Under-Reporting of Patient-Reported Outcome in Hematological Malignancies Trials

Introduction: Patient-reported outcomes (PRO) provide meaningful insight into patient perspectives on treatment effect. Clinically relevant outcomes such as improvements in overall survival (OS) and quality of life (QOL) should guide clinical decision-making, furthermore, the FDA encourages the implementation of patient-centric PRO measures in clinical trials. Objectives: To evaluate the frequency at which PRO measures included in 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 evaluating patients with hematological malignancies, completing enrollment between the years 2007-2017, for which PRO endpoints were listed. We excluded trials evaluating supportive care. 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 recorded type of publication (abstract or full text), year, reported outcomes, and 13 criteria of CONSORT-PRO that reflect the completeness of reporting. Results: We identified 362 trials through our search. 53 trials were listed as including at least one PRO endpoint, of which 8 were never published. Indications are listed in Table. PRO endpoints were assessed utilizing 26 PRO different tools, 7 were disease specific, 2 were treatment specific. PRO was the primary outcome in two trials. EORTC-QLQ-30 was most frequently used tool. Study sponsor was industry-only in 21 trials, industry-academic in six, and academic in 18. Of the 45 trials analyzed, only 19 (42%) published any PRO data. Eleven of all trials (24%) were judged as comprehensively reporting PRO. The median number of CONSORT-PRO quality indicators was eight criteria. Of the 45 trials, 12 provided information about missing PRO data. Of the 15 trials that showed PFS benefit with no OS benefit, 8(53%) did not publish any results the PRO, to support a patient centric outcome. 36 of the trials were published as full-text, and nine as abstract. In considering the 36 full text publications, 17 (47%) did not report any PRO. Nine of the full-text publications, reported PRO as part of the primary publication or within the following 6 months. 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 hematologic malignancies 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. Disclosures No relevant conflicts of interest to declare.

Download Full-text

The State of the Science in Patient-Reported Outcomes for Patients with Lung Cancer

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0040-1712099 ◽

2020 ◽

Vol 41 (03) ◽

pp. 377-385

Author(s):

Canhua Xiao ◽

Newton Hurst ◽

Benjamin Movsas

Keyword(s):

Lung Cancer ◽

Clinical Trials ◽

Clinical Decision Making ◽

Treatment Effectiveness ◽

Clinical Decision ◽

Patient Reported Outcome ◽

Cancer Clinical Trials ◽

Cancer Type ◽

Patient Reported ◽

State Of The Science

AbstractTraditionally, clinicians have assumed the primary responsibility for evaluating disease- and treatment-related outcomes. In the past few decades, however, a series of recommendations and standards promulgated by professional societies and regulatory agencies have resulted in increased use of patient-reported outcome (PRO) measures in cancer clinical trials. PROs, such as quality of life (QOL) measures, are important in establishing overall treatment effectiveness in cancer clinical trials, and they can inform clinical decision making. This article discusses the current state of the science in PRO research for patients with lung cancer, the cancer type with the highest incidence rate and the lowest survival rate worldwide. The discussion focuses on (1) PRO and survival; (2) electronic PRO reporting and interventions; (3) PROs and immunotherapy; (4) PRO, biomarkers, and precision health; (5) key issues in applying PROs in clinical trials; and (6) future directions for research.

Download Full-text

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

Blood ◽

10.1182/blood-2018-99-114464 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3583-3583

Author(s):

Liat Vidal-Fisher ◽

Kelly K. Curtis ◽

Laura Vidal ◽

Keren R. Moss

Keyword(s):

Clinical Trials ◽

Primary Endpoint ◽

Full Text ◽

Conflicts Of Interest ◽

Recent Decade ◽

Patient Reported Outcome ◽

Lymphocytic Leukemia ◽

Included Trial ◽

Non Hodgkin Lymphoma ◽

Patient Reported

Abstract 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. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

End-points in clinical trials for liver cancer and their value in evidence based clinical decision making: an unresolved Gordian knot.

Journal of Hepatology ◽

10.1016/j.jhep.2021.01.033 ◽

2021 ◽

Author(s):

Jordi Bruix

Keyword(s):

Decision Making ◽

Clinical Trials ◽

Liver Cancer ◽

Clinical Decision Making ◽

Clinical Decision ◽

Evidence Based ◽

End Points

Download Full-text

Between a logic of disruption and a logic of continuation: Negotiating the legitimacy of algorithms used in automated clinical decision-making

Health An Interdisciplinary Journal for the Social Study of Health Illness and Medicine ◽

10.1177/1363459321996741 ◽

2021 ◽

pp. 136345932199674

Author(s):

Rikke Torenholt ◽

Henriette Langstrup

Keyword(s):

Decision Making ◽

Clinical Practice ◽

Patient Reported Outcomes ◽

Patient Involvement ◽

Clinical Decision Making ◽

Diagnostic Procedures ◽

Clinical Decision ◽

Patient Reported ◽

Pro Tools

In both popular and academic discussions of the use of algorithms in clinical practice, narratives often draw on the decisive potentialities of algorithms and come with the belief that algorithms will substantially transform healthcare. We suggest that this approach is associated with a logic of disruption. However, we argue that in clinical practice alongside this logic, another and less recognised logic exists, namely that of continuation: here the use of algorithms constitutes part of an established practice. Applying these logics as our analytical framing, we set out to explore how algorithms for clinical decision-making are enacted by political stakeholders, healthcare professionals, and patients, and in doing so, study how the legitimacy of delegating to an algorithm is negotiated and obtained. Empirically we draw on ethnographic fieldwork carried out in relation to attempts in Denmark to develop and implement Patient Reported Outcomes (PRO) tools – involving algorithmic sorting – in clinical practice. We follow the work within two disease areas: heart rehabilitation and breast cancer follow-up care. We show how at the political level, algorithms constitute tools for disrupting inefficient work and unsystematic patient involvement, whereas closer to the clinical practice, algorithms constitute a continuation of standardised and evidence-based diagnostic procedures and a continuation of the physicians’ expertise and authority. We argue that the co-existence of the two logics have implications as both provide a push towards the use of algorithms and how a logic of continuation may divert attention away from new issues introduced with automated digital decision-support systems.

Download Full-text

ALK inhibitors, resistance development, clinical trials

Current Oncology ◽

10.3747/co.25.3760 ◽

2018 ◽

Vol 25 ◽

pp. 59 ◽

Cited By ~ 22

Author(s):

J.M. Rothenstein ◽

N. Chooback

Keyword(s):

Clinical Trials ◽

Patient Outcomes ◽

Clinical Decision Making ◽

Clinical Decision ◽

Current Treatment ◽

Resistance Development ◽

Ongoing Research ◽

Alk Positive ◽

Emergence Of Resistance ◽

Key Questions

The treatment of advanced non-small-cell lung cancer (nsclc) has undergone a paradigm shift since the early 2000s. The identification of molecular subtypes of the disease, based on oncogenic drivers, has led to the development of personalized medicine and the ability to deliver molecularly targeted therapies to patients. In the 10 years that have elapsed since the discovery of the ALK gene in a patient with nsclc, several active drugs have moved rapidly from bench to bedside, and multiple others are currently in clinical trials. Those developments have led to important improvements in patient outcomes, while simultaneously raising key questions about the optimal treatment for ALK-positive nsclc. The inevitable emergence of resistance to alk-directed therapy is central to ongoing research and daily clinical practice for affected patients. In the present review, we highlight the current treatment landscape, the available and emerging clinical trials, and the evolving clinical decision-making in ALK-positive nsclc, with a focus on Canadian practice.

Download Full-text

Patient-reported outcomes in drug development for hematology

Hematology ◽

10.1182/asheducation-2015.1.496 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 496-500 ◽

Cited By ~ 4

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.

Download Full-text

Beyond the Development of Health-Related Quality-of-Life (HRQOL) Measures: A Checklist for Evaluating HRQOL Outcomes in Cancer Clinical Trials—Does HRQOL Evaluation in Prostate Cancer Research Inform Clinical Decision Making?

Journal of Clinical Oncology ◽

10.1200/jco.2003.12.121 ◽

2003 ◽

Vol 21 (18) ◽

pp. 3502-3511 ◽

Cited By ~ 182

Author(s):

Fabio Efficace ◽

Andrew Bottomley ◽

David Osoba ◽

Carolyn Gotay ◽

Henning Flechtner ◽

...

Keyword(s):

Prostate Cancer ◽

Decision Making ◽

Clinical Trials ◽

Clinical Decision Making ◽

Clinical Decision ◽

Cancer Clinical Trials ◽

Health Related Quality ◽

Related Quality ◽

Health Related

Purpose: The aim of this study was to evaluate whether the inclusion of health-related quality of life (HRQOL), as a part of the trial design in a randomized controlled trial (RCT) setting, has supported clinical decision making for the planning of future medical treatments in prostate cancer. Materials and Methods: A minimum standard checklist for evaluating HRQOL outcomes in cancer clinical trials was devised to assess the quality of the HRQOL reporting and to classify the studies on the grounds of their robustness. It comprises 11 key HRQOL issues grouped into four broader sections: conceptual, measurement, methodology, and interpretation. Relevant studies were identified in a number of databases, including MEDLINE and the Cochrane Controlled Trials Register. Both their HRQOL and traditional clinical reported outcomes were systematically analyzed to evaluate their consistency and their relevance for supporting clinical decision making. Results: Although 54% of the identified studies did not show any differences in traditional clinical end points between treatment arms and 17% showed a difference in overall survival, 74% of the studies showed some difference in terms of HRQOL outcomes. One third of the RCTs provided a comprehensive picture of the whole treatment including HRQOL outcomes to support their conclusions. Conclusion: A minimum set of criteria for assessing the reported outcomes in cancer clinical trials is necessary to make informed decisions in clinical practice. Using a checklist developed for this study, it was found that HRQOL is a valuable source of information in RCTs of treatment in metastatic prostate cancer.

Download Full-text