Trials. 2023 Jan 18;24(1):37. doi: 10.1186/s13063-022-07049-3.
ABSTRACT
BACKGROUND: A randomized clinical trial assessing plasma rich in growth factors (PRGF) versus hyaluronic acid for knee osteoarthritis was published in 2012 (sponsor trial ID BTI-01-EC/07/ART). Evidence of misreporting was discovered following access to unpublished materials. In accordance with the principles of the Restoring Invisible and Abandoned Trials (RIAT) initiative, we sought to re-analyse Study PRGF based on the unpublished trial materials.
METHODS: Reanalysis was made possible primarily based on two unpublished study documents (original trial protocol and final report) obtained from the authors of the original publication. A call to action, calling on the authors to correct the original publication, was publicly issued. The involved ethics committee was repeatedly approached and extensive discussion with the authors ensued. After no agreement to correct the paper was reached, we embarked on this restoration. Reanalysis was focused on providing updated analyses for efficacy and safety.
RESULTS: The efficacy of PRGF was not statistically different from hyaluronic acid for any prespecified primary or secondary efficacy outcomes. For the primary endpoint, the percent of patients on PRGF compared to hyaluronic acid with a decrease >40% in WOMAC pain subscale score was 5.4% higher; 95% confidence interval (CI) -10.4% to 21.3%; p = 0.505. This differs from the original publication that reported a non-prespecified primary endpoint (decrease >50% in WOMAC pain subscale score) which was 14.1% higher; 95% CI 0.5 to 27.6%; p=0.044. Furthermore, in contrast to the article statement that all the adverse events disappeared in 48 h, at least two patients in the hyaluronic arm and five patients in the PRGF arm reported persistent adverse events. Inadequate disclosure of conflicts of interest in the original publication was also noted.
CONCLUSIONS: This reanalysis of Study PRGF found no clinically or statistically significant benefit from PRGF compared to hyaluronic acid. The restoration of Study PRGF shows the urgency of important changes to trial reporting and oversight practices. In the future, timely access to all clinical trial documents is needed to minimize the risk of reporting bias. Similarly, ethics committees should be ready to intervene whenever a case of potential misconduct arises.
TRIAL REGISTRATION: This is a RIAT project, whose original trial was approved and registered on 19 December 2007 by the Ethics Committee of the Basque Country, Spain, as BTI-01-EC/07/ART.
PMID:36653802 | DOI:10.1186/s13063-022-07049-3
