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Multiple sclerosis functional composite: impact of reference population and interpretation of changes
B M J Uitdehaag1, H J Adèr, T J A Roosma
1Department of Neurology, VU Medical Centre, Amsterdam, The Netherlands. bmj.uitdehaag@vumc.nl
Abstract:
The Multiple sclerosis functional composite (MSFC) has been recommended as a clinical outcome measure to be used in future MS trials. A specific characteristic of the MSFC is that it is defined as a measure of impairment relative to a reference population. Using different reference populations affects actual MSFC scores. If the selection of a reference population also has an effect on sensitivity to change of the MSFC, comparison of data from clinical trials will be almost impossible when different reference populations are used We studied the effect of the selection of a reference population on the outcome of a trial by simulating 343 intervention trials and comparing results obtained by using three different reference populations: two previously published MS patient populations and a healthy population. Scores of the healthy population were collected in the first part of the study. The effects of sex, age and education level on test scores of healthy subjects were studied as well. In the healthy controls, sex, age and education level had a different impact on individual test scores of MSFC components and overall MSFC score. Our study shows that, with the use of the MSFC, the selection of different reference populations does not affect the trial statistics and significance, but it does affect comparability of results between different trials, and complicates the dinical interpretation of any observed change.
Insights
Choosing different reference populations for the Multiple Sclerosis Functional Composite (MSFC) impacts score comparability. While trial statistics remain unaffected, clinical interpretation of MSFC changes becomes more complex.
Area of Science:
- Neurology
- Clinical Trials
- Biostatistics
Background:
- The Multiple Sclerosis Functional Composite (MSFC) is a recommended clinical outcome measure for multiple sclerosis (MS) trials.
- MSFC is defined relative to a reference population, and different populations can affect scores.
Purpose of the Study:
- To investigate the effect of selecting different reference populations on MSFC outcomes in simulated clinical trials.
- To assess the impact of reference population choice on the sensitivity to change and comparability of MSFC scores.
Main Methods:
- Simulated 343 intervention trials using the MSFC.
- Compared results using three distinct reference populations: two MS patient groups and one healthy control group.
- Analyzed the influence of sex, age, and education on MSFC scores in healthy controls.
Main Results:
- The selection of reference populations did not alter trial statistics or statistical significance.
- However, different reference populations significantly affected the comparability of results between trials.
- Clinical interpretation of observed changes in MSFC scores was complicated by the choice of reference population.
Conclusions:
- While MSFC trial statistics are robust to reference population choice, inter-trial comparability is compromised.
- Standardizing reference populations is crucial for accurate clinical interpretation and comparison of MSFC data across multiple sclerosis studies.