Main findings and contrast with original published article
knee osteoarthritis, pain
ADVERSE EVENTS, SECONDARY, KNEE OSTEOARTHRITIS
Our RIAT appraisal of Study PRGF underlined that no substantial differences in pain relief and other efficacy estimates were proved when adult participants with knee osteoarthritis were treated with plasma rich in growth factors or hyaluronic acid. As far as safety is concerned, there is no sound evidence about a different profile between both interventions, while some data on type and persistent adverse events make advisable further research. This analysis is well aligned with the final report authored by Sánchez and colleagues but it is not the case concerning the published article in We assessed and reported the Study PRGF in accordance with the original protocol, which had no amendments reported by the study authors or the corresponding ethics committee. The re-assessment of the dossier has shown a marked discrepancy in the main efficacy outcome based on the fact that unlike study authors, in the analysis the RIAT investigators stuck to the protocol and original final report. A specific section in the protocol devoted to ethical considerations (page 35) clearly stated that ‘no changes or deviations of the protocol will be permitted without evidence of approval’. However, the authors reported a non-approved main efficacy outcome, which should be seen as a protocol major change, reaching statistically significant differences in favour of the investigational product. It has been previously described that changes to endpoints can compromise the scientific integrity of a trial, leading to misguided research and suboptimal patient care [Our re-analysis has shown in detail how an inappropriate shift in a primary outcome can dramatically influence final results. In this sense, it should be noted that the original statistical analysis was performed by the own trial sponsor, which stresses the need to rely on fully independent bodies for this crucial task.Other issues such as secondary outcomes reported but not pre-specified and vice versa and the unexpected change in the analysis plan from a per-protocol to an intention-to-treat strategy were also identified. Theoretically, such a switch might have come from the journal review process or a late realization from the original team that intention-to-treat was most appropriate. However, the change should have been explained and justified in the original work, as should the switch of the primary outcome from 40% to 50% reduction. Interestingly, as Table With regard to harms caused by the interventions, inconsistencies between text and figures appeared on persistent symptoms. Finally, the study authors failed to report their conflicts of interest in the authorship and publication of this article. In particular, one of them (EA) was the Scientific Director of the BTI Biotechnology Institute, manufacturer of PRGF-Endoret®, and others (JJA, SP, GO) were employees of the company [