Timing is everything: The importance of patient-reported outcome assessment frequency when characterizing symptomatic adverse events

Abstract

Objective Although patient-reported symptoms and side effects are increasingly measured in cancer clinical trials, an appropriate assessment frequency has not yet been established. To determine whether differences in assessment frequency affect the apparent incidence and severity of patient-reported symptoms using two well-established patient-reported outcome measures used within the same clinical trial. Methods We examined patient-reported outcome results from AURA3 (NCT02151981), a randomized open-label study comparing Tagrisso (osimertinib) with platinum-based chemotherapy in patients with previously treated estimated glomerular filtration rate/T790M mutation-positive metastatic non-small cell lung cancer. The outcome of interest was the proportion of patients in each arm that reported worsening of nausea, vomiting, fatigue, diarrhea, constipation, and appetite loss from baseline measured using the patient-reported outcome—common terminology criteria for adverse event (weekly) or European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (every 6 weeks). Results Similar trends were observed for all six symptoms investigated. Using nausea in the chemotherapy arm as an example, 76% of patients reported any worsening from baseline based on weekly patient-reported outcome—common terminology criteria for adverse event assessments. When using an every 6-week assessment of Quality of Life Questionnaire Core 30 nausea and restricting analysis to an every 6-week assessment for patient-reported outcome—common terminology criteria for adverse event nausea, the proportion of chemotherapy arm patients reporting any worsening of nausea was 40% for both measures. Across the six patient-reported symptomatic adverse events, we observed differential proportions when comparing frequent versus sparse assessment. Conclusion This analysis demonstrates that more frequent assessment of patient-reported symptomatic adverse events will lead to improved detection, and therefore a more complete understanding of the tolerability of experimental anti-cancer therapies.

Methodological standards for using the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in cancer clinical trials

“…The purpose of adverse event reporting is to capture continuous data throughout a trial to detect all incident adverse events. If the frequency of eliciting adverse events from patients does not match the recall period, then there will be periods of missing data, as demonstrated in the study by King-Kallimanis et al 10 This study provides highly compelling evidence that the frequency of PRO-CTCAE reports should match the recall period of items and reinforces the value of weekly PRO-CTCAE collection in cancer clinical trials.…”

“…However, there has not been prior evidence demonstrating whether spacing out frequency of administration of 7-day recall PRO items to be longer than weekly results in loss of information. The paper in the current issue of Clinical Trials by King-Kallimanis et al 10 from the U.S. Food & Drug Administration (FDA) addresses this question eloquently. In this study, data submitted to the FDA for the AURA3 randomized controlled trial of an oral targeted agent versus standard chemotherapy for lung cancer was evaluated, to compare symptom worsening between trial arms for items administered either weekly or every 6 weeks for nausea, vomiting, fatigue, diarrhea, constipation, and appetite loss.…”

Guidelines for the Use and Reporting of Patient-Reported Outcomes in Multiple Myeloma Clinical Trials

“…The minimum recommended TPs of the PRO assessment are TP-1 at baseline, TP-2 at trial visit that evaluates the primary endpoint, TP-3 at disease progression or study completion or early termination if it does not coincide with TP-2. Additional TPs are recommended at intermediate visits and during the follow-up period within the trial [74].…”

Patient Perspectives on Value Dimensions of Lung Cancer Care: Cross-sectional Web-Based Survey

“…They highlight the relevance of the patient's perspective as a standard outcome measure and the importance of incorporating PROMs in the evaluation of treatment in both clinical trials and clinical practice [9,15,16]. Nevertheless, despite this accepted importance and increasing use, PROMs are still insufficiently incorporated into clinical trials and clinical practice [7,12,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”