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Editorial Commentary: Meta-analysis Shows That Platelet-Rich Plasma Is Safe and Effective for Knee Osteoarthritis: Future Randomized Controlled Trials Must Be of High Quality—Not High Quantity

      Abstract

      The use of platelet-rich plasma in knee osteoarthritis is still controversial, and meta-analysis shows that platelet-rich plasma can be effective and safe for nonoperative management of knee osteoarthritis. Randomized controlled trials (RCTs) are essential tools for evaluating the effectiveness and safety of new therapeutic interventions. Meta-analysis of these RCTs is critical to try to approximate the truth but also reminds us that sometimes, “value does not necessarily derive from quantity but rather from quality.” Given the fact that approximately 92.8% of published abstracts of RCTs report at least 1 significant outcome (indicated as at least P < .05), there is a notion that significant outcomes are most likely to become published, suggesting a potential publication bias. Therefore, additional studies repeating the significant outcomes are sometimes necessary.
      Οὐκ ἐν τῷ πολλῷ τὸ εὖ, ἀλλ᾿ ἐν τῷ εὖ τὸ πολύValue does not necessarily derive from quantity but rather from quality.Diogenes Laërtius (180-240 ad)
      Platelet-rich plasma (PRP) showed great promise and attracted the attention of the orthopaedic community to the degree that it was initially considered a panacea for all different kinds of orthopaedic diseases.
      • Lubowitz J.
      Editorial Commentary: The promise of platelet-rich plasma.
      After some initial controversy, high–level of evidence studies showed that PRP can be effective and safe for nonoperative management of knee osteoarthritis.
      • Lin K.Y.
      • Yang C.C.
      • Hsu C.J.
      • Yeh M.L.
      • Renn J.H.
      Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: A randomized, double-blind, triple-parallel, placebo-controlled clinical trial.
      In their article “Platelet-Rich Plasma Versus Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Meta-analysis of 26 Randomized Controlled Trials,” Tan, Chen, Zhao, and Huang
      • Tan J.
      • Chen H.
      • Zhao L.
      • Huang W.
      Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: A meta-analysis of 26 randomized controlled trials.
      analyzed data from 26 studies that compared PRP and hyaluronic acid (HA) for the management of knee osteoarthritis. They found that PRP was associated with higher Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and International Knee Documentation Committee scores at 6 and 12 months compared with HA, without a difference in adverse events.
      I was extremely happy to realize that there are already 26 (!) randomized controlled trials (RCTs) comparing PRP and HA for knee osteoarthritis. But my second thought was, Wait, why do we need 26 RCTs? Why do we need a meta-analysis of so many high–level of evidence studies to prove whether an intervention works or not? Is it the more the better? Or does it mean that the results are controversial so as to need many studies to resolve the controversy?
      The easy answer is that the initial controversy surrounding PRP motivated extensive and detailed research. Also, in the medical field, we are hesitant to accept early findings. Given the fact that approximately 92.8% of published abstracts of RCTs report at least 1 significant outcome (indicated as at least P < .05), there is a notion that significant outcomes are most likely to become published, suggesting a potential publication bias.
      • Chavalarias D.
      • Wallach J.D.
      • Li A.H.
      • Ioannidis J.P.
      Evolution of reporting P values in the biomedical literature, 1990-2015.
      Therefore, additional studies repeating the significant outcomes are sometimes necessary.
      Undeniably, performing more RCTs is a step toward the right direction to improve quality in research. In the arthroscopic literature, the number of RCTs has increased significantly over the past 20 years (Fig 1). Despite a small decline in the number of RCTs involving knee arthroscopy in the past 5 years, continuous increases in the number of RCTs in shoulder arthroscopy and hip arthroscopy are seen. This suggests that orthopaedic surgeons trust their clinical decisions on higher–level of evidence studies and welcome RCTs to guide decisions on recent innovative interventions.
      Figure thumbnail gr1
      Fig 1Average number of published randomized controlled trials (RCTs) per year per 5-year period.
      However, we need to improve the quality of published RCTs. One lesson learned is that reporting of P values is inefficient and effect sizes should be included in our studies.
      • Harris J.D.
      • Brand J.C.
      • Cote M.P.
      • Dhawan A.
      Research pearls: The significance of statistics and perils of pooling. Part 3: Pearls and pitfalls of meta-analyses and systematic reviews.
      Furthermore, not all RCTs are the same in terms of quality. The quality of different studies can differ, and this can skew outcomes. Moreover, a meta-analysis is totally dependent on the quality of the included studies. Meta-analysis also has limitations, given the fact that the heterogeneity of the studies most of the time prevents pooling of the data.
      • Harris J.D.
      • Brand J.C.
      • Cote M.P.
      • Dhawan A.
      Research pearls: The significance of statistics and perils of pooling. Part 3: Pearls and pitfalls of meta-analyses and systematic reviews.
      RCTs and meta-analyses may be the best tools we have so far, but we need to acknowledge their limitations and optimize their quality toward achieving the ultimate research goal—the quest for truth.

      Supplementary Data

      References

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        Editorial Commentary: The promise of platelet-rich plasma.
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        • Yang C.C.
        • Hsu C.J.
        • Yeh M.L.
        • Renn J.H.
        Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: A randomized, double-blind, triple-parallel, placebo-controlled clinical trial.
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        Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: A meta-analysis of 26 randomized controlled trials.
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        Research pearls: The significance of statistics and perils of pooling. Part 3: Pearls and pitfalls of meta-analyses and systematic reviews.
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