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Introduction to Quality of Life in Drug Development

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Handbook of Quality of Life in Cancer

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Abstract

The inclusion of quality of life (QoL) in cancer clinical trials to support drug development requires thoughtful pre-planning and additional resource to ensure that the results obtained from the trial are interpretable and meaningful to all stakeholders. While clinical endpoints such as overall survival are well established for cancer clinical trials, this is not true for endpoints captured using patient-reported outcome (PRO) measures. In this chapter, we discuss the different regulatory requirements for patient-reported data and how this has led to differences in the drug labels developed for the US by the Food and Drug Administration (FDA) and for Europe by the European Medicines Agency (EMA). We also present considerations for endpoints related to efficacy and safety/tolerability as well as different treatment settings. This chapter also dedicates a section to both the patient and the clinician perspective on the use of patient-reported data in drug development.

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References

  1. FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource. Silver Spring, MD; 2016.

    Google Scholar 

  2. Amir E, Seruga B, Kwong R, Tannock IF, Ocaña A. Poor correlation between progression-free and overall survival in modern clinical trials: are composite endpoints the answer? Eur J Cancer. 2012;48(3):385–8.

    Article  Google Scholar 

  3. Gyawali B, Hey SP, Kesselheim AS. Assessment of the clinical benefit of cancer drugs receiving accelerated approval. JAMA Intern Med. 2019;179(7):906–13.

    Article  Google Scholar 

  4. US Food and Drug Administration. Guidance for industry use in medical product development to support labeling claims guidance for industry. Clin Fed Regist. 2009;(12):1–39.

    Google Scholar 

  5. US Food and Drug Administration. FDA patient-focused drug development guidance series for enhancing the incorporation of the patient’s voice in medical product development and regulatory decision making [Internet]. [cited 2021 Feb 28]. Available from: https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical.

  6. European Medicines Agency. Reflection paper on the regulatory guidance for the use of health- related quality of life (HRQL) measures in the evaluation of medicinal products. Reproduction. 2005;(1):1–5.

    Google Scholar 

  7. European Medicines Agency. Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man. 2014;44(4):1–18. Available from: www.ema.europa.eu/contact.

  8. Pe M, Dorme L, Coens C, Basch E, Calvert M, Campbell A, et al. Statistical analysis of patient-reported outcome data in randomised controlled trials of locally advanced and metastatic breast cancer: a systematic review. Lancet Oncol. 2018;19(9):e459–69.

    Article  Google Scholar 

  9. The PROTEUS Consortium [Internet]. 2020 [cited 2020 Dec 15]. Available from: www.theproteusconsortium.org.

  10. European Organisation for Research and Treatment of Cancer. Setting International Standard in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints [Internet]. [cited 2021 Mar 26]. Available from: https://event.eortc.org/sisaqol/.

  11. Kluetz PG, Slagle A, Papadopoulos EJ, Johnson LL, Donoghue M, Kwitkowski VE, et al. Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms. Clin Cancer Res. 2016;22(7):1553–8.

    Article  Google Scholar 

  12. Kluetz PG, O’Connor DJ, Soltys K. Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada. Lancet Oncol. 2018;19(5):e267–74.

    Article  Google Scholar 

  13. Wilson IB, Paul D. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. JAMA. 1995;273:59–65.

    Article  Google Scholar 

  14. US Food and Drug Administration. Methods to identify what is important to patients select, develop or modify fit-for-purpose clinical outcomes assessments. Patient-Focused Drug Dev Guid Public Work Oct 15–16 [Internet]. 2018; Available from: https://www.fda.gov/downloads/Drugs/NewsEvents/UCM620708.pdf.

  15. King-Kallimanis BL. Incorportaitng relevant and meaningful patient reported outcomes. In: 17th international kidney cancer symposium. Miami, FL; 2018.

    Google Scholar 

  16. Food and Drug Administration Safety and Innovation Act, S 3187, 112th Congress [Internet]. 2012 [cited 2020 Dec 20]. Available from: https://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf%0A/PLAW-112publ144.pdf.

  17. 21st Century Cures Act.114th Congress [Internet]. 2016 [cited 2020 Dec 20]. Available from: https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.

  18. Gnanasakthy A. Multi-stakeholder perspectives on the patient experience data summary section in new product approvals: current state & future considerations. In: International society for pharmacoeconomics and outcomes research. Virtual; 2020.

    Google Scholar 

  19. Novartis Pharmaceuticals Corporation. Zykadia® (ceritinib) [package insert] [Internet]. US Food and Drug Administration website. 2019 [cited 2021 Dec 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205755s010lbl.pdf.

  20. Pfizer Inc. Xalkori® (crizotinib) [package insert] [Internet]. U.S Food and Drug Administration website. [cited 2020 Dec 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202570s030lbl.pdf.

  21. Gnanasakthy A, Barrett A, Evans E, D’Alessio D, Romano C. A review of patient-reported outcomes labeling for oncology drugs approved by the FDA and the EMA (2012–2016). Value Health. 2019;22(2):203–9.

    Article  Google Scholar 

  22. US Food and Drug Administration. Draft guidance to industry: multiple endpoints in clinical trials. US Food and Drug Administration; 2017.

    Google Scholar 

  23. Novartis Pharmaceuticals Corporation. Summary of product characteristics: Zykadia® (ceritinib) [Internet]. 2012. Available from: https://www.ema.europa.eu/en/documents/product-information/zykadia-epar-product-information_en.pdf.

  24. US Food and Drug Administration. Project patient voice [Internet]. 2020 [cited 2021 Mar 3]. Available from: https://www.fda.gov/about-fda/oncology-center-excellence/project-patient-voice.

  25. Center for Drug Evaluation and Research. Gemzar® (gemcitibine hydrochloride) [orginal review] [Internet]. 1996 [cited 2021 Jan 10]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020509Orig1s000rev.pdf.

  26. Deisseroth A, Kaminskas E, Grillo J, Chen W, Saber H, Lu HL, et al. US Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212–7.

    Article  Google Scholar 

  27. Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, et al. Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst. 2009;101(23):1624–32.

    Article  Google Scholar 

  28. United States National Cancer Institute. Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAEâ„¢). [Internet]. [cited 2021 Feb 14]. Available from: https://healthcaredelivery.cancer.gov/pro-ctcae/.

  29. Chung AE, Shoenbill K, Mitchell SA, Dueck AC, Schrag D, Bruner DW, et al. Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). J Am Med Inform Assoc. 2019;26(4):276–85.

    Article  Google Scholar 

  30. Fiero MH, Roydhouse JK, Vallejo J, King-Kallimanis BL, Kluetz PG, Sridhara R. US Food and Drug Administration review of statistical analysis of patient-reported outcomes in lung cancer clinical trials approved between January, 2008, and December, 2017. Lancet Oncol. 2019;20(10):E582–9.

    Article  Google Scholar 

  31. Calvert M, Kyte D, Mercieca-Bebber R, Slade A, Chan AW, King MT. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols the spirit-pro extension. J Am Med Assoc. 2018;319(5):483–94.

    Article  Google Scholar 

  32. Austin E, LeRouge C, Hartzler AL, Chung AE, Segal C, Lavallee DC. Opportunities and challenges to advance the use of electronic patient-reported outcomes in clinical care: a report from AMIA workshop proceedings. JAMIA Open. 2019;2(4):407–10.

    Article  Google Scholar 

  33. Coons SJ, Eremenco S, Lundy JJ, O’Donohoe P, O’Gorman H, Malizia W. Capturing patient-reported outcome (PRO) data electronically: the past, present, and promise of ePRO measurement in clinical trials. Patient. 2015;8(4):301–9.

    Article  Google Scholar 

  34. Merzoug L, King-Kallimanis B, Bhatnagar V, Kanapuru B, Kim J, Li X, et al. Reporting of patient-reported outcomes and quality of life data in oncology drug development trials: a literature review. In: Quality of life research; 2019. p. S111–2.

    Google Scholar 

  35. Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, et al. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(10):1404–16.

    Article  Google Scholar 

  36. US Food and Drug Administration. Guidance for industry: non-inferiority clinical trials to establish effectiveness [Internet]. November, 2016. [cited 2021 Mar 4]. Available from: https://www.fda.gov/media/78504/download.

  37. Bernhard J, Cella DF, Coates AS, Fallowfield L, Ganz PA, Moinpour CM, et al. Missing data workshop, 1–3 July, 1996: missing quality of life data in cancer clinical trials: serious problems and challenges. Stat Med. 1998;17(5–7):517–32.

    Article  Google Scholar 

  38. European Organisation for Research and Treatment of Cancer. EORTC Quality of Life FAQ [Internet]. [cited 2021 Mar 3]. Available from: https://qol.eortc.org/faq-category/scoring/.

  39. Fairclough DL, Peterson HF, Chang V. Why are missing quality of life data a problem in clinical trials of cancer therapy? Stat Med. 1998;17(5–7):667–77.

    Article  Google Scholar 

  40. King-Kallimanis BL, Johnson LL. Systematically defining research objectives and framing questions using the estimand framework. In: FDA-ASCO Public Workshop: 2019 Clinical Outcome Assessments in Cancer Clinical Trials Fourth Annual Workshop. Silver Spring, Maryland; 2019.

    Google Scholar 

  41. International Concil for Harmonisation (ICH). Addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials E9(R1). Fed Regist. 2019;9(9)

    Google Scholar 

  42. European Organisation for Research and Treatment of Cancer. Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium [Internet]. Available from: https://event.eortc.org/sisaqol/.

  43. Basch E, Trentacosti AM, Burke LB, Kwitkowski V, Kane RC, Autio KA, et al. Pain palliation measurement in cancer clinical trials: the US Food and Drug Administration perspective. Cancer. 2014;120(5):761–7.

    Article  Google Scholar 

  44. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016;34(12):1402–18.

    Article  Google Scholar 

  45. Reeve BB, Mitchell SA, Dueck AC, Basch E, Cella D, Reilly CM, et al. Recommended patient-reported core set of symptoms to measure in adult cancer treatment trials. J Natl Cancer Inst. 2014;106(7):dju129.

    Article  Google Scholar 

  46. Basch EM, Campbell A, Hudgens S, Jones L, King-Kallimanis BL, Kluetz P, et al. Broadening the definition of tolerability in cancer clinical trials to better measure the patient experience. Friends Cancer Res. 2018;10

    Google Scholar 

  47. US Food and Drug Administration. Real-World Evidence [Internet]. [cited 2021 Mar 15]. Available from: https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence.

  48. Anatchkova M, Donelson SM, Skalicky AM, McHorney CA, Jagun D, Whiteley J. Exploring the implementation of patient-reported outcome measures in cancer care: need for more real-world evidence results in the peer reviewed literature. J Patient Rep Outcomes. 2018;2(1):64.

    Article  Google Scholar 

  49. Basu Roy U, King-Kallimanis BL, Kluetz PG, Selig W, Ferris A. Learning from patients: reflections on use of patient-reported outcomes in lung cancer trials. J Thorac Oncol. 2018;13(12):1815–7.

    Article  Google Scholar 

  50. Basch E, Deal AM, Dueck AC, Scher HI, Kris MG, Hudis C, et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. J Am Med Assoc. 2017;318(2):197–8.

    Article  Google Scholar 

  51. Denis F, Lethrosne C, Pourel N, Molinier O, Pointreau Y, Domont J, et al. Randomized trial comparing a web-mediated follow-up with routine surveillance in lung cancer patients. J Natl Cancer Inst. 2017;109(9):21–2.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Patient-Focused Research Center, LUNGevity Foundation, Bethesda, MD, USA

    Bellinda L. King-Kallimanis

  2. Arlington, VA, USA

    Lee Jones

  3. Asheville, NC, USA

    Lynn Howie

Authors
  1. Bellinda L. King-Kallimanis
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  2. Lee Jones
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  3. Lynn Howie
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Corresponding author

Correspondence to Bellinda L. King-Kallimanis .

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Editors and Affiliations

  1. Department of Applied Health Research, University College London, London, UK

    Angelos P. Kassianos

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King-Kallimanis, B.L., Jones, L., Howie, L. (2022). Introduction to Quality of Life in Drug Development. In: Kassianos, A.P. (eds) Handbook of Quality of Life in Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-84702-9_21

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  • DOI: https://doi.org/10.1007/978-3-030-84702-9_21

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-84701-2

  • Online ISBN: 978-3-030-84702-9

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