scholarly journals CLINICALLY MEANINGFUL CHANGE FOR PHYSICAL PERFORMANCE: PERSPECTIVES OF THE ICFSR TASK FORCE

2019 ◽  
pp. 1-5
Author(s):  
J. Guralnik ◽  
K. Bandeen-Roche ◽  
S.a.r. Bhasin ◽  
S. Eremenco ◽  
F. Landi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Physical Performance ◽  
Performance Measures ◽  
Patient Reported Outcomes ◽  
Task Force ◽  
Meaningful Change ◽  
Patient Reported ◽  
Research Task ◽  
Definition Of ◽  
Clinical Meaningfulness

For clinical studies of sarcopenia and frailty, clinically meaningful outcome measures are needed to monitor disease progression, evaluate efficacy of interventions, and plan clinical trials. Physical performance measures including measures of gait speed and other aspects of mobility and strength have been used in many studies, although a definition of clinically meaningful change in performance has remained unclear. The International Conference on Frailty and Sarcopenia Research Task Force (ICFSR-TF), a group of academic and industry scientists investigating frailty and sarcopenia, met in Miami Beach, Florida, USA in February 2019 to explore approaches for establishing clinical meaningfulness in a manner aligned with regulatory authorities. They concluded that clinical meaningful change is contextually dependent, and that both anchor- based and distribution-based methods of quantifying physical function are informative and should be evaluated relative to patient-reported outcomes. In addition, they identified additional research needed to enable setting criteria for clinical meaningful change in trials.

scholarly journals Characterization of Patient-Reported Outcomes in Multiple Myeloma Registrational Trials Submitted to the U.S. FDA

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Laura Fernandes ◽  
Jiaxi Zhou ◽  
Bellinda L King-Kallimanis ◽  
Thomas Gwise ◽  
Paul Kluetz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Patient Reported Outcomes ◽  
Core Outcome Set ◽  
Core Outcome ◽  
Outcome Set ◽  
Patient Reported ◽  
Assessment Frequency ◽  
Definition Of ◽  
Collection Methods

Introduction Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells. The US Food and Drug Administration (FDA) has approved numerous therapies for the treatment of MM over the past 13 years. During the same time period, there have been advances in characterizing the patient experience in oncology clinical trials, primarily using patient-reported outcomes (PRO). Although there have been advances in MM and collection of patient experience in clinical trials, this review aims to provide details on the heterogeneity of PRO measures and data analyses used in MM registrational trials. Methods We reviewed FDA databases for NDA/BLA submissions supporting therapies to treat patients with MM between 2007 and 2020. Pivotal trial protocols, clinical study reports, and FDA clinical/ statistical reviews supporting each application were reviewed for descriptions of included PROs. We focused on PRO measures, collection methods, baseline definition, assessment frequency, compliance, definition of thresholds for clinically meaningfulness, and statistical methods for analysis of PRO. Results We examined the results from 25 clinical trials that led to 20 new indications. PRO data were included in 17 of the 25 trials (68%). Of the 17 trials with PRO data, three were single arm trials, and the remainder were randomized trials. All trials were open label except for one blinded randomized trial. Seven trials collected data electronically, five in paper format, and five trials did not specify the collection format. The majority of trials had at least two PRO measures (82%) with two trials (12%) utilizing four measures. Among trials included for analysis, nine unique PRO measures were used, most commonly the EORTC QLQ-30 (87%), EQ-5D (65%), both cancer agnostic and QLQ-MY20 (47%), specifically for MM patients. We found differences in terms of definition of baseline. One trial defined measurements taken only at screening as the baseline assessment, while the remainder defined baseline as any measurement taken on or before day 1 cycle 1. Assessment frequency was highly variable (e.g. every cycle, every other cycle, every three months) and was largely dependent on cycle length (ranged from 21 to 42 days). We also noted that assessment may have been after a period of drug washout (e.g. the anti-MM regimen was administered on days 1-21 of a 28 day cycle; PRO assessment occurred on day 1 of the next cycle, thus following a 7-day washout). Definition of compliance of the PRO measures varied across the trials ranging from "completing all items" (6%), "completing 50% of the items" (12%), and "completing enough items to calculate the score in any domain" or some variant (82%). There was variability in the definition and justification of clinically meaningful thresholds across trials despite use of the same instrument and similar MM populations. Differences in statistical methods used for analyses of the PRO endpoints were also noted when analyzing data from the same measure across trials. For example, one of the two trials using the BPI-SF analyzed pain severity and intensity as composite endpoints (change from baseline analysis using a mixed model with treatment arm, time point, and baseline score as covariates). The other trial using the BPI-SF used pain response which was defined as a 30% reduction from baseline in worst pain score over the last 24 hours without an increase in analgesic use at 2 consecutive evaluations as an endpoint, and used the stratified Cochran-Mantel-Haenszel test to report treatment differences. Conclusions We encountered substantial heterogeneity in terms of PRO collection methods, measures, definitions and analyses in recent MM registrational trials. These differences may hinder the utility of this data for healthcare policy as well as clinician and patient decision making. FDA has proposed a core outcome set to be included in cancer clinical trials which includes assessment of patient-reported adverse events, disease symptoms, physical function, role function, and overall side effect bother. Use of this core outcome set in future MM registration trials is one step towards consistency in PRO collection and analysis. Further work needs to be done to determine the best approach for statistical and analytical methodologies. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Potential of patient-reported outcomes as nonprimary endpoints in clinical trials

2013 ◽  
Vol 11 (1) ◽  
pp. 83 ◽  
Author(s):  
Ari Gnanasakthy ◽  
Sandra Lewis ◽  
Marci Clark ◽  
Margaret Mordin ◽  
Carla DeMuro
Keyword(s):  
Clinical Trials ◽  
Patient Reported Outcomes ◽  
Patient Reported

scholarly journals SAT0121 PAIN AND OTHER PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO DID OR DID NOT ACHIEVE TREATMENT RESPONSE BASED ON IMPROVEMENT IN SWOLLEN JOINTS IN TOCILIZUMAB CLINICAL TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 994.2-995
Author(s):  
A. Sebba ◽  
J. Han ◽  
S. Mohan
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Pain Score ◽  
Patient Reported Outcomes ◽  
Component Score ◽  
Link Type ◽  
Pain Scores ◽  
Sf 36 ◽  
Patient Reported ◽  
Nonresponder Group

Background:Significant improvements in pain and other patient-reported outcomes (PROs) have been shown in large clinical trials in patients with rheumatoid arthritis (RA) who receive tocilizumab (TCZ) compared with placebo (PBO). Recent data suggest that pain in RA may be noninflammatory as well as inflammatory, and improvement in pain scores and other PROs may be seen in patients who do not respond to treatment based on disease activity measures that evaluate inflammation.Objectives:To assess changes in pain scores and other PROs in patients with RA who did or did not achieve ≥ 20% improvement in SJC in TCZ clinical trials.Methods:Data from patients with active RA who received intravenous TCZ 8 mg/kg + MTX or PBO + MTX in 3 Phase III studies (OPTION [NCT00106548], TOWARD [NCT00106574] and LITHE [NCT00109408]) were included. All patients had moderate to severe RA with an inadequate response or intolerance of MTX (OPTION, LITHE) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; TOWARD). Changes in pain (visual analog scale [VAS], 0-100 mm), Health Assessment Questionnaire Disability Index (HAQ-DI, 0-3), 36-Item Short Form Survey (SF-36) physical component score (PCS) and mental component score (MCS; 0-50) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (0-52) from baseline to Week 24 were evaluated. Results were compared between patients receiving TCZ + MTX and those receiving PBO + MTX in both patients who achieved ≥ 20% improvement in SJC (responders) and those who did not (nonresponders). The changes from baseline were analyzed using a mixed model with repeated measures, including the following covariates and interactions: treatment, visit, baseline of endpoint, region, baseline DAS28 and interactions of visit with treatment and baseline of endpoint.Results:Data from 1254 responders (TCZ + MTX, n = 831; PBO + MTX, n = 423) and 620 nonresponders (TCZ + MTX, n = 225; PBO + MTX, n = 395) were included. Patients receiving TCZ + MTX had significantly greater improvement in pain scores and HAQ-DI compared with PBO + MTX in the responder group (–27.19 vs –16.77 and –0.55 vs –0.34, respectively;P< 0.0001 for both) and nonresponder group (–9.59 vs 2.53 and –0.20 vs 0.01;P< 0.0001 for both) at Week 24 (Figure 1). Similar results were seen at Week 16 in the nonresponder group (–11.06 vs –2.38 and –0.23 vs –0.04;P< 0.0001 for both) prior to initiation of rescue treatment. At Week 24 in the responder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS and MCS (9.16 vs 5.71 and 6.55 vs 3.79, respectively;P< 0.0001 for both) (Figure 2) and FACIT-Fatigue (8.39 vs 5.11;P< 0.0001). In the nonresponder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS at Week 16 (3.81 vs 1.65;P= 0.0006) and Week 24 (4.42 vs 1.01;P< 0.0001) (Figure 2) and FACIT-Fatigue at Week 16 (3.82 vs 1.32;P= 0.0039) and Week 24 (3.90 vs 1.40;P= 0.0111).Conclusion:Patients with RA who received TCZ + MTX had significantly greater improvements in pain score and other PROs than those who received PBO + MTX regardless of whether they achieved ≥ 20% improvement in SJC. Clinical outcome at Week 24 correlated well with PROs, with a relatively larger improvement in pain score and other PROs in the responder group than in the nonresponder group; relative to PBO + MTX, these improvements appear numerically similar in the responder and nonresponder groups with consistently smaller difference between the groups in TCZ-treated arms. The consistent effect of TCZ on PROs in both responder and nonresponder groups warrants further study on the impact of TCZ on sources of pain independent of that caused by joint inflammation.Figure:Acknowledgments:This study was sponsored by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc, was provided by Genentech, Inc.Disclosure of Interests:Anthony Sebba Consultant of: Genentech, Gilead, Lilly, Regeneron Pharmaceuticals Inc., Sanofi, Speakers bureau: Lilly, Roche, Sanofi, Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.

scholarly journals Longitudinal Analysis of Patient-Reported Outcomes in Clinical Trials: Applications of Multilevel and Multidimensional Item Response Theory

Psychometrika ◽  
2021 ◽  
Author(s):  
Li Cai ◽  
Carrie R. Houts
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Latent Variable ◽  
Patient Reported Outcomes ◽  
Multilevel Models ◽  
Latent Variable Models ◽  
Trial Data ◽  
Regulatory Science ◽  
Measurement Information ◽  
Patient Reported

AbstractWith decades of advance research and recent developments in the drug and medical device regulatory approval process, patient-reported outcomes (PROs) are becoming increasingly important in clinical trials. While clinical trial analyses typically treat scores from PROs as observed variables, the potential to use latent variable models when analyzing patient responses in clinical trial data presents novel opportunities for both psychometrics and regulatory science. An accessible overview of analyses commonly used to analyze longitudinal trial data and statistical models familiar in both psychometrics and biometrics, such as growth models, multilevel models, and latent variable models, is provided to call attention to connections and common themes among these models that have found use across many research areas. Additionally, examples using empirical data from a randomized clinical trial provide concrete demonstrations of the implementation of these models. The increasing availability of high-quality, psychometrically rigorous assessment instruments in clinical trials, of which the Patient-Reported Outcomes Measurement Information System (PROMIS®) is a prominent example, provides rare possibilities for psychometrics to help improve the statistical tools used in regulatory science.

Overview of the Patient Perspective at OMERACT 10 — Conceptualizing Methods for Developing Patient-Reported Outcomes

2011 ◽  
Vol 38 (8) ◽  
pp. 1699-1701 ◽  
Author(s):  
JOHN R. KIRWAN ◽  
PETER S. TUGWELL
Keyword(s):  
Clinical Trials ◽  
Experimental Work ◽  
Patient Reported Outcomes ◽  
Patient Perspective ◽  
Methodological Issues ◽  
Instrument Selection ◽  
Patient Reported ◽  
The Impact ◽  
Choice Of Instruments ◽  
The Way

This overview draws out the main conclusions from the 4 workshops focused on incorporating the patient perspective into outcome assessment at the 10th Outcome Measures in Rheumatology (OMERACT 10) conference. They raised methodological issues about the choice of outcome domains to include in clinical trials, the development or choice of instruments to measure these domains, and the way these instruments might capture the impact of a disease and its treatment. The need to develop a more rigorous conceptual model of quantifying the way conditions affect health, and the need to ensure patients are directly involved in the decisions about domains and instruments, emerged clearly. The OMERACT participants voted to develop guidelines for domain and instrument selection, and conceptual and experimental work will be brought forward to revise and upgrade the OMERACT Filter.

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