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Background: Patient-reported outcomes (PROs) are captured within cancer trials to help future patients and their clinicians make more informed treatment decisions. However, variability in standards of PRO trial design and reporting threaten the validity of these endpoints for application in clinical practice.Methods: We systematically investigated a cohort of randomized controlled cancer trials that included a primary or secondary PRO. For each trial, an evaluation of protocol and reporting quality was undertaken using standard checklists. General patterns of reporting where also explored.Results: Protocols (101 sourced, 44.3%) included a mean (SD) of 10 (4) of 33 (range = 2-19) PRO protocol checklist items. Recommended items frequently omitted included the rationale and objectives underpinning PRO collection and approaches to minimize/address missing PRO data. Of 160 trials with published results, 61 (38.1%, 95% confidence interval = 30.6% to 45.7%) failed to include their PRO findings in any publication (mean 6.43-year follow-up); these trials included 49 568 participants. Although two-thirds of included trials published PRO findings, reporting standards were often inadequate according to international guidelines (mean [SD] inclusion of 3 [3] of 14 [range = 0-11]) CONSORT PRO Extension checklist items). More than one-half of trials publishing PRO results in a secondary publication (12 of 22, 54.5%) took 4 or more years to do so following trial closure, with eight (36.4%) taking 5-8 years and one trial publishing after 14 years.Conclusions: PRO protocol content is frequently inadequate, and nonreporting of PRO findings is widespread, meaning patient-important information may not be available to benefit patients, clinicians, and regulators. Even where PRO data are published, there is often considerable delay and reporting quality is suboptimal. This study presents key recommendations to enhance the likelihood of successful delivery of PROs in the future. [ABSTRACT FROM AUTHOR]

Background: The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment.Methods: Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent-maintenance cediranib group.Results: The rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent-maintenance group (+4.5; 95% confidence interval, -2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self-reported diarrhea.Conclusions: The 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression-free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian cancer. Cancer 2017;123:2752-61. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Background: Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. Methods/Design: PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. Discussion: The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. [ABSTRACT FROM AUTHOR]

Importance: Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high.Objective: To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)-guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines-directed care and myocardial perfusion scintigraphy (MPS)-guided care in reducing unnecessary angiography.Design, Setting, and Participants: Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016.Interventions: Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing.Main Outcomes and Measures: The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications.Results: Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95]).Conclusions and Relevance: In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline-directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates.Trial Registration: Clinicaltrials.gov Identifier: NCT01664858. [ABSTRACT FROM AUTHOR]

Until recently, insufficient attention has been paid to the fact that surgical interventions are complex. This complexity has several implications, including the way in which surgical interventions are described and delivered in trials. In order for surgeons to adopt trial findings, interventions need to be described in sufficient detail to enable accurate replication; however, it may be permissible to allow some aspects to be delivered according to local practice. Accumulating work in this area has identified the need for general guidance on the design of surgical interventions in trial protocols and reports. Key issues to consider when designing surgical interventions include the identification of each surgical intervention and their components, who will deliver the interventions, and where and how the interventions will be standardised and monitored during the trial. The trial design (pragmatic and explanatory), comparator and stage of innovation may also influence the extent of detail required. Thoughtful consideration of surgical interventions in this way may help with the interpretation of trial results and the adoption of successful interventions into clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Following publication of national guidelines on detection and management of psychosocial problems in oncology, this study explores frequency of discussion of emotional and social issues in outpatient oncology consultations. Methods: Analysis of baseline data from 212 outpatients participating in a randomized controlled trial. Baseline data included content analysis of audio recordings of consultations, Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire subscale scores, and patient and clinician self-rated preferences and perceptions of communication. Results: Fifty-nine percent patients and 75% clinicians expressed preferences to discuss emotional issues during consultations. Analysis of audio recordings showed that they were discussed in 27% of the consultations, regardless of severity of emotional problems reported by patients (FACT-G Emotional well-being subscale). Fifty percent of clinicians reported discussing emotional issues 'often' or 'almost always', compared with 18% of patients. Forty-four percent patients and 39% clinicians reported that they would discuss social activities, but they were actually discussed in 46% of consultations. Patients predominantly initiated discussion of emotional and social issues (85 and 60% consultations, respectively). Conclusions: Low prevalence of discussion of psychosocial issues cannot be accounted for by patient or clinician communication preferences. If clinicians rely on patients to initiate discussion of psychosocial issues, patients' problems may go unaddressed. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An abstract of the article "Statistical issues in the design of randomised surgical trials: a practical example of the possible solutions," by Helen Marshall and colleagues, is presented.

Background: Relapsed multiple myeloma has no standard treatment, and the role of autologous stem-cell transplantation (ASCT) has not been fully defined. We aimed to compare high-dose melphalan plus salvage ASCT with cyclophosphamide in patients with relapsed multiple myeloma who had previously undergone ASCT. Methods: This multicentre, randomised, open-label, phase 3 study recruited patients aged at least 18 years with multiple myeloma who needed treatment for first progressive or relapsed disease at least 18 months after a previous ASCT from 51 centres across the UK. Before randomisation, eligible patients received bortezomib, doxorubicin, and dexamethasone (PAD) induction therapy and then underwent peripheral blood stem-cell mobilisation and harvesting if applicable. Eligible patients (with adequate stem-cell harvest) were randomly assigned (1:1), using an automated telephone randomisation line, to either high-dose melphalan 200 mg/m² plus salvage ASCT or oral cyclophosphamide (400mg/m² per week for 12 weeks). Randomisation was stratified by length of first remission or plateau and response to PAD re-induction therapy. The primary endpoint was time to disease progression, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00747877, and EudraCT, number 2006-005890-24. Findings: Between April 16, 2008, and Nov 19, 2012, 297 patients were registered, of whom 293 received PAD re-induction therapy. Between Aug 26, 2008, and Nov 16, 2012, 174 patients with sufficient PBSCs were randomised to salvage ASCT (n=89) or cyclophosphamide (n=85). After a median follow-up of 31 months (IQR 19-42), median time to progression was significantly longer in the salvage ASCT than in the cyclophosphamide group (19 months [95% CI 16-25] vs 11 months [9-12]; hazard ratio 0·36 [95% CI 0·25-0·53]; p<0·0001). Frequently reported (in >10% of patients) grade 3-4 adverse events with PAD induction, salvage ASCT, and cyclophosphamide were: neutropenia (125 [43%] of 293 patients after PAD, and 63 [76%] of 83 patients in the salvage ASCT group vs 11 [13%] of 84 patients in the cyclophosphamide group), thrombocytopenia (150 [51%] after PAD, and 60 [72%] vs four [5%], respectively), and peripheral neuropathy (35 [12%] after PAD, and none vs none, respectively). Interpretation: This study provides evidence for the improved efficacy of high-dose melphalan plus salvage ASCT when compared with cyclophosphamide in patients with relapsed multiple myeloma eligible for intensive therapy, which might help to guide clinical decisions regarding the management of such patients. Funding: Cancer Research UK. [ABSTRACT FROM AUTHOR]

Introduction and aim: In a randomised trial investigating the effects of regular use of health-related quality of life (HRQOL) in oncology practice, we previously reported an improvement in communication (objective analysis of recorded encounters) and patient well-being. The secondary aims of the trial were to measure any impact on patient satisfaction and patients’ perspectives on continuity and coordination of their care. Methods: In a prospective trial involving 28 oncologists, 286 cancer patients were randomised to: (1) intervention arm: regular touch-screen completion of HRQOL with feedback to physicians; (2) attention-control arm: completion of HRQOL without feedback; and (3) control arm: no HRQOL assessment. Secondary outcomes were patients’ experience of continuity of care (Medical Care Questionnaire, MCQ) including ‘Communication’, ‘Coordination’ and ‘Preferences to see usual doctor’ subscales, patients’ satisfaction, and patients’ and physicians’ evaluation of the intervention. Analysis employed mixed-effects modelling, multiple regression and descriptive statistics. Results: Patients in the intervention arm rated their continuity of care as better than the control group for ‘Communication’ subscale (p =0.03). No significant effects were found for ‘Coordination’ or ‘Preferences to see usual doctor’. Patients’ evaluation of the intervention was positive. More patients in the intervention group rated the HRQOL assessment as useful compared to the attention-control group (86% versus 29%), and reported their doctors considered daily activities, emotions and quality of life. Conclusion: Regular use of HRQOL measures in oncology practice brought changes to doctor-patient communication of sufficient magnitude and importance to be reported by patients. HRQOL data may improve care through facilitating rapport and building inter-personal relationships. [Copyright &y& Elsevier]

Abstract: Aim: To review reporting standard, presentation and interpretation for quality of life (QOL) outcomes in randomised controlled trials (RCTs) using the European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 (EORTC QLQ-C30). Methods: Cancer RCTs reporting EORTC QLQ-C30 data were identified and reviewed against a reporting quality checklist. Interpretation/presentation methods for QOL data were also recorded. Results: Eighty-two papers were reviewed. Seventy percent met criteria for high quality reporting; 94% reported mean scores; 84% presented results in tables/graphs; 80% reported p-values or statistical significance. Clinical significance was addressed in 38%. Where clinical significance was not addressed, reliance was usually on statistical significance to interpret the results. Discussion: EORTC QLQ-C30 results are generally reported well, although it was common to rely on statistical significance alone for interpreting results. Whilst interpretation in terms of clinical significance has improved in recent years, there is still a lack of robust clinical interpretation of QOL results even in papers reported to a high standard. [Copyright &y& Elsevier]