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Background: Patient-reported physical function (PF) is a key endpoint in cancer clinical trials. Using complex statistical methods, common metrics have been developed to compare scores from different patient-reported outcome (PRO) measures, but such methods do not account for possible differences in questionnaire content. Therefore, the aim of our study was a content comparison of frequently used PRO measures for PF in cancer patients. Methods: Relying on the framework of the International Classification of Functioning, Disability and Health (ICF) we categorized the item content of the physical domains of the following measures: EORTC CAT Core, EORTC QLQ-C30, SF-36, PROMIS Cancer Item Bank for Physical Function, PROMIS Short Form for Physical Function 20a, and the FACT-G. Item content was linked to ICF categories by two independent reviewers. Results: The 118 items investigated were assigned to 3 components (‘d – Activities and Participation’, ‘b – Body Functions’, and ‘e – Environmental Factors’) and 11 first-level ICF categories. All PF items of the EORTC measures but one were assigned to the first-level ICF categories ‘d4 – Mobility’ and ‘d5 – Self-care’, all within the component ‘d – Activities and Participation’. The SF-36 additionally included item content related to ‘d9 – Community, social and civic life’ and the PROMIS Short Form for Physical Function 20a also included content related to ‘d6 – domestic life’. The PROMIS Cancer Item Bank (v1.1) covered, in addition, two first-level categories within the component ‘b – Body Functions’. The FACT-G Physical Well-being scale was found to be the most diverse scale with item content partly not covered by the ICF framework. Discussion: Our results provide information about conceptual differences between common PRO measures for the assessment of PF in cancer patients. Our results complement quantitative information on psychometric characteristics of these measures and provide a better understanding of the possibilities of establishing common metrics.

BackgroundThe ACTION trial evaluated the effect of a modified version of the Respecting Choices´ advance care planning programme in patients with advanced cancer in six European countries. For this purpose, an advance directive acceptable for all six ACTION countries to be used for documenting the wishes and preferences of patients and as a communication tool between patients, their caregivers and healthcare staff, was needed.AimTo describe the development of a multinational cancer specific advance directive, the ´My Preferences form´, which was first based on the 2005 Wisconsin ‘Physician Orders of Life Sustaining Treatment´ Form, to be used within the ACTION trial.MethodsFramework analysis of all textual data produced by members of the international project team during the development of the ACTION advance directives (e.g. drafts, emails, meeting minutes…).Setting/participantsACTION consortium members (N = 28) with input from clinicians from participating hospitals (N = 13) and ´facilitators´ (N = 8) who were going to deliver the intervention.ResultsTen versions of the ACTION advance directive, the ´My Preferences form´, were developed and circulated within the ACTION consortium. Extensive modifications took place; removal, addition, modification of themes and modification of clinical to lay terminology. The result was a thematically comprehensive advance directive to be used as a communication tool across the six European countries within the ACTION trial.ConclusionThis article shows the complex task of developing an advance directive suitable for cancer patients from six European countries; a process which required the resolution of several cross cultural differences in law, ethics, philosophy and practice. Our hope is that this paper can contribute to a deeper conceptual understanding of advance directives, their role in supporting decision making among patients approaching the end of life and be an inspiration to others wishing to develop a disease-specific advance directive or a standardised multinational advance directive.

Background Missing data are common in end-of-life care studies, but there is still relatively little exploration of which is the best method to deal with them, and, in particular, if the missing at random (MAR) assumption is valid or missing not at random (MNAR) mechanisms should be assumed. In this paper we investigated this issue through a sensitivity analysis within the ACTION study, a multicenter cluster randomized controlled trial testing advance care planning in patients with advanced lung or colorectal cancer. Methods Multiple imputation procedures under MAR and MNAR assumptions were implemented. Possible violation of the MAR assumption was addressed with reference to variables measuring quality of life and symptoms. The MNAR model assumed that patients with worse health were more likely to have missing questionnaires, making a distinction between single missing items, which were assumed to satisfy the MAR assumption, and missing values due to completely missing questionnaire for which a MNAR mechanism was hypothesized. We explored the sensitivity to possible departures from MAR on gender differences between key indicators and on simple correlations. Results Up to 39% of follow-up data were missing. Results under MAR reflected that missingness was related to poorer health status. Correlations between variables, although very small, changed according to the imputation method, as well as the differences in scores by gender, indicating a certain sensitivity of the results to the violation of the MAR assumption. Conclusions The findings confirmed the importance of undertaking this kind of analysis in end-of-life care studies.

Patient-reported outcomes (PROs), such as symptoms, function, and other health-related quality-of-life aspects, are increasingly evaluated in cancer randomised controlled trials (RCTs) to provide information about treatment risks, benefits, and tolerability. However, expert opinion and critical review of the literature showed no consensus on optimal methods of PRO analysis in cancer RCTs, hindering interpretation of results. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium was formed to establish PRO analysis recommendations. Four issues were prioritised: developing a taxonomy of research objectives that can be matched with appropriate statistical methods, identifying appropriate statistical methods for PRO analysis, standardising statistical terminology related to missing data, and determining appropriate ways to manage missing data. This Policy Review presents recommendations for PRO analysis developed through critical literature reviews and a structured collaborative process with diverse international stakeholders, which provides a foundation for endorsement; ongoing developments of these recommendations are also discussed.

Background There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform product labeling, clinical guidelines, and health policy. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data for Cancer Clinical Trials (SISAQOL) Consortium aims to develop guidelines and recommendations to standardize analyses of patient-reported outcome data in cancer RCTs. Methods and Results Members from the SISAQOL Consortium met in January 2017 to discuss relevant issues. Data from systematic reviews of the current state of published research in patient-reported outcomes in cancer RCTs indicated a lack of clear reporting of research hypothesis and analytic strategies, and inconsistency in definitions of terms, including “missing data,”“health-related quality of life,” and “patient-reported outcome.” Based on the meeting proceedings, the Consortium will focus on three key priorities in the coming year: developing a taxonomy of research objectives, identifying appropriate statistical methods to analyze patient-reported outcome data, and determining best practices to evaluate and deal with missing data. Conclusion The quality of the Consortium guidelines and recommendations are informed and enhanced by the broad Consortium membership which includes regulators, patients, clinicians, and academics.

Background To optimise measurement precision, relevance to patients and flexibility, patient-reported outcome measures (PROMs) should ideally be adapted to the individual patient/study while retaining direct comparability of scores across patients/studies. This is achievable using item banks and computerised adaptive tests (CATs). The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) is one of the most widely used PROMs in cancer research and clinical practice. Here we provide an overview of the research program to develop CAT versions of the QLQ-C30's 14 functional and symptom domains. Methods The EORTC Quality of Life Group's strategy for developing CAT item banks consists of: literature search to identify potential candidate items; formulation of new items compatible with the QLQ-C30 item style; expert evaluations and patient interviews; field-testing and psychometric analyses, including factor analysis, item response theory calibration and simulation of measurement properties. In addition, software for setting up, running and scoring CAT has been developed. Results Across eight rounds of data collections, 9782 patients were recruited from 12 countries for the field-testing. The four phases of development resulted in a total of 260 unique items across the 14 domains. Each item bank consists of 7–34 items. Psychometric evaluations indicated higher measurement precision and increased statistical power of the CAT measures compared to the QLQ-C30 scales. Using CAT, sample size requirements may be reduced by approximately 20–35% on average without loss of power. Conclusions The EORTC CAT Core represents a more precise, powerful and flexible measurement system than the QLQ-C30. It is currently being validated in a large independent, international sample of cancer patients. © 2018. This is the authors’ accepted and refereed manuscript to the article. Locked until 21..2019 due to copyright restrictions. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Although patient-reported outcomes (PROs), such as health-related quality of life, are important endpoints in randomised controlled trials (RCTs), there is little consensus about the analysis, interpretation, and reporting of these data. We did a systematic review to assess the variability, quality, and standards of PRO data analyses in advanced breast cancer RCTs. We searched PubMed for English language articles published in peer-reviewed journals between Jan 1, 2001, and Oct 30, 2017. Eligible articles were those that reported PRO results from RCTs of adult patients with advanced breast cancer receiving anti-cancer treatments with reported sample sizes of at least 50 patients—66 RCTs met the selection criteria. Only eight (12%) RCTs reported a specific PRO research hypothesis. Heterogeneity in the statistical methods used to assess PRO data was observed, with a mixture of longitudinal and cross-sectional techniques. Not all articles addressed the problem of multiple testing. Fewer than half of RCTs (28 [42%]) reported the clinical significance of their findings. 48 (73%) did not report how missing data were handled. Our systematic review shows a need to improve standards in the analysis, interpretation, and reporting of PRO data in cancer RCTs. Lack of standardisation makes it difficult to draw robust conclusions and compare findings across trials. The Setting International Standards in the Analyzing Patient-Reported Outcomes and Quality of Life Data Consortium was set up to address this need and develop recommendations on the analysis of PRO data in RCTs.

Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making.

Cancer has increasingly become a chronic condition and the routine collection of patient-reported outcomes (PROs) like quality of life is widely recommended for clinical practice. Nonetheless, the successful implementation of PROs is still a major challenge, although common barriers to and facilitators of their beneficial use are well known. To support health care professionals and other stakeholders in the implementation of the EORTC PRO measures, the EORTC Quality of Life Group provides guidance on issues considered important for their use in daily clinical practice. Herein, we present an outline of the newly developed “'Manual for the use of EORTC measures in daily clinical practice”, covering the following issues: * a rationale for using EORTC measures in routine care *selection of EORTC measures, timing of assessments, scoring and presentation of results * aspects of a strategic implementation * electronic data assessment and telemonitoring, and * further use of EORTC measures and ethical considerations. Next to an extensive overview of currently available literature, the manual specifically focuses on knowledge about EORTC measures to give evidence-based recommendations whenever possible and to encourage readers and end-users of EORTC measures to contribute to further needed high-quality research. The manual will be accessible on the EORTC Quality of Life Group website's homepage and will be periodically updated to take into account any new knowledge due to medical, technical, regulatory and scientific advances. Keywords: EORTC Quality of Life Group, Patient-reported outcomes, Quality of life, Neoplasms, Manual, Implementation, Daily clinical routine, Guideline

Hypothyroidism is often detected, and subsequently treated, due to health-related quality of life (HRQL) considerations. However, disease specific HRQL impairments and changes following thyroid hormone substitution have not previously been assessed with a validated disease specific instrument. Eighty-one patients with autoimmune hypothyroidism answered disease-specific (ThyPRO) and generic (SF-36) HRQL questionnaires before and 6 months after initiation of levothyroxine substitution. ThyPRO consists of 85 items that assess physical, mental, and social domains of functioning and well-being in patients with benign thyroid disorders. The items are summarized in 13 scales. SF-36 consists of 36 items summarized in 8 scales. NormativeThyPRO(n= 739) and SF-36 (n = 6,638) data were collected from representative general population samples. Score differences between patients and the general population and associations between thyroid stimulating hormone (TSH) and HRQL were assessed with multivariate linear regression analyses adjusted for age, gender, comorbidity and educational status. Changes following treatment were analyzed with the paired t-test. All analyses were adjusted for multiple testing (Hochberg method). Prior to treatment, patients' ThyPRO scores were impaired, compared to the general population, on all 9 comparable scales ( p-values

Breast cancer and its treatment have been associated with psychological morbidity. In this study our aim was to quantify the excess anxiety and depression resulting from breast cancer. We compared 538 newly diagnosed breast cancer patients at low risk of recurrence (87.0% responded) to 872 women randomly selected from the Danish general population (69.7% responded) using the Hospital Anxiety and Depression Scale (HADS). Contrary to expectations, the proportions classified as "cases" of anxiety and depression were not significantly different in the two groups. The breast cancer patients' mean HADS scores were significantly lower than those in the general population sample (anxiety, P = 0.021; depression, P