Wide Variation in Methodology in Level I and II Studies on Cartilage Repair: A Systematic Review of Available Clinical Trials Comparing Patient Demographics, Treatment Means, and Outcomes Reporting

Abstract

Background The management of complex cartilage pathology in young, otherwise healthy patients can be difficult. Purpose To determine the nature of the design, endpoints chosen, and rate at which the endpoints were met in published studies and ongoing clinical trials that investigate cartilage repair and restoration procedures. Study Design Systematic review. Methods A systematic review of the publicly available level I/II literature and of the publicly listed clinical trials regarding cartilage repair and restoration procedures for the knee was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Seventeen published studies and 52 clinical trials were included. Within the 17 published studies, the most common procedure studied was microfracture (MFX) + augmentation ( N = 5; 29.4%) and the most common comparison/control group was MFX ( N = 10; 58.8%). In total, 13 different cartilage procedure groups were evaluated. For published studies, the most common patient-reported outcome (PRO) measures assessed is the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale–Pain (VAS) ( N = 10 studies, 58.8% each, respectively). Overall, there are 10 different PROs used among the included studies. Ten studies demonstrate superiority, 5 demonstrate noninferiority, and 2 demonstrate inferiority to the comparison or control groups. For the clinical trials included, the most common procedure studied is MFX + augmentation ( N = 16; 30.8%). The most common PRO assessed is KOOS ( N = 36 trials; 69.2%), and overall there are 24 different PROs used among the included studies. Conclusions Recently published studies and clinical trials evaluate a variety of cartilage repair and restoration strategies for the knee, most commonly MFX + augmentation, at various time points of outcome evaluation, with KOOS and VAS scores being used most commonly. MFX remains the most common comparison group for these therapeutic investigations. Most studies demonstrate superiority versus comparison or control groups. Understanding the nature of published and ongoing clinical trials will be helpful in the investigation of emerging technologies required to navigate the regulatory process while studying a relatively narrow population of patients.

Systematic Review and Meta-Analysis of the Clinical Evidence on the Use of Autologous Matrix-Induced Chondrogenesis in the Knee

“…35 The demographic characteristics of the patients included in the meta-analysis, the studies' duration, and the outcome reporting are almost identical to the recently published clinical trials review comparing level I and II studies, patient demographics, outcomes reporting, and methodology in cartilage repair. 36 These authors reported the following:…”

“…• • A majority of VAS, IKDC, and Lysholm scoring as outcomes, MRI being performed in only 53% of the studies as a primary or secondary endpoint • • A mean follow-up of 3.77 ± 3.88 years This comparison allows to consider that the patient demographics among the 12 reported studies, the outcome measures used, and the follow-up duration are aligned with the most recent characteristics of clinical trials on cartilage repair in the knee. 36 This comparison with published outcomes used for the evaluation of knee chondral defects repair was also the background for the selection of the most frequently used outcomes to be used for the meta-analysis.…”

Enhanced microfracture using acellular scaffolds improves results after treatment of symptomatic focal grade III/IV knee cartilage lesions but current clinical evidence does not allow unequivocal recommendation

“…Secondgeneration techniques may overcome clinical limitations of MFX, leading to regeneration of hyaline-like repair tissue with potential to improve long-term clinical outcomes. A systematic review on high-level evidence (level I and II studies) related to ongoing clinical trials of cartilage repair and restoration procedures for the knee highlighted that there is significant variation in methodology and study designs which hinders drawing of concrete conclusions [38].…”