Rare use of patient-reported outcomes in childhood cancer clinical trials – a systematic review of clinical trial registries

Multilevel Models ◽

Latent Variable Models ◽

Trial Data ◽

Regulatory Science ◽

Measurement Information ◽

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.

Collecting Patient-Reported Outcomes in Cancer Clinical Trials

JAMA ◽

10.1001/jama.2021.12277 ◽

2021 ◽

Vol 326 (5) ◽

pp. 379

Author(s):

Bridget M. Kuehn

Keyword(s):

Clinical Trials ◽

Cancer Clinical Trials ◽

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

Blood Advances ◽

10.1182/bloodadvances.2019000882 ◽

2019 ◽

Vol 3 (23) ◽

pp. 3982-4001 ◽

Cited By ~ 5

Author(s):

Ann T. Farrell ◽

Julie Panepinto ◽

C. Patrick Carroll ◽

Deepika S. Darbari ◽

Ankit A. Desai ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

End Points ◽

Additional Clinical Trial ◽

Patient Reported ◽

The Brain

Abstract To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_159514 ◽

2016 ◽

pp. 67-73 ◽

Cited By ~ 44

Author(s):

Paul G. Kluetz ◽

Diana T. Chingos ◽

Ethan M. Basch ◽

Sandra A. Mitchell

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Patient Perspective ◽

Cancer Clinical Trials ◽

Cancer Therapies ◽

Systematic Assessment ◽

Promising Tool ◽

Patient Reported ◽

The Common

Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration’s (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP’s perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials.

The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis

Health and Quality of Life Outcomes ◽

10.1186/s12955-019-1220-z ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 12

Author(s):

Samantha Cruz Rivera ◽

Derek G. Kyte ◽

Olalekan Lee Aiyegbusi ◽

Anita L. Slade ◽

Christel McMullan ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trial ◽

Clinical Trials ◽

Case Studies ◽

Real World ◽

Clinical Trial Data ◽

Research Impact ◽

Trial Data ◽

Patient Reported ◽

The Impact

Abstract Background Patient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies. Methods Two independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial. Results Thirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals. Conclusions PRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste. Trial registration Systematic Review registration PROSPERO CRD42017067799.

Patient-reported outcomes in HIV clinical trials evaluating antiretroviral treatment: a systematic review

AIDS Care ◽

10.1080/09540121.2020.1852160 ◽

2020 ◽

pp. 1-9

Author(s):

Karolina Akinosoglou ◽

Stefania Antonopoulou ◽

Ioannis Katsarolis ◽

Charalambos A. Gogos

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Antiretroviral Treatment ◽

Patient Reported ◽

Hiv Clinical Trials

Time to deterioration in cancer randomized clinical trials for patient-reported outcomes data: a systematic review

Quality of Life Research ◽

10.1007/s11136-019-02367-7 ◽

2019 ◽

Vol 29 (4) ◽

pp. 867-878 ◽

Cited By ~ 3

Author(s):

E. Charton ◽

B. Cuer ◽

F. Cottone ◽

F. Efficace ◽

C. Touraine ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Issues and Challenges With Integrating Patient-Reported Outcomes in Clinical Trials Supported by the National Cancer Institute–Sponsored Clinical Trials Networks

Journal of Clinical Oncology ◽

10.1200/jco.2007.11.3324 ◽

2007 ◽

Vol 25 (32) ◽

pp. 5051-5057 ◽

Cited By ~ 51

Author(s):

Deborah Watkins Bruner ◽

Charlene J. Bryan ◽

Neil Aaronson ◽

C. Craig Blackmore ◽

Michael Brundage ◽

...

Keyword(s):

Clinical Trials ◽

Online Survey ◽

Cancer Control ◽

The United States ◽

Cancer Clinical Trials ◽

Cooperative Group ◽

Cooperative Groups ◽

End Points ◽

Purpose The objective of this report is to provide a historical overview of and the issues and challenges inherent in the incorporation of patient-reported outcomes (PROs) into multinational cancer clinical trials in the cancer cooperative groups. Methods An online survey of 12 cancer cooperative groups from the United States, Canada, and Europe was conducted between June and August of 2006. Each of the cooperative groups designated one respondent, who was a member of one of the PRO committees within the cooperative group. Results There was a 100% response rate, and all of the cancer clinical trial cooperative groups reported conducting PRO research. PRO research has been conducted in the cancer cooperative groups for an average of 15 years (range, 6 to 30 years), and all groups had multidisciplinary committees focused on the design of PRO end points and the choice of appropriate PRO measures for cancer clinical trials. The cooperative groups reported that 5% to 50% of cancer treatment trials and an estimated 50% to 75% of cancer control trials contained PRO primary and secondary end points. There was considerable heterogeneity among the cooperative groups with respect to the formal and informal policies and procedures or cooperative group culture towards PROs, investigator training/mentorship, and resource availability for the measurement and conduct of PRO research within the individual cooperatives. Conclusion The challenges faced by the cooperative groups to the incorporation of PROs into cancer clinical trials are varied. Some common opportunities for improvement include the adoption of standardized training/mentorship mechanisms for investigators for the conduct of PRO assessments and data collection and the development of minimal criteria for PRO measure acceptability. A positive cultural shift has occurred in most of the cooperative groups related to the incorporation of PROs in clinical trials; however, financial and other resource barriers remain and need to be addressed.