Study outlines struggles with diet trials

Most clinical trails involving diet, even those published in reputable journals, lack the rigor of most drug trials, according to a new study published in JAMA Network Open.

Diet trials are often small, of short duration, and unable to rigorously control subjects' adherence to the test diets, the study says. Moreover, the research concludes that 86 percent of diet trials amended their desired study outcomes along the way. That raises the possibility of bias, the researchers said.  

The authors, David Ludwig, MD, PhD, Cara Ebbeling, PhD, and Steven Heymsfield, MD, call for more investment in rigorous diet research. They note that nutrition research is not only under-funded, but also more challenging to conduct than drug studies.

For the study, the team conducted a literature search of drug trials for obesity published in top journals, including The New England Journal of Medicine, The Lancet, Annals of Internal Medicine, and The American Journal of Clinical Nutrition, from 2009 to 2019. They identified 343 diet studies, and, for comparison, 148 drug trials for obesity.

All studies were registered in advance on ClinicalTrials.gov, a measure intended to keep investigators accountable to what they originally planned to test, ensuring that they don't report findings selectively. But when the researchers compared the original registry description with the final published papers, 18 diet trials (86 percent) versus only two of the drug trials (22 percent) showed substantive discrepancies.

Typically, these involved a change in the time frame of the primary outcome or the number of co-primary outcomes. One diet trial, for example, initially listed "weight at five years" as the primary outcome, but later amended this to "change in body fat at one year." Other trials initially planned several primary outcomes or measurements at several time points, but later pared these down to a single outcome or single time point in the published study.

The investigators propose several immediate remedies, such as creating specialized registries for diet trials to reflect their special challenges. While this would require a substantial investment, they write, "the amounts involved would total a fraction of a cent for every dollar spent treating diet-related conditions like obesity, Type 2 diabetes, and cardiovascular disease."