blueberries and bone health funded by the National Institutes of Health, this paper will illustrate the elements of those best practices that apply specifically to plant-based intervention clinical trials. Unique study design considerations for human feeding interventions with bioactive plant compounds include the difficulty of blinding the intervention, background nutritional status of participants, carry-over effects of the intervention, benefits of a run-in period, lack of safety/tolerability data, and nutrition-specific regulatory policies. Human nutrition randomized controlled trials are the gold standard for establishing causal relations between an intervention and health outcome measures. Rigorous studies and documentation define the quality of the evidence-base to inform public health guidelines and to establish personalized dietary recommendations for the health-promoting plant components.

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