Nutrient Drug Interaction Probability Scale (NDIPS): A Creation and Validation Process

Abstract

Background:Drug-nutrient interactions (DNIs) are interactions between drugs and nutrients that can result in clinically relevant physiological alterations. Despite their potential impact, the importance of DNIs is heavily undervalued and overlooked. Evaluation of drug safety mainly focuses on single drugs or drug-drug interactions, while DNIs are not specifically considered during drug development phases. The prevalence of potential DNIs reported in studies ranges widely from 6% to 70%, indicating substantial underreporting. Contributing factors include limited nutritional expertise among clinicians, reliance on outdated anecdotal evidence, and lack of consensus on objectively assessing DNIs. As a result, DNIs often go undetected, leading to preventable adverse events or unnecessary dietary restrictions. Methods: The Nutrient Drug Interaction Probability Scale (NDIPS) was developed by adapting the DIPS questionnaire (Horn, J; Hansten, D; and Chan, L-N) to assess the probability of DNIs. An internal validation process was conducted by testing the NDIPS on published case reports describing DNIs. An external validation to assess consistency in question interpretation involved practicing clinicians who used the NDIPS to assess a selected case report and provided feedback on question clarity. Results: The internal validation trial revealed some unexpected results. While all the case reports described "established" DNIs, not all were assigned a high probability by the NDIPS tool. Analysis showed that certain question responses strongly correlated with the probability result determined by the NDIPS tool. These key determinant questions are generally not considered in current practice when assessing for DNIs, highlighting the importance of shifting the existing thought process when considering the presence of an interaction. The external validation with clinicians showed consistency in interpreting the NDIPS questions, with some suggestions to clarify certain questions and condense the questionnaire for practicality. Conclusion: The NDIPS was designed to serve as a thought process for clinicians to assess the probability of DNIs on a case-by-case basis. By guiding a comprehensive evaluation of the clinical presentation, timeframe, and alternative causes, the NDIPS supports personalized healthcare models and evidence-based management of potential DNIs. Future improvements based on validation feedback could further improve the tool's utility in addressing the underreported yet clinically relevant issue of DNIs in practice.