The primary variable was the overall KOOS score at 24 ± 2 months after treatment. The primary analysis was performed according to a prospectively defined hierarchical scheme. First, the ACI group was tested for relevant clinical improvement from baseline. If a significant difference (P < .05) was found, then the 2 treatment groups were compared by repeated-measures ANCOVA: if the lower 95% confidence limit for the difference between the changes in the overall KOOS score was above –8.5, ACI was to be regarded as significantly noninferior to microfracture, and if this lower confidence limit was positive, then ACI was to be regarded as superior to microfracture. The study was powered for noninferiority but not for superiority. All testing other than the above was at the descriptive level or analyzed exploratively at the full level of significance (α = 5%).
The analyses described here were performed with the intention-to-treat (ITT) population, defined as comprising all patients who (1) were successfully randomized, (2) underwent either ACI on the day of implantation or microfracture on the day of arthroscopic surgery, and (3) completed the KOOS questionnaire at baseline. A supporting per-protocol (PP) analysis was performed. The overall KOOS and MOCART scores were investigated for prospectively defined subgroups for the ITT and PP populations (age as stratified variable [as defined above], diagnosis, defect localization, sex). All parameters were tabulated by treatment group, in which categorically scaled variables are presented as absolute and relative frequencies and continuously scaled variables are reported as mean ± SD. In case of relevant clinical improvement, the least squares mean (difference in the KOOS score from baseline to 24 months) was used to estimate the adjusted 1-sided 97.5% CI. The mean overall KOOS score as well as the change from baseline were illustrated using error bars by treatment.
The clinical improvement from baseline was also analyzed for secondary variables using a 1-sample t test: the Bern score, modified Lysholm score, and IKDC score (current health assessment form, subjective knee evaluation form). Furthermore, noninferiority and superiority analyses were performed for the KOOS subscales (Pain, Other Symptoms, Function in Activities of Daily Living, Function in Sports and Recreation, and Knee-related Quality of Life).
The Kruskal-Wallis test was applied for the final grade or IKDC knee examination form. The change in the grade from baseline was analyzed by the Wilcoxon signed-rank test.
The change from baseline of the overall KOOS and MOCART scores was further investigated for prospectively defined subgroups: age as a stratification variable (18-34 and 35-50 years), diagnosis (traumatic cartilage lesion, osteochondritis dissecans, osteoarthritis, avascular necrosis, and other), defect localization (femur, tibia, and patella), and sex (male and female). For the overall KOOS and MOCART scores, a Spearman correlation analysis was performed for each visit and dosage group.
The frequencies of adverse events (or serious adverse events) were tabulated by severity, relationship to the study drug, preferred term/system organ class, and outcome for each treatment group as well as overall. Statistical analyses were performed by StatConsult.
The analyses described here were performed with the intention-to-treat (ITT) population, defined as comprising all patients who (1) were successfully randomized, (2) underwent either ACI on the day of implantation or microfracture on the day of arthroscopic surgery, and (3) completed the KOOS questionnaire at baseline. A supporting per-protocol (PP) analysis was performed. The overall KOOS and MOCART scores were investigated for prospectively defined subgroups for the ITT and PP populations (age as stratified variable [as defined above], diagnosis, defect localization, sex). All parameters were tabulated by treatment group, in which categorically scaled variables are presented as absolute and relative frequencies and continuously scaled variables are reported as mean ± SD. In case of relevant clinical improvement, the least squares mean (difference in the KOOS score from baseline to 24 months) was used to estimate the adjusted 1-sided 97.5% CI. The mean overall KOOS score as well as the change from baseline were illustrated using error bars by treatment.
The clinical improvement from baseline was also analyzed for secondary variables using a 1-sample t test: the Bern score, modified Lysholm score, and IKDC score (current health assessment form, subjective knee evaluation form). Furthermore, noninferiority and superiority analyses were performed for the KOOS subscales (Pain, Other Symptoms, Function in Activities of Daily Living, Function in Sports and Recreation, and Knee-related Quality of Life).
The Kruskal-Wallis test was applied for the final grade or IKDC knee examination form. The change in the grade from baseline was analyzed by the Wilcoxon signed-rank test.
The change from baseline of the overall KOOS and MOCART scores was further investigated for prospectively defined subgroups: age as a stratification variable (18-34 and 35-50 years), diagnosis (traumatic cartilage lesion, osteochondritis dissecans, osteoarthritis, avascular necrosis, and other), defect localization (femur, tibia, and patella), and sex (male and female). For the overall KOOS and MOCART scores, a Spearman correlation analysis was performed for each visit and dosage group.
The frequencies of adverse events (or serious adverse events) were tabulated by severity, relationship to the study drug, preferred term/system organ class, and outcome for each treatment group as well as overall. Statistical analyses were performed by StatConsult.