Nutrients, Vol. 18, Pages 331: Using Dose–Response Correlation Re-Analyzing to Distinguish Placebo from Standardized Rose-Hip Powder (Lito) in a Clinical Trial on Osteoarthritis Where Data Initially Looked Identical
Nutrients doi: 10.3390/nu18020331
Authors:
Alzahraa Mahmoud Motawei
Kristian Marstrand Warholm
Kaj Winther
Background: Large positive responses to placebo are common in clinical trials and pose a major challenge when evaluating different treatments, including new foods. Standard between-group comparisons may fail to detect true effects when placebo improvements are significant. We aimed to demonstrate how a simple dose–response correlation method can help differentiate genuine positive responses from those experienced with placebo through secondary analysis of a randomized controlled clinical trial of powdered Rosa-canina fruits. Methods: Data were reanalyzed from a multicenter, double-blind, randomized, placebo-controlled trial (N = 120; ClinicalTrials.gov NCT01459939) evaluating the effects of standardized Rosa-canina powder in hip and knee osteoarthritis (OA). Participants received fixed doses, leading to variability in mg/kg exposure due to different body weights. Pearson correlations between dose/kg and changes in WOMAC pain and function at 6 and 12 weeks were calculated separately for the active and placebo groups. Standard between-group comparisons were also performed. Results: Both groups showed significant improvement, over 50%, with no statistically significant differences between them in WOMAC pain or function. However, only the active group, which received a food supplement, exhibited a consistent negative correlation between body weight and symptom improvement at 6 and 12 weeks, suggesting greater benefit with higher dose per kilogram of body weight. No dose–response relationship was observed in the placebo recipients. Therefore, weight-stratified plots revealed an exposure–response gradient in the active group. Conclusions: Dose–response correlation analysis uncovered positive effects of Rosa-canina as a nutrient that were not detectable through standard between-group comparisons. This is consistent with findings from earlier rose-hip research. This low-cost, easy-to-implement method may help distinguish active effects from placebo responses in trials with large nonspecific improvements. Incorporating such analyses could improve the identification of nutrients containing biologically active preparations and support dose selection in future clinical research.
Background: Large positive responses to placebo are common in clinical trials and pose a major challenge when evaluating different treatments, including new foods. Standard between-group comparisons may fail to detect true effects when placebo improvements are significant. We aimed to demonstrate how a simple dose–response correlation method can help differentiate genuine positive responses from those experienced with placebo through secondary analysis of a randomized controlled clinical trial of powdered Rosa-canina fruits. Methods: Data were reanalyzed from a multicenter, double-blind, randomized, placebo-controlled trial (N = 120; ClinicalTrials.gov NCT01459939) evaluating the effects of standardized Rosa-canina powder in hip and knee osteoarthritis (OA). Participants received fixed doses, leading to variability in mg/kg exposure due to different body weights. Pearson correlations between dose/kg and changes in WOMAC pain and function at 6 and 12 weeks were calculated separately for the active and placebo groups. Standard between-group comparisons were also performed. Results: Both groups showed significant improvement, over 50%, with no statistically significant differences between them in WOMAC pain or function. However, only the active group, which received a food supplement, exhibited a consistent negative correlation between body weight and symptom improvement at 6 and 12 weeks, suggesting greater benefit with higher dose per kilogram of body weight. No dose–response relationship was observed in the placebo recipients. Therefore, weight-stratified plots revealed an exposure–response gradient in the active group. Conclusions: Dose–response correlation analysis uncovered positive effects of Rosa-canina as a nutrient that were not detectable through standard between-group comparisons. This is consistent with findings from earlier rose-hip research. This low-cost, easy-to-implement method may help distinguish active effects from placebo responses in trials with large nonspecific improvements. Incorporating such analyses could improve the identification of nutrients containing biologically active preparations and support dose selection in future clinical research. Read More