• INTERNATIONAL JOURNAL OF PHARMACEUTICAL MEDICINE 2000,14:74-77 74

ORIGINAL ARTICLE

Assessment methods for quality oflife in cancer patients: EORTCTeresa Young

MountVernon Centre for CancerTreatment, Ricksmansworth Road, Northwood, Middx HA6 2RN,UK

Received 4 February 2000; accepted 9 February 2000

SummaryThe European Organization for Research and Treatment of Cancer (EORTC) is one of theoldest and largest clinical trial organizations in Europe. Within this structure, the Quality ofLife Study Group (QLSG) was founded with two objectives: (1) to determine how quality oflife (QOL) should be defined and measured, and (2) to advise on the design, imple­mentation and analysis of QOL studies within EORTC trials. To fulfil its first objectives,the QLSG set forth to develop and validate a modular multidimensional QOL question­naire specific for cancer patients. This resulted in a core questionnaire (the EORTC QLQ­C30) with additional modules that are designed for specific diagnoses and treatments. Thecontent of the questionnaires had to be brief and capable of patient self-report.Psychometric criteria for the questionnaires include reliability, validity (including cross­cultural validity), and responsiveness to changes in the clinical condition of the patient. Anoverview of the processes of developing the core questionnaire and modules is included inthis article.

To fulfil their second objective the QLSG have been collaborating with other EORTCcooperative groups and the Quality of Life Unit at the EORTC Data Centre. The QLSGhas also produced a number of publications and guidelines. A discussion of the guidelinesfor assessing QOL in EORTC trials, including protocol writing, selection of trials, timing ofassessments, and strategies to enhance compliance of patients, physicians, nurses, and datamanagers, has also been included in this article.

Keywords: cancer, quality of life, EORTC QLQ-C30, assessment, questionnairedevelopment.

Introduction

A number of assessment tools that measure quality of life(QOL) have been developed over the past few decades. Thereare two important scales that are used specifically for assessmentof QOL in cancer patients are: (1) the scale developed by theEuropean Organization for Research and Treatment of Cancer(EORTC) and (2) the Functional Assessment of Chronic IllnessTherapy (FACIT) scale. A detailed discussion of the FACITscale is included in a separate article within this issue, while thisarticle focuses on the EORTC scale.

The EORTC is one of the oldest and largest clinical researchorganizations in Europe. Within this organization, the Quality ofLife Study Group (QLSG) was founded in 1980 to determinehow QOL should be defined and measured, and to advise on thedesign, implementation and analysis of QOL studies within

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EORTC trials. To fulfil its first objective, the QLSG set forth todevelop and validate a multidimensional QOL questionnairespecifically for cancer patients. The content of the questionnairehad to be brief and capable of patient self-report. Psychometriccriteria for this questionnaire included reliability, validity(including cross-cultural validity), and responsiveness to changesin the clinical condition of the patient.

The QLSG decided to adopt a modular approach to QOLassessment. This approach resulted in a core questionnaire thatis applicable to all cancer patients, which was supplemented by aseries of diagnosis- or treatment-specific modules (e.g. modulesspecific for breast cancer and high-dose chemotherapy). Therationale for this approach was to allow uniformity across studiesevaluating QOL in patients with various types of cancer, whileretaining flexibility to collect disease- or treatment-specific QOL

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data. The FACIT assessment tool, discussed in an article in thisissue, also follows a modular approach.

Development of the core questionnaire

The core questionnaire, also called QLQ-C30, consists of sixfunctional scales with questions related to physical, role,emotional, cognitive and social functioning, and a global QOLscale. Each scale consists of two to five questions. For example,the physical functioning scale consists of five questions related tothe patient's daily activities and ability to walk (Table 1), whilethe emotional functioning scale consists of four questions.Patient responses are recorded on a 4-point Likert-type scale(i.e. l=not at all; 2=a little; 3=quite a bit; 4=very much).Therefore, the total scores for the physical functioning scale canrange from 5 to 20 whilst those for emotional functioning rangefrom 4 to 16. To ease interpretation, the scores for all scales areconverted to an inverted scale from 100 to 0, where a high scoredenotes good physical functioning. For instance, a score of 5 onthe physical functional scale is converted to 100 on the invertedscale indicating good physical functioning.

In addition to the functional scales, the core questionnaireconsists of a series of symptom scales specific for fatigue, pain,nausea and vomiting, appetite loss, dyspnoea, sleep disturbance,constipation, diarrhoea, and financial impact. Methods of scorecalculation for symptom scales are similar to those described forfunctional scales except that the scores are not inverted, so ahigh score on the inverted scale indicates that the patient isexperiencing severe symptoms while a low score indicates thepatient is experiencing mild or no symptoms.

A number of revisions have been made since the publicationof the first version of the core questionnaire in 1993. Thepurpose of these revisions is to improve the reliability andvalidity of the scales. Currently, the core questionnaire isEORTC QLQ-C30, version 3.0. The internal consistency andtest-retest reliability of the scales can be estimated by evaluatingthe correlation between the individual questions within a scaleby using the Cronbach's coefficient a and the Pearson's rank­correlation coefficients, respectively [1, 2]. Coefficients higherthan 0.7 are usually considered sufficient in group comparisonsto indicate adequate reliability. The clinical validity of the scalescan also be assessed with the use of statistical methods, such asknown group comparisons to assess disease stage, performancestatus and weight loss, and to measure responsiveness for test­retest, pretreatment versus 'on treatment', and treatmenttoxicity. Overall, studies assessing the reliability and validity ofthe core scale showed that the majority of patients could quicklyand easily complete QLQ-C30 [2]. Data were supportive of its

Table 1. Examples of questions from the EORTC-QLQ 30 PhysicalFunctioning Scale

'Do you have any trouble doing strenuous activities, like carrying aheavy shopping bag or a suitcase?'

'Do you have any trouble taking a long walk?'

'Do you have any trouble taking a short walk outside the house?'

'Do you have to stay in bed or a chair for most of the day?'

'Do you need help with eating, dressing, washing yourself or usingthe toilet?'

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ASSESSMENT METHODS FOR QUALITY OF LIFE IN CANCER PATIENTS 75

clinical validity and reliability, and showed responsiveness tochange in clinical status of the patient over time. In addition, theresults were highly consistent across language and culturalgroups [3].

Development of the module

A module is a set of questions referring to disease symptoms,treatment side effects, and additional QOL issues not includedin the core questionnaire. The QSLG modules need to becompatible with QLQ-C30 in response format and time neededto complete the test. For these reasons, a four-point Likert-typescale was used. The modules need to be relatively brief, with lessthan 30 questions, to assure they can be completed in a timelyfashion. At the same time, the questions need to be easy tounderstand. In addition, the modules should be verified forclinical applicability and cross-cultural applicability through peerreview for use in international oncology research [3].

Guidelines for developing a module were published bySprangers et at. in 1993 [4]. These guidelines were developedin an attempt to standardize the procedures and provideuniformity in both the process and the end products of moduledevelopment. According to these guidelines, the moduledevelopment process consists of four phases: (1) generation ofrelevant QOL issues, (2) operationalization of the QOL issuesinto a set of questions, (3) pretesting the module questionnaire,and (4) large-scale field-testing.

Within the EORTC QLSG, a module development committeehas also been established to coordinate, monitor, and review allstages of the development of the module. The biannual meetingsof the group present an opportunity for the members to sharetheir experiences gained from developing a specific module.

Phase 1: generating QOL issuesThe purpose of this phase is to compile extensive information onQOL issues relevant to the disease. First, relevant QOL issuesare identified by researching the literature and existing ques­tionnaires. Second, this information is presented to health careprofessionals with specialization related to the disease beinginvestigated to determine the appropriateness of the content anddepth of coverage, and relative importance of the QOL issuesthat were identified. Based on physician response and sugges­tions, a list of pertinent QOL issues is developed. Finally, this listof issues is presented to a small sample of 10-15 patients todetermine whether patients actually experience the effectsdescribed in the questionnaire. Additional QOL issues areidentified based on patient responses, which leads to furthermodification of the list. By the end of phase I, a comprehensivelist of QOL issues has been established, including informationregarding prevalence and the extent of distress caused by eachQOL issue identified.

Phase II: operationalizationDuring the operationalization phase, the list of QOL issues istransformed into structured questions to create questionnaireitems. For ease of writing, items may be adapted from existingquestionnaires that already have established validity andreliability; however, it is important to obtain permission fromthe authors of those questionnaires. Hence, construction of newitems is rare and should only be considered a last resort. The

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76 YOUNG

product of phase II is a provisional module for testing inpatients.

Phase III: pretestingThe goals of pretesting are: (1) to identify and solve potentialproblems in the administration of the module (i.e. phrasing ofquestions, the sequence of questions), (2) to determine the needfor any additions or deletions to the module, and (3) to obtainpreliminary information on the prevalence and distribution ofpossible patient responses to each question. Pretesting involvesadministration of the provisional module and the core ques­tionnaire to 10-15 patients from the target population, followedby structured interviews with each patient to identify specificissues or problems related to the questionnaire. Based onpatient responses some questions may be modified (i.e. additionsor deletions). Finally, the revised module is submitted to themodule development committee for review.

Phase W' field-testingUpon approval of the module by the module developmentcommittee, the module questionnaire is field-tested in a largergroup of patients to determine its validity, reliability, and cross­cultural applicability. Since this phase requires administration ofthe module to a large number of patients, it has been proposedthat the modules be incorporated into larger ongoing clinicaltrials such as EORTC QOL Study Group field studies, EORTCtrials, and trials sponsored by pharmaceutical companies.

Currently, there are three phase IV modules: lung, head andneck, and breast cancer. These modules have been validated andhave demonstrated reliability. They have been published andinvestigators may obtain permission to use them by contactingthe EORTC data centre. As listed in Table 2, there are severalother modules currently in development.

Translation procedures

Much attention is paid to translation because of the need toprovide clear, easy to read and understandable questionnaires to

Table 2. EORTC QlQ Modules Under Development*

Bladder

Gastric

Ophthalmic

Pancreatic

leukaemia

Brain

Myeloma

Ovarian

Prostate

Colorectal

Oesophageal

Supportive care

cu,High-dose chemotherapy

*Phase II/IIICll=Chronic lymphocytic leukaemia

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patients and clinicians in their own languages. Additionally, theuse of appropriate semantics is important for administration ofquestionnaires in countries with similar language, but differentcultures. For example, there are linguistic and cultural variationsbetween French spoken in France and in Canada. The EORTCtherefore provides multiple translations in French, Spanish,Chinese, Dutch, and Portuguese.

The translation procedure is as follows. Two native speakersindependently translate the questionnaire from English (thesource language) to the target language. Accuracy of translationis verified by checking that the two translations are substantiallyidentical. In case of a disagreement, the process is repeated.When the repeat translations agree, the translated questionnaireundergoes backward translations from the target language toEnglish by two independent native English speakers. This newEnglish version of the questionnaire is compared with theoriginal questionnaire in English. If there is a poor match, theentire translation from the original English version may need tobe repeated. However, if there is a good match the translatedquestionnaire in the target language then undergoes pilottesting. The EORTC QLQ-C30 version 3.0 is currently availablein 30 different languages.

The advisory role of EORTe QLSG

As part of its role to advise on the design, implementation andanalysis of QOL studies within EORTC Trials, the QLSG hasbeen responsible for producing documentation, conductingtraining courses, developing and maintaining a website, andcollaborating with other QOL groups for special projects. Anumber of manuscripts have been published including a manualof reference values, which is also available on CD-ROM.

A considerable amount of data has already been accumulatedfrom the many QOL studies conducted by the QLSG. Thesample sizes range from 70 to 2000 patients and most studiesprovide specific information on patient age, gender, site ofcancer, performance status, treatment, and tumour histology.These data are also available in graphic format. The referencedata collected from these studies can be utilized in many ways (Figure 1). These include: (1) as a comparison reference withscores from a group under study, (2) as a learning aid forinvestigators to gain familiarity with distribution of scores, (3) asa reference for use in sample size calculation, (4) as acomparison reference for individual patient scores, and (5) asa quality control tool for translation procedures.

Another useful publication is Guidelines for Assessing Qualityof Life in EORTC Clinical Trials. Addressing, among otherissues, enhancing complete data collection for the QLQ-C30.According to these guidelines, there are three key individualsresponsible for enhancing complete data collection: the patient,the physician, and the nurse or data manager. To ensurecompletion by patients, it is important to explain the studycarefully. Only instruments with questions the patients are likelyto think are appropriate should be used. Clear instructionsshould be provided and someone should be available to providehelp if requested on the first occasion that the patient completesa questionnaire. Cooperation from physicians can be enhancedby providing examples of published QOL data, by establishinggoals and rationale for the QOL study, and by making QOLassessment mandatory instead of optional in large clinical trials.Cooperation from nurses or data managers can be improved byincreasing awareness of the goals and rationale of the study, by

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ASSESSMENT METHODS FOR QUALITY OF LIFE IN CANCER PATIENTS 77

1. Osoba D, Aaronson N, Zee B, Sprangers M, te Velde A. Modificationof the EORTC QlQ-C30 (version 2.0) based on content validity andreliability testing in large samples of patients with cancer. The StudyGroup on Quality of life of the EORTC and the Symptom Control andQuality of life Committees of the NCI of Canada Clinical Trials Group.Qual Life Res 1997; 6:103-8.

2. Hjermstad MJ, Fossa SD, Bjordal K, Kaasa S. Test/retest study of theEuropean Organization for Research and Treatment of Cancer CoreQuality-of-Life Questionnaire. J Clin Onco/1995; 13:1249-54.

3. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ,et al.. The European Organization for Research and Treatment ofCancer QlQ-C30: a quality-of-life instrument for use in internationalclinical trials in oncology. J Nat! Cancer Inst 1993; 85:365-76.

4. Sprangers MA, Cull A, Bjordal K, Groenvold M, Aaronson NK. TheEuropean Organization for Research and Treatment of Cancer.Approach to quality of life assessment: guidelines for developingquestionnaire modules. EORTC Study Group on Quality of life. QualLife Res 1993; 2:287-95.

5. Fayers P, Weeden S and Curran D. EORTC QLQ-C30 ReferenceValues. Brussels: EORTC QlSQ; 1998.

References

In conclusion, several valid, reliable and sensitrve tools formeasurement of QOL in cancer patients are currently available.There is a need, however, for better infrastructure for datacollection in QOL. Despite availability of the tools, QOL isinsufficiently assessed in many cancer patients. More studieswith QOL as a main endpoint are needed if the impact of canceris to be fully appreciated. Clinicians who understand the clinicalsignificance of changes in QOL scores may then be able to usethis information to improve management of cancer in clinicalpractice.

Conclusions

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Figure 1 Comparison of Functioning Scale Profiles. A comparison ofquality of life data from a sample to EORTC reference data. The samplewas 1314 patients with pancreatic cancer undergoing treatment atSahlgrenska University Hospital, Gothenburg, Sweden. Quality of lifewas assessed using the six modules of the EORTC-QlQ. The referencevalues for pancreatic cancer were taken from the EORTC manual [5].

maintammg adequate and effective communication with theclinician, and by providing appropriate communication and datacollection skills. Finally, obtaining feedback about compliance todate and any early results can increase motivation and enhanceparticipation from everyone involved.

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