New opinions and trends in oncology PROs

Learnings from the 2022 FDA COA in cancer trials workshop

Kelly Dumais, Ph.D. – Director, eCOA Science & consulting at Clario
Jowita Marszewska, Ph.D. – Scientific Advisor at Clario

The FDA’s Oncology Center of Excellence (OCE) conducts annual public workshops on clinical outcome assessments (COAs) in cancer clinical trials. These workshops bring top leaders (and importantly, patient advocates) together for interactive conversations that seek to answer our most critical questions related to the use of patient reported outcomes (PROs) in oncology trials and to ignite innovative thinking. This year in June, the 7^th Annual Clinical Outcome Assessment in Cancer Clinical Trials Workshop discussed the topic of using PROs in open label trials. We learned about overcoming barriers to incorporating PROs in open-label trials, and so much more.

Here are some key takeaways from this year’s workshop:

• Patient-reported data should be the gold standard in understanding patient symptoms and experiences. Patients know their bodies best, and therefore, it is crucial to capture reports of their experiences with the drug using PROs. The importance of including PROs in clinical trials cannot be stressed enough considering the fact that ClinROs and ObsROs are subjective and prone to bias, with evidence that clinicians and caregivers underreport patient’s symptoms for adult and pediatric patients.^1,2 Additionally, regulators often take a more conservative approach with the drug approval when PRO data is not available to complement clinician’s observations.

• The risk of open-label bias should not prohibit the use of PROs in open label oncology trials. Most oncology trials use an open label trial design, leading to concern that the patient’s perception of their symptoms may be influenced by their knowledge of their treatment (i.e., open label bias). While the concern and need for further research was acknowledged, the collective opinion from the panelists, supported by recent literature^3,4 (Atkinson et al., 2017; Efficace et al., 2022), is that there is little evidence or concern for open label bias in oncology trials and that their use in open label trials are valid and supported. Further, most oncology drug approvals that include PROs in the label were open label trials, supporting that this is an accepted practice by the FDA.

To me, the message was clear. For Oncology trials, you must use PROs to fully understand the patient experience and to better evaluate tolerability. PROs should be included as early as possible in your drug development program.

Kelly Dumais, Ph.D., Principal Scientific Advisor at Clario

• PROs should be a standard practice in every cancer clinical trial, even in early phases. Omitting PROs in early stages of assessing drug’s safety, tolerability and pharmacokinetics can have serious implications: Drug dose can be toxic or poorly tolerated but still would be moved forward to another phase. In addition to clinician reported tolerability and adverse events (AEs), optimal dose finding should include evidence of patient tolerability via PROs. PROs that assess tolerability (e.g., PRO-CTCAE) provide complimentary information to provide a more comprehensive and granular evaluation and should be included in all cancer trials, starting at phase 1.
• Communicate to sites and patients the value of PROs. Both experts and patients on the panel emphasized the value of an education and training of sites and patients. Patients participate in clinical trials for altruistic reasons and the more they know what is important and why, the more accurate and complete their reporting will be, leading to higher patient satisfaction and better compliance.

The industry is making significant strides in using PROs to bring the patient back to the forefront of clinical trials and making the patient voice heard. This year’s FDA workshop on COA in cancer clinical trials provided another successful display of what can be accomplished when bringing everyone to the table: Regulators, academia, international experts and patient advocates.

Written by

Kelly Dumais, Ph.D.

Principal Scientific Advisor at Clario

Jowita Marszewska, Ph.D.

Scientific Advisor at Clario

References

¹Basch E, Jia X, Heller G, et al. Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes. JNCI: Journal of the National Cancer Institute. 2009;101(23):1624-1632. doi:10.1093/jnci/djp386

²Freyer DR, Lin L, Mack JW, et al. Lack of Concordance in Symptomatic Adverse Event Reporting by Children, Clinicians, and Caregivers: Implications for Cancer Clinical Trials. JCO. 2022;40(15):1623-1634. doi:10.1200/JCO.21.02669

³Atkinson TM, Wagner JS, Basch E. Trustworthiness of patient-reported outcomes in unblinded cancer clinical trials. JAMA Oncology. 2017;3(6):738-9.

⁴Efficace F, Cella D, Aaronson NK, Calvert M, Cottone F, Di Maio M, Perrone F, Sparano F, Gamper EM, Vignetti M, Giesinger JM. Impact of blinding on patient reported outcome differences between treatment arms in cancer randomized controlled trials. JNCI. 2022; 114(3):471-4.