Pain as a PRO Deserves a Second Look

Doctors may want to reconsider how patient reported outcomes are measured, researchers suggest in a recent Arthritis Care and Research article.

German researchers examined the relationship between rheumatoid arthritis pain relief and patient reported outcomes improvement.

The authors sought to determine if patients reported outcomes (PROs) related to pain, fatigue and function would correlate well with objective measures like the Disease Activity Score in 28 joints score for rheumatoid arthritis.

In a previous article, the authors described a novel statistical measure to determine the critical difference (d_crit) looking at the minimum change in the patient’s perceived change in disease activity compared with the Disease Activity Score in 28 joints (DAS28). This measure is based on the idea that significant patient responses should be reflected in objective measurements. Specifically the critical difference is used in this study to quantify the magnitude of clinical change needed to elicit a patient response indicating improvement of pain, fatigue and function.

The study utilized a prospective cohort design enlisting patients from two German cohorts from multiple centers with active rheumatoid arthritis being started on adalimumab for treatment. An analysis of variance model was employed to determine critical differences for the minimum changes leading to significant patient responses in patients on stable therapy, the discovery cohort. The authors then examined patient reported outcomes in the treatment cohort consisting of rheumatoid arthritis patients starting adalimumab in a non-interventional study. The discovery cohort consisted of 700 participants on stable therapy for rheumatoid arthritis between months 12 and 24 of adalimumab therapy.  The treatment cohort enrolled 2,788 patients yet to start adalimumab.

Reported outcomes related the determined critical difference exceeding that expected due to random variation to the disease activity score in 28 joints, with significant patient reported outcomes being compared between the discovery cohort and treatment arm.

Results suggest that patients that report high disease activity even though objective measures are favorable, would benefit from better pain management strategies. Patient reported outcomes were shown to be reliable and reproducible indicators of disease status with only modestly lower reliability coefficients than the disease activity score.

A large change in a patient’s status was required to obtain a significant patient response above normal variation. Changes of 20-40% on scales for pain, fatigue and function were required in order for patient reports to be affected.

The authors point out that the determination of critical difference differs from the reliability change index and the smallest detectible difference methods of determining change above normal variation in that reliability is examined over one year rather than hours or days which more closely mirrors actual patient care.

When correlation between patient reported outcomes and the disease activity score in 28 joints is examined, a strong association was not found. Pain was the highest associated patient reported outcome with patient’s global assessment even when objective measures were positive. Fatigue and function reports were far less influential predictors of clinical change.

Three groups were identified in the treatment cohort:

• Patients who were doing well from reporting and objective measures.
• Patients who reported improvement but had no response on their disease activity score.
• Responders on the disease activity score without reported improvement.

The authors suggest that that the first group requires no change in treatment while treatment should be changed in the second group. Further analysis of the third group, for pain in particular, is suggested.

For more information, see the related slidesehow:  "Lessons Learned: Reconsidering Patient Reported Outcomes"

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References:

Hans-Peter Tony, et al.

"Association of Improvement in Pain With Therapeutic Response as Determined by Individual Improvement Criteria in Patients With Rheumatoid Arthritis,"

Arthritis Care and Research

. Oct. 1, 2016. DOI: 10.1002/acr.22884