Incomplete reporting of key information on patient-reported outcomes (PROs) in randomized controlled trials (RCTs) in oncology has been highlighted repeatedly as a major barrier to the use of study ...findings in clinical practice. We investigated whether the quality of reporting of PRO data in cancer RCTs has improved over the last 15 years.
We identified all cancer RCTs with PRO endpoints conducted across the most prevalent solid tumor types worldwide published between 2004 and 2019. The quality of PRO reporting was assessed using the International Society for Quality of Life Research recommended standards, which include important aspects related to assessment methodology, statistical analyses, and interpretation of data.
We assessed a total of 631 cancer RCTs in breast (n = 187), lung (n = 131), prostate (n = 120), colorectal (n = 107), and gynecological (n = 86) cancer. We observed a higher adherence to the International Society for Quality of Life Research reporting criteria in the more recently published studies. In a multivariable linear regression analysis, we observed a statistically significant improvement in the quality of PRO reporting over time (P<.001), and this relationship was independent of other measured confounding factors, such as sample size and study sponsorship. Overall, the quality of PRO reporting was higher for studies published after the publication of the Consolidated Standards of Reporting Trials-PRO Extension.
The quality of PRO reporting in cancer RCTs published in the last 15 years has improved significantly. Our findings are encouraging because better reporting of PRO results may translate into a greater impact of study findings on real-world practice.
•Patient-reported outcomes (PROs) are increasingly included as endpoints in randomized controlled trials (RCTs). Previous studies have highlighted poor standards of PRO reporting from cancer RCTs, which may compromise the understanding and impact of PRO study findings.•Results from our multivariable analyses of more than 600 solid cancer RCTs published between 2004 and 2019 indicate a statistically significant improvement in the quality of PRO reporting over time. This finding may have important implications for the greater role that PRO data could play in the clinical arena.•The improvement of the quality of reporting of PRO findings in trial publications may strengthen the role of PROs in clinical practice and enhance their impact on cancer treatment policy and recommendations. Among other factors, the publication of high-quality standards for the reporting of PRO results, such as the International Society for Quality of Life Research reporting criteria and the Consolidated Standards of Reporting Trials-PRO Extension, may have contributed to the observed improvement.
Despite international recommendations of including patient-reported outcomes (PROs) in randomised clinical trials (RCTs), a 2014 review concluded that few RCTs of bladder cancer (BC) report PRO as an ...outcome. We therefore aimed to update the 2014 review to synthesise current evidence-based knowledge of PROs from RCTs in BC. A secondary objective was to examine whether quality of PRO reporting has improved over time and to provide evidence-based recommendations for future studies in this area.
We conducted a systematic literature search using PubMed/Medline, from April 2014 until June 2018. We included the RCTs identified in the previous review as well as newly published RCTs. Studies were evaluated using a predefined electronic-data extraction form that included information on basic trial demographics, clinical and PRO characteristics and standards of PRO reporting based on recommendation from the International Society of Quality of Life Research.
Since April 2014 only eight new RCTs for BC included PROs as a secondary outcome. In terms of methodology, only the proportion of RCTs documenting the extent of missing PRO data (75% vs 11.1%, p = 0.03) and the identification of PROs in trial protocols (50% vs 0%, p = 0.015) improved. Statistical approaches for dealing with missing data were not reported in most new studies (75%).
Little improvement into the uptake and assessment of PRO as an outcome in RCTs for BC has been made during recent years. Given the increase in (immunotherapy) drug trials with a potential for severe adverse events, there is urgent need to adopt the recommendations and standards available for PRO use in bladder cancer RCTs.
Background
While open‐label randomized controlled trials (RCT) are common in oncology, some concerns have been expressed with regard to Patient‐Reported Outcomes (PRO)‐based claims stemming from ...these studies. We aimed to investigate the impact of open‐label design in the context of prostate cancer (PCa) RCTs with PRO data.
Methods
Randomized controlled trials of PCa with a PRO endpoint published between 2004 and 2018 were considered. RCTs were systematically evaluated on the basis of previously defined criteria, including international PRO reporting quality standards and the Cochrane Collaboration's tool for assessing Risk of Bias. The rate of concordance was estimated and compared between traditional clinical outcomes (eg, survival or tumor response) and PRO in open and blinded RCTs.
Results
We identified 110 RCTs published between 2004 and 2018, of which 62% (n = 68) were open‐label. The general characteristics of PCa RCTs were not different according to their design (open‐label vs blinded). The proportion of PCa RCTs with high‐quality PRO reporting was not different between open‐label RCTs and blinded RCTs (41.2% vs 38.1%; P = .75). No statistically significant difference was found between PRO results and concordance with traditional clinical outcomes according to the study design.
Conclusion
Our findings suggest that there is no evidence of significant bias for PROs due to the absence of blinding in the context of PCa RCTs. Further analyses should be conducted in other cancer disease sites.
The systematic review of phase III in prostate cancer suggests that there is no evidence of significant bias on PRO results due to the absence of blinding.
Background
Given the growing importance of patient‐reported outcomes (PROs) as part of “big data” in improving patient care, there is a need to provide a state‐of‐the‐art picture of the added value ...of using PROs in prostate cancer (PCa) randomized controlled trials (RCTs). We aimed to synthetize the most recent high‐quality PRO evidence‐based knowledge from PCa RCTs and to examine whether quality of PRO reporting in PCa research improved over time.
Methods
We conducted a systematic literature search using PubMed, from April 2012 until February 2019. For benchmarking purposes, we also included RCTs identified in our previously published review of RCTs (2004‐2012). Methodology for study identification and evaluation followed standardized criteria and a predefined data extraction form was used to information. PRO quality of the studies was evaluated using the International Society of Quality of Life Research (ISOQOL) recommended criteria.
Results
A total of 55 new RCTs were published between April 2012 and February 2019. About 24 (43.6%) RCTs were found to be of high‐quality regarding PRO assessments. Of these, 13 (54.2%) have been reported in the most recent European Association of Urology (EAU) PCa Guidelines. Overall QoL and sexual, urinary, and bowel function were the most commonly reported PROs. FACT‐P, EPIC‐26, and EORTC QLQ‐C30 and/or its module PR25 were most frequently used as measurement tools. An overall improvement in the completeness of PRO reporting was noted over time.
Conclusion
Many PRO trials are currently not included in the EAU guidelines. Our findings suggest that there has to be a better consensus on the use of PRO data for PCa patients, which will then be reflected in the PCa Guidelines and future data collection. Homogeneity in PROs collection and measurement tools will in turn enable “big data” Consortia to increase the patients’ voice in clinical research.
Patient reported outcomes need to become the standard in prostate cancer RCTs. There is need for consensus on the use of PRO data, which will reflect their use in the guidelines and future data collection.
The inclusion of patient‐reported outcome (PRO) measures in chimeric antigen receptor (CAR) T‐cell therapy research is critical for understanding the impact of this novel approach from a unique ...patient standpoint. We performed a scoping review to map the available literature on the use of PRO measures in CAR T‐cell therapy studies of patients with hematologic malignancies published between January 2015 and July 2022. Fourteen studies were identified, of which 7 (50%) were investigational early‐phase trials, 6 (42.9%) were observational studies, and 1 (7.1%) was a pilot study. The EQ‐5D and the PROMIS‐29 were the 2 most frequently used PRO measures, being included in 6 (42.9%) and 5 (35.7%) studies, respectively. Despite differences in study designs, there seems to be evidence of improvements over time since CAR T‐cell infusion in important domains such as physical functioning and fatigue, at least in patients who respond to therapy. Overall, the studies identified in our review have shown the added value of PRO assessment in CAR T‐cell therapy research by providing novel information that complements the knowledge on safety and efficacy. However, there are several questions which remain to be answered in future research. For example, limited evidence exists regarding patient experience during important phases of the disease trajectory as only 4 (28.6%) and 5 (35.7%) studies provided information on PROs during the first 2 weeks from CAR T‐cell infusion and after the first year, respectively. Time is ripe for a more systematic implementation of high‐quality PRO assessment in future clinical trials and in real‐life settings of patients treated with CAR T‐cell therapy.
Digital health tools are increasingly being used in cancer care and may include electronic patient-reported outcome (ePRO) monitoring systems. We examined physicians' perceptions of usability and ...clinical utility of a digital health tool (GIMEMA-ALLIANCE platform) for ePRO monitoring in the real-life practice of patients with hematologic malignancies. This tool allows for the collection and assessment of ePROs with real-time graphical presentation of results to medical staff. Based on a predefined algorithm, automated alerts are sent to medical staff. Participating hematologists completed an online survey on their experience with the platform. Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) agreed to enter the platform and had a median age of 57 years. Twenty-three hematologists with a median age of 42 years and an average of 17 years of experience in clinical practice were surveyed. All hematologists agreed or strongly agreed that the platform was easy to use, and 87%, agreed or strongly agreed that ePROs data were useful to enhance communication with their patients. The majority of physicians (78%) accessed the platform at least once per month to consult the symptom and health status profile of their patients. The frequency of access was independent of physician sex (
=0.393) and years of experience in clinical practice (
=0.404). In conclusion, our preliminary results support the clinical utility, from the perspective of the treating hematologist, of integrating ePROs into the routine cancer care of patients with hematologic malignancies.
Notable treatment advances have been made in recent years for patients with myelodysplastic syndromes/neoplasms (MDS), and several new drugs are under development. For example, the emerging ...availability of oral MDS therapies holds the promise of improving patients' health‐related quality of life (HRQoL). Within this rapidly evolving landscape, the inclusion of HRQoL and other patient‐reported outcomes (PROs) is critical to inform the benefit/risk assessment of new therapies or to assess whether patients live longer and better, for what will likely remain a largely incurable disease. We provide practical considerations to support investigators in generating high‐quality PRO data in future MDS trials. We first describe several challenges that are to be thoughtfully considered when designing an MDS‐focused clinical trial with a PRO endpoint. We then discuss aspects related to the design of the study, including PRO assessment strategies. We also discuss statistical approaches illustrating the potential value of time‐to‐event analyses and their implications within the estimand framework. Finally, based on a literature review of MDS randomized controlled trials with a PRO endpoint, we note the PRO items that deserve special attention when reporting future MDS trial results. We hope these practical considerations will facilitate the generation of rigorous PRO data that can robustly inform MDS patient care and support treatment decision‐making for this patient population.
Background Financial toxicity (FT) indicates the harmful consequences of cancer-related costs on patients' clinical outcomes and health-related quality of life (HRQoL). Although literature on this ...subject in patients with solid tumors is growing, little is known on patients with hematologic malignancies treated within a universal healthcare system. For example, despite being cured of their disease, long-term survivors of acute promyelocytic leukemia (APL) may still report health status problems which may be associated with financial constraints. Aims Our primary objective was to investigate the prevalence of clinically important problems and symptoms in survivors of APL with or without FT treated within a universal healthcare system. A secondary objective was to examine potential risk factors associated with FT. Methods We did a cross-sectional analysis of two multicenter studies conducted by the GIMEMA Group that enrolled long-term survivors of APL treated with either standard chemotherapy or arsenic trioxide (ATO). FT was evaluated using the financial difficulties item of the EORTC QLQ-C30 questionnaire. Patients treated in Italian centers were selected and classified as experiencing or not FT based on evidence-based thresholds for defining clinically important problems and symptoms of the QLQ-C30, established to help to improve the interpretation of this questionnaire in clinical practice. Using the same criteria, we assessed the prevalence of clinically important problems and symptoms at the patient level, in the groups of survivors of APL with or without FT. Multivariable binary logistic regression analysis was performed to examine potential risk factors associated with FT. The following covariates were considered: sex (female vs male), age at study entry, time since diagnosis, living arrangements (living alone vs living with others), receiving a salary/pension (no vs yes), level of education (high education level vs middle-low level), comorbidities (≥1 vs 0), and type of treatment received (chemotherapy vs ATO). All statistical tests were two-sided with a nominal α=0.05, and there was no adjustment for multiple testing due to the exploratory nature of the study. Results Overall, 365 survivors of APL were analyzed and 23.8% of them reported FT. Most patients (n=304, 83.3%) were treated with chemotherapy and 61 (16.7%) with ATO. Median age at study entry was 53.5 years (IQR: 43.9 - 63.0) and median time since diagnosis was 10.9 years (IQR: 7.9 - 15.7). More than half of survivors of APL were female (n=192; 52.6%), and 68 (18.9%) were living alone. The following characteristics were well-balanced between patients with and without FT: treatment, age, time since diagnosis, living arrangements, and sex. Some one-third of survivors (n=113, 31.4%) was not receiving a salary/pension, and this prevalence was higher among survivors with FT than those without FT (41.9% vs 28.1%). Prevalence of comorbidities was also higher among survivors with FT versus those without FT (87.4% vs 74.5%). The prevalence of clinically important problems and symptoms was statistically significant higher for survivors of APL who reported FT across all scales of the QLQ-C30, except for appetite loss and constipation (Figure 1). For example, with regard to the functioning scales the prevalence of clinically important emotional functioning problems was 50.6% and 19.8% in the group of survivors with and without FT, respectively. The prevalence of clinically important cognitive functioning problems was 41.4% for survivors with FT vs 16.9% in those without FT. The trend for symptom burden was similar, for example the prevalence of clinically important dyspnea was 51.7% and 25.3% in the group of survivors with and without FT, respectively. In the multivariable analysis, the presence of FT was independently associated with having at least one comorbidity (OR 2.44; p = .012), and not receiving a salary/pension (OR 1.90; p = .014). Conclusions Despite being treated within a universal healthcare system and being cured of their disease, some one-fourth of survivors of APL experience FT and these patients report a higher prevalence of clinically important problems and symptoms compared to those without FT. Considering the expected growing population of survivors, owing to the remarkable APL treatment advances, efforts to mitigate FT may be critical to improve long-term HRQoL outcomes.
Abstract
Some concerns have been raised about potential bias in patient-reported outcome (PRO) results from open-label cancer randomized controlled trials (RCTs). We investigated if open-label trials ...favor the experimental treatment over the standard treatment more frequently than blinded trials. We also examined if the effect of blinding differs for distal vs more proximal PROs. We assessed 538 RCTs with a PRO endpoint conducted in the most prevalent cancers, of which 366 (68.0%) were open-label, 148 (27.5%) were blinded, and 24 (4.5%) were categorized as unclear. In our multivariable logistic regression model, we did not observe a statistically significant association of the independent variable treatment concealment (blinded vs open-label) on the dependent variable measuring the proportion of trials favoring the experimental treatment (adjusted odds ratio = 1.19, 95% confidence interval = 0.79 to 1.79; 2-sided P = .40). This was also the case when comparing distal and proximal PROs. Our findings provide novel evidence-based data that support the validity of PRO results from open-label cancer RCTs.
We performed a systematic literature review to identify the most recently published randomized controlled trials (RCTs) in multiple myeloma (MM) with a patient-reported outcome (PRO) endpoint, and to ...summarize both clinical and PRO results, as well as to examine the quality of reporting by phase of disease. We also aimed to describe main type of PRO analysis used and interpretation of clinical significance of PRO findings.
We searched PubMed and the Cochrane Central Register of Controlled Trials to identify RCTs of cancer-directed therapy in patients with MM published between January 2014 and April 2021.
Thirty-two RCTs with a total of 19,798 patients enrolled were identified in our review. In all studies, PROs were secondary or exploratory endpoints. Half of the studies (n = 16) included newly diagnosed patients, 15 RCTs included patients with relapsed/refractory MM, and one study included patients with smoldering MM.
Progression-free survival was the most frequently used primary endpoint. All studies provided unique PRO information that could be used to more comprehensively assess the risk/benefit of the newly tested drugs. However, the identified RCTs were heterogeneous regarding the presentation, and interpretation of PRO results.
The number of RCTs including PROs in MM research has notably increased in recent years. However, more consistency in the methodological approach to PRO assessment, and interpretation of outcomes is needed to ensure that PRO findings will be more impactful on patient care.
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