To our knowledge, this is the first within‐trial comparison of the improvement of knee and hip osteoarthritis during treatment with naproxen. As the mean of the baseline scores were lower for the knee group than for the hip group, the greater improvement found in the knee patients during treatment with naproxen is unlikely to be caused by a regression to the mean. Is this a true difference in naproxen efficacy between hip and knee, or does the WOMAC questionnaire have a higher responsiveness for knee osteoarthritis compared with hip osteoarthritis? The fact that a higher proportion of both patients and investigators rated the overall treatment as good or very good for the knee than for the hip supports the first explanation. The subscales of SF‐36 most relevant to musculoskeletal problems and most comparable to the content of WOMAC are physical functioning, role–physical, and bodily pain. Seeing the same pattern of improvement in two of these three subscales as in WOMAC implies the difference between knee and hip being a treatment effect and not a psychometric phenomenon with regard to the WOMAC instrument.
An effect size of 0.5, which was found for the hip in the present study, is considered a moderate change, while an effect size of 0.8 as found for the knee is considered large.11,12,13
However, the placebo response was not subtracted from these effect size values.
The mean knee–hip differences in the WOMAC subscales pain (4.7 mm), stiffness (6.6 mm), and physical functioning (4.8 mm) were less than the proposed minimal perceptible clinical improvement (MPCI) of 10 mm for WOMAC.14
However, in that study the baseline values were considerably higher than in the present study, at 65.0 mm VAS v
44.2 mm for pain (knee, naproxen; table 2), 65.9 v
48.9 mm for stiffness, and 63.9 v
47.1 mm for physical functioning, and it has been shown that higher baseline scores require larger raw changes to represent a clinically important difference.15
Further, to be included in that study, the patients had to have at least a 15 mm increase in the pain walking score after the washout, and a washout score of
Neither of this was required in the present study.
The cited studies deal with the concept of how a patient perceives a change during the course of a treatment.14,15
This might not be the same as a perceived difference between
treatments. Therefore, it is difficult on the basis of those studies to draw any firm conclusions as to whether the difference between hip and knee in the present study is clinically relevant or not, but using the 11‐point numerical rating scale, it was concluded that a pain reduction of approximately 30% represents a clinically important difference.15
In the present study the reduction in WOMAC knee pain for naproxen was 38% (16.6/44.2) and in WOMAC hip pain 26% (12.3/47.3). Using the suggested cut off point of 30% would imply that the reduction in pain was clinically important for the knee but not for the hip.
The results of the present study strongly influence trial power and number of patients needed per treatment arm in clinical trials. Based on the effect sizes for pain, 108 subjects with hip osteoarthritis compared with only 54 subjects with knee osteoarthritis would need to be included in a clinical trial to determine a significant difference against baseline with 80% power. The findings support the recommendation that trials concerning efficacy of treatment for osteoarthritis of the knee and hip should be stratified with respect to target joint or evaluated separately,7
and they warrant further investigation concerning the clinical relevance for the individual patient.