Patient-reported Outcomes In Trials Research Articles

Regression to the mean for physical function and quality of life in clinical trials for symptomatic knee osteoarthritis

ObjectiveTo estimate size of regression to the mean (RTM) for common patient-reported outcomes in trials for knee osteoarthritis (OA). DesignLongitudinal cohort study; we included participants of the Osteoarthritis Initiative who fulfilled typical inclusion criteria for enrolment in a trial. These included: age 40-79 years, symptomatic knee OA, Kellgren-Lawrence grade 2-3, use of pain medication more than half the days of a month in past 12 months, numerical rating scale pain of 4 to 9. We studied observed changes in WOMAC physical function and KOOS quality of life (QOL). ResultsWe identified 547 subjects who fulfilled inclusion criteria on at least one annual follow-up between year 1 and year 8. The mean level of physical function and QOL at each follow-up time point was similar, about 18, and about 51, respectively. However, at the time of theoretical inclusion in a trial, the mean levels in the same subjects were 23 and 43, respectively (both worse scores). The mean improvement in physical function between inclusion and 1 and 2 years later, respectively, was 2.5 (95% confidence interval 1.7 to 3.2) and 3.1 (2.3 to 3.8). The corresponding improvement in QOL was 2.7 (1.7 to 3.7) and 4.2 (3.1 to 5.3). ConclusionRTM in trials for knee OA is likely to explain improvement in physical function and QOL, not only in knee pain. RTM often misleads investigators to overinterpret effectiveness as RTM neither represents improvement from the intervention nor placebo effect from the intervention and its context.

Data collection methods for patient-reported outcome measures in cancer randomised controlled trials: a protocol for a rapid scoping review

BackgroundThere are different modes and ways to assess patient-reported outcomes (PROs) in clinical trials. However, there is little systematic information on how often different modes of assessment (MOA) are used...

The inclusion of health-related quality of life and other patient-reported outcomes in landmark trials for Food and Drug Administration oncology drug approvals: An analysis of cancer drug approvals between 2006 and 2022.

1569 Background: How patients feel and function are essential elements of the clinical benefit of interventions which is often not captured by traditional measures of clinical benefit such as progression-free survival and overall survival. Health-related quality of life, functional status, symptom burden, and other patient-reported outcomes (PROs) assess the impact of interventions from the patient’s point of view. The aim of this study is to assess the inclusion of PROs in landmark trials leading to FDA oncology drug approvals. Methods: This is a retrospective cross-sectional study of pivotal trials leading to FDA oncology approvals between January 2006 and December 2022 based on the FDA oncology approval notifications. The trial protocols of all pivotal trials were evaluated for inclusion of health-related quality of life or other PROs as an outcome measure. The approved therapies were classified into first-line, adjuvant/maintenance, and second or later line of treatment. Chi-square tests were used to assess the relationship between the line of treatment and the inclusion of PROs in the trial protocol. Results: There were 420 oncology approvals during the study period with the highest number of approvals in a single year in 2020 (56) and the least in 2007 (7). Lung cancer has the highest number of approvals (61, 14.5%) followed by lymphoma (50, 12%), leukemia (49, 11.7%), genitourinary malignancies (48, 11.4%), breast cancer (36, 8.6%), gastrointestinal malignancies (32, 7.6%), plasma cell disorders (30, 7.1%) melanoma (20, 4.8%), gynecological malignancies (20, 4.8%), hepatobiliary malignancies (14, 3.3%) and head/neck cancers (14, 3.3%). The approved therapies were first line (146, 34.8%), second or higher line (226, 53.8%), and adjuvant/maintenance therapies (48, 11.4%). PROs were included in 40.7% of the pivotal trials. There is a rising trend in the inclusion of PROs from 5.5% of pivotal trials in 2006 to 31% in 2022. Trials on first-line therapies are more likely to include PROs compared to second or higher-line therapies (44.5% vs 36.7%; p = 0.13). Conclusions: Although there is a rising trend in the inclusion of health-related quality of life and other PROs in pivotal trials for FDA oncology drug approvals, most pivotal trials did not include PROs as outcome measures.[Table: see text]

Use of patient-reported outcomes in heart failure: from clinical trials to routine practice.

Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient-reported outcomes (PROs) aim to switch traditional care to a more patient-centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care.

Use and Reporting of Patient-Reported Outcomes in Trials of Palliative Radiotherapy

Approximately 50% of all patients with cancer have an indication for radiotherapy, and approximately 50% of radiotherapy is delivered with palliative intent, with the aim of alleviating symptoms. Symptoms are best assessed by patient-reported outcomes (PROs), yet their reliable interpretation requires adequate reporting in publications. To investigate the use and reporting of PROs in clinical trials of palliative radiotherapy. This preregistered systematic review searched PubMed/Medline, EMBASE, and the Cochrane Center Register of Controlled Trials for clinical trials of palliative radiotherapy published from 1990 to 2020. Key eligibility criteria were palliative setting, palliative radiotherapy as treatment modality, and clinical trial design (per National Institutes of Health definition). Two authors independently assessed eligibility. Trial characteristics were extracted and standard of PRO reporting was assessed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. The association of the year of publication with the use of PROs was assessed by logistic regression. Factors associated with higher CONSORT-PRO adherence were analyzed by multiple regression. This study is reported following the PRISMA guidelines. Among 7377 records screened, 225 published clinical trials representing 24 281 patients were eligible. Of these, 45 trials (20%) used a PRO as a primary end point and 71 trials (31%) used a PRO as a secondary end point. The most prevalent PRO measures were the Numeric Rating Scale/Visual Analogue Scale (38 trials), European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (32 trials), and trial-specific unvalidated measures (25 trials). A more recent year of publication was significantly associated with a higher chance of PROs as a secondary end point (odds ratio [OR], 1.04 [95% CI, 1.00-1.07]; P = .03) but not as primary end point. Adherence to CONSORT-PRO was poor or moderate for most items. Mean (SD) adherence to the extension adherence score was 46.2% (19.6%) for trials with PROs as primary end point and 31.8% (19.8%) for trials with PROs as a secondary end point. PROs as a primary end point (regression coefficient, 9.755 [95% CI, 2.270-17.240]; P = .01), brachytherapy as radiotherapy modality (regression coefficient, 16.795 [95% CI, 5.840-27.751]; P = .003), and larger sample size (regression coefficient, 0.028 [95% CI, 0.006-0.049]; P = .01) were significantly associated with better PRO reporting per extension adherence score. In this systematic review of palliative radiotherapy trials, the use and reporting of PROs had room for improvement for future trials, preferably with PROs as a primary end point.

Reporting of patient-reported outcomes in trials on alcohol use disorder: a meta-epidemiological study

ObjectivesCurrently, limited research exists to assess the extent of patient-reported outcome (PRO) reporting among randomised controlled trials (RCTs) evaluating alcohol use disorder (AUD). We sought to investigate the completeness of...

Patient-Reported Outcomes in Pediatric Cancer Registration Trials: A US Food and Drug Administration Perspective.

Pediatric patient-reported outcome (PRO) data can help inform the U.S. Food and Drug Administration's (FDA) benefit-risk assessment of cancer therapeutics by quantifying symptom and functional outcomes from the patient's perspective. This study assessed use of PROs in commercial pediatric oncology trials submitted to FDA for regulatory review. FDA databases were searched to identify pediatric oncology product applications approved between 1997 and 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (sample size, completion rates, and use of fit-for-purpose instruments). The role of PROs in each trial (endpoint hierarchy) was also recorded, along with whether any PRO endpoints were included in product labeling. Seventeen pediatric oncology applications were reviewed, 4 included PRO data: Denosumab, Tisagenlecleucel, Larotrectinib, and Selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. Trials collecting PRO data were Phase II or Phase I/II single-arm studies with sample sizes of 28 to 88 patients. Symptomatic Adverse Events were characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient self-report. PROs were infrequently utilized in pediatric cancer registration trials. When used, PRO data were limited by lack of a clear research objective and corresponding prospective statistical analysis plan. Contemporary PRO symptom libraries such as the National Cancer Institute's Pediatric PRO-CTCAE may provide an opportunity to better evaluate the occurrence and impact of symptomatic Adverse Events, from the patient's perspective, in pediatric oncology trials.

Emerging trends and utilization of patient-reported outcomes (PROs) in clinical trials of chimeric antigen receptor (CAR) T-cell therapies.

e19142 Background: Patient-reported outcomes (PROs) are an important tool to assess the impact of new therapies on health-related quality of life (HRQoL). This study aimed to describe if and what PRO instruments are currently being utilized in CAR-T cell therapy studies in solid and hematological malignancies while assessing the patterns of inclusion and trends of HRQoL data reporting. Methods: We used Citeline to search for clinical trials between Jan 2008 - Jan 2020, excluding planned or terminated studies, non-oncology, non-treatment, and duplicates. Reviewers extracted various parameters for included trials, then cross-matched data with EU Clinical Trials Register, Clinical trials.gov, trial protocols (when available), and Google. The reporting of PRO data was then assessed for those Closed/Completed trials that included a PRO via PubMed/MEDLINE, Sponsor, and Google. Results: A sample of 664 CAR-T trials was identified. PROs were included in only 6.17% (41/664) studies. Of the 41 trials that included a PRO, 63.41% (26/41) utilized more than one PRO, with the generic EORTC QLQ-C30 and the EQ-5D being used predominately. Median HRQoL follow-up was 5-years on most trials. No studies used PROs as primary endpoints. The majority of PROs were observed to be utilized in early phase trials (phase I, 12; Phase I/II, 17). PROs were first incorporated in CAR-T trials beginning in 2014, and the utilization rate has increased steadily, except for 2019. PROs were included in 3 first line trials, 22 second line, 5 third line, and 11 fourth line or greater. PRO utilization between solid tumor trials and hematologic malignancies was comparable (6.04% [9/149], and 6.26% [32/511]). Of the completed/closed trials, 28.57% (3/14) published PRO data and met at least eight of the CONSORT-PRO quality indicators. Conclusions: The utilization of PROs in CAR-T trials (6.17%) is under the industry average of 27%, despite the growing importance of HRQoL and its impact on value-based care. The findings from this review reflect the overall increased attention to CAR-T as a new therapeutic entity and the continued deficiency of including and reporting of PROs in trial designs.

Surrogate End Points and Patient-Reported Outcomes for Novel Oncology Drugs Approved Between 2011 and 2017

This review of novel oncology drugs approved by the US Food and Drug Administration examines the use of surrogate end points for overall survival, evaluates the use of patient-reported outcomes in trials supporting approvals, and seeks to determine whether drugs initially approved without evidence of overall survival or patient-reported outcome benefits demonstrate improvements in either measure postapproval.

Health-related quality of life and its association with medication adherence in active pulmonary tuberculosis- a systematic review of global literature with focus on South Africa.

IntroductionTuberculosis (TB) is a leading cause of morbidity and mortality in South Africa. Clinical parameters are important objective outcomes in TB; however they often are not directly correlated with subjective well-being of the patient, but can be assessed using patient-reported outcome (PRO) measures. Health-related quality of life (HRQOL) is a specific PRO generally multi-dimensional in nature and includes physical, mental and social health domains. The inclusion of HRQOL PROs in trials and clinical practice can provide additional information beyondclinical and microbiological parameters. Furthermore, HRQOL may be associated with medication adherence. This review focuses on patient-reported HRQOL and its association with medication adherence in TB patients in South Africa.MethodsA comprehensive search strategy was developed focusing on the impact of TB on patient-reported HRQOL,the existence of a conceptual framework of TB-specific HRQOL, determinants of medication adherence and the association of HRQOL with medication adherence. Data were extracted from all identified articles and additionaldata extraction was performed by two independent reviewers with special focus on longitudinal studies in order to understand changes of HRQOL and adherence over time. Research gaps were identified with regard to patient-reported HRQOL and medication adherence.ResultsA total of 66 articles met the eligibility criteria. Ten HRQOL studies and one adherence study used a longitudinal design, none of these in South Africa. A variety of different generic and disease-specific HRQOL measures were identified in the articles. In South Africa four HRQOL and five adherence studies (non-longitudinal) were published. Similar factors (socio-demographic, socio-economic, disease-related, therapy-related and psycho-social aspects) affect HRQOL and adherence. Although standard TB treatment improved all health domains, psychological well-being and social functioning remained impaired in microbiologically cured patients after treatment.ConclusionWhile evidence of TB impact on HRQOL and medication adherence and their association exists, it is verylimited for the South African situation. No valid and reliable TB-specific HRQOL measures were identified in this systematicreview. An assessment of HRQOL in TB patients in South Africa is required as this may assist with improving current disease management programmes, medication adherence and national treatment guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-016-0442-6) contains supplementary material, which is available to authorized users.

Patient-reported outcomes in trials of patients with polymyalgia rheumatica: a systematic literature review.

Patient-reported outcomes (PROs) are being increasingly recognized as important measures by rheumatologists. The objective of this review was to evaluate the frequency of use of PROs in studies of patients with polymyalgia rheumatica (PMR). A systematic literature search was performed in PubMed (up to April 2015) to identify any type of clinical studies reporting any type of PROs in patients with PMR. Articles were excluded if they did not include adults with PMR or did not report any PROs. Characteristics of each study such as study design, follow-up, treatment assessed if any, number of patients, mean age, gender, and a description of PROs used were collected to perform a descriptive analysis. From 118 initial studies captured, 28 articles met the predefined criteria, and 20 were finally included in this review. Ten studies (50%) were randomized clinical trials (RCTs), and 8 (40%) were cohorts. The most frequently reported domains were: pain (90%), being the most frequent tool using a visual analogue scale; morning stiffness in minutes (85%); and function (25%), evaluated through the Health Assessment Questionnaire. Other domains such as patient global assessment, fatigue, quality of life, and anxiety and depression were infrequently reported. A larger proportion of PROs were included in cohorts in comparison with RCT. Pain and morning stiffness are the most frequently reported PROs. Other domains that may appear relevant for patients are infrequently reported, especially function.

The CONSORT Patient-Reported Outcome (PRO) extension: implications for clinical trials and practice.

To inform clinical guidelines and patient care we need high quality evidence on the relative benefits and harms of intervention. Patient reported outcome (PRO) data from clinical trials can “empower patients to make decisions based on their values” and “level the playing field between physician and patient”. While clinicians have a good understanding of the concept of health-related quality of life and other PROs, evidence suggests that many do not feel comfortable in using the data from trials to inform discussions with patients and clinical practice. This may in part reflect concerns over the integrity of the data and difficulties in interpreting the results arising from poor reporting.The new CONSORT PRO extension aims to improve the reporting of PROs in trials to facilitate the use of results to inform clinical practice and health policy. While the CONSORT PRO extension is an important first step in the process, we need broader engagement with the guidance to facilitate optimal reporting and maximize use of PRO data in a clinical setting. Endorsement by journal editors, authors and peer reviewers are crucial steps. Improved design, implementation and transparent reporting of PROs in clinical trials are necessary to provide high quality evidence to inform evidence synthesis and clinical practice guidelines.

Patient-Reported Outcomes Assessment in Cancer Trials: Taking Stock, Moving Forward

To evaluate and improve the use of cancer trial end points that reflect the patient's own perspective, the National Cancer Institute organized an international conference, Patient-Reported Outcomes Assessment in Cancer Trials (PROACT), in 2006. The 13 preceding articles in this special issue of the Journal were commissioned in preparation for or in response to the PROACT conference, which was cosponsored by the American Cancer Society. Drawing from these articles and also commentary from the conference itself, this concluding report takes stock of what has been learned to date about the successes and challenges in patient-reported outcome (PRO) assessment in phase III, phase II, and symptom management trials in cancer and identifies ways to improve the scientific soundness, feasibility, and policy relevance of PROs in trials. Building on this synthesis of lessons learned, this article discusses specific administrative policies and management procedures to improve PRO data collection, analysis, and dissemination of findings; opportunities afforded by recent methodologic and technologic advances in PRO data collection and analysis to enhance the scientific soundness and cost efficiency of PRO use in trials; and the importance of better understanding the usefulness of PRO data to the full spectrum of cancer decision makers, including patients and families, health providers, public and private payers, regulatory agencies, and standards-setting organizations.