Analysis Of Patient-reported Outcomes Research Articles

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.

Development of a Core Set of Patient-Reported Outcomes for Population-Based Cancer Survivorship Research: Protocol for an Australian Consensus Study.

BackgroundCore outcome sets seek to improve the consistency and quality of research by providing agreed-upon recommendations regarding what outcomes should be measured as a minimum for a population and setting. The problems arising from a lack of outcome standardization in population-based cancer survivorship research indicate the need for agreement on a core set of patient-reported outcomes (PROs) to enhance data quality, consistency, and comparability.ObjectiveThis study aims to identify a core set of PROs, representing the most important issues impacting on cancer survivors' long-term health, functioning and quality of life, to inform population-based research on cancer survivorship.MethodsIn Phase I, a list of all potentially important outcomes will be generated through focus group discussions with cancer survivors and a review of measures for assessing quality of life in cancer survivorship. The consolidated list will be advanced to Phase II, where a stakeholder consensus process will be conducted with national experts in cancer survivorship to refine and prioritize the outcomes into a core outcome set. The process will consist of a two-round Delphi survey and a consensus meeting. Cancer survivors, oncology health care professionals, and potential end users of the core outcome set with expertise in cancer survivorship research or policy will be invited to participate. In Phase III, recommended measures for assessment of the core outcome set will be selected with advice from experts on the assessment, analysis, and interpretation of PROs.ResultsAs of April 2019, data collection for Phase I is complete and data analysis is underway. These data will inform the list of outcomes to be advanced into Phase II. Recruitment for Phase II will commence in June 2019, and it is anticipated that it will take 6 months to complete the three-step consensus process and identify a provisional core outcome set. The study results are expected to be published in early 2020.ConclusionsExpert consensus-driven recommendations on outcome measurement will facilitate the inclusion of survivorship outcomes considered important by cancer survivors and health professionals in future research. Adoption of the core outcome set will enable comparison and synthesis of evidence across studies and enhance the quality of PRO data collected in cancer survivorship research, particularly when applied to address macro-level questions.International Registered Report Identifier (IRRID)DERR1-10.2196/14544

Health-Related Quality-of-Life Outcomes in Patients with Classical Hodgkin Lymphoma: A Prospective, Observational Study in US Oncology Practices

Introduction: Classical Hodgkin lymphoma (cHL) is highly curable with front-line multi-agent chemotherapy with or without radiotherapy. The treatment landscape is rapidly evolving, with a continued focus on optimizing available therapies in order to improve outcomes and minimize toxicity. Randomized controlled trials provide valuable insights into new treatments and outcomes; however, real-world data describing treatment effectiveness, safety, and health-related quality of life (HRQoL) are limited. This analysis was conducted to understand patient-reported outcomes (PROs) in patients who were treated for newly diagnosed cHL across a range of academic and community settings. Methods: Study CA209655 is an ongoing, prospective, observational study (NCT02856646) at ~80 US oncology practices with a target enrollment of 500 patients and a planned follow-up of ≤ 5 years. Eligible patients are ≥ 18 years old with histologically confirmed cHL and are treatment naive or within ± 2 weeks of beginning any line of therapy at time of enrollment. HRQoL is a secondary endpoint and evaluated using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire. The FACT-Lym combines a generic cancer-related core consisting of the FACT-General (FACT-G; 27 items) that assesses physical (PWB; 7 items), social/family (SWB; 7 items), emotional (EWB; 6 items), and functional well-being (FWB; 7 items), and a 15-item disease-specific lymphoma subscale (LymS) that assesses lymphoma-specific symptoms. PROs were assessed using questionnaires at baseline (BL), every 3-6 months for ≤ 2 years, and annually thereafter. All patients with BL and ≥ 1 post-BL assessment were included in the PRO analysis. Completion rates and changes from BL scores were evaluated descriptively and analyzed based on published estimates for clinically important differences and individual responder definitions (Hlubocky et al. Lymphoma 2013; Carter et al. Blood 2008; Yost and Eton. Eval Health Prof 2005). High scores indicate better health/functioning for all scales/subscales. Results: Of 278 enrolled patients at data cutoff (Feb 2019), 226 (81%) were treatment naive; for those, the most common index therapy was chemotherapy (n = 210; 93%). The most common index chemotherapies were ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; n = 187, 83%) and AAVD (adriamycin, brentuximab, vinblastine, dacarbazine; n = 10, 5%). Only patients receiving index chemotherapy were included in the full analysis set. In all, 89% (87/210) of patients had BL and ≥ 1 post-BL assessment and were included in the PRO analysis. PRO completion rate at BL was 97% (204/210) and remained > 70% up to 24 months for the expected population. Analysis of PROs was not feasible after 24 months owing to small patient numbers (≤ 10); therefore, PRO analyses were focused on the first 18 months. At BL, mean (SD) scores were: FACT-Lym total, 122 (24); FACT-G, 82 (15); PWB, 21 (6); SWB, 25 (3); EWB, 18 (4); FWB, 18 (6); and LymS, 40 (11). At 3 months there was a deterioration in mean scores from baseline in FACT-G (−3.8) and PWB (−3.0) (Figure A). Clinically meaningful improvement of mean scores was observed starting at 6 months in LymS (+4.4) and at 9 months in FACT-G (+7.1), PWB (+3.1), FWB (+2.8), and FACT-Lym total (+15.6). There were no clinically meaningful improvements in SWB and EWB. Based on individual responder definitions, ≥ 50% of patients had improvements in PWB (Figure B) and FACT-G from 12 months, and FACT-Lym total from 9 months. Conclusions: Initial data from this observational study suggest most patients receive multi-agent cytotoxic chemotherapy as first-line treatment of cHL. Patient-reported PWB initially declined with chemotherapy, but improved with time, and patients had a clinically meaningful improvement in HRQoL by 9 months. The timing of this improvement may be due to discontinuation of chemotherapy due to disease control. Future analyses will evaluate the relationship between improvements in HRQoL and other factors including response, use of immunotherapies versus chemotherapy, and the timing of treatment discontinuation. Study support: Bristol-Myers Squibb. Disclosures Svoboda: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. Armand:Roche: Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; Infinity: Consultancy; Genentech: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding. Taylor:Adelphi Values: Employment, Other: I am an employee of Adelphi Values, a consulting firm who has received payment from Bristol-Myers Squibb for statistical data analysis in Bristol-Myers Squibb's trials. Sun:Adelphi Values: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Peterson:Bristol-Myers Squibb: Employment, Equity Ownership. Chen:Bristol-Myers Squibb: Employment.

Quality-of-Life Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Treated with Elotuzumab Plus Lenalidomide/Dexamethasone or Lenalidomide/Dexamethasone: Final Analysis of the Phase 3 ELOQUENT-2 Study

Introduction: The development of numerous novel therapies for the treatment of relapsed or refractory multiple myeloma (MM) has resulted in improved response rates and durable responses that prolong survival. Assessment of health-related quality of life (HRQoL) has therefore become increasingly important as HRQoL decreases with increasing lines of therapy (LoTs) (Despiégel et al. Clin Lymphoma Myeloma Leuk 2019). In the phase 3 ELOQUENT-2 study (NCT01239797), elotuzumab (E) plus lenalidomide/dexamethasone (Ld) showed a 30% reduction in the risk of progression/death versus Ld in patients with relapsed or refractory MM and 1-3 prior LoTs (median follow-up: 24.5 months; Lonial et al. N Engl J Med 2015). The initial analysis of patient-reported outcomes (PROs) from ELOQUENT-2 at a 3-year extended follow-up showed that the improvement in efficacy observed with ELd was achieved without a detriment to HRQoL (Cella et al. Ann Hematol 2018). Here we present the final analysis of PRO data from ELOQUENT-2. Methods: In ELOQUENT-2, patients with relapsed or refractory MM and 1-3 prior LoTs were randomized 1:1 to receive ELd or Ld in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The Brief Pain Inventory-Short Form (BPI-SF; pain severity, pain interference, and worst pain), the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 questionnaire (QLQ-C30; prespecified key domains were physical function, fatigue, global health status/QoL, and pain), and the myeloma-specific module (QLQ-MY20; includes assessment of symptoms and treatment side effects) were administered at baseline (BL), on Day 1 of each treatment cycle, and at the end of treatment/study withdrawal. All randomized patients with ≥1 post-BL assessment were included in each PRO analysis. Overall mean change from BL was compared between treatment groups based on a mixed-effect model for repeated measures; statistical tests for the overall population only included treatment cycles with >30 patients in each treatment group. A paired t-test was used to compare scores at each cycle with BL; an unpaired t-test compared mean values between treatment groups. BPI-SF scores range from 0-10 with lower scores representing better pain outcomes. EORTC QLQ-C30 scores range from 0-100 with higher scores representing better physical functioning and global health status/QoL, and worse fatigue and pain; EORTC QLQ-MY20 scores range from 0-100 with higher scores representing worse symptoms and problems. Results: In total, 646 patients were treated with ELd (n=321) or Ld (n=325); 319 and 311 patients had ≥1 post-BL assessment and were included in the PRO analysis, respectively (minimum follow-up: 70.6 months). BL BPI-SF mean scores for ELd versus Ld were low across all domains: pain severity (2.6 vs 2.9), pain interference (2.5 vs 2.8), and worst pain (3.6 vs 3.8). Scores for all BPI-SF domains remained stable over the course of the study (eg, pain severity: Figure A). ELd-treated patients with BL moderate/severe pain severity (score of ≥5) had significantly lower mean pain severity scores versus Ld-treated patients in Cycles 1-5. A higher proportion of clinical responders (complete or partial response per European Group for Blood and Marrow Transplantation criteria) versus non-responders had a sustained reduction in pain score across all BPI-SF domains: pain severity (18% vs 6%), pain interference (15% vs 6%), and worst pain (30% vs 13%); the difference in time to sustained improvement was not statistically significant between the clinical responders and non-responders for any pain endpoint. For both treatment groups, there was no clinically meaningful change (≥10 points) from BL scores at any cycle (>30 patients) across all key domains for EORTC QLQ-C30 (eg, global health status/QoL: Figure B) and QLQ-MY20. Conclusions: This final analysis of PROs in ELOQUENT-2 confirms that the efficacy benefits observed with addition of elotuzumab to Ld in patients with relapsed or refractory MM treated with 1-3 prior LoTs were achieved without negatively affecting HRQoL compared with Ld. Study support: BMS. Medical writing: Kenny Tran, Caudex, funded by BMS. Disclosures Cella: FACIT.org: Equity Ownership. McKendrick:PRMA Consulting Ltd.: Employment, Other: I am employed by PRMA Consulting Ltd who provide consulting services to a number of pharmaceutical companies. Davis:PRMA Consulting Ltd.: Employment, Other: I am employed by PRMA Consulting Ltd who provide consulting services to a number of pharmaceutical companies.. Vij:Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Chen:Bristol-Myers Squibb: Employment.

PCN457 THE SISAQOL INITIATIVE: ESTABLISHING INTERNATIONAL STANDARDS AND RECOMMENDATIONS FOR THE ANALYSIS OF PATIENT-REPORTED OUTCOMES AND QUALITY OF LIFE DATA IN ONCOLOGY RANDOMIZED CLINICAL TRIALS

Patient-reported outcome (PRO) data, such as symptoms and health-related quality of life, are increasingly being captured in cancer randomized clinical trials (RCTs) to provide valuable information on treatment risks, benefits and tolerability. Our literature review showed heterogeneity in analysis, interpretation and reporting of these data in various cancer fields, hindering comparability in results across trials. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium was convened to set recommendations for PRO analysis in cancer RCTs. The Consortium comprises 40 international experts including PRO researchers and statisticians, representatives from regulatory bodies, academic societies, pharmaceutical industry, cancer institutes and patient organizations to work on four priorities: (a) specification of well-defined PRO research objectives, (b) recommendations for appropriate statistical PRO analysis methods, (c) standardization of statistical terminology and (d) development of guidelines for analyzing missing data. Recommendations were developed through literature review, surveys, meeting discussions and ratified through voting in a final meeting. A taxonomy of research objectives was developed. Appropriate statistical methods, with the exception of summary measures, were proposed. Consensus was reached on the taxonomy of research objectives and statistical methods, along with a missing data definition and two rates to report missing data occurrence. While some statements concerning handling missing data or statistical analyses are still to be discussed, many statements were ratified for each of the priorities. A robust first set of PRO analyses recommendations were established in a joint process with diverse international stakeholders. Addressing the needs and requirements of these stakeholders provides a strong foundation for widespread endorsement of these recommendations. Ultimately, we expect enhanced interpretability and better impact of PRO data in cancer RCTs from harmonization of current research practices. Disclaimer: This publication reflects solely the views of the individual authors

Considerations in testing treatment effects on transient event driven health status changes measured by patient reported outcomes.

Many treatments and drugs are intended to reduce the occurrence of negative events of interest, control the severity of the events, accelerate recovery from the events, or a combination of these effects. While assessing the clinical effect is typically the primary objective of a trial, testing the treatment effect on the health status of patients based on patient reported outcome (PRO) can be a useful component in determining the value of a treatment. Analysis of PROs in this setting, however, face the following challenges: the PRO value immediately after the event occurrence is often not captured, and the effect of the event on health status measured by the PRO is transient as subjects recover over time. Therefore, traditional statistical methods used to assess treatment effects suffer from low power for PROs. In this manuscript, we apply a kernel smoothing technique to estimate before- and after-event PRO values. We also propose new test outcomes based on observed and estimated PRO values and evaluate tests that focus on the tail distributions. We demonstrate that the tail distribution tests using the new outcomes can achieve high power under certain conditions.

The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis

BackgroundPatient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies.MethodsTwo independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial.ResultsThirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals.ConclusionsPRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste.Trial registrationSystematic Review registration PROSPERO CRD42017067799.

357P - Patient Reported Outcomes (PRO) in patients (pts) with HER2- advanced breast cancer (ABC) and a germline BRCA1/2 mutation (gBRCAm) receiving talazoparib (TALA) vs physician’s choice chemotherapy (PCT) in the EMBRACA trial: A focus on subgroups with/ without visceral disease

BackgroundAs part of the key subgroup analyses of EMBRACA, a randomized 2:1 open-label phase 3 study (NCT01945775), improvements in PFS with TALA vs PCT were observed in both subgroups: HER2- gBRCAm ABC pts with/without visceral disease at baseline; these post hoc analyses evaluated PRO. MethodsPRO was assessed on baseline, at start of each 3-week cycle, and at end of treatment, using the EORTC QLQ-C30 and breast cancer module, QLQ-BR23. Higher scores indicate better functioning/global health status (GHS)/QoL or worse symptom severity. PRO analyses performed separately in pts with/without visceral disease, for GHS/QoL, functional and symptom scales include: Overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive clinically meaningful deterioration (TTD) (per survival analysis methods). Between-arm comparisons of TTD were made using stratified log-rank test and Cox proportional hazards model. ResultsBaseline scores were similar between arms. A statistically significant estimated overall change from baseline in GHS/QoL favored TALA vs PCT for both subgroups with {8.8 [95%CI: (4.1, 13.5)] P<0.001} and without {7.4 [95%CI: (0.4, 14.3)] P=0.04} visceral disease. A statistically significant estimated overall change from baseline in patient reported pain symptoms favored TALA vs PCT for both subgroups with (P<0.001) and without (P=0.03) visceral disease. A statistically significant delay in TTD favoring TALA was observed in GHS/QoL for both subgroups with [median: 21.1 vs 6.0 mos, HR=0.36 (95%CI: 0.23, 0.57); P<0.001] and without [median: 26.3 vs 12.2 mos, HR=0.38 (95%CI: 0.18, 0.80); P=0.009] visceral disease. A statistically significant delay in TTD favoring TALA was observed in pain symptoms for both subgroups with (P<0.001) and without (P=0.002) visceral disease. ConclusionsIn HER2- gBRCAm ABC, TALA (vs PCT) resulted in significantly better change from baseline and delayed TTD in GHS/QoL and pain in both pts subgroups with/without visceral disease. Clinical trial identificationNCT01945775. Editorial acknowledgementEditorial/writing support was provided by Chantel Cadwell, PhD, and Dena McWain at Ashfield Healthcare Communications, Middletown, CT. Legal entity responsible for the studyPfizer Inc. FundingPfizer Inc. DisclosureJ. Ettl: Honoraria (self), Advisory / Consultancy: Lily; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Eisai; Research grant / Funding (self), Travel / Accommodation / Expenses: Celgene; Honoraria (self): TEVA; Honoraria (self): AstraZeneca. R.G.W. Quek: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. H. Bhattacharyya: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. H.S. Rugo: Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Pfizer Inc.; Research grant / Funding (institution): Plexxikon; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Puma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Pfizer Inc.; Research grant / Funding (institution): Plexxikon; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Puma. S.A. Hurvitz: Research grant / Funding (institution): Ambryx; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BI Pharma; Research grant / Funding (institution): Biomarin; Research grant / Funding (institution): Cascadian; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Dignitana; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merrimack; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Roche, Seattle Genetics. A. Gonçalves: Travel / Accommodation / Expenses: Pfizer Inc.; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Boehringer Ingelheim.

Burst Spinal Cord Stimulation: A Systematic Review and Pooled Analysis of Real-World Evidence and Outcomes Data.

ObjectiveThis review provides a comprehensive assessment of the effectiveness of burst spinal cord stimulation (SCS). Ratings of pain intensity (visual analog scale or numeric rating scale) and patient-reported outcomes (PROs) on functional/psychometric domains such as depression (Beck Depression Index), catastrophizing (Pain Catastrophizing Scale), surveillance (Pain Vigilance and Attention Questionnaire), and others are addressed.DesignArticles were identified and selected from the literature according to prospective, replicable methods. Effectiveness data—pain scores and PRO ratings—were weighted by study sample sizes and pooled. The effects of burst SCS were compared against values at baseline and with tonic SCS. For PROs, published population norms were used for comparison.ResultsFifteen articles, with a combined sample size of 427, were included. Follow-up ranged from a few hours to two years. A variety of prospective designs were employed, including crossover studies, single-arm cohorts, and a randomized controlled trial, as well as retrospective case reports. The weighted pooled mean pain rating across articles at baseline was 76.7 (±27.4). With tonic SCS, this was reduced to 49.2 (±12.9), and with burst SCS it was further reduced to 36.7 (±11.6), a 12.5-point difference between tonic and burst values. Psychometric analyses of PROs noted preferential improvement with burst SCS. In addition, 65% of subjects stated a preference for burst SCS.ConclusionsIn pooled analyses that incorporated all available published evidence, the improvement over baseline for burst SCS was shown to have a clinically important incremental benefit over tonic SCS. In addition, burst SCS may support resolution of the emotional or cognitive aspects of pain that are mediated by medial thalamo-cortical pathways. This study highlights the value in considering the entire knowledge base in therapeutic assessments as well as adopting a consistent set of outcome variables within neuromodulation. Burst SCS is a valuable intervention, providing both analgesia and psychometric benefits that warrant further thoughtful applications.

Quality of life (QoL) and symptom burden in patients (pts) with advanced melanoma during the treatment-free interval (TFI) after discontinuation of nivolumab (NIVO) or NIVO plus ipilimumab (IPI).

9568 Background: The TFI after discontinuation of study therapy has been reported to be longer with NIVO+IPI compared to NIVO or IPI alone, but QoL during the TFI has not been reported in advanced melanoma (MEL) studies. 1-y data from CheckMate (CM) 067 showed maintenance of QoL after treatment (tx) discontinuation with NIVO or NIVO+IPI. Here, we present long-term QoL results from CM 067 during the TFI (period off study tx and free of subsequent therapy), based on an updated 4-y dataset. Methods: In CM 067, 945 pts were randomized 1:1:1 to receive NIVO 3 mg/kg + placebo; NIVO 1 mg/kg + IPI 3 mg/kg × 4, then NIVO 3 mg/kg; or IPI 3 mg/kg × 4 + placebo. Patient-reported outcomes (PRO) were collected using the EORTC QLQ-C30 (5 functional domains, 9 symptoms, global health status) and EQ-5D-3L (utility index, visual analog scale) at baseline, on-tx visits, and follow-up (FU) visits 1 (FU1; 30 d after last dose) and 2 (FU2; 84 d after FU1). EQ-5D-3L was also collected at survival FU visits every 3 mo after FU2 in the first year and every 6 mo thereafter. Within the PRO analysis population, 480 of 764 pts who discontinued protocol tx (for any reason, including drug toxicity; n = 155) had PRO scores, collected prior to initiation of subsequent anticancer therapy, evaluated. Mean changes in PRO scores from last on-tx visit were reported for each FU visit. Results: Across tx arms, PRO scores were maintained from last on-tx visit to FU1 or FU2 for pts who discontinued for any reason. EORTC QLQ-C30 functional and symptom scales remained stable during the TFI. Among pts who discontinued tx due to toxicity, clinically meaningful deterioration in QoL was observed in a few subscales at FU1, but QoL was restored to the same level as the last on-tx visit in all except one subscale by FU2. PRO scores remained stable beyond FU2 for the EQ-5D-3L, regardless of reason for discontinuation. Data interpretation at later FU visits was limited due to smaller sample sizes. Sensitivity analyses for mean change in PRO scores from randomization to FU visits will be presented. Conclusions: QoL was maintained during the TFI, compared to last on-tx visit, in pts with MEL treated with NIVO or NIVO+IPI.

Patient-reported quality of life (QoL) of advanced melanoma patients in a Phase 3 study of nivolumab (NIVO) with or without ipilimumab (IPI) versus IPI: CheckMate 067 4-year data.

9551 Background: Early CheckMate 067 data showed maintenance of QoL in patients with advanced melanoma treated with NIVO with or without IPI based on 1-year data; however, the long-term QoL of these patients has not been evaluated previously. The patient-reported outcomes (PRO) analyses presented here for CheckMate 067 is the first time QoL results have been evaluated in this melanoma population over a 4-year period. Methods: In CheckMate 067, 945 patients were randomized 1:1:1 to receive NIVO (3mg/kg Q2W) + placebo (PBO), NIVO+IPI (1mg/kg+3mg/kg Q3W X 4) followed by NIVO (3mg/kg Q2W), or IPI (3mg/kg Q3W X 4) + PBO. PRO data were collected using the EORTC QLQ-C30 (5 functional domains, 9 symptoms, global health status) and EQ-5D-3L (utility index, VAS) at baseline, weeks 1 and 5 of each 6-week tx cycle, and off-tx follow-up (FU) visits. Mean changes in PRO scores from baseline (randomization) were evaluated descriptively for the PRO analysis population, with conclusions drawn from time points with ≥30 patients completing assessments per tx arm. Least square mean changes from baseline were assessed using a longitudinal mixed model analysis adjusting for repeated measures, including all on-tx data for patients. Results: Completion rates at baseline ranged from 89-92% across tx arms. Of 813 patients included in the PRO analysis population (278 NIVO, 274 NIVO+IPI, 261 IPI), &gt; 200 receiving tx remained for the first year, &gt; 100 receiving tx remained after 2 years, and &gt; 50 receiving tx remained after 3 years. QoL, including assessment of functioning and symptom burden, was maintained for the duration of tx and in FU, with no sustained clinically meaningful deterioration in any tx arm. Global health status (EORTC QLQ-C30) and general QoL (EQ-5D-3L VAS) were also maintained during prolonged tx. Overall, results from the mixed model analysis support the long-term maintenance of QoL over the course of tx. Conclusions: Patient-reported QoL and symptoms in patients with advanced melanoma were maintained from baseline during extended tx with NIVO with or without IPI. Clinical trial information: NCT01844505.

Variations in patient-reported outcome (PRO) collection and reporting in novel FDA approved anticancer therapies.

e18202 Background: Patient-reported outcomes (PROs) are increasingly valued as a key tool in patient-focused treatment decisions. However, a lack of standardization leads to significant variability in PRO collection and reporting in ground-breaking clinical trials of novel agents. We sought to characterize the mechanisms of assessment and variability by which PROs are reported for newly approved anti-cancer therapies. Methods: We reviewed the U.S. Food and Drug Administration (FDA) approvals between 2011 and 2017 for anti-cancer new molecular entities (NMEs) and new biologic approvals (BLAs). For each therapy, the pivotal clinical trial leading to FDA approval was identified using the national clinical trial (NCT) number and assessed for inclusion of PROs. A separate PubMed search was conducted to evaluate for PRO publication distinct from the original trial based on national clinical trial registry number. Results: From 2011 to 2017, the FDA approved 66 NMEs/BLAs based on 74 clinical trials for cancer treatment. Of the 74 clinical trial publications, 21 (28%) of the trials published PRO data in their original clinical publication, 18 (24%) published a separate PRO analysis, and 35 (47%) did not publish PRO data in either format. Among the 32 clinical trials (43%) that listed PROs as pre-specified outcomes, 72% published PROs (23/32). The separate PRO analyses (N = 18) were published considerably later following FDA approval (mean 605 days) than the original clinical trials (mean 20 days, N = 74, P &lt; 0.001). Conclusions: As cancer treatment options expand, therapy decisions become increasingly nuanced. PROs assist decision-making by providing detailed information on important aspects of quality of life and tolerability. Our research has identified a significant lag in the publication of companion studies of PRO data associated with pivotal clinical trials, representing a meaningful gap in information critical to patients and oncologists in the process of making informed decisions.

Convenience, satisfaction, health-related quality of life of once-weekly 70 mg/m2 vs. twice-weekly 27 mg/m2 carfilzomib (randomized A.R.R.O.W. study)

We compared patient-reported outcomes (PROs) with once-weekly carfilzomib 70 mg/m2 (Kd70 mg/m2) vs. twice-weekly carfilzomib 27 mg/m2 (Kd27 mg/m2) plus dexamethasone in relapsed or refractory multiple myeloma (RRMM). Patient-reported convenience/satisfaction collected at Cycle 2, Day 1 was compared between groups using logistic regression. European Organization for Research and Treatment of Cancer QOL Questionnaire (QLQ-C30), MM-module (QLQ-MY20), and EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) questionnaires were administered at baseline, then every other cycle. PROs were compared between groups using mixed models for repeated measures. Times from randomization to first deterioration (TTD) in scores were analyzed using Cox regression. PRO analyses included 469 patients. Once-weekly Kd70 mg/m2 patients reported greater convenience (odds ratio [OR], 4.98; p < 0.001) and satisfaction (OR, 2.41; p = 0.059) vs. twice-weekly Kd27 mg/m2. The mixed models for repeated measures demonstrated no clinically meaningful differences in scores between treatment arms. Clinically meaningful deterioration in QLQ-C30 Global Health Status/QOL rates were 34.2% (once-weekly Kd70 mg/m2) vs. 40.3% (twice-weekly Kd27 mg/m2). TTD was longer for once-weekly Kd70 mg/m2 vs. twice-weekly Kd27 mg/m2 for QLQ-C30 fatigue (HR, 0.79; p = 0.035), QLQ-MY20 disease symptoms (HR, 0.67; p = 0.008), EQ-5D-5L index score (HR, 0.58; p = 0.002), and EQ-5D-5L Visual Analog Scale (HR, 0.75, p = 0.031). Once-weekly Kd70 mg/m2 improved convenience/satisfaction, and reduced HRQOL deterioration vs. twice-weekly Kd27 mg/m2, supporting convenient, once-weekly Kd70 mg/m2 dosing in RRMM.

Measuring Patient Reported Outcomes in Multiple Myeloma: Are Legacy Instruments Fit for Purpose

Introduction:Measuring patient-reported outcomes (PROs) in oncology clinical trials is important to capture the patient perspective on quality of survival and the outcomes of health-related quality of life (HRQoL), symptoms, and functional status. In multiple myeloma (MM) randomized clinical trials (RCTs) the common PRO instruments include the EORTC QLQ-C30 and the EQ-5D as generic measures of a patient's health status. While these legacy PRO instruments have been widely used in the MM population, it is important to continue to assess the instruments psychometric properties for the specific context of use and target population.The purpose of this research was to investigate the strengths and limitations of the PRO instruments when analyzed free from developer construct and scoring recommendations to assess fit for purpose in various MM clinical trial populations.Methods:Data for the analysis included 3 MM RCTs (n=1,773) (Dimopoulos 2016, Palumbo 2016, Mateos 2018). The PRO analysis set consisted of 33 items from the EORTC QLQ-C30 and EQ-5D-5L collected at baseline and during the treatment phase of the RCTs. Item analysis and modern psychometric methods were applied to the PRO item pool as a 4-step process: (1) descriptive analysis of the items, (2) assessment of factor structure, (3) performance of factors across RCT populations (treatment naive, relapsed/refractory MM), and (4) assessment of meaningful change.Items were characterized using polychoric correlations to examine the inter-item association and relationships before determining appropriate factor structures. An exploratory factor analysis (EFA) followed by multidimensional item response theory (MIRT) and bifactor IRT models were conducted to determine how items fit into factors and to test a total symptom and total impact scoring option. Differential item functioning (DIF) was conducted to evaluation item and domain performance across study populations (treatment naïve vs. relapsed/refractory) and longitudinally (baseline vs. week 24). Meaningful change in these new domain constructs was evaluated using anchor-based techniques based on the EORTC-QLQ-C30 and EQ-5D-5L global items. A novel provisional latent class model approach creating responder groups was also developed and applied to assess meaningful change.Results:The 33 items from the EORTC QLQ-C30 and EQ-5D-5L demonstrated strong inter-item correlations supportive of pre-specified domain structures and consistent across RCT study populations. The EFA supported 3-domain structures for both symptoms and impacts separately. These domains were broadly consistent with the PRO instrument developer specifications but unique in several regards. These domains were statistically identical across RCTs. Model fit showed that a proposed bi-factor IRT (Symptom domain and Impact domain) fit better than the MIRT suggesting that subdomains are less useful than total domain scores. An extensive DIF analysis within this IRT framework found no evidence of substantial DIF effects. All evidence indicated that the items performed similarly across sample populations and time points.Anchor-based meaningful change calculations for the newly created total symptom score and the total impact score demonstrated separation between global health anchor groups but the meaningful change estimates were small. The latent class models demonstrated that treatment arms differed significant in responder rates within 1 RCT.Conclusions:The analyses confirmed psychometrically robust EORTC QLQ-C30 and EQ-5D-5L items in the MM population under newly specified factor structures. In addition, performance of the items allows for calculation of a total symptom score and total impacts score. The newly developed total domains performed identically across MM populations (treatment naïve versus relapsed/refractory). The results only focus on the on-treatment phase of the RCT so future research is needed to determine how psychometric methods can be adjusted to better accommodate survival status and censoring for progression in oncology RCTs. The psychometric properties and consistency of the findings across the newly created symptom and impact total domain structures support the results that daratumumab maintains HRQoL in patients with MM. DisclosuresGries:Janssen Research & Development, LLC: Employment. Fastenau:Janssen Research & Development, LLC: Employment. Iaconangelo:Janssen Research &Development, LLC: Consultancy. Serrano:Janssen Research & Development, LLC: Consultancy.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P113. Crossing the cervicothoracic junction in cervical spine fusion surgery involves higher operative risks, but superior long-term outcomes

BACKGROUND CONTEXT Whether the cervicothoracic (CT) junction should be crossed in cervical spine fusion surgery remains up for debate. Keeping C7 as the distal end of the fusion risks adjacent segment disease (ASD) and can result in myelopathy or radiculopathy. Longer fusions are thought to increase operative risk and complexity, but result in lower rates of ASD. This study evaluates the risks and benefits of crossing the CT junction in cervical spine fusion surgery, considering both surgical and patient-reported outcomes (PROs). PURPOSE To determine whether the CT junction should be crossed in cervical spine fusion surgery. STUDY DESIGN/SETTING Retrospective review. PATIENT SAMPLE One hundred seventy-seven patients. OUTCOME MEASURES Surgical outcomes: estimated blood loss (EBL), operative time and length of hospital stay.Patient-reported outcomes (PROs): NDI and SF-12 (PCS12 and MCS12). METHODS A total of 177 patients were included (mean age 57.4 years) and divided into a C7 end-of-fusion cohort (nC7=61) and a CT-crossing, T1 end-of-fusion cohort (nT1=116). To evaluate operative risk, EBL, operative time and length of hospital stay were assessed. Revision surgery data was also obtained. To evaluate PROs, Neck Disability Index (NDI) and SF-12 questionnaires (PCS12 and MCS12) were obtained both preoperatively and at follow-up. Changes in PRO scores (∆) were analyzed. In terms of PROs, available data was limited (nC7=5–10, nT1=9–12). RESULTS Multivariate regression analysis adjusting for age, gender and race showed that EBL (262vs. 456 mL, p=.02) and operative time (254vs. 317 min, p=.03) are significantly increased in the T1 cohort. Length of hospital stay was not significantly different (4.0vs. 5.7days, p=.41). Mann–Whitney analysis of PROs showed no significant difference in ∆NDI (−6.4vs. −4.3 pts, p=1), ∆PCS12 (−1.6vs. 0.1 pts, p=.16) or ∆MCS12 (3.2vs. −0.5 pts, p=.25). Fisher analysis showed significantly higher revision rates in the C7 cohort (C7: 6/61vs. T1: 2/116, OR=5.6, CI=[1.0, 58.8], p=.03). CONCLUSIONS Crossing the CT junction increases blood loss and operative time, resulting in a longer, riskier operation that may not be suitable for fragile patients. However, crossing the CT junction also leads to lower revision rates, likely due to the avoidance of ASD, and comparable PROs. Thus, the higher short-term risks of crossing the CT junction may be justified given it can help prevent complications without negatively affecting long-term PROs.

Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial

In the LATITUDE trial, addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improved overall survival compared with placebos plus ADT in patients with newly diagnosed, high-risk, metastatic castration-naive prostate cancer. Understanding the effects of treatments on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) is important for treatment decisions; therefore we aimed to analyse the effects of ADT plus abiraterone acetate and prednisone versus ADT plus placebos on PROs and HRQOL in patients in the LATITUDE study. In the multicentre, international, randomised, phase 3 LATITUDE trial, eligible patients were aged 18 years or older, had newly diagnosed, high-risk, metastatic castration-naive prostate cancer confirmed by bone scan (bone metastases) or by CT or MRI (visceral, soft tissue, or nodal metastases), and an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Patients from 235 clinical sites in 34 countries were randomly assigned (1:1) following a country-by-country scheme done by permuted block randomisation (with two blocks) and stratified by the presence of visceral metastasis and ECOG performance status to receive ADT plus 1000 mg oral abiraterone acetate and 5 mg oral prednisone once daily or ADT plus placebos. Selection of ADT, chemical or surgical, was at the investigator's discretion. The co-primary endpoints of the trial, overall survival and radiographic progression-free survival, have been published. PRO data were collected directly on electronic tablet devices at the clinical sites during screening and before any other visit procedure on day 1 of cycles 1-3, monthly during cycles 4-13, and then every 2 months until the end of treatment, by use of the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy Prostate scale (FACT-P), and the EuroQol (EQ-5D-5L) questionnaires. PRO analyses were an exploratory endpoint. Analyses were by intention-to-treat. Results from the first pre-planned interim analysis (Oct 31, 2016), are presented here. This ongoing study is registered with Clinicaltrials.gov, number NCT01715285. Between Feb 12, 2013, and Dec 11, 2014, 1199 patients were randomly assigned: 597 to ADT plus abiraterone acetate and prednisone and 602 to ADT plus placebos. Median follow-up was 30·9 months (IQR 21·2-33·2) in the ADT plus abiraterone acetate and prednisone group versus 29·7 months (1·4-43·5; 16·1-31·3) in the ADT plus placebos group. Median time to worst pain intensity progression assessed by the BPI-SF score was not reached in either group (ADT plus abiraterone acetate and prednisone, not reached [95% CI not reached to not reached]; 25th percentile 11·07 months [95% CI 9·23-18·43]; ADT plus placebos group, not reached [95% CI not reached to not reached]; 25th percentile 5·62 [95% CI 4·63-7·39]; hazard ratio [HR] 0·63 [95% CI 0·52-0·77]; p<0·0001). Median time to worst fatigue intensity was not reached in either the ADT plus abiraterone acetate and prednisone group (not reached [95% CI not reached to not reached]; 25th percentile 18·4 months [95% CI 12·9-27·7]) or the ADT plus placebos group (not reached [95% CI not reached to not reached]; 25th percentile 6·5 months [95% CI 5·6-9·2]; HR 0·65 [95% CI 0·53-0·81], p=0·0001). Median time to deterioration of functional status assessed by the FACT-P total score scale was 12·9 months (95% CI 9·0-16·6) in the ADT plus abiraterone acetate and prednisone group versus 8·3 months (7·4-11·1) in the ADT plus placebos group (HR 0·85 [95% CI 0·74-0·99]; p=0·032). The addition of abiraterone acetate plus prednisone to ADT in patients with newly diagnosed, high-risk metastatic castration-naive prostate cancer improved overall PROs by consistently showing a clinical benefit in the progression of pain, prostate cancer symptoms, fatigue, functional decline, and overall HRQOL. Janssen Research & Development.

Patient-Reported Outcomes and Opioid Use by Outpatient Cancer Patients

The Memorial Sloan Kettering Pain Registry contains patient characteristics, treatments, and outcomes for a prospective cohort of 1,534 chronic pain cancer patients who were seen at outpatient pain service clinics. Average pain intensity (Brief Pain Inventory) was reported as mild by 24.6% of patients, moderate by 41.5%, and severe by 33.9%. The patient's report of average percent pain relief and health state (EuroQOL 5 dimensions) was inversely related to average pain intensity category, whereas measures of pain interference, number of worst pain locations, and physical and psychological distress were directly related to pain intensity category. Eighty-six percent of patients received an opioid at 1 or more clinic encounters. Regression analysis revealed that male sex or being younger (65 years of age or younger) was associated with a greater likelihood of an opioid ordered. Male sex nearly doubled the likelihood of a higher dose being ordered than female sex. Bivariate analysis found that patients receiving opioids reported significantly more pain relief than no-opioid patients. However, patients receiving opioids had higher pain interference scores, lower index of health state, and more physical distress than no-opioid patients Our results identify the need to consider opioid use and dosage when attempting to understand patient-reported outcomes (PROs) and factors affecting pain management. PerspectiveThis report describes the results of the analyses of PROs and patient-related electronic health record data collected under standard of care from cancer patients at outpatient pain management clinics of Anesthesiology and Palliative Care at the Memorial Sloan Kettering Cancer Center. Consideration of sex and age as predictors of opioid use is critical in attempting to understand PROs and their relationship to pain management.

Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma

ObjectiveReport results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma. Patients and methodsPatients received pembrolizumab 10 mg/kg every 2 (Q2W) or every 3 weeks (Q3W) for up to 2 years, or four cycles of ipilimumab 3 mg/kg Q3W. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was administered at baseline and throughout the study. Patient-reported outcome (PRO) analyses were pre-specified exploratory endpoints; the primary PRO assessment was the score change from baseline to week 12 in EORTC QLQ-C30 global health status (GHS)/HRQoL score between the arms using constrained longitudinal data analysis. ResultsThe PRO analysis population included 776 patients: pembrolizumab Q2W (n = 270); pembrolizumab Q3W (n = 266); ipilimumab (n = 240). Baseline GHS was similar across arms. QLQ-C30 compliance rates at week 12 were 87% (n = 214), 97% (n = 226), and 96% (n = 178), for the pembrolizumab Q2W, pembrolizumab Q3W, and ipilimumab arms, respectively. From baseline to week 12, GHS/HRQoL scores were better maintained with pembrolizumab than with ipilimumab (decrease of −1.9 and −2.5 for pembrolizumab versus −10.0 for ipilimumab; p < 0.001 for each pembrolizumab arm versus ipilimumab). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31% for pembrolizumab Q2W; 29% for Q3W and 44% for ipilimumab), with similar trends observed for individual functioning and symptoms scales. ConclusionsHRQoL was better maintained with pembrolizumab than with ipilimumab in patients with ipilimumab-naive advanced melanoma. ClinicalTrials.gov identifierNCT01866319.

A systematic evaluation of compliance and reporting of patient-reported outcome endpoints in ovarian cancer randomised controlled trials: implications for generalisability and clinical practice

BackgroundThis study aimed to evaluate the patient-reported outcome (PRO) content of ovarian cancer randomised-controlled trial (RCT) publications, describe PRO compliance, and explore potential relationships among these and completeness of PRO protocol content.MethodsPublications of Phase III ovarian cancer RCTs with PRO endpoints were identified by Medline and Cochrane systematic search: January 2000 to February 2016. Two reviewers determined the number of Consolidated Standards of Reporting Trials (CONSORT)-PRO Extension items addressed in publications. Compliance rates (defined as the proportion of participants included in the principal PRO analysis, of those from whom PRO assessments were expected) were extracted. The relationship between CONSORT-PRO score and compliance rates was explored using scatter plots. Additionally CONSORT-PRO score and PRO compliance rates respectively were compared with corresponding PRO protocol scores obtained from a previous study.ResultsThirty-six eligible RCTs (n = 33 with secondary PRO endpoint) were identified and analysed. The average number of CONSORT-PRO items addressed in publications was 6.7 (48%; Range 0–13.5/14). Three RCTs did not report PRO results; in 1 case due to poor compliance. Some compliance information was reported in 26 RCTs, but was considered complete for only 10 (28%) RCTs. Compliance rates were poor overall, ranging from 59 to 83%; therefore missing PRO data from 17 to 41% of participants in these trials could have been avoided.Of the 26 (73%) RCTs for which PRO protocol completeness scores were available, 6 RCTs reported complete compliance information and the 3 of these RCTs with highest PRO compliance had highest protocol checklist scores.ConclusionsFew RCTs reported PRO compliance information in a manner enabling assessment of the generalisability of PRO results. This information is particularly important in RCTs of advanced ovarian cancer because it is important to be able to determine if missing data was due to worsening illness compared to methodological issues. Poor compliance appeared related to poor PRO protocol content, and in one case prevented PRO results from being reported, highlighting the need to address compliance strategies in the protocol. Adhering to protocol and CONSORT-PRO reporting guidance should improve PRO implementation and reporting respectively in ovarian cancer RCTs and allow results to meaningfully inform clinical practice.

Intraprostatic botulinum toxin type "A" injection in patients with benign prostatic hyperplasia and unsatisfactory response to medical therapy: A randomized, double-blind, controlled trial using urodynamic evaluation.

The injection of botulinum neurotoxin A (BTA) into the prostate represents a minimally invasive treatment in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). We evaluated the effectiveness of BTA in treating patients with BPH unresponsive to combined medical therapy (CMT), using urodynamic investigations. This is a randomized, placebo-controlled, double blind trial. Twenty consecutive patients were randomly assigned to receive intraprostatic BTA injection (n = 10) or saline solution (SS) (n = 10). Patients in the intervention group (IG) received 200-300 UI of BTA diluted in 6-8 mL of SS and injected into the transitional zone. Patients in the control group (CG) were treated with SS alone. Primary endpoint was International Prostate Symptom Score (IPSS). Secondary endpoints were: maximum flow rate (Qmax), postvoid residual volume (PVR), maximum cystometric capacity (MCC), bladder outlet obstruction index (BOOI), safety, quality of life (QoL) score, and Patient Reported Outcome (PROs). All patients in the IG reported subjective improvement starting after 1 month. At 3 months of follow-up IPSS, QoL, PVR were reduced by 55,3% (P < 0.01), and 50% (P < 0.01), 80,6%, (P < 0.01), respectively. Qmax was increased by 68% (P < 0.01). MCC increased by 27% (P < 0.01) and BOOI decreased by 54% (P < 0.01). PROs analysis revealed that 90% of patients in the IG reported a subjective symptomatic relief and treatment satisfaction. No local or systemic side effects were observed in any group. These results indicated that intraprostatic BTA is safe and can improve LUTS and QoL in patients with BPH and unsatisfactory response to CMT.