Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.

Recommendations on the use of item libraries for patient-reported outcome measurement in oncology trials: findings from an international, multidisciplinary working group.

The use of item libraries for patient-reported outcome (PRO) measurement in oncology allows for the customisation of PRO assessment to measure key health-related quality of life concepts of relevance to the target population and intervention. However, no high-level recommendations exist to guide users on the design and implementation of these customised PRO measures (item lists) across different PRO measurement systems. To address this issue, a working group was set up, including international stakeholders (academic, independent, industry, health technology assessment, regulatory, and patient advocacy), with the goal of creating recommendations for the use of item libraries in oncology trials. A scoping review was carried out to identify relevant publications and highlight any gaps. Stakeholders commented on the available guidance for each research question, proposed recommendations on how to address gaps in the literature, and came to an agreement using discussion-based methods. Nine primary research questions were identified that formed the scope and structure of the recommendations on how to select items and implement item lists created from item libraries. These recommendations address methods to drive item selection, plan the structure and analysis of item lists, and facilitate their use in conjunction with other measures. The findings resulted in high-level, instrument-agnostic recommendations on the use of item-library-derived item lists in oncology trials.

A multicenter international prospective study of the validity and reliability of a COVID-19-specific health-related quality of life questionnaire.

PURPOSE: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. METHODS: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach's α, and intra-class correlation coefficient). RESULTS: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68-0.92) and test-retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. CONCLUSION: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.

Quality of life of long-term childhood acute lymphoblastic leukemia survivors: Comparison with healthy controls.

OBJECTIVE: Improved treatment landscape has led to better outcomes for paediatric acute lymphoblastic leukemia (ALL) survivors. As the number of survivors increase, we need to elucidate the long-term quality of life (QoL) and domains of complaints in these patients. Furthermore, the main priorities of these patients need to be clarified. We assessed long-term QoL outcomes of survivors of childhood ALL compared to matched population controls. METHODS: QoL data were collected from survivors recruited in France and Belgium between 2012 and 2017, including the Short Form Health Survey (SF-12) and the Quality of Life Systemic Inventory (QLSI). The Wilcoxon test was used to compare SF-12 scale scores between survivors and matched population controls. For the QLSI, comparisons were mainly descriptive. RESULTS: One hundred and eighty-six survivors (mean age: 27.6 years; range: 18.1-52.8) at follow-up completed QoL measures, amongst whom 180 were matched to controls. Overall, survivors had higher QoL on all SF12 scale scores, indicating that they had better functioning compared to controls. Statistically significant differences on the SF12 were observed for Vitality, Social Functioning, Role Limitations due to Emotional Problems and Mental Health scales. QLSI outcomes suggested that survivors were happier than controls with Couple and Social Relations. Controls were unhappiest compared to survivors with Money, Love life, Self-esteem, Nutrition and Paid Work. CONCLUSIONS: Our findings suggest that survivors of childhood ALL have better QoL outcomes on some domains compared to the general population, specifically around social and emotional functioning, and that they tend to prioritize their relationships more. Interventions for improving QoL outcomes, might build on existing positive experiences with family, friends and partners.

Clustering of EORTC QLQ-C30 health-related quality of life scales across several cancer types: Validation study.

INTRODUCTION: The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) measures 15 health-related quality of life (HRQoL) scales relevant to the disease and treatment of patients with cancer. A study by Martinelli (2011) demonstrated that these scales could be grouped into three main clusters: physical, psychological and gastrointestinal. This study aims to validate Martinelli's findings in an independent dataset and evaluate whether these clusters are consistent across cancer types and patient characteristics. METHODS: Pre-defined criteria for successful validation were three main clusters should emerge with a minimum R-squared value of 0.51 using pooled baseline-data. A cluster analysis was performed on the 15 QLQ-C30 HRQoL-scales in the overall dataset, as well as by cancer type and selected patient characteristics to examine the robustness of the results. RESULTS: The dataset consisted of 20,066 patients pooled across 17 cancer types. Overall, three main clusters were identified (R2 = 0.61); physical-cluster included role-functioning, physical-functioning, social-functioning, fatigue, pain, and global-health status; psychological-cluster included emotional-functioning, cognitive-functioning, and insomnia; gastro-intestinal-cluster included nausea/vomiting and appetite loss. The results were consistent across different levels of disease severity, socio-demographic and clinical characteristics with minor variations by cancer type. Global-health status was found to be strongly linked to the scales included in the physical-functioning-related cluster. CONCLUSION: This study successfully validated prior findings by Martinelli (2011): the QLQ-C30 scales are interrelated and can be grouped into three main clusters. Knowing how these multidimensional HRQoL scales are related to each other can help clinicians and patients with cancer in managing symptom burden, guide policymakers in defining social-support plans and inform selection of HRQoL scales in future clinical trials.

Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure.

BACKGROUND: We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development. METHODS: Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions. RESULTS: The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire. CONCLUSION: The resulting COVID-19 questionnaire covers health-related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients' acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).

Equivalence testing of a newly developed interviewer-led telephone script for the EORTC QLQ-C30.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously available. The aim of this study was to develop a voice script for interviewer administration via telephone. METHODS: Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. RESULTS: Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n = 63; mean age 55.48; 65.1% female). Total ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48-0.86) to 0.90 (global health status/QoL, 95% CI 0.80-0.95; pain, 95% CI 0.79-0.95; constipation, 95% CI 0.80-0.95). For paper first administration, all ICCs were above 0.70, except nausea and vomiting (ICC 0.55; 95% CI 0.24-0.76) and financial difficulties (ICC 0.60; 95% CI 0.31-0.79). For phone first administration, all ICCs were above 0.70. CONCLUSIONS: The equivalence testing results support the voice script's validity for administration of the QLQ-C30 via telephone.

Health-related quality of life issues, including symptoms, in patients with active COVID-19 or post COVID-19; a systematic literature review.

PURPOSE: This systematic review was performed to identify all relevant health-related quality of life (HRQoL) issues associated with COVID-19. METHODS: A systematic literature search was undertaken in April 2020. In four teams of three reviewers each, all abstracts were independently reviewed for inclusion by two reviewers. Using a pre-defined checklist of 93 criteria for each publication, data extraction was performed independently by two reviewers and subsequently compared and discussed. If necessary, a third reviewer resolved any discrepancies. The search was updated in February 2021 to retrieve new publications on HRQoL issues including issues related to the long-term consequences of COVID-19. RESULTS: The search in April 2020 identified 3342 potentially relevant publications, and 339 publications were selected for full-text review and data extraction. We identified 75 distinct symptoms and other HRQoL issues categorized into 12 thematic areas; from general symptoms such as fever, myalgia, and fatigue, to neurological and psychological issues. The updated search revealed three extra issues experienced during active disease and long-term problems with fatigue, psychological issues and impaired cognitive function. CONCLUSION: This first comprehensive systematic review provides a detailed overview of the wide range of HRQoL issues experienced by patients with COVID-19 throughout the course of the disease. It demonstrates the devastating impact of the disease and provides critically important information for clinicians, to enable them to better recognize the disease and to provide knowledge important for treatment and follow-up. The results provided the foundation for the international development of a COVID-19 specific patient-reported HRQoL questionnaire.

Reference values for the EORTC QLQ-C30 in patients with advanced stage Hodgkin lymphoma and in Hodgkin lymphoma survivors.

OBJECTIVES: To provide reference values for the European Organisation for Treatment and Research of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) in advanced-stage Hodgkin lymphoma (HL) patients and 5-year HL survivors. The QLQ-C30 is the most widely used cancer-specific questionnaire to assess Health-Related Quality of Life (HRQoL). METHODS: The EORTC database was searched to identify HL RCTs in which patients' and survivors' HRQoL was assessed by the QLQ-C30. HRQoL mean scores were calculated and stratified by age and gender. Minimal important differences were used to assess the clinical relevance of the findings. Data from one RCT with HRQoL scores available at baseline (n = 343) and four RCTs with HRQoL scores available at follow-up (n = 1665) were analyzed. RESULTS: Patients reported worse HRQoL scores than survivors across most functioning scales and symptoms' scales. These scores varied as a function of gender but not age. Survivors' HRQoL reports were comparable to the ones of the general population. CONCLUSIONS: These values provide an assessment framework for the comparison and interpretation of QLQ-C30 scores in advanced-stage HL. Our findings suggest that although HL patients' HRQoL scores are worse than the general population, HRQoL scores may normalize over long-term survival.

Objective neurocognitive functioning and neurocognitive complaints in patients with high-grade glioma: Evidence of cognitive awareness from the European Organisation for Research and Treatment of Cancer brain tumour clinical trials.

BACKGROUND: Neurocognitively impaired patients with brain tumour are presumed to have reduced cognitive awareness preventing them from adequately valuing and reporting their own functioning, for instance, when providing patient-reported outcomes (PROs) such as health-related quality of life instruments. In this cross-sectional study, we aimed at assessing the concordance of neurocognitive complaints (NCCs) and objective neurocognitive functioning (NCF) as a measure of cognitive awareness. METHODS: NCF was assessed using an internationally accepted clinical trial battery. NCC was assessed using the cognitive functioning questionnaire from the Medical Outcome Study (MOS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire cognitive functioning subscale. Patients were divided in cognitively impaired and unimpaired groups, based on their NCF performance. Pearson's correlation coefficients between NCF and NCCs were calculated. The same procedure was used to evaluate the correlation of NCF and QLQ-C30 CF subscale. RESULTS: Data from EORTC trials 26091 and 26101 were pooled into a data set of 546 patients. Twenty percent of patients could be characterised as unimpaired (109) and 80% as impaired (437). Impaired patients reported more cognitive complaints on the MOS scale than unimpaired patients. Correlations between NCF and NCCs were weak but significant for impaired patients and non-significant for unimpaired ones. Similar results were found for the correlation between NCF test performance and the QLQ-C30 CF subscale. CONCLUSION: Correlations between NCF test scores and complaints were weak but suggesting that neurocognitive impairment in patients with HGG does not preclude cognitive awareness. However, considering the findings of this study, we would suggest not to use PROs as a surrogate of performance-based neurocognitive evaluation.

Sociodemographic and Medical Determinants of Quality of Life in Long-Term Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC CLG Studies.

BACKGROUND: due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive. We investigated potential risk factors for decreased daily life quality and life challenges in long-term childhood ALL survivors enrolled between 1971 and 1998 in EORTC studies. METHODS: self-report questionnaires were collected from 186 survivors (109 females; mean age at diagnosis 5.62 years, range 0.2-14.7; median time since diagnosis of 20.5 years (12.9-41.6)), including the Short-Form Health Survey (SF-12) and Impact of Cancer-Childhood Survivors (IOC-CS). Multivariable linear regression models were used to assess the impact of gender, age at diagnosis, relapse/second neoplasm, National Cancer Institute (NCI) risk group and cranial radiotherapy on 2 subscales of the SF-12 (physical and mental health) and five subscales of the IOC-CS (life challenges, body and health, personal growth, thinking and memory problems and socializing). RESULTS: mental component scores of SF-12 were not significantly associated with any risk factor. Physical component scores were lower in relapsed, irradiated and NCI high-risk patients. Regarding IOC-CS negative impact subscales, life challenges was more negatively impacted by cancer in female, younger (i.e., <6 years) and relapsed patients. Regarding the positive impact scales, personal growth was more positively impacted in relapsed patients, whereas body and health, and socializing, were less positively impacted in these patients, compared to non-relapsed patients. Socializing was more positively impacted in older patients (>6 years). CONCLUSIONS: this study demonstrates that long-term outcomes can be both adverse and positive, depending on the patient's demographic and clinical characteristics. Younger, female, and relapsed patients might encounter more life challenges years after their disease, while physical challenges could occur more often in relapsed and high-risk patients. Finally, the positive effect on socializing in the older patients sheds new light on the importance of peer interactions for this subgroup. Specific individual challenges thus need specialized support for specific subgroups.

Demystifying the estimand framework: a case study using patient-reported outcomes in oncology.

Patient-reported outcome (PRO) measures describe how a patient feels or functions and are increasingly being used in benefit-risk assessments in the development of cancer drugs. However, PRO research objectives are often ill-defined in clinical cancer trials, which can lead to misleading conclusions about patient experiences. The estimand framework is a structured approach to aligning a clinical trial objective with the study design, including endpoints and analysis. The estimand framework uses a multidisciplinary approach and can improve design, analysis, and interpretation of PRO results. On the basis of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use E9(R1) addendum, we provide an overview of the estimand framework intended for a multistakeholder audience. We apply the estimand framework to a hypothetical trial for breast cancer, using physical function to develop specific PRO research objectives. This Policy Review is not an endorsement of a specific study design or outcome; rather, it is meant to show the application of principles of the estimand framework to research study design and add to ongoing discussion. Use of the estimand framework to review medical products and label PROs in oncology can improve communication between stakeholders and ultimately provide a clearer interpretation of patient experience in the development of oncological drugs.

Results from a 1-day workshop on the assessment of quality of life in cancer patients: a joint initiative of the Japan Clinical Oncology Group and the European Organisation for Research and Treatment of Cancer.

This report summarizes the presentations and discussion in the first Japan Clinical Oncology Group-European Organisation for Research and Treatment of Cancer Quality of Life/Patient-Reported Outcome workshop funded by the National Cancer Center Hospital that was held on Saturday, 1 September 2018 in Tokyo, Japan. The infrastructure and understanding regarding the Quality of Life/Patient-Reported Outcome assessment of cancer patients in Japan is still immature, in spite of the increased demand for oncological Patient-Reported Outcome research felt not only by researchers but also by patients or other stakeholders of cancer drug development. The workshop aimed to share each perspective, common issues to be considered and future perspectives regarding the strong alliance between the European Organisation for Research and Treatment of Cancer Quality of Life Group and the Japan Clinical Oncology Group for Quality of Life/Patient-Reported Outcome research as well as explore the possibility of conducting collaborative research. European Organisation for Research and Treatment of Cancer is a leading international cancer clinical trials organization, and its Quality of Life Group is a global leader in the implementation of Quality of Life research in cancer patients. The three invited speakers from the European Organisation for Research and Treatment of Cancer Quality of Life Group presented their perspective, latest methodology and ongoing projects. The three speakers from the Japan Clinical Oncology Group presented their current status, experience and some issues regarding data management or interpretation of the Patient-Reported Outcome data. The two patient advocates also shared their expectations in terms of advances in cancer research based on the Patient-Reported Outcome assessment. As the next steps after this workshop, the Japan Clinical Oncology Group and European Organisation for Research and Treatment of Cancer have decided to cooperate more closely to facilitate Patient-Reported Outcome research in both the groups, and the Japan Clinical Oncology Group has approved the establishment of a new committee for Quality of Life/Patient-Reported Outcome research in Japan.

International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium.

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.

Reference values for the EORTC QLQ-C30 in early and metastatic breast cancer.

BACKGROUND: Considering the worldwide incidence of breast cancer (BC) and the importance of health-related quality of life (HRQoL) assessment, there is a growing need to have accurate and up-to-date reference values (RVs). RVs are useful for the design of randomised controlled trials (RCTs) and as benchmarks for comparison of cancer RCTs and health care interventions. This study aimed to provide RVs for the QLQ-C30 in early BC (EBC) and metastatic BC (MBC). General patterns of main results from the EORTC dataset (main dataset) were compared with the PDS dataset (comparison dataset) to see whether they would be consistent across pre-defined covariates. METHODS: European Organization for Research and Treatment of Cancer (EORTC) (main dataset) and Project Data Sphere (PDS) (comparison dataset) were searched to identify BC RCTs where baseline HRQoL (before treatment) was assessed with the QLQ-C30. RVs were calculated and stratified by disease stage, age, and when available, performance status (PS), comorbidity and region. RVs were reported using descriptive statistics. RESULTS: Data from three EORTC (n = 4115) and three PDS RCTs (n = 1406) were included in the analysis. While EBC patients presented better HRQoL with high baseline functioning scores and low prevalence of symptoms, MBC patients reported worse HRQoL with lower functioning scores and more prevalence of symptoms. In MBC, poor PS and presence of comorbidities reflected worse baseline HRQoL. No consistent differences were found for age and countries. CONCLUSION: These up-to-date RVs for the EORTC QLQ-C30 in BC show differences in HRQoL scores between stages, PS, and comorbidities. These findings, supported by an independent dataset, will help the clinical interpretation of scores for BCpatients.

Prognostic value of patient-reported outcomes from international randomised clinical trials on cancer: a systematic review.

A previous review published in 2008 highlighted the prognostic significance of baseline patient-reported outcomes (PROs) as independent predictors of the overall survival of patients with cancer in clinical studies. In response to the methodological limitations of studies included in the previous review, recommendations were subsequently published in the same year to promote a higher level of methodological rigour in studies of prognostic factors. Our systematic review aimed to provide an update on progress with the implementation of these recommendations and to assess whether the methodological quality of prognostic factor analyses has changed over time. Of the 44 studies published between 2006 and 2018 that were included in our review, more standardisation and rigour of the methods used for prognostic factor analysis was found compared with the previous review. 41 (93%) of the trials reported at least one PRO domain as independently prognostic. The most common significant prognostic factors reported were physical functioning (17 [39%] studies) and global health or quality of life (15 [34%] studies). These findings highlight the value of PROs as prognostic or stratification factors in research across most types of cancer.

Sequential effects of reappraisal and rumination on anger during recall of an anger-provoking event.

In everyday life, people often combine strategies to regulate their emotions. However, to date, most research has investigated emotion regulation strategies as if they occur independently from one another. The current study aims to better understand the sequential interplay between strategies by investigating how reappraisal and rumination interact to affect anger experience. After participants (N = 156) recalled a recent anger-provoking event, they were instructed to either a) reappraise the event twice, b) reappraise the event, and then ruminate about the event, c) ruminate about the event, and then reappraise the event, or d) ruminate twice about the event. The effects of the first strategy used replicated a large body of research: reappraisal was associated with a decrease in anger, but rumination was associated with no change in anger. There was a small interactive effect of the combination of the two strategies, such that those who ruminated and then reappraised showed a larger decrease in anger than those who reappraised and then ruminated. There were no other differences between groups. This suggests that the second strategy does have an effect over and beyond the first strategy, but this effect is small in size, highlighting the importance of the initial emotion regulation strategy used.

Statistical analysis of patient-reported outcome data in randomised controlled trials of locally advanced and metastatic breast cancer: a systematic review.

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.

Moving forward toward standardizing analysis of quality of life data in randomized cancer clinical trials.

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.