# 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

## TL;DR

This study shows how a simple dose-response analysis can reveal real benefits of a rose-hip supplement in osteoarthritis, even when standard methods couldn't tell it apart from a placebo.

## Contribution

The novel use of dose-response correlation in distinguishing active treatment effects from placebo in clinical trials with nonspecific improvements.

## Key findings

- Standard comparisons found no difference between active and placebo groups, but dose-response analysis revealed a treatment effect.
- Only the active group showed a consistent negative correlation between body weight and symptom improvement.
- Weight-stratified plots revealed an exposure-response gradient in the active group.

## Abstract

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.