Development of an EORTC questionnaire measuring instrumental activities of daily living (IADL) in patients with brain tumours: phase I–III

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) guidelines for module development [14] were followed, consisting of four phases: (I) Generation of items, (II) Construction of the item list, (III) Pre-testing, and (IV) Field testing. This paper reports the results of phases I–III of the developmental process (for more details, see Supplemental File 1; Fig. 1).

The study population consisted of patients with a primary or metastatic brain tumour, their informal caregivers as proxies, and centre-affiliated health care professionals (HCPs) in the field of neuro-oncology. Patients were eligible if they had either a histologically confirmed glioma (based on WHO 2007 criteria) or brain metastases and a histologically confirmed primary tumour. Further inclusion criteria were age (≥ 18 years) and contact frequency between the patient and their proxy (daily or weekly) to ensure a reliable assessment of the patient’s daily functioning. The exclusion criterion was an insufficient understanding of the official language of the country of residence to complete study procedures.

Participant recruitment for phase I took part consecutively in both academic and non-academic outpatient clinics in the Netherlands, Italy, and the United Kingdom and for phase III in three European regions, namely Northern Europe (The Netherlands and Austria), Southern Europe (Italy), an English-speaking region (the United Kingdom, i.e. England and Scotland), and a non-European country (Japan). Patients meeting the in- and exclusion criteria, who were also determined to be physically (i.e. performance status) and mentally (i.e. able to consent to research and have the mental capacity to complete the study procedures) fit to participate by their treating physicians, were approached to participate in the study. Following EORTC QLG module development guidelines, patient recruitment targeted an even distribution across the relevant variables, i.e. tumour type (high-grade glioma (HGG)/low-grade glioma (LGG)/1–3 brain metastases/ > 3 brain metastases) in phase I and, additionally, the presence of cognitive deficits (present/not present) in phase III. Both patient and proxies provided written informed consent before participation.

Phase I aimed to compile an extensive list of IADL relevant to brain tumour patients. Five sources of information were used: (1) the relevant A-IADL-Q [7] activities from a previous study (referred to as ‘pilot study’) in glioma patients [9], and in accordance with EORTC QLG module development guidelines, (2) the literature, (3) the EORTC Item library [15], and semi-structured interviews with (4) patients and their proxies and (5) HCPs.

During the pilot study (source 1), HCPs (N = 6) judged if the activities from the A-IADL-Q could be considered as ‘IADL’ using the definition: ‘IADL are complex activities with little automated skills for which multiple cognitive processes are necessary [6]?’. If ≥ 2 HCPs rated an activity as not being IADL, it was excluded from further analysis. Subsequently, HCPs as well as patients (N = 12) and proxies (N = 12) had to rate if the proposed activities were ‘likely to be affected in brain tumour patients’. Activities were excluded if more than half of all participant groups rated the activity as not affected. Finally, patients, proxies, and HCPs evaluated if the activities from the A-IADL-Q were ‘clearly formulated’. In this case, if an activity was rated unclear by > 4 HCPs or > 10 patients or > 10 proxies, the formulation was reviewed and the item rephrased.

From a literature review of the electronic databases PubMed, Embase, Cochrane, PsycINFO and CINAHL conducted up to April 2017 (source 2) and a review of the items in the EORTC Item Library (source 3), additional potentially relevant IADL were extracted.

Subsequently, a new group of patients (N = 28), proxies (N = 27) and HCPs (N = 18) participated in the semi-structured interviews. Each IADL activity generated from sources 1–3 was rated on both relevance and importance (4‐point Likert‐scale) by patients and proxies, and missing IADL were identified. HCPs also rated the activities on relevance, and in addition provided a top 10 of the most important IADL activities. Items with an average score of < 2.0 on both relevance and importance by either the patients or proxies, or with ≥ 6 HCPs rating them as not relevant, were excluded, except if they were in ≥ 2 HCPs top 10 most important activities.

Finally, another group of patients (N = 2), proxies (N = 2), and HCPs (N = 2) cognitively debriefed the remaining items resulting from sources 1–5 item generation and selection process, and evaluated the appropriateness of the wording of the items, and any potential redundancies (for more details, see Supplemental File 1).

In Phase II, the activities were converted into questionnaire items and a preliminary IADL questionnaire was constructed. Both a patient‐based and proxy‐based version of the IADL questionnaire were constructed and subsequently translated by the EORTC Translation Unit [16] into the languages of the countries participating in phase III (English, Dutch, Italian, German, and Japanese). The proxy-based version consists of the same items but refers to the patient (e.g. ‘has he/she had difficulties’).

Phase III aimed to pre-test the preliminary IADL questionnaire by means of semi-structured interviews and neuropsychological testing. The interview consisted of four parts: (1) completion of the IADL questionnaire (4‐point Likert‐scale [‘not at all’- ‘very much’], and not applicable), (2) rating each activity on relevance and importance (4‐point Likert‐scale) and acceptability (e.g. not too difficult/confusing/annoying/upsetting), (3) identification of the 10 most important activities, and (4) identification of missing activities. For the known-group comparison analysis, patients were classified as with or without cognitive impairments using the standard neuropsychological test battery used in EORTC trials which comprises three objective tests (six outcomes) and a subjective cognitive complaints questionnaire (one outcome) (for more details, see Supplemental File 1). Patients scoring < 2 standard deviations (SD) below the mean of the official norm scores on ≥ 2 out of 7 outcomes were classified as cognitively impaired.

The review of the pilot study’s [9] activities (n = 32) reconfirmed that all items were considered IADL, affected in brain tumour patients and clearly defined. The literature search of 342 unique records resulted in 103 relevant records which described 54 unique questionnaires comprising a total of 1376 items. Out of these 1376 items, 310 were related to IADL. Furthermore, 23 IADL were extracted from qualitative studies. The review of the items in the EORTC Item Library identified 526 unique items of which 12 reflected IADL. The 345 IADL were clustered and merged based on content, and IADL similar to the pilot study items were excluded. On top of the 32 items from the pilot study (source 1), an additional 30 IADL were identified with sources 2 and 3, resulting in 62 activities. The semi-structured interviews generated two new activities (i.e. ‘being independent’ and ‘doing calculations’) and excluded two activities based on HCPs’ assessment of relevance (i.e. ‘arts and crafts’ and ‘following an instruction manual’). The remaining 62 activities were subsequently cognitively debriefed, resulting in the exclusion of two redundant activities (i.e. ‘putting ideas into words’ and ‘engaging socially with other people’) and one unclear activity (i.e. ‘getting started with a task without prompting’) (Fig. 1) (for more details, see Supplemental File 2). In phase II, the remaining 59 activities were formulated as items.