What is important to patients in oncology clinical studies?
Considering patient burden when incorporating patient-reported outcomes in oncology
Kelly Dumais, Ph.D., Stephen Raymond, Ph.D.
When measuring what is important to oncology patients, we must look beyond traditional endpoints to get a complete picture of treatment benefits. In recent years, there has been growing expectation that indicators like quality of life and disease symptoms be measured and incorporated into the risk-benefit evaluation for cancer trials. Patient-reported outcome (PRO) measures are the best way to evaluate these indicators.
When creating patient-focused drug development programs, we must understand what matters to patients and consider them when determining which PRO measures to use and how to use them. One key area for consideration is patient burden. How do we make completing these PROs motivating instead of burdensome? What is the right balance between collecting a thorough picture of the patient’s symptoms, experiences, and quality of life and not over-burdening patients with PROs?
First, let’s consider how long it takes patients to complete PROs. The FDA recently drafted guidance on “Core Patient-Reported Outcomes in Cancer Clinical Trials”1 incorporating core PRO measurements. The guidance states sponsors can collect additional PROs beyond the five core PROs but should be “carefully considered to minimize patient burden and improve the quality of data collected by focusing on the most meaningful and measurable outcomes.” Following this guidance, Clario created an example PRO strategy for Multiple Myeloma and Breast Cancer studies and evaluated the time it would take to complete PRO assessments in each example (Table 1). The table models the scenario of the highest patient burden where patients would complete all PROs at a single study visit (or at the same time).
Implement electronic patient-reported outcomes (ePRO)
While patients in oncology clinical trials prefer ePRO for several reasons (i.e., preferred and recommended by patients, reduces missing data, increases quality of life and survival2-6), our data suggests it may also decrease patient burden by reducing time to complete assessments. The FDA’s new draft oncology PRO guidance supports this, citing ePRO as a way to decrease patient burden.
Offer training to reduce assessment time
Although the time it takes to complete PROs may be minimal, 10 minutes of PRO completion may still be a lot to ask due to busy lives or debilitating symptoms. Therefore, an additional step we can take to minimize patient burden related to PRO completion is providing training for patients on the importance of PROs. Training ensures that patients understand the importance of reporting honestly and helps them realize the valuable contribution of their participation. The desire to advance therapeutic options is a significant motivator for patients in cancer clinical trials.7 It is important to let patients know we listen and respond to their needs.
Consider patient preference for reporting symptoms
Finally, let’s consider further that patients want to report on their symptoms. A long instrument is not necessarily burdensome if it helps the patient tell a story that matters to them. In a recently published data set, we found that 95% of participants with a history of cancer want to report their symptoms during a clinical trial. Most participants indicated there would be a significant benefit to them in doing so.8 Additionally, most respondents preferred a higher frequency of reporting (as symptoms occur or daily) versus a lower frequency (weekly), and there was a significant preference to report symptoms in an electronic diary versus a paper diary or verbally to their doctor during study visits (Figure 1).
We must be thoughtful and targeted when developing a PRO strategy to avoid increasing patient burden. Consider the FDA’s five core PRO categories released in their new draft Oncology PRO Guidance and align reporting frequency with research objectives. Avoid repetitive questions, focus on the most meaningful and measurable outcomes, and consider whether the item content justifies extending the reporting time. In training, genuinely recognize the value of learning from the patient experience. Use ePROs to minimize the time spent completing assessments and to align with patient preference for electronic reporting. Finally, take the opportunity to explore content directed at measuring what matters most to patients.
1 FDA Draft Guidance for Industry: Core Patient-Reported Outcomes in Cancer Clinical Trials. June 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/core-patient-reported-outcomes-cancer-clinical-trials
2 Ring et al., 2008. A randomized study of electronic diary versus paper and pencil collection of patient-reported outcomes in patients with non-small cell lung cancer. Patient 1(2):105-113.
3 Velikova et al., 1999. Automated collection of quality-of-life data: a comparison of paper and computer touch-screen questionnaires. J Clin Oncol, 17(3):998-1007.
4 Mody et al., 2021. Electronic patient-reported outcomes monitoring during lung cancer chemotherapy: A nested cohort within the PRO-TECT pragmatic trial (AFT-39). Lung Cancer 162:1-8.
5 Basch E, et al. 2016. Symptom monitoring with patient-reported outcomes during routine cancer treatment: A randomized controlled trial. J Clin Oncol.;34(6):557-65.
6 Basch E, et al. 2017. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA, 318(2):197-198.
7 Godskesen et al., 2015. Hope for a cure and altruism are the main motives behind participation in phase 3 clinical cancer trials. Eur J Cancer Care (Engl) 24(1):133-41.
8 Peechatka AL, Gerzon, M, Ly, JJ, Dallabrida SM, 2020. Oncology patient preferences in reporting on symptoms. Int J of Clinical Trials 7(1):11-17.