SELECT data provide the opportunity to evaluate the RD of the MSIS-29 PHYS using several anchors, including EDSS change, SF-12 PCS, EQ-5D, and EQ-5D VAS. Because these anchor instruments are most closely related to the MSIS-29 PHYS, and because most MS disease-modifying therapies slow, but do not reverse, disability progression, only the MSIS-29 PHYS RD for worsening was evaluated using SELECT data. The term ‘responder’ requires some clarification in the context of this analysis. For the study presented here, we use ‘responder’ in the psychometric sense of having a change on the outcome of interest, progression of disability; as opposed to ‘responder’ in the clinical sense of experiencing some improvement in response to a treatment. As data from all subjects in the trial who had confirmed disability progression were treated equally in the estimation of the RD, the treatment effect of DAC HYP did not impact this analysis.
Longitudinal correlation was used to confirm that each of the proposed anchors had good correlation with the MSIS-29 PHYS. Longitudinal correlations of MSIS-29 PHYS change scores with change in EDSS and change scores from the EQ-5D summary health index, EQ-5D VAS, and SF-12 PCS score were examined at each post-baseline time point. Change scores at 12, 24, and 52 weeks identified which measures change together with the MSIS-29, and a change score correlation >0.30 was preferred.25 (link)Patients were dichotomized as responders or non-responders based on the predefined RD of an anchor measure. Responders in this study referred to patients who deteriorated by at least a predefined threshold value of an anchor measure (i.e. their score worsened on the anchor measure; these patients were classified as non-responders in relation to daclizumab treatment). The primary anchor of interest was the EDSS. Sustained disability progression in SELECT could only be confirmed at a scheduled visit during which EDSS assessment was made (i.e. 12, 20, 24, 36, 48, and 52 weeks). However, measurement of MSIS-29 only occurred at pre-specified time points (12, 24, and 52 weeks) that did not always occur simultaneously with confirmation of progression using the EDSS. Therefore, assessment of changes in MSIS-29 scores from baseline used four scenarios: (1) following onset of progression; (2) at or after confirmation of progression; (3) at or before confirmation of progression; and (4) within ±4 weeks of the confirmed progression.
In this analysis, RD was calculated using mean or median change scores in MSIS-29 PHYS scores at 12, 24, and 52 weeks (for the EQ-5D summary health index, EQ-5D VAS, and SF-12 PCS anchors) among patients who met the predefined anchor-specific thresholds for responders (i.e. those with worsening health-related quality of life).
Longitudinal correlation was used to confirm that each of the proposed anchors had good correlation with the MSIS-29 PHYS. Longitudinal correlations of MSIS-29 PHYS change scores with change in EDSS and change scores from the EQ-5D summary health index, EQ-5D VAS, and SF-12 PCS score were examined at each post-baseline time point. Change scores at 12, 24, and 52 weeks identified which measures change together with the MSIS-29, and a change score correlation >0.30 was preferred.25 (link)Patients were dichotomized as responders or non-responders based on the predefined RD of an anchor measure. Responders in this study referred to patients who deteriorated by at least a predefined threshold value of an anchor measure (i.e. their score worsened on the anchor measure; these patients were classified as non-responders in relation to daclizumab treatment). The primary anchor of interest was the EDSS. Sustained disability progression in SELECT could only be confirmed at a scheduled visit during which EDSS assessment was made (i.e. 12, 20, 24, 36, 48, and 52 weeks). However, measurement of MSIS-29 only occurred at pre-specified time points (12, 24, and 52 weeks) that did not always occur simultaneously with confirmation of progression using the EDSS. Therefore, assessment of changes in MSIS-29 scores from baseline used four scenarios: (1) following onset of progression; (2) at or after confirmation of progression; (3) at or before confirmation of progression; and (4) within ±4 weeks of the confirmed progression.
In this analysis, RD was calculated using mean or median change scores in MSIS-29 PHYS scores at 12, 24, and 52 weeks (for the EQ-5D summary health index, EQ-5D VAS, and SF-12 PCS anchors) among patients who met the predefined anchor-specific thresholds for responders (i.e. those with worsening health-related quality of life).
