Principal Investigator

Ethan M.
Basch
Awardee Organization

Univ Of North Carolina Chapel Hill
United States

Fiscal Year
2023
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Analyzing and Interpreting PRO-CTCAE with CTCAE and Other Clinical Data to Characterize Drug Tolerability

In cancer clinical trials, it is essential to understand and communicate the negative impact of drugs on patient participants in order to balance risks and benefits. Symptom side effects such as nausea and diarrhea are particularly common and impactful on the patient experience. However, historically this information has been reported by clinicians on behalf of their patients rather than by patients themselves – a process that has been shown to miss up to half of patients' symptoms. Therefore, the National Cancer Institute (NCI) supported development of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), a library of questions to enable systematic patient self-reporting of side effect information. To date, the PRO-CTCAE questions have been developed and tested for validity and feasibility of use in clinical trials – work that was led by the investigators on this proposal under contracts to the NCI. However, it is not yet established how best to combine PRO-CTCAE information with traditional measures of treatment impact such as clinician-reported adverse events, time on treatment, drug dose levels, performance status, and hospitalizations. The purpose of this supplement is to complete work towards understanding the role of the PRO-CTCAE in combination with these traditional measures of treatment impact in assessments of drug tolerability. In this supplement, advanced statistical methods will be used to analyze data from newly available clinical trials, delayed by the pandemic, accessible to the team through the National Clinical Trial Network (cooperative groups) and industry. The specific aims are to: 1) characterize relationships between the PRO-CTCAE and traditional measures of treatment impact and tolerability; 2) test and standardize analytic techniques for the PRO-CTCAE; 3) refine approaches to analyzing missing PRO-CTCAE data; and 4) develop and refine tabular and graphical data visualizations for longitudinal PRO-CTCAE data. To accomplish these aims, our multi-disciplinary team will work collaboratively and flexibly with other investigators and stakeholders through the U01 consortium chaired by Dr. Amylou Dueck, and will continue to share data, statistical programming code, and ideas freely. This work is intended to inform best practices for tabulating and reporting PRO-CTCAE data, and will enable more systematic and patient-centered evaluations of tolerability in cancer clinical trials. This supplement will extend the grant by 12 months.

Publications

  • Mazza GL, Petersen MM, Ginos B, Langlais BT, Heon N, Gounder MM, Mahoney MR, Zoroufy AJ, Schwartz GK, Rogak LJ, Thanarajasingam G, Basch E, Dueck AC. Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2022 Apr;31(4):1069-1080. Epub 2021 Aug 21. PMID: 34420143
  • Langlais B, Mazza GL, Thanarajasingam G, Rogak LJ, Ginos B, Heon N, Scher HI, Schwab G, Ganz PA, Basch E, Dueck AC. Evaluating Treatment Tolerability Using the Toxicity Index With Patient-Reported Outcomes Data. Journal of pain and symptom management. 2022 Feb;63(2):311-320. Epub 2021 Aug 8. PMID: 34371138
  • Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. PMID: 37270691
  • Thanarajasingam G, Basch E, Mead-Harvey C, Bennett AV, Mazza GL, Schwab G, Roydhouse J, Rogak LJ, Dueck AC. An Exploratory Analysis of the "Was It Worth It?" Questionnaire as a Novel Metric to Capture Patient Perceptions of Cancer Treatment. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2022 Jul;25(7):1081-1086. Epub 2022 Jan 3. PMID: 35779938
  • Thanarajasingam G, Minasian LM, Bhatnagar V, Cavalli F, De Claro RA, Dueck AC, El-Galaly TC, Everest N, Geissler J, Gisselbrecht C, Gormley N, Gribben J, Horowitz M, Ivy SP, Jacobson CA, Keating A, Kluetz PG, Kwong YL, Little RF, Matasar MJ, Mateos MV, McCullough K, Miller RS, Mohty M, Moreau P, Morton LM, Nagai S, Nair A, Nastoupil L, Robertson K, Sidana S, Smedby KE, Sonneveld P, Tzogani K, van Leeuwen FE, Velikova G, Villa D, Wingard JR, Seymour JF, Habermann TM. Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies. The Lancet. Haematology. 2022 May;9(5):e374-e384. PMID: 35483398
  • Basch E, Thanarajasingam G, Dueck AC. Methodological standards for using the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in cancer clinical trials. Clinical trials (London, England). 2022 Jun;19(3):274-276. Epub 2022 May 15. PMID: 35575014
  • Dueck AC, Scher HI, Bennett AV, Mazza GL, Thanarajasingam G, Schwab G, Weitzman AL, Rogak LJ, Basch E. Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial. JAMA oncology. 2020 Feb 1;6(2):e193332. Epub 2020 Feb 13. PMID: 31556911
  • Lee MK, Basch E, Mitchell SA, Minasian LM, Langlais BT, Thanarajasingam G, Ginos BF, Rogak LJ, Mendoza TR, Bennett AV, Schrag D, Mazza GL, Dueck AC. Reliability and validity of PRO-CTCAE® daily reporting with a 24-hour recall period. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2023 Jul;32(7):2047-2058. Epub 2023 Mar 10. PMID: 36897529
  • Basch E, Becker C, Rogak LJ, Schrag D, Reeve BB, Spears P, Smith ML, Gounder MM, Mahoney MR, Schwartz GK, Bennett AV, Mendoza TR, Cleeland CS, Sloan JA, Bruner DW, Schwab G, Atkinson TM, Thanarajasingam G, Bertagnolli MM, Dueck AC. Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Clinical trials (London, England). 2021 Feb;18(1):104-114. Epub 2020 Dec 1. PMID: 33258687
  • Thanarajasingam G, Leonard JP, Witzig TE, Habermann TM, Blum KA, Bartlett NL, Flowers CR, Pitcher BN, Jung SH, Atherton PJ, Tan A, Novotny PJ, Dueck AC. Longitudinal Toxicity over Time (ToxT) analysis to evaluate tolerability: a case study of lenalidomide in the CALGB 50401 (Alliance) trial. The Lancet. Haematology. 2020 Jun;7(6):e490-e497. PMID: 32470440
  • Atkinson TM, Dueck AC, Satele DV, Thanarajasingam G, Lafky JM, Sloan JA, Basch E. Clinician vs Patient Reporting of Baseline and Postbaseline Symptoms for Adverse Event Assessment in Cancer Clinical Trials. JAMA oncology. 2020 Mar 1;6(3):437-439. PMID: 31876902