Misreporting of a Plasma-Rich-in-Growth-Factors Trial on Knee Osteoarthritis

Abstract

As attentive readers of your prestigious journal, we are deeply concerned by a potentially serious case of misreporting affecting Arthroscopy. Early in 2019, our publicly funded research team was commissioned to assess the evidence on platelet-rich plasma and analogues in traumatology. We retrieved, among the appraised publications, the high-impact article published by Sánchez et al.1Sánchez M. Fiz N. Azofra J. et al.A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.Arthroscopy. 2012; 28: 1070-1078Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar evaluating plasma rich in growth factors versus hyaluronic acid for knee osteoarthritis. We asked the authors for additional information, namely the protocol, clinical study report (or similar final report), and ethics committee approval. They reacted positively to our request by providing all 3 unpublished documents. Nonetheless, as they were examined, important discrepancies arose among the protocol, final report, and published article. In particular, the main efficacy outcome prespecified in the protocol (percentage of patients with a decrease > 40% in the score in the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain subscale at the final visit [week 24] with respect to baseline) did not show statistically significant differences according to the final report provided. In contrast, the Arthroscopy publication reported a different main efficacy outcome (decrease ≥ 50% in the score in the WOMAC pain subscale instead of 40%), reaching statistically significant differences in favor of the investigational product. This undoubtedly major change in the protocol caused the trial main result to change from “no differences” to “plasma rich in growth factors is better.” For this reason, it appeared to us to be serious enough to be corrected accordingly. Other issues affecting secondary outcomes reported but not prespecified and vice versa—inconsistencies with safety results, lack of pre-planned intention-to-treat analysis, and inadequate disclosure on conflicts of interest—were also identified, deserving proper correction. Our concerns have been extensively discussed with the authors for several months. Unfortunately, they have refused to promote any kind of change in the published article. They mainly argue that (1) the published article uses stricter and more demanding criteria than the previous prespecified main efficacy outcome and (2) the ethics committee reviewed their new strategy of analysis and approved it in a follow-up meeting. We find both arguments highly disappointing. First, the fundamental strict and demanding criteria should be derived from respecting the integrity of the protocol, especially in aspects as sensitive as the main outcome of the study. Second, no official amendment to the protocol has ever been proved. The involved ethics committee has been approached several times, but no collaboration was provided to cast additional light on the case. Third, taking into account that the trial was completed in September 2010 and the final report with the results of the prespecified main outcome (decrease > 40% in WOMAC pain subscale score) is dated December 2010, this major change to the protocol had to take place after completion of the study, which should be considered a misleading practice without adequate scientific justification. As a result, in our opinion a deep correction or retraction is warranted as soon as possible to match the article information with both the original protocol and the unpublished final report results. Ideally, the process should eventually lead to revision of other articles directly affected (mainly reviews), some of them also published by this journal.2Anitua E. Sánchez M. Aguirre J.J. et al.Efficacy and safety of plasma rich in growth factors intra-articular infiltrations in the treatment of knee osteoarthritis.Arthroscopy. 2014; 30: 1006-1017Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Thus, we urge Arthroscopy to assess the relevant unpublished documents facilitated by our research team, investigate in detail this case of potential scientific bad practice, and lead the restoration process in a timely manner. Download .pdf (.29 MB) Help with pdf files ICMJE author disclosure forms A Randomized Clinical Trial Evaluating Plasma Rich in Growth Factors (PRGF-Endoret) Versus Hyaluronic Acid in the Short-Term Treatment of Symptomatic Knee OsteoarthritisArthroscopyVol. 28Issue 8PreviewThis multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. Full-Text PDF Response to Saiz et al., “Misreporting of a Plasma Rich in Growth Factors Trial on Knee Osteoarthritis”ArthroscopyVol. 36Issue 3PreviewThis letter is a response to the letter by Saiz et al. that argued misreporting in the publication by Sanchez et al.1 Full-Text PDF