Evaluation of the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite as clinical endpoints in multiple sclerosis clinical trials: quantitative meta-analyses

Abstract

Objectives: This study compared the sensitivity of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) as clinical endpoints in multiple sclerosis (MS) clinical trials.

Methods: Medline (1946 through 12 September 2014) and Embase (1974 through 12 September 2014) databases searches were conducted using keywords and Medical Subject Heading (MeSH) terms related to MS, EDSS, and MSFC. Only studies that used the EDSS and MSFC as endpoints were assessed. All statistical analyses were conducted using comprehensive meta-analysis (CMA). The percentages of the overall changes in EDSS and MSFC were compared. The relative risks were calculated in randomized clinical trials (RCTs).

Results: A total of 123 studies were identified. There were nine studies (6 case series and 3 RCTs) included in the analysis. In the case series, the EDSS change rate in MS patients was 33.5% (95% CI: 12.9–63.2%) and the MSFC change rate was 30.3% (95% CI: 9.2–65.2%). In RCTs, patients who take the drug would be 22.9 times as likely as patients who did not take the drug to experience a change in the EDSS scale (RR = 22.9, 95% CI = 0.996–1.517, p = 0.055). Patients who take the drug would be 48.9 times as likely as patients who did not take the drug to experience a change in the MSFC scale (RR = 48.9, 95% CI = CI = 0.916–2.419, p = 0.108).

Limitations: This study focused only on MS patient improvement (positive changes) on the EDSS and MSFC. More studies are needed to include patient deterioration (negative changes) on EDSS and MSFC.

Conclusions: There is controversy about the sensitivity of the EDSS and MSFC in detecting the progression of MS disease. The EDSS and MSFC are effective tools to assess the clinical severity and progression of MS disease. MSFC is more sensitive than EDSS in detecting the progression of MS disease.

Keywords:

• Analysis
• Clinical endpoints
• Clinical trials
• EDSS
• Expanded Disability Status Scale
• Meta-analysis
• MSFC
• Multiple sclerosis
• Multiple Sclerosis Functional Composite
• Quantitative

Transparency

Declaration of funding

This study was not funded.

Declaration of financial/other relationships

A.B.S., E.S.-V., R.R.-M., and F.T. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank the reviewers and the editor for their helpful comments and suggestions.

Previous presentation

The abstract was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 21st Annual International Meeting, 21–25 May 2016, Washington, DC, USA.