English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

The paper published by Henrotin et al. [1] reported the results from a double-blind multi-center randomized placebo controlled study of bio-optimized Curcuma longa (BCL) extract in patients with symptomatic knee osteoarthritis (OA). This bio-optimized curcuma extract is a widely used food supplement. We received two letters that highlight six potential shortcomings in the design of this study and the interpretation of the results. As the content of these letters is virtually similar, we decided to answer both letters in one document. The first shortcoming was about the timeline of study registration. This prospective study was recorded in September 2016 while the first patient was enrolled in 2014. In contrast with medicinal products and biologics and medical devices, there are no legal requirements for registry of a clinical trial investigating dietary supplements. However, in order to comply with the Declaration of Helsinki and WHO recommendations, for the sake of transparency, and for scientific publication, the trial was indeed registered on Clinical trial.gov on September 13, 2016 (NCT02909621). The second point concerns the selection of the coprimary endpoints. A particularity of this study was the use of two unusual co-primary endpoints. One endpoint was the Patient Global Assessment of Disease Activity (PGADA) and the other the serum levels of Coll2-1, a specific peptide and epitope of type II collagen and considered as a biomarker of cartilage degradation. Indeed, these co-primary endpoints are not recommended by any regulatory agency, but they were defined based on the results obtained in a previous pilot study [2]. Importantly, the design of this study was exploratory and gave interesting data about innovative biomarkers. Further, this approach was in line with OARSI-FDA consortium recommendation 23 which encouraged the collection of biological fluids in randomized clinical trials to investigate the metabolic effect of a treatment on joint tissues and to qualify a biomarker or a cluster of biomarkers for treatment development and use in the context of a personalized approach of OA management [3]. Again, this study has an objective to provide useful information for the design of a potential larger phase III study including the sample size estimate, the choice of the dose, and the selection of primary outcome. The third point concerns the calculation of the sample size. The sample size calculation was challenged by the statistician of the journal and ultimately considered as correctly addressed. The sample size was calculated following the highest standard. Indeed, the sample size was defined according the International Clinical Harmonization (ICH) E9 guidelines for clinical trials (ICH E9—see additional file 2 in the original paper). Sample size considered also the results obtained in a preceding pilot study [2]. We calculated a sample size of 150 patients based on a decrease in Coll2-1 biomarker levels of 44.4 nmol/L with standard deviation of 53 or a decrease in patient assessment of global disease activity of 21mm with standard deviation of 25 in the treated groups and no change in the control group, an alpha risk of 5% that was divided by 2 (2.5%) as a correction for multiple testing, a power of 85%, and a drop-out rate of 15%. Taken individually, the two co-primary endpoints lead to the same sample size.

arthritis research and therapy

Responses to “Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study”: authors’ reply