Michael Koller

Clinical and psychometric validation of an EORTC questionnaire module, the EORTC QLQ-OES18, to assess quality of life in patients with oesophageal cancer

Quality of life (QOL) assessment requires clinically relevant questionnaires that yield accurate data. This study defined measurement properties and the clinical validity of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module to assess QOL in oesophageal cancer. The oesophageal module the QLQ-OES24 and core questionnaire, the Quality of Life-Core 30 questionnaire (QLQ-C30) was administered patients undergoing treatment with curative (n=267) or palliative intent (n=224) and second assessments performed 3 months or 3 weeks later respectively. Psychometric tests examined scales and measurement properties of the module. Questionnaires were well accepted, compliance rates were high and less than 2% of items had missing data. Multi-trait scaling analyses and face validity refined the module to four scales and six single items (QLQ-OES18). Selective scales distinguished between clinically distinct groups of patients and demonstrated treatment-induced changes over time. The EORTC QLQ-OES18 demonstrates good psychometric and clinical validity. It is recommended for use with the core questionnaire, the QLQ-C30, to assess QOL in patients with oesophageal cancer.

Clinical and psychometric validation of the EORTC QLQ-CR29 questionnaire module to assess health-related quality of life in patients with colorectal cancer

This international study aimed to test the measurement properties of the updated European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module for colorectal cancer, the QLQ-CR29. The QLQ-CR29 was administered with the QLQ-C30, core questionnaire, to 351 patients from seven countries. Questionnaire scaling and reliability were established and clinical and psychometric validity examined. Patient acceptability and understanding were assessed with a debriefing questionnaire. Multi-trait scaling analyses and face validity refined the module to four scales assessing urinary frequency, faecal seepage, stool consistency and body image and single items assessing other common problems following treatment for colorectal cancer. Scales distinguished between clinically distinct groups of patients and did not correlate with QLQ-C30 scales, demonstrating construct validity. The QLQ-CR29 scores were reproducible over time in stable health. The EORTC QLQ-CR29 demonstrates sufficient validity and reliability to support its use to supplement the EORTC QLQ-C30 to assess patient-reported outcomes during treatment for colorectal cancer in clinical trials and other settings.

Development of an EORTC disease-specific quality of life module for use in patients with gastric cancer

Quality of life (QL) is an important outcome in clinical trials in oncology. There is currently no valid international QL measure for gastric cancer. This paper describes the development of a QL module for gastric cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ-C30) questionnaire. Phases I to III of module development were conducted in the United Kingdom, France, Germany and Spain according to EORTC QL Group guidelines. Twenty relevant QL issues were generated from the literature and interviews with health professionals (n=24) and patients (n=58). This produced a 24 item provisional module. Further testing in 115 patients resulted in the QLQ-STO22, containing 22 questions, conceptualised into five scales and four single items, related to disease symptoms, treatment side-effects and emotional issues specific to gastric cancer. The use of the QLQ-C30 supplemented by the QLQ-STO22 will provide a comprehensive QL measure for international trials in gastric cancer.

Role of mesenchymal stem cells in tissue engineering of meniscus

Tissue engineering is a promising approach for the treatment of tissue defects. Mesenchymal stem cells are of potential use as a source of repair cells or of important growth factors for tissue engineering. The purpose of this study was to examine the role of mesenchymal stem cells in meniscal tissue repair. This was tested using several cell and biomaterial-based treatment options for repair of defects in the avascular zone of rabbit menisci. Circular meniscal punch defects (2 mm) were created in the avascular zone of rabbit menisci and left empty or filled with hyaluronan-collagen composite matrices without cells, loaded with platelet-rich plasma, autologous bone marrow, or autologous mesenchymal stem cells. In some experiments, matrices with stem cells were precultured in chondrogenic medium for 14 days before implantation. Rabbits were then allowed free cage movement after surgery for up to 12 weeks. Untreated defects and defects treated with cell-free implants had muted fibrous healing responses. Neither bone marrow nor platelet-rich plasma loaded in matrices produced improvement in healing compared with cell-free implants. The implantation of 14 days precultured chondrogenic stem cell-matrix constructs resulted in fibrocartilage-like repair tissue, which was only partially integrated with the native meniscus. Non-precultured mesenchymal stem cells in hyaluronan-collagen composite matrices stimulated the development of completely integrated meniscus-like repair tissue. The study shows the necessity of mesenchymal stem cells for the repair of meniscal defects in the avascular zone. Mesenchymal stem cells seem to fulfill additional repair qualities besides the delivery of growth factors.

The Tinnitus Research Initiative (TRI) database: A new approach for delineation of tinnitus subtypes and generation of predictors for treatment outcome

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity and treatment is elusive. A large variety of different treatment options have been proposed and from most of them some patients benefit. However, a particular treatment that helps one patient may fail for others. This suggests that there are different forms of tinnitus which differ in their pathophysiology and their response to specific treatments. Therefore, it is a major challenge for tinnitus treatment to identify the most promising therapy for a specific patient.However, most published clinical treatment studies have enrolled only relatively small patient samples, making it difficult to identify predictors of treatment response for specific approaches. Furthermore, inter-study comparability is limited because of varying methods of tinnitus assessment and different outcome parameters. Performing clinical trials according to standardized methodology and pooling the data in a database should facilitate both clinical subtypisation of different forms of tinnitus, and identification of promising treatments for different types of tinnitus. This would be an important step towards the goal of individualized treatment of tinnitus.For these reasons, an international database of tinnitus patients, who undergo specific treatments, and are assessed during the course of this treatment with standardized instruments (e.g., psychoacoustic measures, questionnaires) has been established. The primary objectives of this database are (1) collecting a standardized set of data on patient characteristics, treatments, and outcomes from tinnitus patients consulting specialized tinnitus clinics all over the world (at present 13 centers in 8 countries), (2) delineating different subtypes of tinnitus based on data that has been systematically collected and (3) identifying predictors for individual treatment response based on the clinical profile. Starting in 2008, the database currently contains data from more than 400 patients. It is expected that more centers will join the project and that the patient numbers will rapidly grow, so that this international database will further facilitate future research and contribute to the development of evidence based on individualized treatment.

Methodological aspects of clinical trials in tinnitus: A proposal for an international standard

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus.

A simulation study provided sample size guidance for differential item functioning (DIF) studies using short scales

OBJECTIVE Differential item functioning (DIF) analyses are increasingly used to evaluate health-related quality of life (HRQoL) instruments, which often include relatively short subscales. Computer simulations were used to explore how various factors including scale length affect analysis of DIF by ordinal logistic regression. STUDY DESIGN AND SETTING Simulated data, representative of HRQoL scales with four-category items, were generated. The power and type I error rates of the DIF method were then investigated when, respectively, DIF was deliberately introduced and when no DIF was added. The sample size, scale length, floor effects (FEs) and significance level were varied. RESULTS When there was no DIF, type I error rates were close to 5%. Detecting moderate uniform DIF in a two-item scale required a sample size of 300 per group for adequate (>80%) power. For longer scales, a sample size of 200 was adequate. Considerably larger sample sizes were required to detect nonuniform DIF, when there were extreme FEs or when a reduced type I error rate was required. CONCLUSION The impact of the number of items in the scale was relatively small. Ordinal logistic regression successfully detects DIF for HRQoL instruments with short scales. Sample size guidelines are provided.

Expectations and quality of life of cancer patients undergoing radiotherapy.

Summary Expectations, real or false, affect the way patients respond to their illnesses. We assessed therapy-related expectations in relation to global quality of life in 55 cancer patients before and after radiotherapy. Factor analysis indicated that therapy-related expectations come into three broad categories—pain/emotional control, healing and tumour/symptom control. 35 patients expected ‘healing’ even though curative treatment was intended in only 19 and all patients had been fully informed. The expectation of healing was associated with high quality of life, and the same was true of perception of healing after radiotherapy. In the group as a whole, quality of life was little altered by radiotherapy, but it became substantially worse in those patients who had expected healing but perceived that this had failed, even though physician-assessed Karnofsky status did not change. These findings indicate that the expectation of healing, in cancer patients, is a component of a good global quality of life, whereas more limited expectations (pain control, tumour control) relate to lower quality of life. Patients’ expectations deserve further study as a novel approach to improving care.

Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

BackgroundDifferential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application.MethodsA review of logistic regression DIF analyses in HRQoL was undertaken. Methodological articles from other fields and using other DIF methods were also included if considered relevant.ResultsThere are many competing approaches for the conduct of DIF analyses and many criteria for determining what constitutes significant DIF. DIF in short scales, as commonly found in HRQL instruments, may be more difficult to interpret. Qualitative methods may aid interpretation of such DIF analyses.ConclusionsA number of methodological choices must be made when applying logistic regression for DIF analyses, and many of these affect the results. We provide recommendations based on reviewing the current evidence. Although the focus is on logistic regression, many of our results should be applicable to DIF analyses in general. There is a need for more empirical and theoretical work in this area.

The relationship between overall quality of life and its subdimensions was influenced by culture : analysis of an international database

OBJECTIVE To investigate whether geographic and cultural factors influence the relationship between the global health status quality of life (QL) scale score of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire and seven other subscales representing fatigue, pain, physical, role, emotional, cognitive, and social functioning. STUDY DESIGN AND SETTING A large international database of QLQ-C30 responses was assembled. A linear regression model was developed predicting the QL scale score and including interactions between geographical/cultural groupings and the seven other scale scores. RESULTS The pain subscale appeared to have relatively greater influence and fatigue relatively lower influence for those from other European regions compared with respondents from the UK when predicting overall quality of life (QoL). For Scandinavia physical functioning appeared to contribute relatively less. There was evidence of greater emphasis on cognitive functioning for those from South Asia and Latin America compared with the UK, whereas for those from Islamic countries, the role functioning scale appeared to have less influence and physical and social functioning more influence. CONCLUSION These results provide evidence that different cultural groups may emphasize different aspects of their QoL. This has implications for studies using QoL questionnaires in international comparisons.