scholarly journals Results on patient-reported outcomes are underreported in summaries of product characteristics for new drugs

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Susanne Haag ◽  
Lisa Junge ◽  
Fabian Lotz ◽  
Natalie McGauran ◽  
Marios Paulides ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patient Reported Outcomes ◽  
Drug Approval ◽  
Study Data ◽  
Reporting Rate ◽  
New Drugs ◽  
Product Characteristics ◽  
Disease Category ◽  
Early Benefit Assessment ◽  
Patient Reported

Abstract Background Summaries of product characteristics (SmPCs) are regulatory documents published upon drug approval. They should report all relevant study data and advise how to use drugs safely and effectively. Patient-reported outcomes (PROs) are increasingly used in clinical trials to incorporate the patient perspective—SmPCs should thus adequately report PROs. In Germany, new drugs undergo mandatory early benefit assessment. Pharmaceutical companies submit dossiers containing all evidence; the subsequent dossier assessments focus on patient-relevant outcomes and comprehensively report PROs. Objective The primary aim was to investigate to what extent PROs recorded as outcomes in clinical trials of new drugs are reported in SmPCs. Methods We analysed dossier assessments with randomized controlled trials (RCTs) of new drugs entering the market between 01/2014 and 07/2018 and the corresponding SmPCs, and compared PRO reporting in both document types. For this purpose, we evaluated dossier assessment characteristics (e.g. drug name, indication, disease category) and study characteristics (e.g. evaluable PROs available?). PROs were divided into symptoms and health-related quality of life (HRQoL). SmPCs were screened to identify RCTs. We conducted 3 main evaluation steps: (1) Did the RCT included in the dossier assessment contain evaluable PROs? (2) If yes, was the RCT included in the SmPC? (3) If yes, were the PROs reported in the SmPC? Results are presented descriptively. Results 88 dossier assessments including 143 RCTs on 72 drugs were considered: 109 (76.2%) RCTs included evaluable PROs, of which 89 were included in SmPCs. 38 RCTs (42.7%) investigated oncologics, 18 (20.2%) anti-infectives, and 33 (37.1%) other drugs. The RCTs considered symptoms more often than HRQoL (82 vs. 66 RCTs). In SmPCs, PROs were reported for 41 RCTs (46.1%), with a slightly higher reporting rate for RCTs considering HRQoL (43.9%) than for RCTs considering symptoms (41.5%). In oncologic indications, PROs were reported for 36.7% of RCTs considering HRQoL and 33.3% of RCTs considering symptoms. In infectious diseases, the rates were 21.4% (symptoms) and 0% (HRQoL), and for other diseases about 60% (symptoms) to 70% (HRQoL). Conclusion Even though a large amount of PRO data on new drugs is available from clinical trials included in SmPCs, the corresponding results are underreported.

scholarly journals Patient-reported outcomes in drug development for hematology

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 496-500 ◽  
Author(s):  
Catherine Acquadro ◽  
Antoine Regnault
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Patient Reported Outcomes ◽  
Clinical Decision Making ◽  
Well Being ◽  
New Drugs ◽  
Specific Situation ◽  
Treatment Benefit ◽  
Hematologic Diseases ◽  
Patient Reported

Abstract Patient-reported outcomes (PROs) are any outcome evaluated directly by the patient himself and based on the patient's perception of a disease and its treatment(s). PROs are direct outcome measures that can be used as clinical meaningful endpoints to characterize treatment benefit. They provide unique and important information about the effect of treatment from a patient's view. However, PROs will only be considered adequate if the assessment is well-defined and reliable. In 2009, the FDA has issued a guidance, which defines good measurement principles to consider for PRO measures intended to give evidence of treatment benefit in drug development. In hematologic clinical trials, when applied rigorously, they may be used to evaluate overall treatment effectiveness, treatment toxicity, and quality of patient's well-being at short-term and long-term after treatment from a patient's perspective. In situations in which multiple treatment options exist with similar survival outcome or if a new therapeutic strategy needs to be evaluated, the inclusion of PROs as an endpoint can provide additional data and help in clinical decision making. Given the diversity of the hematological field, the approach to measurement needs to be tailored for each specific situation. The importance of PROs in hematologic diseases has been highlighted in a number of international recommendations. In addition, new perspectives in the regulatory field will enhance the inclusion of PRO endpoints in clinical trials in hematology, allowing the voice of the patients with hematologic diseases to be taken into greater consideration in the development of new drugs.

Dare voce ai pazienti nella ricerca sulle malattie rare e sui famaci orfani / Giving patients a voice in the rare diseases and orphan drugs research

2018 ◽  
Vol 67 (1) ◽  
pp. 25-40
Author(s):  
Elena Mancini ◽  
Roberta Martina Zagarella
Keyword(s):  
Clinical Trials ◽  
Rare Diseases ◽  
Patient Reported Outcomes ◽  
Narrative Medicine ◽  
Orphan Drugs ◽  
New Drugs ◽  
Patient Centered ◽  
Patient Reported ◽  
Critical Issues ◽  
The Impact

L’articolo ha l’obiettivo di mettere in luce potenzialità e criticità dell’inclusione della prospettiva dei pazienti nella ricerca sulle malattie rare e sui farmaci orfani. A tal fine, nella prima parte, si propone un’analisi epistemologica dell’utilizzo dei racconti dell’esperienza individuale della malattia nella ricerca scientifica e nei trial clinici, facendo emergere, anche attraverso gli strumenti della medicina narrativa, le sfide teoriche e operative poste dall’inclusione della soggettività del paziente e del vissuto di malattia nonché l’importanza della valorizzazione della prospettiva del paziente, sia in generale sia nella ricerca sulle malattie rare e sui farmaci orfani. Nella seconda parte, il testo analizza in particolare il ruolo degli esiti riportati dai pazienti o Patient Reported Outcomes (PROs), misure per la valutazione complessiva della salute basate sulla prospettiva dei pazienti stessi, incentrandosi sulla sperimentazione clinica nel campo delle malattie rare. In questo contesto, infatti, i racconti di malattia, raccolti e valorizzati da fonti istituzionali e associazioni di pazienti, hanno contribuito a far emergere importanti questioni critiche e difficoltà nell’impiego di outcome centrati sul paziente nello sviluppo di nuovi farmaci e trattamenti, generando una serie di documenti e raccomandazioni relative al loro utilizzo per il benessere della comunità dei malati rari. ---------- This paper aims to highlight the potentiality and criticality of including patients’ perspective in rare diseases and orphan drugs research. In the first part, we propose an epistemological analysis of individual narrations of disease experience as they are used in scientific research and clinical trials. With the help of narrative medicine approach, this analysis points out theoretical and operational challenges of a perspective that includes patient’s subjectivity and illness experience. Furthermore, it reveals the significance of patients’ standpoints in general and in rare diseases as well as in the orphan drugs research. The second part of our article focuses on the role of the Patient reported Outcomes (PROs) – which are measures for the health’s overall assessment based on patient’s perspective – by investigating the impact on clinical trials for rare diseases. In this context, illness stories, which are collected and promoted by institutional sources and patients’ associations, contribute to underline important critical issues at stake in the employment of patient-centered outcomes both in new drugs and in the treatments development. Moreover, these stories are crucial to elaborate documents and recommendations concerning the use of PROs for the rare patients’ community welfare.

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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