Developing alert thresholds and self-management advice for people receiving immune checkpoint inhibitors: a Multinational Association for Supportive Care in Cancer modified Delphi survey

Abstract

Background: Remote monitoring using electronic patient-reported outcomes (ePROs) may help identify immune-related adverse events (irAEs) and direct self-management. There is no consensus regarding thresholds to alert providers about potentially severe irAEs or when to instigate evidence-based self-management. We aimed to develop consensus around alert thresholds and self-management advice for side-effects suggestive of an irAE which can be deployed as part of remote monitoring systems.

Methods: A two-round international modified Delphi survey including co-authors of major international irAE guidelines and selected immuno-oncology experts was conducted. Round 1 (R1): participants reviewed alert thresholds graded as per the Common Terminology Criteria for Adverse Events (CTCAE) and self-management statements for 36 side-effects. Participants stated whether they agreed or disagreed with the proposed thresholds and self-management statements. If ≥ 75% of participants agreed, consensus was reached. Prior to Round 2 (R2), thresholds and self-management statements that did not reach consensus in R1 were modified. In R2, participants were asked whether they agreed or disagreed with the modifications.

Results: In R1, 34 participants responded (North America: 18, 52.9%; Europe: 12, 35.3%; Asia-Pacific: 4, 11.8%; median duration of experience in current role, 13.5 years (range, 3-46 years)), with 33 complete responses received. Twenty-nine alert thresholds and 33 self-management statements reached consensus. For R2, seven alert thresholds were increased from CTCAE Grade 1 to 2 based on participant comments, and three self-management statements were amended. Six self-management statements which achieved consensus were amended and re-presented in R2. In R2, 31 participants responded (North America: 18, 58.1%; Europe: 9, 29%; Asia-Pacific: 4, 12.9%; median duration of experience in current role, 13 years (range, 3-40 years)), with 30 complete responses received. All seven alert thresholds and nine self-management statements achieved consensus.

Conclusion: This survey developed international consensus regarding alert thresholds and self-management advice for common, clinically relevant side-effects suggestive of an irAE for ePRO monitoring systems with international applicability. Self-management statements will inform written materials for patients.

Keywords: Delphi; Digital health; Electronic patient-reported outcomes; Immune checkpoint inhibitors; Immunotherapy; Patient-reported outcomes; Symptom monitoring.