Patient-reported Outcome Measures In Clinical Trials Research Articles

Recalling what we thought we knew about recall periods: a qualitative descriptive study of how adults diagnosed with cancer use recall periods for patient-reported outcome items about physical function.

In cancer studies, assessment of patients' physical function can provide insight into cancer-related symptoms and the side effects of treatment. Physical function can be assessed using patient-reported outcome measures (PROMs), which may or may not include a recall period-the amount of time the questionnaire asks the respondent to think back to answer the questions. More understanding is needed about how patients interpret and respond to items posed with different recall periods, and which recall period they actually use. We conducted a qualitative study with 72 adults diagnosed with cancer to describe response processes when answering PROM items about physical function. When describing their physical function during concept elicitation interviews, most participants recalled their functioning over 1month or more. When presented with PROM items with no recall period, the most used period was more than 4weeks. When presented with a 7-day recall, the most used period was 7days. However, almost 30% of responses used recall periods greater than 1week. Including a 7-day recall period improves recall consistency for patients when answering physical function PROM items, but there is still room for improvement. The inaccuracy of recall for PROMs in clinical trials influences the ability to calculate the change in treatment outcomes over time and may conceal or emphasize actual treatment effects.

Patient-reported assessments of chronic cough in clinical trials: accessory or primary endpoints?

Chronic cough is a complex disorder that affects up to 5-10% of the general population. It can be challenging to manage as there are few effective treatments, although several novel antitussives are in clinical development. The endpoints used to assess their efficacy in clinical trials should be optimal; most large clinical trials currently use objective measures as the primary outcome, especially cough frequency. There are strengths in this approach, although taking the view that other measures of chronic cough are less important, including patient-rated cough severity, psychosocial impact and other associated symptoms. Patient-reported outcome measures (PROMs) explore patients' personal experiences of health and disease, and the effects of particular conditions on their lives. Numerous validated PROMs exist for chronic cough, from simple visual analogue scales, to those that focus on cough hypersensitivity and cough-specific quality of life. Medicine regulators in the European Union (EU) and United States of America (USA) encourage the use of PROMs in clinical trials but have voiced concerns over their content validity, clinically meaningful thresholds for change, and discordance with objective measures. There are recent and ongoing studies to address these limitations. This review discusses currently available PROMs used to assess chronic cough and discusses their potential role as primary outcome measures in clinical trials.

Identifying Existing Guidelines, Frameworks, Checklists, and Recommendations for Implementing Patient-Reported Outcome Measures: Protocol for a Scoping Review.

Implementing patient-reported outcome measures (PROMs) to measure and evaluate health outcomes is increasing worldwide. Along with this emerging trend, it is important to identify which guidelines, frameworks, checklists, and recommendations exist, and if and how they have been used in implementing PROMs, especially in clinical quality registries (CQRs). This review aims to identify existing publications, as well as publications that discuss the application of actual guidelines, frameworks, checklists, and recommendations on PROMs' implementation for various purposes such as clinical trials, clinical practice, and CQRs. In addition, the identified publications will be used to guide the development of a new guideline for PROMs' implementation in CQRs, which is the aim of the broader project. A literature search of the databases MEDLINE, Embase, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials will be conducted since the inception of the databases, in addition to using Google Scholar and gray literature to identify literature for the scoping review. Predefined inclusion and exclusion criteria will be used for all phases of screening. Existing publications of guidelines, frameworks, checklists, recommendations, and publications discussing the application of those methodologies for implementing PROMs in clinical trials, clinical practice, and CQRs will be included in the final review. Data relating to bibliographic information, aim, the purpose of PROMs use (clinical trial, practice, or registries), name of guideline, framework, checklist and recommendations, the rationale for development, and their purpose and implications will be extracted. Additionally, for publications of actual methodologies, aspects or domains of PROMs' implementation will be extracted. A narrative synthesis of included publications will be conducted. The electronic database searches were completed in March 2024. Title and abstract screening, full-text screening, and data extraction will be completed in May 2024. The review is expected to be completed by the end of August 2024. The findings of this scoping review will provide evidence on any existing methodologies and tools for PROMs' implementation in clinical trials, clinical practice, and CQRs. It is anticipated that the publications will help us guide the development of a new guideline for PROMs' implementation in CQRs. PROSPERO CRD42022366085; https://tinyurl.com/bdesk98x. DERR1-10.2196/52572.

Patient adherence and response time in electronic patient-reported outcomes: insights from three longitudinal clinical trials.

Patient-reported outcome measures (PROMs) are used to collect data on disease symptoms in support of clinical trial endpoints. Clinical studies can last a year or more, and the patients' adherence and response time to daily at-home questionnaires may vary significantly over time. The aim of this study was to understand patterns and changes in patients' completion of daily PROMs during longitudinal clinical studies. Data were collected from 1342 patients randomized into three respiratory clinical trials (NCT03401229, NCT03347279, and NCT03406078). PROMs were completed by patients using electronic handheld devices that collected the starting and completion times. A Bayesian generalized linear mixed-effects model was used to identify unbiased coefficients associated with PROM adherence and response time using patient, site, and calendar features as covariates. Adherence decreased over time after randomization, and the rate of decrease was higher in younger patients. The 14-day pre-randomization adherence was correlated with adherence throughout the study. Patients were also more adherent during working days compared to non-working days. Oldest patients took twice as long to complete PROMs throughout the study; however, the response time for all patients decreased during the first month of the study regardless of age. Response time increased 7days before and after the date of a scheduled clinic visit and when a patient-reported higher symptom burden. Detailed analyses of adherence and response time for daily PROMs in clinical trials can provide significant insights about trends of patient behavior in longitudinal clinical studies with high baseline adherence.

Abstract 153: Use Of Patient-reported Outcome Measures (PROMS) In The Primary Publications Of Acute Stroke Clinical Trials (2010-2020)

Background: Patient-reported outcome measures (PROMs) describe health status from the perspective of the patient. There is growing interest in the use of PROMs in clinical trials and there have been major efforts to develop PROMs for neurological conditions (e.g., Neuro-QOL, PROMIS). However, the extent to which such measures are used in stroke trials is uncertain. We sought to determine how often contemporary acute stroke trials included PROMs as primary or secondary outcome measures. Methods: We searched MEDLINE for completed RCTs published in one of nine major journals between 2010 and 2020. Eligible studies were phase 2 or 3 trials undertaken to test therapeutic interventions within one month of stroke onset. For each trial we accessed the primary publication as well as the published protocol and supplement when available. We abstracted key trial characteristics including all primary and secondary efficacy outcome measures. We defined PROMs using online databases (qolid.org) with the focus on self-reported measures of quality of life, symptoms, and function collected without interpretation of an external party. Results: 115 trials met eligibility criteria. Only one trial used a PROM for its primary outcome measure (visual analogue pain scale), but 40 trials (35%) listed at least one PROM as a secondary outcome measure in its primary publication. An additional 15 trials (13%) listed at least one PROM in their protocol. Among the 55 trials that defined at least one PROM as a secondary outcome measure, the most commonly used measure was Euro-QOL (n=42, 76%) followed by SIS-16 (n=9, 16%), SF-36 (n=7, 13%), and the stroke-specific QOL scale (n=5, 9%). Other PROMs included various measures of anxiety and depression (n=9, 16%). Only one study used a Neuro-QOL based measure. Of the 41 trials that listed a PROM as a primary or secondary outcome in the primary publication, 39 (95%) provided PROM results, but of these only 7 (18%) found statistically significant treatment differences. Conclusions: While about half of acute stroke trials listed at least one PROM as a secondary outcome, they played a minor role in the presentation of trial results. Inclusion of PROMs in acute stroke trials requires greater attention during both the design and reporting phases of the trial.

Developing a conceptual model of symptoms and impacts in progressive fibrosing interstitial lung disease to evaluate patient-reported outcome measures.

BackgroundAn understanding of the experience of patients with progressive fibrosing interstitial lung disease (PF-ILD) is needed to select appropriate patient-reported outcome measures (PROMs) to evaluate treatment effect in clinical trials.MethodsA systematic literature review was conducted to develop a preliminary conceptual model of the symptoms experienced by patients with PF-ILD and the impacts the disease has on them. An online survey and consensus meetings were then conducted with 12–14 stakeholders (patients, clinicians, regulatory and payer advisors) to refine the conceptual model and critically appraise how key concepts should be measured by PROMs. PROMs assessed included Living with Idiopathic Pulmonary Fibrosis, Living with Pulmonary Fibrosis, the King's Brief Interstitial Lung Disease questionnaire, Cough and Sputum Assessment Questionnaire, Evaluating Respiratory Symptoms, Leicester Cough Questionnaire, Functional Assessment of Chronic Illness Therapy (Dyspnoea/Fatigue) and St George's Respiratory Questionnaire for Idiopathic Pulmonary Fibrosis.ResultsThe literature review identified 36 signs/symptoms and 43 impacts directly or indirectly related to pulmonary aspects of PF-ILD. The most relevant symptoms identified by participants included shortness of breath on exertion, fatigue and cough; relevant impacts included effects on physical functioning, activities of daily living and emotional wellbeing. These are presented in a conceptual model. Consensus opinion was that existing PROMs need further modification and validation before use in clinical trials.ConclusionsThe conceptual model improves understanding of the symptoms and impacts that living with PF-ILD has on patients’ wellbeing. It can help to inform the choice of PROMs in clinical trials and highlight aspects to assess in the clinical care of patients with PF-ILD.

The Role of Patient-reported Outcomes and Medication Adherence Assessment in Patient-focused Drug Development for Solid Organ Transplantation.

The Role of Patient-reported Outcomes and Medication Adherence Assessment in Patient-focused Drug Development for Solid Organ Transplantation.

2024-P: A Qualitative Study in Obesity to Explore Clinically Meaningful Change on Patient-Reported Outcome (PRO) Measures

Background: Obesity is a chronic disease with significant impacts on health-related quality of life (HRQoL) specifically physical functioning (PF), which is increasingly assessed using PRO measures in clinical trials. A review of existing literature suggested that further qualitative research was required to establish patient-perceived clinically important change (CIC) thresholds for two PRO measures used in obesity studies: the acute 36-item Short Form Health Survey (SF-36v2) and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT). Objective: To explore the level of change on the SF-36v2 (acute) and IWQOL-Lite-CT that individuals living with obesity consider to be meaningful, noticeable and indicative of treatment success. Methods: Semi-structured interviews were conducted in the U.S. with adults who have overweight or obesity (Body Mass Index [BMI] ≥ 27 kg/m2). Open-ended concept elicitation (CE) questions allowed participants to discuss the amount of body weight loss needed to have a noticeable improvement on PF. Cognitive tasks were later used during cognitive debriefing (CD) to explore what participants considered a CIC on each PRO measure. Results: A total of 33 participants were interviewed (mean BMI: 37.6 kg/m2 [27.4 to 56.6 kg/m2] mean age: 45 years [19 to 81 years]). In CE, participants identified 5-10% weight loss as the threshold for having a noticeable improvement on PF and contextualized meaningful weight loss by using real-life examples (e.g., climbing stairs without becoming breathless). In CD, the majority of participants considered a 1-point change at the item level to be indicative of meaningful improvement on both PRO measures. Conclusions: The combined CE and CD approach facilitated better understanding of meaningful change by participants, providing evidence that a 1-point change, the smallest detectable change on both the SF-36v2 (acute) and IWQOL-Lite-CT, is a CIC in people with overweight or obesity. Disclosure J. Poon: Employee; Self; Eli Lilly and Company. C. Marshall: Other Relationship; Self; Eli Lilly and Company. C. Johnson: Other Relationship; Self; Eli Lilly and Company. H. Pegram: Other Relationship; Self; Eli Lilly and Company. M. Hunter: Other Relationship; Self; DRG Abacus. H. Kan: Employee; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company.

Under-Reporting of Patient Reported Outcome (PRO) in Clinical Trials

Introduction: Clinically relevant outcomes as improvements in overall survival (OS) or quality of life (QOL) should guide decision-making. The FDA encourages the implementation of patient-centric PRO measures in clinical trials. In the recent decade there have been a growing number of protocols including PROs in their outcome measures, and an increase in pre-market submissions including those measures. We aimed to evaluate the frequency at which PRO measures, incorporated into clinical trials, are made publicly available, when trial results are published.Methods: We searched Citeline® Trialtrove database, a registry of clinical trials, for randomized phase 2/3 and 3 clinical trials including patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), initiated between the years 2005-2015, with PRO endpoints listed. We excluded trials involving patients with acute leukemia or involving stem cell transplantation. For these trials we recorded the following data: indication, treatment and comparator, phase, primary endpoint, type of scale or questionnaire used for PRO endpoint. We then identified all available publications associated with the trial, and recoded type of publication (abstract or full text), year, number of randomized patients, reported outcomes.Results: 120 CLL and NHL trials were identified through our search. 44 trials (23 CLL, 21 NHL) were listed with at least one PRO endpoint. Eleven trials were excluded (1 extension of an included trial, 4 not completed, 4 not published, 2 cancelled with little or no recruitment). PRO endpoints were assessed utilizing - EORTC-QLQ30 QoL, QLQ-CLL16, FACIT-fatigue, FACT-leu, FACT-lym, EQ-5D, Skindex-29, and Rituximab Administration Satisfaction Questionnaire as relevant per indication. PRO was the primary outcome in two trials, and secondary in the other 31. Study sponsor was industry-only in 27 trials, and industry-academic in five. Of the 33 trials analyzed, 14 (42%) published results of the PRO endpoint - 6/17 (35%) of CLL trials, and 8/16 (50%) of NHL trials. 26/33 of the trials were published as full-text, 6/33 as abstract, and 1 published on clinicaltrials.gov. Of the 26 full text publications, 12 (46%) reported PRO. In 8 of full-text PRO were reported as part of the primary publication or published within 6 months. Nine of all trials provided a comprehensive report of PRO endpoints. Of the 33 trials, only 2 provided information about missing PRO data. 54% of trials in which primary endpoint was reached, and 12.5% of trials in which it was not reached, were published listing PRO results. Of the trials that showed PFS benefit, with no OS benefit, 9/15 (60%) published the results of the PRO endpoints.Conclusions: Despite a growing emphasis on QOL and use of PROs in oncology clinical trials, and despite patient and health provider efforts to record PRO data, most CLL and NHL randomized trials still do not report the PRO endpoints. In several cases they were published later and in a partial manner, minimizing their impact on treatment decisions. This may indicate a disregard to PRO data collected, incomplete collection or methodological flaws in data analysis. Regardless of the reason, PRO data should be routinely included in study publications to allow for a complete assessment of investigational treatment outcome - including disease related outcomes, as well as those reported by the patients themselves. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.