Although the importance of QoL to cancer patients is established , this has yet to translate into increased PRO implementation. Commonly used provider graded adverse event criteria do not necessarily provide enough information on the change in QoL experienced as a consequence of therapy. To better inform decisions made by patients and providers, understanding the impact of treatment on the patient experience is essential and can be facilitated through the use of PROs.
While many studies did not include PROs, some recent trials that have explored targeted therapies such as oral cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) inhibitor palbociclib and oral poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitor talazoparib have demonstrated some improvement in QoL and increased time to definitive clinically meaningful deterioration [12, 14]. The inclusion of PROs in these studies allowed for the investigators to demonstrate that in their case prolonging progression-free survival was coupled with maintenance of QoL. These significant findings are particularly appreciated when these regimens are implemented into clinical practice. Responding to questions spanning from physical and emotional function to pain, nausea, vomiting and hair loss from the patient’s perspective is made possible by the implementation of these PROs. Conveying the true overall impact of treatment on a patient’s wellbeing, beyond clinician reported toxicities, allows physicians to better address some of most pressing concerns patients have when considering treatment options.
Previously reported barriers to implementing PROs in clinical research include engaging providers, the concern of burdening existing workflows, the need for additional staff and increasing costs [3, 4]. Discordance between regulators and industry has also surfaced as a potential challenge . Furthermore, the availability of culturally appropriate validated instruments in languages other than English is another barrier to consider. To overcome these barriers, the concepts of PROs and QoL should be incorporated in educational curricula focusing on patient centered care in preparation for these complexities encountered while engaging in shared decision-making. Groups such as Basch et al.  have since published recommendations specifically addressing the implementation of PROs in clinical trials in adult oncology with aims to further engage providers, regulators and payers. Since 2009, the FDA has held disease-specific patient-focused drug development meetings to more systematically gather patients’ perspectives . In addition, the American Society of Clinical Oncology has subsequently held webinars and workshops intended for providers on the use of PROs in clinical research [13, 17]. The use of electronic PROs and standardized measures through initiatives such as The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS)  may help surmount logistical barriers to implementation. Providing culturally appropriate instruments in languages other than English may continue to be a barrier as the adaptation process can be lengthy and costly .
Study limitations include the possibility of implementation delay following the FDA guidance and the lack of inclusion of PROs as an endpoint in Clinicaltrials.gov’s registry used to collect this data. It is perhaps too soon to fully appreciate the impact of the FDA guidance and subsequent physician led efforts given the possibility of lag time between policy publication and implementation. The time frame used of eight years pre and eight years post adoption of the FDA guidance may limit the ability to capture a meaningful trend. The provision of additional time points in future studies could strengthen the statistical analysis and interpretation of this data.
The FDA Guidance for Industry has yet to translate into significant intermediate term growth in the use of PROs as endpoints in phase two or three studies assessing therapeutic options in MBC. The use of PROs in future clinical trials is necessary to quantify outcomes and allow providers to address issues of importance to patients suffering from MBC.
The authors have no competing interests to declare.
The Voice of the Patient: Breast Cancer. A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. U.S. Food and Drug Administration (FDA); 2015.
Antunes B, Harding R and Higginson IJ. Implementing patient-reported outcome measures in palliative care clinical practice: a systematic review of facilitators and barriers. Palliat Med. 2014; 28: 158–75. DOI: https://doi.org/10.1177/0269216313491619
Basch E and Abernethy AP. Supporting clinical practice decisions with real-time patient-reported outcomes. J Clin Oncol. 2011; 29: 954–6. DOI: https://doi.org/10.1200/jco.2010.33.2668
Basch E, Abernethy AP, Mullins CD, Reeve BB, Smith ML, Coons SJ, Sloan J, Wenzel K, Chauhan C, Eppard W, Frank ES, Lipscomb J, Raymond SA, Spencer M and Tunis, S. Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology. J Clin Oncol. 2012; 30: 4249–55. DOI: https://doi.org/10.1200/jco.2012.42.5967
Basch E, Geoghegan C, Coons SJ, Gnanasakthy A, Slagle AF, Papadopoulos EJ and Kluetz PG. Patient-Reported Outcomes in Cancer Drug Development and US Regulatory Review: Perspectives From Industry, the Food and Drug Administration, and the Patient. JAMA Oncology. 2015; 1: 375–379. DOI: https://doi.org/10.1001/jamaoncol.2015.0530
Bernard-Marty C, Cardoso F and Piccart MJ. Facts and controversies in systemic treatment of metastatic breast cancer. Oncologist. 2004; 9: 617–32. DOI: https://doi.org/10.1634/theoncologist.9-6-617
Carrick S, Parker S, Thornton CE, Ghersi D, Simes J and Wilcken N. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev. 2009; Cd003372. DOI: https://doi.org/10.1002/14651858.CD003372.pub3
Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, Ader D, Fries JF, Bruce B, Rose M and Group PC. The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years. Medical care. 2007; 45: S3–S11. DOI: https://doi.org/10.1097/01.mlr.0000258615.42478.55
Chia SK, Speers CH, D’Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O’Reilly SE and Olivotto IA. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007; 110: 973–9. DOI: https://doi.org/10.1002/cncr.22867
Colozza M, de Azambuja E, Personeni N, Lebrun F, Piccart, MJ and Cardoso F. Achievements in systemic therapies in the pregenomic era in metastatic breast cancer. Oncologist. 2007; 12: 253–70. DOI: https://doi.org/10.1634/theoncologist.12-3-253
Ettl J, Martin M, Roché H, Im, Y-H, Bhattacharyya H, Eiermann W, Blum JL, Litton JK, Hannah AL, Markova D, Quek, RGW, Lee, K-H, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R and Mina LA. Quality of life with talazoparib versus physician’s choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Annals of Oncology. 2018; 29: 1939–1947. DOI: https://doi.org/10.1093/annonc/mdy257
Harbeck N, Iyer S, Turner N, Cristofanilli M, Ro J, Andre F, Loi S, Verma S, Iwata H, Bhattacharyya H, Puyana Theall K, Bartlett CH and Loibl S. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: Patient-reported outcomes from the PALOMA-3 trial. Annals of Oncology. 2016; 27: 1047–1054. DOI: https://doi.org/10.1093/annonc/mdw139
Lin NU, Thomssen C, Cardoso F, Cameron D, Cufer T, Fallowfield L, Francis PA, Kyriakides S, Pagani O, Senkus E, Costa A and Winer EP. International guidelines for management of metastatic breast cancer (MBC) from the European School of Oncology (ESO)–MBC Task Force: Surveillance, staging, and evaluation of patients with early-stage and metastatic breast cancer. The Breast. 2013; 22: 203–210. DOI: https://doi.org/10.1016/j.breast.2013.03.006
McKenna SP, Wilburn J, Thorsen H and Brodersen J. Adapting Patient-Reported Outcome Measures for Use in New Languages and Cultures. Rasch Models in Health; 2012. DOI: https://doi.org/10.1002/9781118574454.ch16
Strong LE. The Past, Present, and Future of Patient-Reported Outcomes in Oncology. 2015 ASCO Annual Meeting; 2015. Chicago. DOI: https://doi.org/10.14694/EdBook_AM.2015.35.e616
Wagner AK, Soumerai SB, Zhang F and Ross-Degnan D. Segmented regression analysis of interrupted time series studies in medication use research. Journal of Clinical Pharmacy and Therapeutics. 2002: 27: 299–309. DOI: https://doi.org/10.1046/j.1365-2710.2002.00430.x
Zafar SY, Alexander SC, Weinfurt KP, Schulman KA and Abernethy AP. Decision making and quality of life in the treatment of cancer: a review. Support Care Cancer. 2009; 17: 117–27. DOI: https://doi.org/10.1007/s00520-008-0505-2