The Individualized Neuromuscular Quality of Life Questionnaire (INQoL); Cultural

translation and psychometric validation for the Dutch population

Femke M Seesing, MSC1§

, Lisanne EWM van Vught, BS1, Michael R Rose, MD ,PhD

2, Gea Drost, MD, PHD

1,3†, Baziel GM van

Engelen, MD, PhD, professor1 and Gert-Jan van der Wilt, PhD, professor

4

1 Department of Neurology, Radboud University Medical Centre, Reinier Postlaan 4, Nijmegen, The

Netherlands

2 Department of Neurology, Kings College Hospital, Denmark Hill, London SE5 9RU, United Kingdom

3 Department of Neurology/ Department of Neurosurgery, University Medical Centre Groningen,

University of Groningen, Hanzeplein 1, Groningen, The Netherlands

4 Department for Health Evidence, Radboud University Medical Centre, Geert Grooteplein noord 21,

Nijmegen, The Netherlands

†Study executed while working at Radboud University Medical Centre, currently working at

University Medical Centre Groningen.

§Corresponding author

Running title: Dutch INQoL validation

Correspondence: F.M. Seesing, Department of Neurology, Radboud University Medical Centre, 935

Neurology, PO BOX 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31243615213; E-mail:

Femke.Seesing@Radboudumc.nl

Word count: 1727 excl abstract and tables

Keywords: Muscle disease, Quality of Life , INQoL, validation, outcome, patient-reported

This article has been accepted for publication and undergone full peer review but has not beenthrough the copyediting, typesetting, pagination and proofreading process which may lead todifferences between this version and the Version of Record. Please cite this article as an‘Accepted Article’, doi: 10.1002/mus.24337

Abstract

Introduction

This paper describes the translation and psychometric evaluation of the Dutch Individualized

Neuromuscular Quality of Life (INQoL) questionnaire.

Methods

Backward and forward translation of the questionnaire was executed, and psychometric properties

were assessed on the basis of reliability and validity.

Results

206 patients were included in the study. Reliability analyses resulted in Cronbach alpha values above

0.70 for all sub-domains. Known group validity showed a significant correlation between INQoL

scores and severity as well as age for the majority of sub-domains. Item-total correlation for overall

QoL was satisfactory. Concurrent validity with SF-36 and EQ-5D was good (range, Spearman

correlation coefficients: -0.43 to -0.76).

Conclusion

This study resulted in a questionnaire which is appropiate for use in the Dutch-speaking population

to measure quality of life of patients with a wide variety of muscle disorders. This confirms and

extends data obtained in the United Kingdom, US, Italy, and Serbia.

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Introduction

Measuring quality of life (QoL) in patients with a muscle disorder is important to identify specific

areas at which to direct interventions that might help retain QoL despite illness progression 1,2

.

Muscle disorders show a wide variety of symptoms, often with a large impact on multiple aspects of

daily living, for which no curative treatments are currently available 3-5

. In contrast to generic QoL

measurement instruments, disease-specific questionnaires allow detection of differences or changes

in specific muscle disorder symptoms such as locking or weakness of the muscles or body image. This

minimizes the questionnaire burden on patients and clinicians caused by irrelevant or potentially

intrusive items and therefore facilitates their use in research and daily clinical practice6. The

Individualized Neuromuscular Quality of Life (INQoL) questionnaire is a muscle disease-specific QoL

questionnaire for patients with muscle disorders that was developed by Rose et al in 2007 7. The

psychometric properties of the INQoL have been tested and shown to be valid, reliable, and, to some

extent, responsive 7-9

. The INQoL was translated and validated for populations in the UK, USA, Italy,

and Serbia 10,7-9

. In this paper, we describe the translation and psychometric evaluation of the Dutch

INQoL questionnaire for patients with a muscle disorder. Psychometric properties were assessed on

the basis of reliability and validity (known-group validity, item-total correlation, and concurrent

validation).

Methods

INQoL questionnaire

The INQoL is constructed of 4 main domains that are divided into 12 sub-domains. Each sub-domain

is composed of questions that vary from 3 to 14 items, with responses given on a 7-point Likert scale.

Raw data are converted to a score from 0-100 for every sub-domain, a higher score indicating a

greater impact on QoL. The 4 main domains of the INQoL include symptoms (sub-domains:

weakness, locking, pain, and fatigue); life domains (sub-domains: activities, independence, social

relationships, emotions, and body image); treatment effects (sub-domains: perceived treatment

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effects and expected treatment effects); and overall QoL, an aggregation of parts of the 5 sub-

domains (activities, independence, social relationships, emotions, and body image). The 4 main

domains are considered to properly reflect the QoL of patients with a muscle disorder7.

Cultural translation

Backward and forward translation of the questionnaire was executed independently by 2

neurologists (CH, NV). Differences were resolved by consensus. Remaining questions were submitted

to the original author (MR) to assure conceptual equivalence with the original questionnaire.

Psychometric evaluation

Psychometric properties of the Dutch INQoL questionnaire were evaluated using data collected from

a randomized controlled trial (RCT) on shared medical appointments for patients with a muscle

disorder. The RCT and the subsequent use of the data for this study were reviewed and approved by

the local medical ethics committee (reference CMO nr. 2008/224) and registered with the Dutch Trial

Register (nr NTR1412)11,12

.

Reliability was assessed by measuring the relationship (Cronbach alpha) of the items within each of

the 12 sub-domains. The internal consistency among items addressing the same underlying domains

should be higher than an alpha value 0.70 13

. Spearman correlation coefficients and interclass

correlations (single measures) were computed to assess the relation between the questions of each

domain14

.

Validity was assessed through known-group validity, item-total correlation, and concurrent validity.

Known-group validity aimed to compare the INQoL scores with demographic or disease-related

factors which are known from previous research to have a significant correlation with the INQoL.

Earlier studies showed that age and severity of disease are correlated negatively with INQoL scores

2,8. Age was divided in 3 groups: 18-35, 36-65, and 66-80 years. Severity of disease was assessed

through the Modified Rankin Scale (MRS), ranging from 0 (no symptoms) to 5 (severe disability;

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bedridden, incontinent, and requiring constant nursing care and attention) 15

. Means and standard

deviations of the INQoL scores for the sub-groups were analyzed. P-values < 0.05 were considered

statistically significant for known-group validity. Item-total correlation was determined by the

correlation between the individual items (activities, independence, social relationships, emotions,

and body image) and overall QoL. The corresponding item was omitted in the total score. Correlation

coefficients should be between 0.20 and 0.90 in order to indicate sufficient item-total correlation 13

.

Concurrent validity was measured by the association of the 12 INQoL sub-domains with the

corresponding Short Form-36 (SF-36) and EuroQol 5D (EQ5D) questions and were expressed in terms

of Spearman correlation coefficients 16,17

Subjects and data collection

Patients were recruited from the Department of Neurology of the Radboud University Medical

Centre (Radboudumc) and identified as patients with a muscle disorder through the Dutch

neuromuscular database (CRAMP) 18

. Patients had to be aged 18 years and above and literate in the

Dutch language. In view of the RCT intervention on shared medical appointments, patients with

hearing problems and those who attended the outpatient clinic less than 6 months ago were

excluded 11

. Of the eligible patients, 70% agreed to participate in the RCT. Data were collected

through a self-administered questionnaire-booklet which contained, besides the Dutch INQoL

questionnaire, the following questionnaires: EQ5D, SF-36, General self-efficacy, social support

subscale from the Dutch Social Support List-Discrepancies, QUality Of care Through the patient’s Eyes

(QUOTE) and satisfaction with the marital relationship. The questionnaires were filled out at home.

Non-responders at 2 weeks were contacted by phone to remind them to complete the questionnaire.

SPSS version 18 was used for statistical analysis.

Results

Cultural translation

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A noteworthy adjustment resolved by discussion with the original author (MR) concerned the English

word for “locking”, which implies myotonia. In Dutch, this is not a common lay term, therefore this

was translated as: “Do you notice that your muscles have difficulties relaxing after sustained

contraction?“. A final version of the Dutch INQoL questionnaire has been deposited with the MAPI

Research Institute Website, and inquiries regarding its use can be obtained from www.mapi-

trust.org.

Patient characteristics

In total, 206 patients with 1 of the following muscle disorders were included in the study: myotonic

dystrophy type 1 (MD), McArdle disease, facioscapulohumeral muscular dystrophy (FSHD), chronic

progressive external ophthalmoplegia (CPEO), oculopharyngeal muscular dystrophy (OPMD),

inclusion body myositis (IBM), non-dystrophic myotonias, and myositis. See table 1 for patient

characteristics. MD type 1 was the largest patient group (N=75), and chronic progressive external

ophthalmoplegia (CPEO) was the smallest (N=5). Slightly more than half of the patients were men

(54%), and the mean age was 51 years, range 18-79. Most patients reported having a slight disability,

and although unable to carry out previous activities, they were still able to look after themselves

without assistance (score 2 on MRS) (N=63).

Reliability

Table 2 shows that all internal consistency values had a Cronbach alpha above 0.70, ranging from

0.721 (relationships) to 0.903 (fatigue). The correlation coefficients ranged from 0.797 (body image)

to 0.331 (relationships). All inter-class correlation coefficients were above 0.400, ranging from 0.478

(expected treatment effects) to 0.792 (body image), except for the sub-domain relationships (0.224).

Validity

Known group validation

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Figure 1 summarizes the relation between severity of disease (MRS) and INQoL sub-domains. The

MRS showed a significantly higher INQoL score for more severely disabled patients for 8 of the 10

sub-domains (P<0.03). Age correlated significantly with INQoL score for 4 of the 10 sub-domains

(P<0.03) (data not shown).

Item-total correlation

In table 3, the correlation between the calculated domain, overall QoL and the individual items

contributing to this score, is presented. Although some items correlated only poorly, overall QoL

correlated quite well with each of its component items. Correlation coefficients were 0.400 or higher

for all sub-domains with overall QoL, ranging from 0.448 (activity) to 0.533 (independence).

Concurrent validation

The data in table 4 show the correlation between the INQoL and the SF-36 questionnaire. The

Spearman correlation coefficient ranged from -0.453 (emotions vs. emotional well being) to -0.769

(Activities vs. Physical functioning). The concurrent validation analysis for the EQ5D VAS score and

the EQ5D index score compared to the INQoL overall QoL score resulted in Spearman correlation

coefficients of -0.472 and -0.4 respectively (data not shown)

Discussion

Main findings

These results show that the translation of the INQoL questionnaire resulted in a Dutch – language

questionnaire with adequate psychometric properties for patients with muscle disease. Reliability,

known group validity, item-total correlation, and concurrent validation were good. The questionnaire

is appropiate for use in the Dutch-speaking population to measure QoL of patients with diverse

muscle disorders. This confirms and extends data obtained in the United Kingdom, US, Italy, and

Serbia 10,7-9

.

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Strengths and limitations

A major strength of our study was the broad range of the study population, including 8 different

diagnoses. In line with the prevalence of the various muscle diseases in the population patients with

MD and FSHD made up the largest number of subjects in this validation study. However we were not

able to detect substantial differences in psychometric properties for these subgroups. This confirms

data from Peric et al who studied the INQoL specifically for patients with MD9 Although some muscle

diseases such as limb-girdle muscular dystrophy (LGMD) were not represented, we doubt that this

weakens the validation of INQoL for muscle disease generally. LGMDs for example were present in

the US and Italian validations of INQoL, and like us, those studies did not find significant differences

between most specific muscle diseases.19,8

. Our sample reflects the Dutch national population of

patients with a muscle disorder even though this is is a single center design, as the Radboudumc is a

Dutch national referral center which sees patients with muscle disease from the whole of the

country. Our study design did not allow for the assessment of a test-retest reliability of the INQoL.

Implications and future research

The assessment of QoL of patients with a muscle disorder can help identify domains that are affected

most by the disease in individual patients. Such findings may help to guide clinical management

decisions and may be used to evaluate the impact of treatments. The INQoL questionnaire is an easy

to administer self-rating scale with an acceptable burden on patients and satisfactory psychometric

properties. It can be used both in daily clinical practice and in research. The availability of

quantitative data on minimal clinical significant differences of the INQoL questionnaire would be

imperative to make optimal use of this instrument. Responsiveness and test-retest analyses should

be performed in future research to further strengthen the validation of the Dutch-language INQoL

questionnaire.

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Acknowledgements

The authors would like to thank Nicol Voermans, MD (NV) and Charlotte Haaxma, MD (CH) for their

contribution to the translation of the Dutch INQoL questionnaire.

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Abbreviations

CPEO: chronic progressive external ophthalmoplegia

CRAMP: Dutch Computer Registry of All Myopathies and Polyneuropathies

EQ5D: EuroQol 5D

FSHD: Facioscapulohumeral muscular dystrophy

HRQoL: Health Related Quality of Life

IBM: Inclusion body myositis

INQoL: Individualized Neuromuscular Quality of Life

MD: Myotonic dystrophy type 1

MRS: Modified Rankin Scale

NTR: Dutch Trial Registration

OPMD: Oculopharyngeal muscular dystrophy

Radboudumc: Radboud University Medical Centre

SF-36: Short Form 36

QoL: Quality of Life

QUOTE: QUality Of care Through the patient’s Eyes

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References

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(Computer Registry of All Myopathies and Polyneuropathies): development and preliminary data.

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Attachments: tables, figures

Table 1 Patient characteristics

Variable Men (N) (%) 111 (54) Age (years), Mean (SD) 51 (14.6) Diagnosis (N):

- Myotonic Dystrophy type 1 75 - McArdle disease 8 - Facioscapulohumeral Muscular Dystrophy 46 - Chronic progressive external ophthalmoplegia 5 - Oculopharyngeal Muscular Dystrophy 22 - Inclusion body myositis 9 - Non-dystrophic myotonias: chloride and sodium channelopathies 21 - Myositis: Dermatomyositis and Polymyositis 19 - Missing 1

Rankin Scale (N): - No symptoms (0) 9 - No significant disability (1) 27 - Slight disability (2) 63 - Moderate disability (3) 31 - Moderate-severe disability (4) 56 - Severe disability (5) 2 - Missing 18

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Table 2 Reliability as measured through item internal consistency (Cronbach alpha)

INQoL sub-domains Number

of items

Correlation

coefficient

95%

Confidence

interval min-

max

ICC

(single

measures)

Cronbach

alpha

Muscle weakness 3 0.729 0.646-0.844 0.717 0.884

Locking 3 0.700 0.586-0.778 0.693 0.871

Muscle pain 3 0.719 0.629-0.819 0.704 0.877

Fatigue 3 0.757 0.714-0.789 0.756 0.903

Activities 4 0.551 0.359-0.716 0.549 0.829

Independence 2 0.712 0.712-0.712 0.712 0.832

Relationships 9 0.331 0.025-0.745 0.224 0.721

Emotions 5 0.545 0.443-0.667 0.524 0.846

Body image 2 0.797 0.797-0.797 0.792 0.884

Perceived treatment effects 3 0.597 0.431-0.706 0.599 0.818

Expected treatment effects 4 0.478 0.283-0.706 0.478 0.785

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Table 3 Item-total correlation overall QoL. Correlation coefficients

Overall

QoL

Activity Independenc

e

Relationships Emotions Body image

Overall QoL - 0.448 0.533 0.468 0.469 0.495

Activity 0.448 - 0.742 0.412 0.279 0.521

Independence 0.533 0.742 - 0.413 0.240 0.570

Relationships 0.468 0.412 0.413 - 0.336 0.313

Emotions 0.469 0.279 0.240 0.336 - 0.279

Body image 0.495 0.521 0.570 0.313 0.279 -

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Table 4 Concurrent validity; correlation between selected INQoL domains and SF-36 items.

Spearman correlation coefficient.

INQoL SF-36 Spearman

correlation

Pain Pain -0.686

Fatigue Energy/fatigue/emotions -0.686

Independence Social functioning -0.510

Overall QoL General Health -0.453

Activities Physical functioning -0.769

Emotions Emotional well being -0.453

Relationships Social functioning -0.504

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Figure 1. Known group validity; INQoL subdomains vs severity of disease as measured by the

Modified Rankin Scale (MRS). Mean values.

MRS 0: No symptoms (n=9); MRS 1: No significant disability (n=27); MRS 2: Slight disability (n=63);

MRS 3: Moderate disability (n=31); MRS 4: Moderate severe disability (n=56); MRS 5: Severe

disability (n=2)

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MRS 0: No symptoms (n=9); MRS 1: No significant disability (n=27); MRS 2: Slight disability (n=63); MRS 3: Moderate disability (n=31); MRS 4: Moderate severe disability (n=56); MRS 5: Severe disability (n=2)

157x243mm (300 x 300 DPI)

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