TY - JOUR
T1 - Validation of the Radiographic Global Impression of Change (RGI-C) score to assess healing of rickets in pediatric X-linked hypophosphatemia (XLH)
AU - Lim, Ruth
AU - Shailam, Randheer
AU - Hulett, Rebecca
AU - Skrinar, Alison
AU - Nixon, Annabel
AU - Williams, Angela
AU - Nixon, Mark
AU - Thacher, Tom D.
N1 - Funding Information:
The authors would like to thank Jennifer Liu PhD for support conducting the statistical analyses and Helen Barham PhD (thetextdoctor) for writing and editing support. This study was funded by Ultragenyx Pharmaceutical Inc. and Kyowa Kirin International plc.
Publisher Copyright:
© 2021 The Authors
PY - 2021/7
Y1 - 2021/7
N2 - Background: Rickets is a primary manifestation of pediatric X-linked hypophosphatemia (XLH) – a rare progressive hereditary phosphate-wasting disease. Severity is quantified from radiographs using the Rickets Severity Scale (RSS). The Radiographic Global Impression of Change (RGI-C) is a complementary assessment in which a change score is assigned based on differences in the appearance of rickets on pairs of radiographs compared side by side. Objective: The current study evaluated the reliability, validity, and sensitivity to change of the RGI-C specifically in pediatric XLH. Methods: The reliability, validity, and sensitivity to change of the RGI-C were evaluated using data from two studies in pediatric XLH (113 children aged 1–12 years) in which burosumab treatment significantly improved rickets severity. Intra-rater and inter-rater reliability were assessed by three pediatric radiologists. Results: Intra-rater reliability for RGI-C global score was >90% for agreement within 1 point, with weighted kappa values >0.5, indicating moderate to almost perfect agreement. Inter-rater reliability was also >90% (0.47–0.52 for all reader pairs; moderate agreement). The RGI-C global score showed significant relationships with changes from baseline to week 64 in serum phosphorus (r = −0.397), alkaline phosphatase (−0.611), total RSS (−0.672), standing height (0.268), and patient-reported global functioning (0.306) and comfort/pain functioning (0.409). Based on standardized response means, RGI-C global scores were sensitive to change in RSS, differentiating between those considered improved and greatly improved. Results for validity and sensitivity to change were similar for the RGI-C wrist, knee, and standing long leg scores. Conclusion: The RGI-C is a reliable, valid, and sensitive measure in pediatric XLH, and complementary to the RSS.
AB - Background: Rickets is a primary manifestation of pediatric X-linked hypophosphatemia (XLH) – a rare progressive hereditary phosphate-wasting disease. Severity is quantified from radiographs using the Rickets Severity Scale (RSS). The Radiographic Global Impression of Change (RGI-C) is a complementary assessment in which a change score is assigned based on differences in the appearance of rickets on pairs of radiographs compared side by side. Objective: The current study evaluated the reliability, validity, and sensitivity to change of the RGI-C specifically in pediatric XLH. Methods: The reliability, validity, and sensitivity to change of the RGI-C were evaluated using data from two studies in pediatric XLH (113 children aged 1–12 years) in which burosumab treatment significantly improved rickets severity. Intra-rater and inter-rater reliability were assessed by three pediatric radiologists. Results: Intra-rater reliability for RGI-C global score was >90% for agreement within 1 point, with weighted kappa values >0.5, indicating moderate to almost perfect agreement. Inter-rater reliability was also >90% (0.47–0.52 for all reader pairs; moderate agreement). The RGI-C global score showed significant relationships with changes from baseline to week 64 in serum phosphorus (r = −0.397), alkaline phosphatase (−0.611), total RSS (−0.672), standing height (0.268), and patient-reported global functioning (0.306) and comfort/pain functioning (0.409). Based on standardized response means, RGI-C global scores were sensitive to change in RSS, differentiating between those considered improved and greatly improved. Results for validity and sensitivity to change were similar for the RGI-C wrist, knee, and standing long leg scores. Conclusion: The RGI-C is a reliable, valid, and sensitive measure in pediatric XLH, and complementary to the RSS.
KW - Clinical outcome assessment (COA)
KW - Metabolic bone disease
KW - Pediatric radiology
KW - Reliability
KW - Sensitivity to change
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=85104645263&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2021.115964
DO - 10.1016/j.bone.2021.115964
M3 - Article
C2 - 33878504
AN - SCOPUS:85104645263
SN - 8756-3282
VL - 148
JO - Bone
JF - Bone
M1 - 115964
ER -