Longitudinal data analysis: an application to construction of a natural history profile of Duchenne muscular dystrophy

Abstract

A 30-month prospective study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was carried out to construct profiles of the natural history of the disease. Assessments which included measures of voluntary muscle strength and function were done at 3 monthly intervals except for the first and second which were separated by 1 month. Recently developed statistical methods for analysis of longitudinal data with repeated observations on the same individual were used avoiding the problem of induced serial correlations. This allowed for the construction of both reference and prediction profiles for the variables %MRC, motor ability, walking time for 10 m and the sum of myometry of seven muscle groups.

Introduction

Duchenne muscular dystrophy (DMD) [1] is characterized by progressive and profound loss of muscle strength which in a given child is said to follow a linear decline in relation to age [2]. The complex inter-relationship between muscle strength, range of motion and physical function means that assessment of outcome of therapeutic intervention requires a holistic approach [3].

From the early 1980s protocols for assessment comprising measures of muscle strength, range of motion and functional task have been developed to provide a quantitative description of the natural history of the disease [4], [5], [6]. These protocols have been used in studies to evaluate intervention and strategies for supportive care and in some cases allowed the prediction of critical periods to be identified [7], [8], [9].

Since publication of the landmark paper of Hoffman et al. [10] in 1987 identifying the defective gene that encodes the protein ‘dystrophin’, and the potential for the development of biotechnologically based curative strategies that it implied, there has been an increased focus on the methodological aspects of these protocols. The renewed interest in the role of steroids as a therapeutic agent has added further impetus to this objective [11]. Inherent problems of the protocols are the data types they produce, mainly ordinal and categorical. Therefore emphasis has been placed on developing quantitative methods for evaluating voluntary muscle strength to replace or augment the traditional manual muscle test [12]. Less emphasis has been placed on adopting the use of recently developed methods of statistical analysis that address fully the longitudinal aspects of data, where there are repeated observations on the same subject [13], [14].

The purpose of this study was to establish a profile of the physical characteristics of Scandinavian boys with DMD for use in future intervention studies and to explore the application of statistical methods for analysis of longitudinal data.