Cross Cultural Validation of the Italian Version of the Bt-DUX: A Subjective Measure of Health Related Quality of Life in Patients Who Underwent Surgery for Lower Extremity Malignant Bone Tumour
Conditions: Quality of Life, Bone Neoplasm
Sponsor: Istituto Ortopedico Rizzoli

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Study Protocol 
 
Cross cultural validation of the Italian version of the Bt-DUX: A subjective measure of 
health related quality of life in patients who underwent surgery for lower extremity 
malignant bone tumour. 
 
 
Prinicpal Investigator:- Mattia Morri, PhT, Physiotherapist Researcher, Servizio di Assistenza 
Infermieristica, Tecnica e della Riabilitazione (SAITeR), IRCCS  Istituto Ortopedico Rizzoli, via 
Pupilli 1, 40136 Bologna, Italy. 
Sign _________________________________ 
 
 
Co- Investiogator  W Peter Bekkering, PhD, PPT. Pediatric Physical Therapist & Postdoc 
researcher, Máxima sports & movement center, Princess Máxima Center for Pediatric Oncology,  
Heidelberglaan 25, 3584 CS Utrecht, The Netherlands  
 
Competing interest: The Authors declare that they have no competing interest 
 
Funding: This work is supported by Nurse Research Center of Istituto Ortopedico Rizzoli and by 
Pediatric Physical Therapist & Postdoc researcher, Máxima sports & movement center. 
No-profit study - without funding 
Address for correspondence:  
 
Mattia Morri, PhT 
Physiotherapist Researcher 
Istituto Ortopedico Rizzoli 
via Pupilli 1, 40136 Bologna, Italy. 
E-mail: mattia.morri@ior.i 
 
 

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1. Background 
 
Malignant bone tumours like osteosarcoma and Ewing sarcoma mostly appear at the teenage years 
and in the long bones of the lower extremity. The survival rates for children and adolescents with 
lower-extremity sarcoma have improved remarkably over the past decades. As result of the 
improved life expectancy, there has been a growing interest in functional outcome and Quality of 
Life (QoL) after surgery.  Most of the studies on the outcome of surgery so far were mainly 
focused on basic daily activities or have used generic instruments for QoL.  With the usage of 
these instruments a number of relevant issues, such as the patient’s valuation of the cosmetic, 
functional and emotional impact of the disease and its surgical treatment, are not specifically 
taken into account. 
These latter dimensions are included in a recently developed questionnaire DUX for bone 
tumours in children and adolescents (Bt-DUX). The Bt-DUX questionnaire was constructed as a 
disease specific questionnaire, modelled upon the generic DUX 25 QoL questionnaire (short 
version of the Dutch Children TNO-AZL Quality of Life Questionnaire / DUCATQOL). The 
DUX 25 has been used in studies among siblings of paediatric cancer patients, children with 
celiac disease, juvenile chronic arthritis, malignant bone tumours and healthy peers and proved to 
be internally consistent and reproducible. The scores on the Bt-DUX reflect patients’ personal 
impact; their individual values for cosmetic, social, emotional and functional aspects of their life 
after the surgery. The Dutch version of the Bt-DUX was found to be a practically applicable 
instrument with a good internal consistency and validity and appeared to have added value 
regarding existing measures of quality of life in patients undergoing surgery for malignant bone 
tumours of the lower extremity (1). The Bt-DUX has been translated into the English language 
and this Bt-DUX translation has also proven to be a valid disease-speciﬁc instrument for 
evaluating QoL of adolescents with lower extremity bone cancer (2). The Bt-DUX has been used 
as disease specific QoL instrument in cross sectional and prospective studies among patients after 
bone cancer surgery and has given a valuable addition to the generic and age specific QoL 
measures (3,4). To examine the validity of the Bt-DUX within bigger and/or international studies 
it’s from importance to translate the instrument in other languages and validate the instrument in 
other cultures / populations.  Therefore we’d like to translate and cross-cultural validate the Bt-
DUX in the Italian language. 

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2. The study 
 
Purpose: The purpose of the presented study is to translate the English Bt-DUX (Bt-DUX-Eng) 
questionnaire into the Italian language and then examine the validity of the Italian version of the 
Bt-DUX (Bt-DUX-It). 
 
Design: Cross sectional study among patients of the Istituto Ortopedico Rizzoli, Bologna, Italy. A 
survey consisting of different QoL questionnaires will be executed. 
 
2.1 
Method: 
The study will be undertaken in two phases: 
• Adaptation into the target language. 
• Validation of the translated Bt-DUX 
 
2.1.1 
Adaptation into the target language 
 
The method used is a well established process set down by Beaton et al, (2). It comprises five 
stages: 
• Initial translation 
• Synthesis of these translations 
• Back translation 
• Expert committee assessment 
• Field testing 
 
Stage I: Initial translation 
 
The first stage in adaptation is the forward translation. At least two forward translations should be 
made of the instrument from the English Bt-DUX into the Italian language. In this way, the 
translations can be compared, and discrepancies which may reflect ambiguous wording in the 
original language, or discrepancies in how a word is translated can be identified. Poorer wording 

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choices can then be discussed and resolved as the best translation between the translators. The 
two independent translations are produced by bilingual translators who have Italian as their 
mother tongue. Translations into the first language of the translator are more likely to accurately 
reflect the nuances of that language. The two translators should have different profiles or 
backgrounds to ensure the best possible translation.  
 
Translator 1: Should be knowledgeable about the type of concepts the questionnaire being 
translated addresses (e.g. cancer / children). Translator 1 adaptations will be aimed at equivalency 
from a more clinical perspective, and may produce a translation that is a more reliable 
equivalence to the original from a measurement perspective. 
 
Translator 2: The other translator should neither be aware nor be informed of the concepts being 
quantified, and preferably have no medical/clinical background. As the so-called “naive” 
translator, he or she is more likely to detect the more subtle differences in meaning of the original 
than the first translator. Translator 2 should not be influenced by an academic goal, and offer a 
translation that reflects the language used by the lay population. This second translation will often 
highlight more ambiguous meanings in the original questionnaire than is found in the first 
translation (3). 
 
The two translators each produce a written report of their translation. Comments are included to 
highlight challenging phrases or uncertainties along with the rationale for final choices. The 
questions, response options and any instructions are all translated using the same process. 
 
Stage II: Synthesis of the translations 
 
To produce a synthesis of the two translations, a third, unbiased person is added to the team. The 
role of this person is to serve as a mediator in discussions of translation differences, and to 
produce a written documentation of the process. Working from the original questionnaire as well 
as the first translator’s version (T1) and the second translator’s (T2), a synthesis of these 
translations is produced, resulting in one common translation (T-12). A written report 
documenting the process, each issue addressed, and how it was resolved is completed. It is 

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important that all issues be resolved by consensus rather than one person compromising their 
feelings. 
 
Stage III: Back-translation: 
 
Working from the T-12 version of the questionnaire, and totally blind to the original version, the 
questionnaire is then translated back into the original language. This is a process of validity 
checking to make sure the translated version accurately reflects the item content of the original 
version. The back translation process often magnifies unclear wording in the translations. 
However, agreement between the back translation and the original source version does not 
guarantee a satisfactory forward translation version (T-12), as an incorrect, but consistent 
translation could occur (4). Back translation is only one type of validity check, and is best at 
highlighting gross inconsistencies or conceptual errors in the translation. As with forward 
translations, two back-translations are considered a minimum. The back-translations (BT1 and 
BT2) are produced by two bilingual persons with English as their mother tongue. The two 
translators should neither be aware nor be informed of the concepts explored, and preferably 
without medical background. The main reasons for this are to avoid information bias and to elicit 
unexpected meanings of the items in the translated questionnaire (T-12) (3,4), thus increase the 
likelihood of “highlighting the imperfections” (4). 
 
Stage IV: Expert Committee 
 
The composition of the Expert Committee is crucial to achieving cross-cultural equivalence of the 
translated instrument. The minimum composition of the Expert Committee should include: 
• A methodologist 
• A health professional 
• All the translators (both forward and backward) 
• The translation synthesis recorder 
 
The original developers of the questionnaire should be in close contact with the Expert 
Committee during this part of the process to respond to questions and provide input. 

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The Expert Committee’s role is to consolidate all the versions and components of the 
questionnaire and all translated versions (T1, T2, T12, BT1, BT2), and develop the final version 
of the questionnaire for field testing. The Committee will review all of the translations and reach 
a consensus on any discrepancy found. Corresponding written reports explaining the rationale of 
each decision at earlier stages of the process should also be available.  
Critical decisions are made by the Expert Committee in finalizing the translated instrument, and 
full written documentation should be made of the issues and rationale for all decisions about any 
of the components. Decisions will need to be made by this Committee to achieve equivalence 
between the source and target version in four areas set out below (3): 
 
• Linguistic equivalence 
Do the words mean the same thing? Are their multiple meanings to a given item? Are there 
grammatical difficulties in the translation? 
• Idiomatic equivalence 
Colloquialisms, or idioms, are difficult to translate. The committee may have to formulate an 
equivalent expression in the target version.  
• Experiential equivalence 
Items seeking to capture and experience of daily life often vary in different countries and cultures. 
In some instances, a given task may simply not be experienced in the target culture, even if it is 
translatable. To address this situation, a questionnaire item addressing a similar action or intent in 
the target culture would need to be identified to replace the original item.  
• Conceptual equivalence 
Often words hold different conceptual meaning between cultures. For instance, the meaning of 
“seeing your family as much as you would like” would differ between cultures based on the 
concept of what defines “family” (i.e., nuclear versus extended family). 
 
The Expert Committee will need to examine the source and back-translated questionnaires for all 
of these types of equivalence items. Consensus among Committee members should be reached on 
all items, and if necessary, the translation/back translation process repeated to clarify how another 
wording of an item would work. The advantage of having all translators present on the Committee 
is that discrepancies or changes in wording could be done immediately. The final questionnaire 

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should be able to be understood by the equivalent of a 12-year-old (roughly a grade six level of 
reading), as this is the general recommended reading level for questionnaires. 
 
2.1.2 
Validation of the Italian Bt-DUX 
The validity of the Bt-DUX-It will be evaluated in accordance with the validation of the original 
Dutch Bt-DUX and Bt-DUX-Eng by computing the internal consistency, construct and 
discriminant validity. Therefore different questionnaires at the domains of Quality of Life and 
Functional Limitations will be employed. 
  
Patients: All patients who underwent a surgical intervention due to a malignant bone tumour in 
the leg will be identified through hospital records. Patients are eligible if they’re aged between 15 
and 25 years at the time of the selection, if the time since surgery is ranged between 12 and 60 
months, if the malignant bone tumour (osteosarcoma or Ewing’s sarcoma) was located around the 
hip or the  knee and the surgical intervention consisted of limb sparing or ablative surgery. 
Patients will be excluded if other medical conditions limit their physical activities. 
 
Instruments: 
Bt-DUX (1). The disease specific Bt-DUX relates to the patient’s subjective feeling about a 
specific aspect, using abstract faces (smiley’s) as answer categories. The expressions from very 
happy to sad (score 1-5) form a five-point Likert scale. The Bt-DUX consists of 20 questions 
which cover the domains social, emotional, cosmetical and physical functioning. Single item 
scores were recoded and computed into raw total and domain scores. These raw scores were 
converted into total and domain scores, ranging from 0-100, with the highest scores indicating 
better QoL .  
 
EORTC QLQ C-30. The European Organization for Research and Treatment of Cancer (EORTC) 
Core Quality of Life Questionnaire is a well-validated instrument that assesses health-related 
quality at life (HRQOL) in cancer patients. It is used in cancer clinical trials in Europe, Canada, 
and the United States, and has demonstrated high reliability and validity in different groups of 
cancer patients. The 30-item EORTC QLQ-C30 questionnaire is composed of scales that evaluate 
physical functioning and role functioning, as well as emotional, social, and cognitive functioning 

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and global QOL. Three symptom scales measure fatigue, pain, and emesis, while six single items 
assess financial impact and physical symptoms such as dyspnoea, sleep disturbance, appetite, 
diarrhoea, and constipation. The time frame is the past week. The questions are formatted with 
either yes or no answers, or by using four-answer categories that range from 1, not at all, to 4, 
very much. The two questions on general health and global QOL are to be answered on a 
numbered visual-analogue scale from I to 7.  
 
The Toronto Extremity Salvage Score (TESS) (7), a validated and reliable disease-specific 
measure developed to evaluate physical disability in patients treated for extremity sarcoma. The 
self-administered questionnaire includes 30 items on activity limitations in daily life, such as 
restrictions in body movement, mobility, self-care and performance of daily tasks and  
routine. The degree of physical disability is rated from 0 (not possible) to 5 (without any 
problem). The raw score is converted to a score ranged from 0 to 100 points, with higher scores 
indicating no functional limitations. 
 
Statistical analysis:  
Descriptive statistics will be used for the patient’s clinical demographic and outcome measures. 
Bar statistics will be viewed to evaluate the distribution of the total and domain scores. Internal 
consistency of the Bt-DUX-It will be determined by calculating Cronbach’s α and by computing 
the correlation between the four domain scores and the total Bt-DUX-It score (domain-total 
correlation). A Cronbach’s α value of 0.85 will be considered as good (9). In order to evaluate the 
preconceived domain structure of the Bt-DUX, an analysis of the item-domain correlation and the 
Cronbach’s α of the four domains will be performed.  
Construct validity of the Bt-DUX-It will be determined by calculating Spearman correlation 
coefficients between the Bt-DUX-It and the measures of quality of life (EORTC QLQ-C30) and 
functional ability domain (TESS). Discriminate validity will be evaluated by the ability of the Bt-
DUX-It to discriminate between patients with worse and better functional status than the median 
value of the outcome measure.  
 
3.  Endpoints:  

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At least 50 patients need to be included to determine the validity of the Italian version of the Bt-
DUX. Final goal of the study is to establish the Bt-DUX as a disease specific instrument to 
evaluate quality of life in children and young adults after surgery due to a malignant bone tumour 
of the leg. 
 
4. Ethics and Regulatory 
 
4.1 
Ethical approval 
Approval for the developmental work on the Dutch version of the Bt-DUX was obtained from the 
Medical Ethical Committee of the Leiden University Medical Centre. It is envisaged that the 
validation of the Italian Bt-DUX will be appropriate to the Italian regulations. Each patient 
involved in the study should complete a written consent form. 
This protocol, the informed consent form and all the necessary relevant information related to the 
study must be submitted to the Ethics Committee for evaluation and must be approved before the 
start of the study. The study will be conducted in accordance with international standards ISO 14: 
155, with the Good Clinical Practice and with the national laws in force. 
It is the responsibility of the investigator to inform the local Ethics Committee if any changes are 
made to the protocol or if any severe adverse effects occur. The investigator stores all 
correspondence with the Ethics regarding the study. 
 
4.2 Patient Information and Informed Consent 
Prior to patient enrollment the Investigator will provide explanation about the study in detail, 
handout the Patient Information and Informed Consent Form. He will also be available for any 
question the patient has about the study. Further he will explain alternative treatment methods and 
that the patients’ data will be protected. Finally a written consent of the patient will be obtained 
prior to patient enrolment by signing the Patient Consent Form. 
The permission for the use of anonymized patient data for medical and scientific purposes is 
given as part of the Patient Consent Form. 
 
5. Publication of  Results  

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The main investigator undertakes to produce the final report, publish all the data collected as 
described in the protocol and to ensure that the data is reported responsibly and consistently. In 
particular, the publication of the data deriving from this study will take place regardless of the 
results obtained. The transmission or dissemination of data, through scientific publications and / 
or presentations in congresses conferences and seminars, will take place exclusively following the 
merely statistical elaboration of the same, or in any case in an absolutely anonymous form. 
 
 
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