Table 4.
Clinician-reported Measures as Potential Indicators of Benefit in Clinical Trials
| Reference | Clinician - Reported Measures | Gold Standard | Study Design Comments | Results |
|---|---|---|---|---|
| Mitchell [66] | Full 2005 NIH spectrum of measures – by transplant clinicians | Subspecialty experts | N=25 children and adults with chronic GVHD (4 consecutive pilot trials) | Supports feasibility of the NIH measures. Inter-rater agreement for skin and oral was satisfactory except for moveable sclerosis and moderate to substantial for functional capacity, GI and global rating measures. |
| Jacobsohn [67] | NIH skin score | Clinician and patient perception of skin improvement or worsening, Overall survival | N=458 prospective multicenter longitudinal observational cohort study | The 0-3 NIH composite skin score correlated with both clinician and patient perception of improvement or worsening. Worsening skin score at 6 months was associated with worse survival. |
| Inamoto [37] | NIH eye score | Clinician and patient perception of eye symptom change | N=387 prospective multicenter longitudinal observational cohort study | Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients. Schirmer's test did not correlate. |
| Treister [39] | NIH oral score and modified OMRS (0-15) | Patient and clinician-reported change in oral chronic GVHD | N=458 prospective multicenter longitudinal observational cohort study | The clinician-reported measurement changes most predictive of perceived change by clinicians and patients were erythema, extent of lichenoid changes, and NIH severity score. |
| Palmer [68] | NIH lung score symptom scale | Non-relapse mortality (NRM), Overall survival (OS), Patient-reported lung symptoms | N=496 prospective multicenter longitudinal observational cohort study | The NIH symptom-based lung score was associated with NRM, OS, patient-reported symptoms, and functional status. Worsening of NIH symptom-based lung score over time was associated with higher NRM and lower survival. |
| Inamoto [69] | NIH joint-fascia score, Hopkins scale, Photographic (P-ROM) | Clinician and patient perception of change | N=567 prospective multicenter longitudinal observational cohort study | Changes in the NIH scale correlated with both clinician- and patient-perceived improvement. Changes in all 3 scales correlated with clinician- and patient-perceived worsening, but the P-ROM scale was the most sensitive. |
| Bassim [70] | NIH modified OMRS (0-15) | Established measures of oral pain, oral function, oral related QOL, nutrition and laboratory parameters. | N=198 prospective cross-sectional observational cohort study (moderate-to-severe chronic GVHD) | This study supports the use of the OMRS and its components (erythema, lichenoid and ulcerations) to measure clinician-reported severity of oral chronic GVHD. No associations were found between mucoceles and any indicator evaluated. |
| Curtis [71] | 18 clinician-reported (‘Form A’) measures | Concurrent parameters: NIH global score, chronic GVHD activity, Lee symptom score and SF36 PCS | N=193 prospective cross-sectional observational cohort study (moderate-to-severe chronic GVHD) | 4-point and 11-point clinician reported global symptom severity scores are associated with the majority of concurrent outcomes. Skin erythema is a potentially reversible sign of chronic GVHD that is associated with survival. |
| Yanik [72] | Response was defined as 10% FEV1 or FVC improvement | 5-year survival | N=34 patients with subacute pulmonary dysfunction (25 obstructive) received etanercept therapy | 5-year survival 90% (95% CI, 73%-100%) for 10 patients who responded to therapy, compared with 55% (95% CI, 37%-83%) for the 21 patients who did not meet response criteria (P = 0.07) |
| Olivieri [73] | NIH criteria, NIH organ score, Couriel criteria | Overall survival | N=40, phase 2 prospective study of imatinib for steroid-refractory chronic GVHD | The 3-year OS was 94% for patients responding at 6 months and 58% for non-responders according to NIH response criteria (P = 0.007) |
| BMT CTN 0801 (unpublished) | NIH criteria | Clinician assessed overall CR+PR | N=151, randomized phase 2 multicenter trial | AUC for organs (lichenoid mouth, joint score) plus clinician assessed 0-10 global rating scale = 0.79 |