Physical Therapist test for muscular dystrophy in pediatrics patients

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RESEARCH ARTICLE

Development of a Functional Assessment Scale for Ambulatory Boys with Duchenne Muscular Dystrophy Elaine Scott1*, Michelle Eagle2, Anna Mayhew2, Jenny Freeman3, Marion Main4, Jennie Sheehan5, Adnan Manzur6, Francesco Muntoni6 & The North Star Clinical Network for Paediatric Neuromuscular Disease†

1Muscular Dystrophy Campaign, London, UK 2Institute of Human Genetics, Newcastle, UK 3University of Sheffield, Sheffield, UK 4Great Ormond Street Hospital, London, UK 5Evelina Children’s Hospital, London, UK 6Dubowitz Neuromuscular Centre, Institute of Child Health, UCL, London, UK

Abstract

Background and Purpose. The aims of this study were to develop a clinical assessment scale to measure functional

ability in ambulant boys with Duchenne muscular dystrophy and to determine the reliability of the scale in multiple

centres in the UK. Methods. Focus groups and workshops were held with experienced paediatric neuromuscular phy-

siotherapists to determine scale content. A manual was prepared with accompanying videos, and training sessions were

conducted. A total of 17 physiotherapists from participating centres used the videos to determine inter-rater reliability.

Five determined the intra-rater reliability. Results. Strength of agreement for these groups based on total subject scores

was very good (0.95 and ≥0.93 for consistency and absolute agreement, respectively). Test–retest ability was high, with perfect agreement between occasions for all but two items of the scale. Conclusions. Our study indicates that the North

Star Ambulatory Assessment is practical and reliable. It takes only 10minutes to perform and incorporates both univer-

sally used timed tests as well as levels of activities, which allow assessment of high-functioning boys with Duchenne

Received 27 January 2011; Revised 21 May 2011; Accepted 26 June 2011

Keywords

ambulant; assessment; Duchenne muscular dystrophy

*Correspondence

Elaine Scott, MPhil, MCSP, c/o Muscular Dystrophy Campaign, 61 Southwark Street, London SE1 0HL, UK.

Email: [email protected]

†The North Star Clinical Network for Paediatric Neuromuscular Disease: Collaborators (53): Manzur A.Y., Muntoni F., Robb S., Main M., Kemp J.

(Great Ormond Street Hospital, London), Scott E. (Muscular Dystrophy Campaign, London), Bushby K., Straub V., A. Sarkozy, E. Strehle, R.

Venkateswaran, Eagle E., Mayhew A. (Institute of Human Genetics, Newcastle), Roper H., McMurchie H., Grace A. (Heartlands Hospital,

Birmingham), Spinty S., Peachey G., Shillington S. (Alder Hey Children’s Hospital, Liverpool), Quinlivan R., Groves L. (Robert Jones and Agnes

Hunt Royal Orthopaedic Hospital, Oswestry), Wraige E., Jungbluth H., Sheehan J., Spahr R. (Evalina Children's Hospital, London), Hughes I.,

Bateman E., Cammiss C. (Royal Manchester Children's Hospital), Childs A.M., Pallant L., Psyden K. (Leeds General Infirmary), Baxter P. (Sheffield

Children's Hospital), Naismith K., Keddie A. (King's Cross Hospital, Dundee), Horrocks I., McWilliam R., Di Marco M. (Yorkhill Children's Hospital,

Glasgow), Hartley L., Sheen B., Fenton-May J. (University Hospital Wales, Cardiff), Jardine P., Majumdar A., Jenkins L. (Frenchay Hospital, Bristol),

Chow G., Miah A. (Queen's Medical Centre University Hospital, Nottingham), de Goede C. (Preston Royal Hospital), Thomas N., Geary M.,

Palmer J (Southampton General Hospital), White C., Greenfield K. (Morriston Hospital, Swansea), MacAuley S. (Royal Belfast Hospital for Sick

Children), Baxter A., Yirrell Y., Longman C. (Royal Hospital for Sick Children, Western General Hospital, Edinburgh).

Published online 23 September 2011 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pri.520

Introduction

The development of validated outcome measures in

Duchenne muscular dystrophy (DMD) has become in-

creasingly important because of the need to monitor

disease progression and the impact of treatments, such

as intermittent or daily steroids (Manzur et al.,

2008a), and the requirement for reliable functional out-

come measures for use in clinical trials (Manzur et al.,

2008b; Mercuri et al., 2008). Since the original work of

Brooke et al. (1981) and Scott et al. (1982) in the early

1980s on outcome measures for DMD, numerous papers

relating to the use of a large variety of outcome measures

for this condition have been published (e.g. McDonald,

2002; Kohler et al., 2005; Scott and Mawson, 2006; Mayhew

et al., 2007; Davis et al., 2010; McDonald et al., 2010), and

much work has been carried out, or is currently underway,

to evaluate the usefulness of these measures in clinical and re-

search settings via the TREAT-NMD clinical and research

EU-funded network of excellence (www.treat-nmd.eu) and

other related programmes. The focus of this study, however,

is on the development and validation of a functional scale for

needs of the North Star Project in the UK.

The North Star Clinical Network for Paediatric Neu-

romuscular Disease Management is a collaboration of

17 specialist neuromuscular centres in the UK whose

overall aim is to optimize the management of children

with DMD (Scott et al., 2007). The key objective of the net-

work was to standardize clinical assessment protocols and

pharmacological interventions such as corticosteroid use for

ambulant boys with DMD. Clinicians and therapists from

the clinical network identified functional measures as the

most clinically relevant outcomes in monitoring disease pro-

gression (North Star network internal report), and patients and

their relatives relate more to measures of function as opposed

merely to muscle strength.There is a need for such functional

measures to be valid for the patient group and context in

which they are to be used, to provide reliable data, which in

the context of the North Star Project means data from mul-

tiple centres, to be responsive to change and to be feasible for

the patient group and setting.

Many scales have been developed previously to assess

the functional abilities of boys with DMD and other

neuromuscular conditions; however, each of these scales

had limitations as evaluation instruments for steroid-trea-

ted ambulant boys with this condition. These included a

lack of sensitivity to change and a lack of data on reliability,

practicality and ease of use across multiple clinical centres.

The scales developed specifically for DMD by Vignos et al.

(1963) and Brooke et al. (1981) provide simple ordinal-

level data, which do not offer the degree of sensitivity re-

quired to assess the effect of novel treatments. The Egen

Klassifikation (EK) Scale (Steffensen et al., 2001, 2002)

and the Motor Function Measure (Bérard et al., 2005,

2006) are both examples of substantial, comprehensively

developed measures for the assessment of neuromuscular

disorders. However, the EK Scale addresses non-ambulant

function only, and the Motor Function Measure is lengthy

and neither disease nor stage specific. The most commonly

used functional scale in the UK, the Hammersmith Motor

Ability Scale (HMAS) (Scott et al., 1982), is satisfactorily

used within a clinical setting; but reliability and validity

have never been established. Furthermore, the scale was

developed before corticosteroids were widely used and suf-

fers from ceiling effects in children benefitting from the

positive effect of this medication (personal observation of

the authors). The focus of this study is therefore on the ini-

tial development of a functional assessment scale for am-

bulant children with DMD, the North Star Ambulatory

Assessment (NSAA).

There were two aims of this study:

• to describe the initial development of the scale as a

clinical assessment tool

• to present the initial training and reliability data from

the North Star group of physiotherapists.

Methods

Development of the North Star Ambulatory Assessment

Year 1 — construction and development

The intent was to develop a clinical scale to evaluate

change in the physical abilities of ambulatory boys with

DMD. This included boys across a range of ability levels

Development of a Scale for Duchenne MD E. Scott et al.

from those only just able to walk to those with higher

functional abilities such as running and jumping. As there

are 17 centres involved in the North Star clinical network,

it was important that minimal equipment should be re-

quired for standardization of use across sites. Given the

behavioural difficulties that are common in young boys

with DMD and the limited time available in clinic settings,

it was also important that the time to complete the scale

should be kept to a minimum.

Although the HMAS has the limitations stated pre-

viously, it has an acknowledged clinical utility and a

long history of use in the UK. It was therefore used

as a basic framework from which the NSAA was devel-

oped. A focus group of specialist neuromuscular phy-

siotherapists (M. M., M. E. and J. S., with E. S.) was

convened to determine the structure and content of

the scale. Domain of content (Portney and Watkins,

2000) for the NSAA was defined as the gross motor

ability in ambulant DMD children. The underpinning

theoretical construct is that these boys lose functional

ambulation in a recognizable pattern due to the pri-

mary underlying pathology of progressive muscle

deterioration and related complications such as con-

tractures. Activities included were those necessary to

remain functionally ambulant including the ability to

rise from the floor and getting from sitting to stand-

ing. Head raise and standing on heels were included

as these are difficult even in the early stages of the

disease while children are still ambulant and were seen

as clinically relevant. Other activities such as hopping,

jumping and running are unusual in non-steroid-

treated children yet are frequently seen in children

treated with steroids, whether on intermittent or daily

regimes. An example of items included in the NSAA is

given in Table 1.

The scores for each item are described in terms of

clinically significant changes in the functional abilities

seen in this patient group, reflecting the pattern of dis-

ease progression. Sensitivity to change has thus been

addressed theoretically with the description of the item

categories in terms of ‘clinically significant change’

(Bain and Dollaghan, 1991), that is, change that

denotes a true change in a patient’s abilities not merely

due to natural variability of performance, or matura-

tion. Following a series of four focus group meetings,

a manual to enable standardized use of the scale was

developed and introduced at a series of eight work-

shops for experienced neuromuscular physiotherapists

in the North Star network. After a six-month period

of clinical use and assessment, the scale was formally

reviewed, and amendments were made to the descrip-

tion of the activities to make it easier to grade each task;

however, no new items were included, and none were

removed. In this manner, face and content validity

were addressed by the initial focus group then further

validated by the wider expert group of the North Star

Table 1. North Star Ambulatory Assessment, example of test items

Test item 1: Stand

Starting position Feet should be no further than 10cm apart and heels on the ground if possible. Arms by sides. NO shoes should be worn.

Instruction Can you stand up tall for me for as long as you can and as still as you can for three seconds with your heels flat on the

ground?

Scoring detail When counting to 3 – Use “And 1 - and 2 - and 3” so that three seconds is achieved on the word of 3.

Best done on the floor rather than on a mat. Whichever is chosen maintain consistency through repeated testing sessions.

Score 2 - Minimum count of 3 seconds.

Score

2 Stands upright, still, symmetrical, without compensation (heels flat legs in neutral) for minimum count of 3 seconds

1 Stands still but with compensation (e.g. on toes or with legs abducted or with bottom stuck out) for minimum count of 3

seconds

0 Cannot stand still or independently, needs support (even minimal)

Test item 14: Jump

Starting position Standing on the floor, feet fairly close together. No shoes should be worn.

Instruction How high can you jump?

Scoring detail Want height, not forward movement. Small amount of forward movement acceptable

Score

2 Both feet at the same time, clear the ground simultaneously

1 One foot after the other (skip) or does not fully clear both feet at the same time.

0 Unable

E. Scott et al. Development of a Scale for Duchenne MD

clinical network. Figure 1 summarizes the process of

development and review of the measure.

Year 2 — reliability testing and ongoing training

Initial training in the use of the scale included work-

shops, centre visits by the project coordinator, where

joint patient assessments were undertaken, and a period

where assessors piloted the scale in clinical practice.

Two sets of reliability data are presented:

• six subjects evaluated by five of the North Star group

of therapists

• three subjects evaluated by 17 therapists from all par-

ticipating centres.

Table 2 provides an outline as to which raters evalu-

ated which subjects for these data sets. Video was taken

of boys with a range of differing abilities, and each eval-

uator was asked to independently score each child.

Scoring was carried out in confidence during group

sessions, with the coordinator present. Video of scale

items could be viewed more than once on request.

Score sheets were submitted to the coordinator.

Further, to this intra-rater reliability was examined with

five experienced physiotherapists who independently

scored the same individual from video on two occasions,

with a one-month interval between evaluations.

The scale has subsequently been adopted as a stan-

dard clinical assessment tool for use in over 17 paediat-

ric neuromuscular centres in the UK.

Statistical analysis

Inter-rater reliability was assessed according to the

methods outlined in the study by Streiner and Norman

(2003). The intraclass correlation coefficient (ICC) for

consistency among raters and the ICC for absolute

agreement were computed. The ICC for consistency

assesses whether raters were consistent in the order in

which they placed individuals, that is, were boys rated

in the same order for functional ability by all raters

from worst to best (irrespective of the actual value).

The ICC for absolute agreement assesses whether raters

agreed with each other with respect to the actual values

they assigned individuals. Given the mathematical

equivalence between the ICC and the kappa statistic

(Fleiss and Cohen, 1973), interpretation of the tabu-

lated ICC values was based on the semantic categories

adapted by Altman (1991) from Landis and Koch, as

shown in Table 3. However, the kappa statistic provides

a poor summary measure of agreement when prevalence

is low, as it was for some of the features investigated here.

As a result, the percentage classified into each category

across all raters and all children (n=30 for the smaller

group of five therapists, and n=51 for the group of 17

therapists) has also been tabulated for each variable.

Intra-rater reliability was assessed using data from five

assessors who each assess the same, single individual on

two occasions. As agreement was perfect for all but two

Figure 1 Summary of the North Star Ambulatory Assessment de-

velopment process

Table 2. Outline of rater to subject evaluations

Subject

Raters

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

A x x x x x x x x x x x x x x x x x

B x x x x x x x x x x x x x x x x x

C x x x x x x x x x x x x x x x x x

D x x x x x

E x x x x x

F x x x x x

Table 3. Interpretation of kappa statistic and intraclass correlation coefficient

Value of K Strength of agreement

<0.20 Poor

0.21–0.40 Fair

0.41–0.60 Moderate

0.61–0.80 Good

0.81–1.00 Very good

Development of a Scale for Duchenne MD E. Scott et al.

of the items on the scale, it was not possible to calculate the

test–retest coefficient, and thus, only the percentage agree-

ment has been presented.

Results

Year 1 — construction and development of the scale

Following a substantial period of development and special-

ist review, a 17-item scale was agreed. Aspects of theoreti-

cal construct and content validity were addressed, as was

the feasibility of use in multiple clinical centres for this pa-

tient group. A document standardizing the test method

was compiled and circulated to all involved in the clinical

network, and workshops and site visits were undertaken to

ensure standardized application of the scale (full test

details are available from www.muscular-dystrophy.org/

how_we_help_you/for_professionals/clinical_databases).

Year 2

Five physiotherapists evaluated the videos of six boys

by using the NSAA scale. Strength of agreement for this

group (Table 4) based on total subject scores was very

good (0.95 for both consistency and absolute agree-

ment). Fifteen of the 17 individual items were rated

good or very good for consistency, and 15 for absolute

agreement. The 17 physiotherapists involved in data

collection for the network evaluated the videos of three

boys. All 17 evaluated all videos. As with the previous

data for the five physiotherapists and six boys, the

strength of agreement (Table 5) when based on total

subject scores was very good (0.95 and 0.93 for consis-

tency and absolute agreement, respectively). Nine of

the individual items were rated good or very good for

consistency, and nine for absolute agreement. Where

items have been rated poor or fair on ICC analysis,

for example, rise from floor, there was an overall good

agreement among therapists by the percentage classi-

fied into category 1, that is, over 90% of the therapists

classified the subjects as scoring 1 (signs of Gowers’

manoeuvre). This, however, meant that there was a

low prevalence across the range of scores — none of

the subjects in this study were scored as unable to rise

from the floor (Tables 4 and 5). This issue of preva-

lence across the range of scores (2,1,0) and its effect

upon results will be returned to in the Discussion and

Conclusion sections.

Although the numbers were small (only five phy-

siotherapists), the agreement between occasion 1 and

occasion 2 was perfect for all but two of the items,

jump and run (Table 6).

Table 4. Inter-rater reliability: percentage classified into each category, together with intraclass correlation coefficients (ICCs), n = 30 (six subjects, five assessors)

Test item

% classified as: ICC:

0 1 2 Consistency Absolute agreement

Stand 3.3 46.7 50.0 0.91 0.90

Walk 53.3 46.7 0.89 0.87

Sit to stand 50.0 50.0 0.78 0.75

Single leg stand (right) 50.0 50.0 1.00 1.00

Single leg stand (left) 33.3 66.7 0.75 0.72

Climb step (right) 16.7 83.3 1.00 1.00

Climb step (left) 20.0 80.0 0.82 0.80

Descend step (right) 23.3 76.7 0.76 0.73

Descend step (left) 40.0 40.0 0.68 0.64

Lying to sitting1 55.2 44.8 0.41 0.38

Rise from floor 96.7 3.3 0.00 0.00

Lift head 66.7 23.3 76.7 0.76 0.73

Stand on heels 10.0 16.7 16.7 0.85 0.83

Jump 30.0 26.7 63.3 0.78 0.75

Hop (right) 36.7 30.0 40.0 0.76 0.73

Hop (left) 23.3 40.0 23.3 0.78 0.75

Run 26.7 50.0 0.74 0.71

Total score 0.95 0.95

1One observation missing.

E. Scott et al. Development of a Scale for Duchenne MD

Discussion

The NSAA has been developed by expert paediatric

neuromuscular physiotherapists specifically for use in

ambulant children with DMD, thus ensuring that the

content of the scale is clinically meaningful and appro-

priate. Experience from clinical use has shown that the

NSAA takes approximately 10 minutes to complete,

including timed tests, and its ease of administration

means that it can be used both in specialist clinics and

community settings. Evaluation of the feasibility of its

administration by the North Star therapists indicates

that compliance is good even in children with learning

or behavioural problems, a feature that characterizes

one-third of all DMD boys (Emery and Muntoni, 2003).

Lead physiotherapists from all 17 centres involved in

data collection for the project participated in the reli-

ability exercise, where the main focus was on ensuring

standardized scoring and rater agreement. Strength of

agreement when based on total subject scores was

found to be excellent. This varied substantially, how-

ever, when individual test items were considered, par-

ticularly for the larger therapist group. Although good

to very good agreement on analysis by ICC was gained

for many test items on the NSAA, very poor results

were gained for six by the larger therapist group. This

apparently poor strength of agreement is confounded

when the percentage classified into each category is

considered. The percentage classified results show that

there was actually excellent agreement among thera-

pists for most of these test items, but the majority of

subjects were considered to fall into one category (see

item 11 (rise from floor) in Tables 3 and 4). The kappa

statistic, and therefore the ICC, provides a poor sum-

mary measure of agreement when prevalence of

Table 5. Inter-rater reliability: percentage classified into each category, together with intraclass correlation coefficients (ICCs), n = 51 (three subjects, 17 assessors)

Test item

% classified as: ICC:

0 1 2 Consistency Absolute agreement

Stand 3.9 60.8 35.3 0.87 0.83

Walk 66.7 33.3 0.88 0.84

Sit to stand 41.2 58.8 0.83 0.78

Single leg stand(right) 68.6 31.4 0.94 0.92

Single leg stand (left) 64.7 35.3 0.94 0.92

Climb step (right) 2.0 98.0 0.00 0.00

Climb step (left) 13.7 86.3 0.38 0.31

Descend step (right) 19.6 80.4 0.28 0.22

Descend step (left) 19.6 80.4 0.30 0.24

Lying to sitting 64.7 35.3 0.70 0.64

Rise from floor 90.2 9.8 0.10 0.08

Lift head 7.8 92.2 0.05 0.04

Stand on heels 66.7 23.5 9.8 0.81 0.77

Jump 21.6 25.5 52.9 0.60 0.53

Hop (right) 29.4 41.2 29.4 0.78 0.73

Hop (left) 39.2 47.1 13.7 0.74 0.68

Run 37.2 21.6 41.2 0.54 0.47

Total score 0.95 0.93

Table 6. Agreement between occasion 1 and occasion 2 (n = 5)

Test item Agreement (%)

Stand 100

Walk 100

Sit to stand 100

Single leg stand (right) 100

Single leg stand (left) 100

Climb step (right) 100

Climb step (left) 100

Descend step (right) 100

Descend step (left) 100

Lying to sitting 100

Rise from floor 100

Lift head 100

Stand on heels 100

Jump 80

Hop (right) 100

Hop (left) 100

Run 60

Development of a Scale for Duchenne MD E. Scott et al.

different categories is low, as it was for some of the fea-

tures investigated here, and so it should be interpreted

with caution. Although the three subjects presented

with varying abilities, all achieved an average total score

of 18 or over. The evaluation of a bigger group of sub-

jects with a wider variety of abilities would have

addressed these issues; however, even this may not alle-

viate this issue where prevalence in any one category is

low (Fleiss and Cohen, 1973).

A subsequent study in Italy by Mazzone et al. (2009)

reported their findings regarding training needs and re-

liability studies for the NSAA for a substantially larger

group of patients. Their initial results, following the

first phase of training, were poor (ICC <0.05), but fol-

lowing a second phase, the ICC for all items was ≥0.75, with all but one item indicating a very good level of

agreement. Two of the items (lift head and run), which

proved problematic to gain agreement in the first phase

of the Italian study, were also the same for the larger

North Star group (Table 4). However, without the per-

centage classified data, it is not possible to know if these

poor ICC results are an artefact of the low prevalence

across categories or of a lack of clarity with the wording

of the scale. Neither of these items were a cause for

concern with the smaller North Star group or the Ital-

ian group following their second phase of training. The

issue of training and in particular consensus building,

as demonstrated in Mazzone’s paper, is an important

one for any clinician-rated assessment scale, such as

the NSAA. The medium that is used to translate the

patient’s performance of an activity to a point on the

scale is observation on the part of the assessor. The

assessor’s interpretation/understanding of the wording

of the scale therefore becomes an important factor in

avoiding measurement error and achieving reliable

results from the scale. Translation into another lan-

guage may also play a factor in the interpretation of

the scale and needs careful consideration in interna-

tional studies. Ongoing training for the North Star clin-

ical network includes an annual reliability review to

ensure consistency and quality of data collated for the

national database. The Italian study reported excellent

inter-rater reliability (ICC = 0.995) based on total

scores comparable with the initial reliability studies

from the North Star group. They also reported a very

high level of intra-rater reliability (0.95) in their com-

prehensive work.

Although the initial phase of both the UK and

the Italian studies indicated potential issues with

reliability indices for a small number of the scale

items, the decision was made, because of expert clini-

cal opinion as to their clinical importance for this pa-

tient group, to continue to include these items.

Further, rigorous evaluation of the psychometric

properties of the scale in a large population of boys

with DMD is currently underway using Rasch meth-

odology. Following this, recommendations may be

made for scale modifications, balancing high levels

of validity and reliability with the need for clinical

and statistical relevance.

The scale has now been in use for more than four

years, and data from over 300 DMD boys are being col-

lated, with the formal consent of families and assent of

patients, on the North Star database in the UK. The da-

tabase holds comprehensive national data on clinical

performance and outcomes from patients who attend

participating centres. Consistent and standardized lon-

gitudinal clinical data, of which the NSAA is part, are

therefore being collated on a cohort of children with

DMD offering a valuable tool for clinical audit and re-

search purposes.

The North Star clinical scale is now also been used to

document clinical response in experimental clinical

trials (Cirak et al., 2009; Kinali et al., 2009). The new

challenge, which is being considered, is how to expand

the scale to include non-ambulant children and young

adults, as natural history data in this group of indivi-

duals are scant.

Conclusion

The NSAA is a reliable, robust, practical test that can be

realistically used across a range of settings with mini-

mal, universally available equipment and completed

in a short timeframe. The initial results of the reliability

analyses for the North Star group of physiotherapy

assessors show an excellent level of agreement, which

is further demonstrated in the Italian study (Mazzone

et al., 2009). The scale incorporates the important dis-

ease milestones such as rising from the floor and walk-

ing ability as well as incorporating new skills that are

acquired by DMD boys treated with steroids. A study

is currently underway to further evaluate the theoreti-

cal content and construct validity, reliability and sensi-

tivity to change of the scale by using the Rasch

methodology. The authors also plan to present the lon-

gitudinal data from the North Star database in due

course.

E. Scott et al. Development of a Scale for Duchenne MD

Acknowledgements

The North Star Project is supported and funded by the

Muscular Dystrophy Campaign. The MRC Neuromus-

cular Centre’s support to the North Star Database and

the Muscular Dystrophy Campaign Centre’s grant to

the Dubowitz Neuromuscular Centre are also gratefully

acknowledged. Professor Muntoni is supported by the

Great Ormond Street Hospital Children’s Charity.

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