Action plan 2011-2013

4 - Outcome measuresBiobanks


1 -

Review and selection of existing measures

Systematically review functional rating scales for adult muscle disease and identify other generic rating scales which could also be introduced. Assess the adequacy of those currently used in order to create a shortlist of high quality functional rating scales applicable to adult muscle disease.

Michael Rose

1.1 -

Assisting in the choice of outcome measures for clinical trials in facioscapulohumeral muscular dystrophy (FSHD)

Conduct a survey and assess the quality of the outcome measures currently being used in FSHD. Take a Rasch analysis of manual muscle testing data from previous FSHD trials. Publish the results.

Michael Rose

1.2 -

Assisting in the choice of outcome measures for clinical trials in inclusion body myositis (IBM)

Conduct a survey and assess quality of outcome measures used in Inclusion Body Myositis. Collect data on functional rating scales and manual muscle testing and conduct Rasch analysis. Publish the results.

Michael Rose

2 -

Development of upper limb module for non-ambulant SMA

Undertake validation studies and cross correlate with existing measures, the recently developed upper-limb module for non-ambulant SMA patients. Conduct Rasch analysis on upper limb module data

3 -

Assessment of non-ambulant DMD
Use clinical studies to identify the most suitable measures or combination of measures for proper validation studies which can then be used to establish natural history data for non-ambulant DMD patients

4 -

New methods of assessing strength and function of the upper limb

Use dynamometers designed to record grip (MyoGrip), pinch (MyoPinch), and wrist (MyoWrist) and MRI of the upper limb in an observational study conducted in London, Newcastle and Paris for patients treatable by exon skipping therapy.

5 -

New methods of assessing daily activity in non-ambulant patients

Assess patients' daily activity and motivation throughout a clinical trial via a wrist monitor.

6 -

Development of new methods of assessment for young infants with DMD

Support for harmonization of protocols that could be used to assess the early phases of motor and general aspects of development in infants affected by DMD.

7 -

Promoting natural history data collection in SMA and DMD

Coordinate natural history data collection and establish any possible effect of regional differences, and different standards of care across countries. Implement standardised training and improve inter-observer reliability across centres.

Eugenio Mercuri

8 -

Analysis techniques to prepare motor performance scales for clinical trials

Develop disease-appropriate scales to measure effective changes in various NMDs based on an established working model taken from DMD.

Anna Mayhew
Eugenio Mercuri

9 -

Further development of MRI and MRS as a quantitative outcome measure

Further develop and refine quantitative NMR protocols that may be reliably applied in a multicentric setting to enable these techniques to be used as non-invasive outcome measures in clinical trials and natural history studies.

10 -

Identification of the most appropriate biochemical outcome measures to use in DMD clinical trials

Further standardize methods for quantifying dystrophin concentration in skeletal muscle biopsies. Develop and disseminate SOPs to quantify dystrophin levels in DMD/BMD muscle biopsies.

Eric Hoffman
(Washington DC)

11 -

Gait characterization by accelerometry

Development of systematic measurement of gait using accelerometry to accompany the qualitative data already collected.

12 -

Refining methods

Further refine evaluation of the strength of flexion and extension around the ankle and knee joints with specific dynamometry for the ankle or with an isokinetic dynamometer for the knee. Extend these methods through various NMDs.

Achievements 2011-2013

Refining existing measures /natural history data

In the last few years there has been a considerable effort to collect natural history data using existing measures, such as the 6MWT that is currently been chosen as the primary outcome measure in all the ongoing clinical trials in ambulant DMD boys and the North Star Ambulatory Assessment . These studies have allowed following possible changes over time and to help to power the study and establish how a treatment would be different from what is expected.

Identification of new clinical measures

a) Development of a revised upper limb module for SMA

As part of a collaborative project between TREAT NMD and ICC a module specifically designed for assessing upper limbs in non-ambulant patients with SMA has been developed as a complement to the existing scales. (Mazzone et al, 2010)  The module has been published and has been included in the protocol of national and international networks and in the forthcoming clinical trials on type II and III SMA.

b) Assessment of upper limbs in DMD

Between 2011 ans 2013 a collaborative international group including DMD boys and their families developed the Performance of Upper Limb (PUL) assessment, a tool specifically designed for assessing upper limb function non-ambulant DMD boys that can already be used in ambulant DMD boys. The PUL provides a tool that can be used across spectrum of functional abilities. A recent study has shown that the scale has excellent interobserver and intraobserver reliability and is suitable for a multicentre setting and can be easily performed in DMD boys and adults from the age of 5 years with no floor effect even in the oldest (>25years) DMD patients.

c) Development of new methods of assessment for young infants with DMD

It has become increasingly accepted that should the novel therapeutic interventions be effective, it would be important to administer them as early as possible in very young DMD children. Two international networks have reported the results of two large studies using neurodevelopmental scales in young DMD boys. Both studies show that a proportion of DMD boys have delayed motor milestones that are more marked in the gross locomotor and language subscales and are partly dependent on the type and site of mutations in the dystrophin gene.

Identification of non-clinical measures

As part of the activities of TREAT-NMD, a number of workshops have been organised in order to explore the role of muscle MRI as an outcome measure. Work is in progress to establish the possibility to use muscle MRI in a multicentre setting and to collect longitudinal data in order to detect possible changes over time in untreated and treated patients.

12 Apr 2017