Contributions
Abstract: P382
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Clinical assessment tools
The purpose of this study was to estimate the extent to which Expanded Disability Status Scale (EDSS) data from different MS clinics are inferentially equivalent and thus, can be pooled for research purposes. Data harmonization using Rasch analysis was performed on EDSS data from 12 clinics, each from a different country, obtained from the MSBase registry. Patients' most recent visit was used to estimate whether clinics scored the Functional System Scores (FSSs) items without bias such that the FSSs/EDSS are inferentially equivalent (have the same meaning). Bias factors are sex, onset age, age, disease duration, and country. A logit difference ≥0.5 and p< 0.05 on the Mantel-Haenzel test indicates item bias (differential item functioning (DIF)) between factors. The Expected Test Score Standardized Difference (ETSSD) estimates total score bias (differential test functioning (DTF)) among the clinics and is interpreted the same as Cohen's d effect size.
Total N=14536 (women = 69%, onset age = 31 years, age = 44 years, disease duration = 13 years). Clinic samples ranged from 236-3392. MS types were relapsing MS =78%, secondary progressive MS=12%, primary progressive MS=7%, and unknown=3%. Median EDSS was 2.5. All items fit the Rasch model after rescoring, with INFIT/OUTFIT mean square fit statistics within the acceptable range (0.5≥ and ≤1.7). Principal component analysis of residuals explaining 55% of variance, but no second component was identified and low response dependency (r< ~0.3) supporting unidimensionality of the FSS items.
FSS items were well distributed along a measurement continuum but were not a good match to the sample; the sample had low disability but there were few items in that measurement range, resulting in an 8.5% ceiling effect. Reliability (α=0.82) was good. All items had DIF (item bias) by clinic. Sensory FSS had the most DIF (7/12 clinics). Vision FSS had the greatest DIF range (> 2 logits). Despite item bias, there was minimal total score bias suggesting biases cancelled. The Rasch transformed FSS total score (EDSSrasch) correlated highly with the EDSS (0.92). Correlation plot shows EDSSrasch was more sensitive to change at the low disability end of the measure.
EDSSrasch, a modification of the familiar EDSS based on a strong statistical model, can better detect change at lower disability. Data harmonization results show that the EDSSrasch from different clinics are inferentially equivalent and can be pooled.
Disclosure: Stanley Hum: has received honoraria from Novartis.
Robert Brown received consultant fees from NeuroRx Research and Biogen.
Yves Lapierre has received support as a consultant and membership on advisory councils from Biogen, Teva, Novartis, and Sanofi-Genzyme.
Lesley Fellows: nothing to disclose.
Nancy Mayo: nothing to disclose.
Eva Kubala Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education [project Progres Q27/LF1].
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague [PRVOUK-P26/LF1/4], Czech Minsitry of Education [PROGRES Q27/LF1] and Czech Ministry of Health [NT13237-4/2012].
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Roche, Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi , Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Marco Onofrj: nothing to disclose.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research.
Raed Alroughani: nothing to disclose.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Helmut Butzkueven has received compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.
Vincent Van Pesch has received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva, Roche and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma, Roche and Bayer Schering.
Thor Petersen received funding or speaker honoraria from Biogen, Merck , Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Bhim Singhal: nothing to disclose.
Hemali Advani: nothing to disclose.
Juan Ignacio Rojas: nothing to disclose.
Edgardo Cristiano received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck, Roche and Novartis.
Abstract: P382
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Clinical assessment tools
The purpose of this study was to estimate the extent to which Expanded Disability Status Scale (EDSS) data from different MS clinics are inferentially equivalent and thus, can be pooled for research purposes. Data harmonization using Rasch analysis was performed on EDSS data from 12 clinics, each from a different country, obtained from the MSBase registry. Patients' most recent visit was used to estimate whether clinics scored the Functional System Scores (FSSs) items without bias such that the FSSs/EDSS are inferentially equivalent (have the same meaning). Bias factors are sex, onset age, age, disease duration, and country. A logit difference ≥0.5 and p< 0.05 on the Mantel-Haenzel test indicates item bias (differential item functioning (DIF)) between factors. The Expected Test Score Standardized Difference (ETSSD) estimates total score bias (differential test functioning (DTF)) among the clinics and is interpreted the same as Cohen's d effect size.
Total N=14536 (women = 69%, onset age = 31 years, age = 44 years, disease duration = 13 years). Clinic samples ranged from 236-3392. MS types were relapsing MS =78%, secondary progressive MS=12%, primary progressive MS=7%, and unknown=3%. Median EDSS was 2.5. All items fit the Rasch model after rescoring, with INFIT/OUTFIT mean square fit statistics within the acceptable range (0.5≥ and ≤1.7). Principal component analysis of residuals explaining 55% of variance, but no second component was identified and low response dependency (r< ~0.3) supporting unidimensionality of the FSS items.
FSS items were well distributed along a measurement continuum but were not a good match to the sample; the sample had low disability but there were few items in that measurement range, resulting in an 8.5% ceiling effect. Reliability (α=0.82) was good. All items had DIF (item bias) by clinic. Sensory FSS had the most DIF (7/12 clinics). Vision FSS had the greatest DIF range (> 2 logits). Despite item bias, there was minimal total score bias suggesting biases cancelled. The Rasch transformed FSS total score (EDSSrasch) correlated highly with the EDSS (0.92). Correlation plot shows EDSSrasch was more sensitive to change at the low disability end of the measure.
EDSSrasch, a modification of the familiar EDSS based on a strong statistical model, can better detect change at lower disability. Data harmonization results show that the EDSSrasch from different clinics are inferentially equivalent and can be pooled.
Disclosure: Stanley Hum: has received honoraria from Novartis.
Robert Brown received consultant fees from NeuroRx Research and Biogen.
Yves Lapierre has received support as a consultant and membership on advisory councils from Biogen, Teva, Novartis, and Sanofi-Genzyme.
Lesley Fellows: nothing to disclose.
Nancy Mayo: nothing to disclose.
Eva Kubala Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education [project Progres Q27/LF1].
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague [PRVOUK-P26/LF1/4], Czech Minsitry of Education [PROGRES Q27/LF1] and Czech Ministry of Health [NT13237-4/2012].
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Roche, Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi , Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Marco Onofrj: nothing to disclose.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research.
Raed Alroughani: nothing to disclose.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Helmut Butzkueven has received compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.
Vincent Van Pesch has received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva, Roche and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma, Roche and Bayer Schering.
Thor Petersen received funding or speaker honoraria from Biogen, Merck , Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Bhim Singhal: nothing to disclose.
Hemali Advani: nothing to disclose.
Juan Ignacio Rojas: nothing to disclose.
Edgardo Cristiano received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck, Roche and Novartis.