Original ArticleBLISS index for analyzing knee osteoarthritis trials data
Introduction
The response to therapeutic interventions can be measured either by the degree of improvement (i.e., response) in health status produced, or by the level of health achieved (i.e., state attainment). Although different approaches to response status assignment have been used in osteoarthritis (OA) clinical studies [1], [2], [3], [4], [5], the former approach is best exemplified by the Osteoarthritis Research Society International (OARSI) responder criteria [6] and the more recent Outcome Measures in Rheumatology Clinical Trials (OMERACT)–OARSI responder criteria [7], which categorize patients as responders based on a combination of absolute and percentage change on one or more OARSI core set clinical measures of pain, physical function, and patient global assessment [8], [9].
The alternative approach is evolutionary and based on state-attainment criteria, which categorize patients not on the basis of change, but based on the level of health achieved. There is currently no international consensus on state-attainment criteria. Methods for developing such criteria have been proposed in rheumatoid arthritis [10], [11], [12], and consideration given to a similar development in OA under a number of different acronyms (Maximal Clinically Acceptable Status [MCAS] [13], Patient Acceptable Symptom State [PASS]) [14]). The MCAS and PASS concepts attempt to provide a threshold value that represents in the perception of a group of patients, the cutpoint between health states that they regard as more acceptable.
We have performed secondary analyses of a previously published clinical study [1], [15], to investigate the capacity of state-attainment criteria to detect between-treatment differences, below the level of MCAS and PASS, in a randomized clinical trial. We report our observations on aspects of the velocity, magnitude, and durability of low pain intensity state attainment, which might form the basis of a Low Intensity Symptom State-attainment Index for clinical research and clinical practice applications. We propose the acronym BLISS (Bellamy et al. Low Intensity Symptom State-attainment) Index, to describe this group of attainment criteria which follow the general paradigm that when treating patients with OA “better is good, but good is best” with respect to goal attainment.
Section snippets
Design
The analyses reported here were performed using the data collected in a health outcomes trial evaluating viscosupplementation with hylan G-F 20 when added to an appropriate care treatment paradigm for patients with symptomatic knee OA (mild to moderate severity). The detailed design of the trial is published elsewhere [1]. The trial was a multicentre, one year, randomized controlled open-label study. Patients were randomized (1:1 ratio) to either “appropriate care with hylan G-F 20” (AC+H) or
Demographic characteristics
A total of 255 patients were enrolled into the study; 127 patients were randomized to AC+H and 128 to AC. Demographic characteristics were similar between treatment groups (Table 1).
The mean duration of OA in the study knee was 9.0 years for the AC+H group and 9.9 years for the AC group (Table 2). Although grade IV OA in the study knee as determined at the sites by the investigators at enrollment was an exclusion criterion, 20% of the patients in the AC+H group and 33% of the patients in the AC
Discussion
There is currently no exact multinational definition of what constitutes an acceptable level of symptom intensity to patients with OA, or of the symptom status of normative populations. The definitions of MCAS and PASS are set at, or about, the level of symptom intensity for study inclusion and are therefore not sufficient, for adjudicating symptom state attainment in a clinical trial. It is also recognized that complete amelioration of pain is not always achievable in knee OA. It is pertinent,
Acknowledgments
The authors thank Genzyme Corporation for study funding. The study agreement with Genzyme Corporation gave the investigators independence to publish regardless of the results. The authors would like to thank the clinical investigators who enrolled patients and are listed in the main manuscripts [1], [15]. This study was funded by Genzyme Corporation.
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