Advocate involvement in Clinical Trials: Lessons from the Patient-centric I-SPY2 Breast Cancer Trial
Main Article Content
Abstract
The innovative I-SPY Breast Trial is presented as an example of an unusually patient-centric clinical trial that has been significantly impacted by extensive advocate involvement. In the introduction we briefly define what we mean by patient-centric trials and describe the overall structure, goals, and evolution of I-SPY. We then describe: 1) the roles and philosophy of advocate involvement; 2) attributes of the trial design that make it especially patient-centric; and 3) educational material and communications approaches aimed at empowering and supporting trial participants. For each section, in addition to describing I-SPY practices, we provide aspirational suggestions that could enhance I-SPY and/or other clinical trials. Embedding advocates into every aspect of clinical trial design and operations, empowering trial participants with excellent patient educational material and incorporating and learning from patient-reported outcomes serves as a model approach to achieve more patient-centric clinical trials.
Article Details
How to Cite
PERLMUTTER, Jane et al.
Advocate involvement in Clinical Trials: Lessons from the Patient-centric I-SPY2 Breast Cancer Trial.
Medical Research Archives, [S.l.], v. 11, n. 7.2, july 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4085>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i7.2.4085.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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25. Food and Drug Administration. Core Patient-Reported Outcomes in Cancer Clinical Trials: Guidance for Industry. Published June 2021. Accessed May 3, 2023. https://www.fda.gov/media/149994/download
26. Wolf DM, Yau C, Wulfkuhle J, et al. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022;40(6):609-623 e6. doi:10.1016/j.ccell.2022.05.005
27. Almirall D, Nahum-Shani I, Sherwood NE, Murphy SA. Introduction to SMART designs for the development of adaptive interventions: with application to weight loss research. Translational behavioral medicine. 2014;4(3):260-274. doi:10.1007/s13142-014-0265-0
28. I-SPY2 Trial Consortium, Yee D, DeMichele AM, et al. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer. Jama Oncol. 2020;6(9):1355-1362. doi:10.1001/jamaoncol.2020.2535
29. Li W, Newitt DC, Gibbs J, et al. Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY2 2 TRIAL. Npj Breast Cancer. 2020;6(1):63. doi:10.1038/s41523-020-00203-7
30. Li W, Newitt DC, Wilmes LJ, et al. Additive value of diffusion‐weighted MRI in the I‐SPY2 2 TRIAL. J Magn Reson Imaging. 2019;50(6):1742-1753. doi:10.1002/jmri.26770
31. Magbanua MJM, Swigart LB, Wu HT, et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. 2021;32(2):229-239. doi:10.1016/j.annonc.2020.11.007
32. Magbanua MJM, Li W, Wolf DM, et al. Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk. Npj Breast Cancer. 2021;7(1):32. doi:10.1038/s41523-021-00239-3
33. Drennan KB. Patient recruitment: the costly and growing bottleneck in drug development. Drug Discov Today. 2002;7(3):167-170. doi:10.1016/s1359-6446(01)02137-7
34. I-SPY2 Trials Consortium. I-SPY2 Trials. Published February 24, 2023. Accessed May 18, 2023. https://www.ispytrials.org/
35. National Academies of Sciences, Engineering and Medicine. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. (Botkin JR, Mancher Michelle, Busta Emily R, Downey AS, eds.). National Academies Press; 2018. doi:10.17226/25094
36. Sgro GM, Maurer M, Nguyen B, Siegel JE. Return of aggregate results to study participants: Facilitators, barriers, and recommendations. Contemp Clin Trials Commun. 2023;33:101136. doi:10.1016/j.conctc.2023.101136
2. Frank L, Basch E, Selby JV, Institute PCOR. The PCORI Perspective on Patient-Centered Outcomes Research. Jama. 2014;312(15):1513-1514. doi:10.1001/jama.2014.11100
3. Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. I-SPY2 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009;86(1):97-100. doi:10.1038/clpt.2009.68
4. Harrington D, Parmigiani G. I-SPY2 2--A Glimpse of the Future of Phase 2 Drug Development? New England Journal of Medicine. 2016;375(1):7-9. doi:10.1056/nejmp1602256
5. Bartsch R, Azambuja E de. I-SPY2 2: optimising cancer drug development in the 21st century. ESMO open. 2016;1(5):e000113. doi:10.1136/esmoopen-2016-000113
6. Woodcock J, LaVange LM. Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both. New England Journal of Medicine. 2017;377(1):62-70. doi:10.1056/nejmra1510062
7. I-SPY2 Trials Consortium. The I-SPY2 Trials | Manuscripts. Published February 4, 2023. Accessed May 18, 2023. https://www.ispytrials.org/results/manuscripts
8. Perlmutter J. Advocate Involvement in I-SPY2 2. Breast Diseases: A Year Book Quarterly. 2011;22(1):21-24.
9. Stires H, Bado I, Brown T, et al. Improving the odds together: a framework for breast cancer research scientists to include patient advocates in their research. Npj Breast Cancer. 2022;8(1):75. doi:10.1038/s41523-022-00440-y
10. Clinical Trials Transformation Initiative. Patient Group Engagement. Published 2023. Accessed May 18, 2023. https://ctti-clinicaltrials.org/our-work/patient-engagement/patients-groups-clinical-trials/
11. Perlmutter J, Bell SK, Darien G. Cancer Research Advocacy: Past, Present, and Future. Cancer Res. 2013;73(15):4611-4615. doi:10.1158/0008-5472.can-12-4553-t
12. National Breast Cancer Coalition. Project LEAD. Published 2023. Accessed May 11, 2023. https://www.stopbreastcancer.org/what-we-do/education/project-lead/
13. American Association for Cancer Research. AACR Scientist↔Survivor Program. Published 2023. Accessed May 11, 2023. https://www.aacr.org/patients-caregivers/patient-advocacy/scientist-survivor-program/
14. Susan G. Komen. Bringing the Patient Experience to Research. Published 2023. Accessed May 11, 2023. https://www.komen.org/about-komen/research-funding/bringing-the-patient-voice-to-research/
15. Research Advocacy Network. Advocate Institute. Published 2023. Accessed May 11, 2023. https://researchadvocacy.org/advocate-institute
16. Lobb EA, Kenny DT, Butow PN, Tattersall MHN. Women’s preferences for discussion of prognosis in early breast cancer. Health Expect. 2001;4(1):48-57. doi:10.1046/j.1369-6513.2001.00119.x
17. Kaplowitz SA, Campo S, Chiu WT. Cancer Patients’ Desires for Communication of Prognosis Information. Health Commun. 2002;14(2):221-241. doi:10.1207/s15327027hc1402_4
18. Esserman LJ. A model for accelerating identification and regulatory approval of effective investigational agents. Cureus. 2012;4(12):e76. doi:10.7759/cureus.76
19. Food and Drug Administration. Guidance for Industry: Pathological Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval.; 2014. https://www.fda.gov/downloads/drugs/guidances/ucm305501.pdf
20. Hayes DF, Schott AF. Neoadjuvant Chemotherapy: What Are the Benefits for the Patient and for the Investigator? JNCI Monographs. 2015;2015(51):36-39. doi:10.1093/jncimonographs/lgv004
21. Perlmutter J, Roach N, Smith ML. Involving Advocates in Cancer Research. Semin Oncol. 2015;42(5):681-685. doi:10.1053/j.seminoncol.2015.07.008
22. Berry DA. The Brave New World of clinical cancer research: Adaptive biomarker-driven trials integrating clinical practice with clinical research. Mendelsohn J, Ringborg Ulrik, Schilsky R, eds. Molecular Oncology. 2015;9(5):951-959. doi:10.1016/j.molonc.2015.02.011
23. Atkinson TM, Ryan SJ, Bennett AV, et al. The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review. Support Care Cancer. 2016;24(8):3669-3676. doi:10.1007/s00520-016-3297-9
24. Food and Drug Administration. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Published December 2009. Accessed May 3, 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims
25. Food and Drug Administration. Core Patient-Reported Outcomes in Cancer Clinical Trials: Guidance for Industry. Published June 2021. Accessed May 3, 2023. https://www.fda.gov/media/149994/download
26. Wolf DM, Yau C, Wulfkuhle J, et al. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022;40(6):609-623 e6. doi:10.1016/j.ccell.2022.05.005
27. Almirall D, Nahum-Shani I, Sherwood NE, Murphy SA. Introduction to SMART designs for the development of adaptive interventions: with application to weight loss research. Translational behavioral medicine. 2014;4(3):260-274. doi:10.1007/s13142-014-0265-0
28. I-SPY2 Trial Consortium, Yee D, DeMichele AM, et al. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer. Jama Oncol. 2020;6(9):1355-1362. doi:10.1001/jamaoncol.2020.2535
29. Li W, Newitt DC, Gibbs J, et al. Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY2 2 TRIAL. Npj Breast Cancer. 2020;6(1):63. doi:10.1038/s41523-020-00203-7
30. Li W, Newitt DC, Wilmes LJ, et al. Additive value of diffusion‐weighted MRI in the I‐SPY2 2 TRIAL. J Magn Reson Imaging. 2019;50(6):1742-1753. doi:10.1002/jmri.26770
31. Magbanua MJM, Swigart LB, Wu HT, et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. 2021;32(2):229-239. doi:10.1016/j.annonc.2020.11.007
32. Magbanua MJM, Li W, Wolf DM, et al. Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk. Npj Breast Cancer. 2021;7(1):32. doi:10.1038/s41523-021-00239-3
33. Drennan KB. Patient recruitment: the costly and growing bottleneck in drug development. Drug Discov Today. 2002;7(3):167-170. doi:10.1016/s1359-6446(01)02137-7
34. I-SPY2 Trials Consortium. I-SPY2 Trials. Published February 24, 2023. Accessed May 18, 2023. https://www.ispytrials.org/
35. National Academies of Sciences, Engineering and Medicine. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. (Botkin JR, Mancher Michelle, Busta Emily R, Downey AS, eds.). National Academies Press; 2018. doi:10.17226/25094
36. Sgro GM, Maurer M, Nguyen B, Siegel JE. Return of aggregate results to study participants: Facilitators, barriers, and recommendations. Contemp Clin Trials Commun. 2023;33:101136. doi:10.1016/j.conctc.2023.101136