Diet in Clinical Trials: FDA Drafts Guidance
The US Food and Drug Administration (FDA) on Monday released new draft guidance on recommendations for optimizing and standardizing dietary management in clinical trials for developing drugs to treat inborn errors of metabolism for which dietary management is a key component of metabolic control.The 8-page draft discusses how sponsors should consider stabilizing patient diets across clinical sites to ensure consistency.
“A trial’s inadequate dietary management can make interpretation of results particularly difficult when the average treatment effect of the new drug product is relatively modest,” FDA says.
Measurements of concentrations of metabolites primarily in serum and urine are often used to inform dietary changes and to determine whether dietary management has been optimized.
“Sponsors should select the duration of the pretrial period for optimizing and stabilizing a patient’s diet based on the specific condition that is being treated, the severity of the metabolic defect, the patient’s age, and the complexity of the dietary management,” the draft says.
It also calls on patients to enter the trial during a period of metabolic control “as demonstrated by appropriate biochemical analytes (e.g., ammonia, plasma amino acids, urine organic acids, plasma acylcarnitines, total and free carnitine). Baseline dietary information (total daily protein, lipid, carbohydrate, and total daily caloric intake) should be documented over an appropriate time period (e.g., 3 days) at enrollment even if metabolic stability has been shown.”
The draft also discusses planned procedures, such as surgeries, clinical trial design, including considerations for optimizing diet, challenges and limitations of diet assessments and use of historical controls.
Inborn Errors of Metabolism That Use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development: Draft Guidance for Industry