The RA-FQ is one of only a few RA measures that can summarize the extent and complexity of the broad impact of RA symptoms on how people feel and function as a single number. We have previously shown the RA-FQ is sensitive to changes in RA symptoms and function . This is the first study to identify within-person minimal and meaningful change scores for the RA-FQ. Values derived from patients are contrasted with those of treating physicians and in relation to change in CDAI levels, the keystone of the treat-to-target approach.
Our results hold implications for researchers, methodologists, and clinicians. First, the thresholds for minimal and meaningful change varied depending on the anchor used. This in turn impacted the proportion of patients who were classified as having improved or worsened. For example, among patients, 59% classified themselves as better or much better, whereas physicians classified 44% as improved; 29% had improved at least one CDAI category. Patients were least likely to be classified as worse using a change in CDAI level (15%) and most likely to be seen as having worsened disease activity by physicians (24%), with patients landing in between (20%). Second, patients had larger thresholds for defining worsening RA whereas physicians had larger thresholds for defining improvement. In effect, physicians were looking for more resolution of symptoms/impacts than patients to be confident RA was much better (score change -7.3 vs. -6.0, respectively), but had a lower threshold to judge symptoms and RA activity as much worse (score change +5.7 vs. +8.9). Establishing the overlap among thresholds that both patients and physicians consider meaningful and worthwhile holds important implications for clinical trials, comparative effectiveness research, and optimal management of RA in care settings. Discrepancies in thresholds are also important to identify as these may contribute to patient dissatisfaction with care, treatment non-adherence, poorer disease outcomes, and increase in health care utilization and costs .
Two recent systematic reviews concluded that patient and physician perspectives regarding RA disease status often significantly differ [34, 35]; when discordance exists, up to 79% of patients generally perceived their disease as being more active than their treating physician. In part this is because pain, disability and for fatigue may feature prominently in patient assessments whereas joint counts and acute phase reactants influence physician ratings . Our data suggest assessments of change also differ where patients are more likely to perceive improvement than providers. Further, among patients the RA-FQ score change associated with meaningful improvement vs. worsening differed. Meaningful improvement for patients was associated with 6-point decrease in RA-FQ whereas meaningful worsening was associated with a 9-point increase; similar patterns were seen for minimal worsening or improvement. This suggests that either patients may be more vigilant to identify improvement, or perhaps that the threshold for disease to be perceived as worse is higher than that for improvement. At the same time, the graphical displays suggest patients appear better able to identify worsening RA at a finer level than improvement.
The pattern observed with physicians differed from patients. First, clinicians classified fewer patients as improved between visits with more classified as the same or a lot worse. In contrast to patients, on average, a numerically larger RA-FQ score change was associated with improvement versus worsening. It is interesting to note that the change in joint count (and CDAI) also was higher for patients rated as a lot worse or a lot better as compared with patient-based assessments of change. This is likely due to the fact that physicians view joint counts as a reliable indicator of inflammatory disease activity. Physicians also appeared less able to differentiate patients who were a little worse from those who had the same level of disease activity at the previous visit. Changes in RA-FQ scores in relation to changes in CDAI levels were robust and similar in the direction of worsening or improvement; scores were also stable between visits in participants whose CDAI level was unchanged. Overall, triangulating meaningful RA-FQ change scores among patients and clinicians ratings with RA disease activity classifications yielded robust results adding further evidence that disease activity as captured by the RA-FQ represents a well-defined concept that can be reliably measured. Evaluation of within-patient change establishes both the responsiveness of the RA-FQ and patient-relevant thresholds of change. The use of multiple anchors also demonstrates that benefits of a treatment as judged by physicians and using a treat-to-target approach are also perceived as clinically meaningful by patients. Conversely, both physicians and CDAI change may suggest patients are deteriorating before patients perceive their RA has changed.
While thresholds identified at the group level can inform policy and comparisons between different treatments, individual-level thresholds are necessary to inform clinical treatment decisions . Examining within-patient change visually also can offer new information. The CDF curves presenting a continuous view of the proportion of patients within each category experiencing scores changes. The curves suggest that the vast majority of patients who said they were a lot better or a lot worse were relatively distinct from those reporting they were a little better or worse or the same throughout most of the continuum of score changes. We also evaluated changes in traditional RA clinical indicators and observed that changes in mean CDAI and joint counts were largest when using the CDAI categories followed by physician change categories. This is not surprising since joint counts and physician global impression of disease activity constitute 3 of 4 components of the CDAI. When physicians rated patients as a lot better CDAI decreased by 12 points; similarly, when patients were rated as a lot worse, CDAI increased 11 points. The change in CDAI scores we observed were notably larger than MCIDs identified for CDAI (i.e., -6 points when starting with moderate disease activity, and 2 points for worsening when starting in remission/low disease activity) in one study . The change in CDAI when using patient reports of feeling a lot better was -5 points, whereas a lot worse was 7 points.
These findings add to the growing body of evidence supporting strong measurement properties (reliability, construct, content and criterion validity, responsiveness) of the RA-FQ. One reason may be that the RA-FQ was developed in accordance with best practice methods [21-23]. The conceptual framework of the RA-FQ evolved from international focus groups with RA patients  and Delphi exercise with RA patients, clinicians, researchers, and other stakeholders . Performance of the RA-FQ was examined in multiple international clinical trials and longitudinal observational studies, including CATCH [18, 25, 26]. Rasch analysis showed acceptable fit to the Rasch model, with items and people covering a broad measurement continuum with appropriate targeting of items to people, ordered thresholds, minimal differential item functioning by language, sex, or age .
The strengths of this study include the use of multiple anchors to identify meaningful change in a well characterized and diverse real-world sample of people with RA. Patients had been recently diagnosed and had started disease modifying treatments which often take several months to reach maximum therapeutic effectiveness; only 21% rated their RA as the same at both visits. We used patient and clinician impressions and CDAI, a disease activity index that combines these perspectives with joint counts is viewed as “the most specific quantitative clinical measure” in RA research and care . In this early RA cohort, many patients reported a change in their RA status at the second visit, and these reports were supported by changes in the standardized indicators of RA disease activity recommended in international clinical practice guidelines [41, 42] and used in clinical trials as part of a treat-to-target approach. We also visualized scores associated with patient change categories with CDFs, a technique recently recommended by the US Food and Drug Administration . There are limitations. We evaluated thresholds in relation to disease activity levels at the first visit for CDAI only. In patients with established RA, different thresholds may be obtained for improvement and worsening as patients gain more experience with disease flares. Meaningful change thresholds may also be influenced by the presence of painful comorbidities such as osteoarthritis.
In summary, in a large diverse cohort of real-world patients recently diagnosed with RA, we compared multiple anchors to derive meaningful and minimal changes from the perspective of patients, clinicians, and using CDAI, a disease activity index used widely as part of treat-to-target approaches. We found similar patterns overall, but some important differences in the actual value of thresholds. Further, our results suggest that the benchmarks used to classify RA treatments as a success or failure differ depending on the anchor used. These findings contribute new information that can be used to interpret RA-FQ scores in research and patient care. They also demonstrate that proportion of patients classified as “responders” to a new treatment could vary considerably depending on the anchor used to define meaningful change.