The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors

Zahra Karimian,Agnès Dechartres,Joe-Elie Salem,Florence Tubach,Sandra Mavoungou

doi:10.1186/s12885-020-07518-5

Abstract

BackgroundWhile immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs.MethodsPubMed was searched to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration on ClinicalTrials.gov and extracted relevant safety data from both the publication and results posted on registry. We then compared the quality of reporting and the value of safety data between both sources.ResultsOf 42 eligible published trials, 34 had results posted on ClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results in ClinicalTrials.gov compared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8 and 8.8% of publications respectively, compared to 11.8 and 5.9% in registry results. Comparing the value of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had matching data in both sources.ConclusionsThe reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.

Highlights

While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities
Eligibility criteria Phase III Randomized controlled trial (RCT) for all FDA-approved ICIs used in cancer treatment which were published in English prior to March 2019 were included in this study
Evaluation of the reporting of safety: We evaluated the reporting of overall safety, and of immune-related adverse event (irAE) and immune-related serious adverse events (irSAE) from the text, tables and figures, as well as supplementary information using the following items based on the CONSORT Extension for Reporting Harms and safety guidelines / recommendations for reporting Adverse event (AE) in Oncology [18,19,20]: Evaluation of general safety information – Population of analysis: we evaluated whether safety was analyzed in all randomly assigned participants or in a defined safety population and we collected the number of participants analyzed in each treatment arm – Use of a validated instrument for coding and grading AEs (MedDRA [21], Common terminology criteria for adverse events (CTCAE), etc.) – Reporting of

Summary

Introduction

While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immunerelated adverse events (irAEs); most have focused on published articles without evaluating trial registries The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs. Immunotherapies have transformed the field of cancer therapy by improving the overall prognosis of patients, especially for recurrent and metastatic cancers [1,2,3]. Registries are recognized as an important source of information when conducting systematic reviews, to identify unpublished trials and evaluate the risk of selective outcome reporting, and to extract results, and in particular safety results [13, 14] This is while previous studies have showed that certain safety information such as serious adverse events (SAEs) were more completely reported at ClinicalTrials. This is while previous studies have showed that certain safety information such as serious adverse events (SAEs) were more completely reported at ClinicalTrials. gov than in corresponding publications [15, 16]

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