You are here

A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors

T. W. Chen, A. R. Razak, P. L. Bedard, L. L. Siu & A. R. Hansen



There are limited data about the quality of immune-related adverse event (irAE) reporting in immune checkpoint inhibitor (ICI) clinical trial publications.


A systematic search of citations from Medline, EMBASE and Cochrane databases identified prospective clinical trials involving ICIs in advanced solid tumors from 2003 to 2013. A 21-point quality score (QS) was adapted from the CONSORT harms extension statement. Linear regression was used to identify factors associated with quality reporting.


After a review of 2628 articles, 50 trial reports were included, with ICIs as either monotherapy (54%) or part of a combination regimen (46%). The mean QS was 11.21 points (range 3.50-17.50 points). The median grade 3/4 AE rate reported was 21% (range 0%-66%) and 29/50 (58%) trials concluded that irAEs were tolerable. Multivariate regression analysis revealed that year of publication (within last 5 years, P = 0.01) and journal impact factor >15 (P = 0.004) were associated with higher QS. Complete reporting of specific characteristics of irAEs including onset, management and reversibility were reported by 14%, 8% and 6% of studies, respectively. The incidence of grade 3/4 adverse events was higher for inhibitors against CTLA-4 compared with other immune checkpoints (P < 0.001).


The reporting of irAEs is suboptimal. A standardized reporting method of irAEs that accounts for tolerability, management and reversibility is needed and would enable a more precise evaluation of the therapeutic risk benefit ratio of ICIs.

Search this site

Stay up-to-date with our monthly e-alert

If you want to regularly receive information on what is happening in Quality of Life in Oncology research sign up to our e-alert.

Subscribe »

QOL (Quality of Life) newsletter e-alert

NEW! Free access to the digital version of a new publication in Cancer Supportive Care

Cancer cachexia: mechanisms and progress in treatment

Authors: Egidio Del Fabbro, Kenneth Fearon, Florian Strasser

This book was supported by an educational grant from Helsinn Healthcare SA.

Featured videos

Quality of Life promotional video

Made possible by an educational grant from Helsinn

Helsinn does not have any influence on the content and all items are subject to independent peer and editorial review

Society Partners

European Cancer Organisation Logo