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.

Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.

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.

68Ga-prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Prostate Cancer Imaging: A Narrative Literature Review.

The 68Ga-prostate-specific membrane antigen ( 68Ga-PSMA) has been recently developed to be used, as a ligand, in positron emission tomography/computed tomography (PET/CT) prostate cancer imaging, to detect prostate disease. The main objective of this review was to collect data and findings from other studies and articles to assess, theoretically, if 68GA-PSMA PET/CT is a more appropriate prostate cancer diagnostic technique in comparison with others available such as CT, 18F-fluoro-2-deoxyglucose PET/CT, or 18F-fluoromethylcholine ( 18F-choline) PET/CT. For that purpose, PubMed, the online scientific articles' database, was consulted where the keywords "PSMA" and "PET" were used to find relevant articles. The clinicaltrials.gov, clinical trials' database, was also consulted where the keywords "68Ga-PSMA" and "prostate" were used to search clinical trials. Based on the reviewed scientific literature, several studies were conducted to assess and compare the 68Ga-PSMA PET/CT detection rate in prostate cancer with other available techniques. One of those studies, conducted by Giesel et al., concluded, within study sample, that 75% of patients with lymph nodes detected by 68Ga-PSMA PET/CT would have not been identified using other conventional morphological criteria based techniques. In Eiber et al.'s study, 68Ga-PSMA PET detected prostatic disease findings in 67% of patients with prostate-specific antigen levels <1 ng/mL, when compared with choline-based PET that presented detection rates between 19% and 36%. In Bluemel et al.'s study, 68Ga-PSMA identified positive prostatic disease in 43.8% of the patients with negative findings in F-choline PET/CT. Findings from this review demonstrate that 68Ga-PSMA PET/C is more effective in detecting metastases, lymph nodes, and recurrent prostate cancer when compared to 18F-choline-based PET/CT and CT. 68Ga-PSMA PET/CT presents also more imaging contrast and can be more cost-effective. 68Ga-PSMA has already been subjected to first-in-human trials, and it is now being tested in Phase II and III trials.

Geriatric oncology: comparing health related quality of life in head and neck cancer patients.

BACKGROUND: Population ageing is increasing the number of people annually diagnosed with cancer worldwide, once most types of tumours are age-dependent. High-quality healthcare in geriatric oncology requires a multimodal approach and should take into account stratified patient outcomes based on factors other than chronological age in order to develop interventions able to optimize oncology care.This study aims to evaluate the Health Related Quality of Life in head and neck cancer patients and compare the scores in geriatric and younger patients. METHODS: Two hundred and eighty nine head and neck cancer patients from the Oncology Portuguese Institute participated in the Health Related Quality of Life assessment. Two patient groups were considered: the geriatric (≥ 65 years old, n = 115) and the younger (45-60 years old, n= 174). The EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires were used. RESULTS: Head and neck cancer patients were mostly males, 77.4% within geriatric group and 91.4% among younger patients group.The most frequent tumour locations were similar in both groups: larynx, oral cavity and oropharynx - base of the tongue.At the time of diagnosis, most of younger male patients were at disease stage III/IV (55.9%) whereas the majority of younger female patients were at disease stage I/II (83.4%). The geriatric patient distribution was found to be similar in any of the four disease stages and no gender differences were observed.We found that age (geriatrics scored generally worse), gender (females scored generally worse), and tumour site (larynx tumours denounce more significant problems between age groups) clearly influences Health Related Quality of Life perceptions. CONCLUSIONS: Geriatric oncology assessments signalize age-independent indicators that might guide oncologic geriatric care optimization. Decision-making in geriatric oncology must be based on tumour characteristics and chronological age but also on performance status evaluation, co-morbidity, and patient reported outcomes assessment.

[Quality of life in oncology: electronic device to collect data]. / Qualidade de vida em oncologia: dispositivo digital de recolha de dados.

INTRODUCTION: We aimed to evaluate an automated method for collecting data for cancer patients' quality of life (QoL). We compared the traditional method of collecting data on paper with the new collecting method using a touch screen computer. We also studied its reliability as a feasible alternative to evaluate the QoL of cancer patients in real time. METHODS: 200 cancer patients completed the EORTC QLQ-C30 on paper and on the computer with a time interval of one hour. The first 100 patients answered first on paper and, subsequently, on the computer; the remaining patients followed the opposite procedure. RESULTS: There were no statistically significant differences between the paper and the computer answers. We observed high correlations and large agreements between them. The best correlation values were obtained for the subscales diarrhea and physical functioning. Besides these findings, we observed a higher acceptability among patients using the computer when comparing with the use of paper. CONCLUSION: The computer version of the QLQ-C30 showed similar results compared to the paper version and it proved to be better accepted and tolerated by the cancer patients included in the study. This method can be valid in oncology setting and useful for monitoring the patients' QoL in daily practice, in real time, and it could be a useful means to support clinical decision making.

Observation of the treatment and outcomes of patients receiving chemotherapy for advanced NSCLC in Europe (ACTION study).

OBJECTIVE: The ACTION (Assessment of Cost and ouTcomes of chemotherapy In an Observational setting) study investigated associations between chemotherapy, patient/disease characteristics and outcomes in advanced non-small cell lung cancer (NSCLC) patients in clinical practice. RESEARCH DESIGN AND METHODS: Chemonaïve NSCLC patients from five European countries were observed for 18 months from initiation of first-line chemotherapy; care was at the physician's discretion. MAIN OUTCOME MEASURES: Survival and associated prognostic factors were estimated using Kaplan-Meier methods and a Cox proportional hazards model, respectively. Cluster analyses of baseline patient characteristics were also performed. Toxicity data were not considered in these analyses. RESULTS: A total of 975 eligible patients with NSCLC (Stage IIIb/IV) were enrolled and provided baseline and response data; cluster analysis was performed on 829 patients and survival data were available from 906 patients. In first-line treatment, a 39.8% response rate, a 39.5% 1-year survival rate and unadjusted median survival of 9.3 months were observed. Prognostic factors for survival included performance status (PS), number of metastatic organs, gender and age. Five patient clusters were identified, highlighting patient heterogeneity in terms of baseline condition and age. PS was maintained or improved throughout first-line and second-line chemotherapy in half the patients receiving these treatments. CONCLUSIONS: ACTION provides valuable information about patient population, disease characteristics, treatment choices, prescribing patterns and outcomes in routine clinical practice in advanced NSCLC in Europe. Our findings suggest that maintenance of PS after first and subsequent lines of chemotherapy, and survival rates may both be higher than previously anticipated. Our results also showed an association between age and survival, which suggests that age should not exclude patients from receiving chemotherapy if they meet all other eligibility criteria.

Patient reported outcomes in head and neck cancer: selecting instruments for quality of life integration in clinical protocols.

BACKGROUND: Health Related Quality of Life has been used in medical research for more than twenty years, being progressively accepted during the last decade as an important patient reported outcome. Considering the multidimensional approach involved in Health Related Quality of Life assessment, instrument applicability and cultural adaptation must be tested for each population. In order to select the most appropriate instrument for Head and Neck cancer patients, two major Health Related Quality of Life specific questionnaires for Head and Neck cancer patients were compared. Conceptual differences, psychometric characteristics, scores, reliability, construct validity and sensitivity to symptomatology, tumour location, tumour size were analyzed. METHODS: 102 consecutive Head and Neck cancer patients completed two different Health Related Quality of Life questionnaires: EORTC QLQ-C30 and its specific head and neck module QLQ-H&N35 and the Functional Assessment of Cancer Therapy Scales (FACT-H&N). Patients completed the questionnaires, immediately before consultation as a part of the routine evaluation. RESULTS: A greater variability was always found in the EORTC QLC-C30 questionnaire's scores for all comparable domains. Both instruments revealed a good internal consistency and demonstrated to be good tools to distinguish symptomatic patients. The EORTC questionnaires still demonstrated sensitivity to distinguish T3 and T4 staging. Conceptual differences and the psychometric characteristics are discussed. Our results suggest that these two instruments assess different aspects of Health Related Quality of Life - the questionnaires should be used separately and chosen according to the study objectives and methodology. CONCLUSIONS: This study emphases the importance in selecting the appropriate tool as a critical success factor in implementing routine Health Related Quality of Life assessment in clinical practice. This decision assumes particularly importance when utilization of results in real time and integration into clinical protocols are considered.

Health-related quality of life: the forgotten outcome in healthcare changes in recent years in Portugal.

Health-related quality of life (HRQoL) issues have acquired an important role not only in clinical trials, but also in daily clinical practice, and HRQoL is considered an important patient-reported outcome, particularly in chronic diseases. HRQoL is frequently forgotten when health outcomes are analyzed, both at the micro and macro level. The improvement of some health indicators of the Portuguese National Health Service in recent years is briefly discussed. Routine HRQoL measurement is rare, and is needed in order to provide better decision-making in Portugese healthcare. Some research groups interested in this theme in Portugal are presented, and give us hope that this picture may already be changing.

[Cancer patients quality of life, measured by themselves and proxys]. / Qualidade de vida dos doentes oncológicos. Avaliada pelo próprio e pelo cuidador.

AIMS: Health Related Quality of Life (HRQoL) is an essential factor for cancer patients, particularly in the evaluation of the care's. Most of the information that health care providers have is given by the patient. Family can also provide information about them, appealed or not and the quality of such information isn't studied for Portuguese population. The aim of this study was to examine whether proxies can provide useful information on HRQoL of cancer patients. METHODS: We studied a sample of 176 ambulatory cancer patients and those 176 respective proxies (family) from Medical Oncology Department. A sociodemographic characterization was made for the simple and a clinical characterization was made only for cancer patients. To measure HRQoL were used the EORTC QLQ-C30. Beyond descriptive techniques, the statistical analysis was done using Interclass Correlation (ICC) and Pearson Correlation (r). RESULTS: We found moderate to good agreement (ICC ranged from 0.55 to 0.82, as well as the Pearson correlation) between responses from patients and those from their proxies for the QLQ-C30 scales. Proxies' group considered patients as having higher degree of fatigue, pain and diarrhea and a more impaired physical and emotional functioning, worse global QoL and total score. Statistically significant differences between patients' and proxies' evaluations were found for these subscales. None of the patients or proxies characteristics showed any relationship with the agreement between patient and proxy QoL evaluations'. CONCLUSION: The results suggest that proxies only provide valid and useful information about cancer patients QoL for QLQ-C30 domains where the agreement between QoL's responses were high and the means diferrence not significant. For using a HRQoL instrument taking into account as source the proxy, is necessary to recognize the agreement of the HRQoL's domains of the instrument. In this case, for several domains of QLQ-C30 the means difference was statistically significant, so, the instrument should be used with caution for physical and emotional functioning, global QoL fatigue, pain, diarrhoea and total QoL. Proxies are a frequent and a mandatory source of information about patient's status, particularly in palliative care. On a clinical point of view, the knowledge of these differences is very important for that such information be ponderous and contextualized in order to improve better care to the patients.