Harmonizing the collection of solicited adverse events in prophylactic vaccine clinical trials

ABSTRACT

Introduction

During the clinical development of a vaccine, study participants are monitored for the occurrence of adverse events (AEs) over a defined period post-vaccination to assess the safety of prophylactic vaccines. Among the safety data collected, a standard practice in prophylactic vaccine clinical trials involves collecting reactogenicity data through daily AE solicitation of pre-defined sets of symptoms (i.e. solicited AEs).

Areas covered

This paper aims to propose recommendations to improve and harmonize the collection of active AE solicitation in prophylactic vaccine clinical trials.

Expert opinion

We recommend using limited lists of solicited AEs adapted to the vaccine technology and target population. While the US Food and Drug Administration toxicity grading scale is commonly used in adolescents/adults, harmonizing grading criteria in infants/children would facilitate the comparison of vaccines’ safety profiles. Solicited systemic AEs should not systematically be considered causally related to vaccination. Collection of solicited AEs should occur in cohorts of a maximum of 1,000 vaccinated participants, as larger cohort sizes do not improve substantially the precision of AE incidence. The incidence of daily solicited AEs should be compared with a control group for improved interpretations of their clinical relevance. These suggestions would improve the characterization of safety profiles of vaccines.

KEYWORDS:

• Prophylactic
• reactogenicity
• solicited adverse event
• severity grading system
• vaccine clinical trial

Article highlights

• Solicited adverse events (AEs) are reported at higher rates than unsolicited AEs

• Vaccine programs should use limited and clinically relevant lists of solicited AEs

• Severity grading criteria should be harmonized in pediatric vaccine trials

• A sample of 1,000 participants is optimal to assess the incidence of solicited AEs

• Vaccine product information should include reactogenicity data from the vaccine vs a control group (ideally a placebo)

Declaration of interests

B Cheuvart is an employee of GSK and holds shares in GSK. F Tavares-Da-Silva was an employee of the GSK at the time of the Zoster-006 study (NCT01165177) and is currently an employee of Organon. B Spiessens and R van Heesbeen are employees of Johnson & Johnson. D Hung and C Andrade are employees of Seqirus. J Korejwo-Peyramond is an employee of Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contribution

BC and FTDS coordinated the conception of the paper. BC, BS, RvH, DH, CA, JKP and FTDS contributed to the development of proposals, reviewed, and edited the manuscript. All authors have read and approved the final manuscript and attest that they meet the ICMJE criteria for authorship.

Trademark statement

Comirnaty is a trademark of BioNTech Manufacturing GmbH; Jcovden is a trademark of the Janssen group of companies; Shingrix is a trademark of GSK; Spikevax is a trademark of the Moderna Biotech group of companies; Vaxzevria is a trademark of the AstraZeneca group of companies.

Data sharing statement

The datasets generated during and/or analyzed during the current study are available in:

[dataset] Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine, Supplementary Materials, 2021, https://doi.org/10.1056/NEJMoa2035389.

[dataset] Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. Table 3: Adverse Events and Reactogenicity, 2015, https://doi.org/10.1056/NEJMoa1501184.

Acknowledgments

The authors would like to thank Paula Barbosa from IFPMA who kindly coordinated the review of the position paper within the IFPMA vaccine subgroup. The authors also thank the Akkodis Belgium platform, on behalf of GSK: Lucienne Duru and Joanne Wolter provided writing support and Carlos Marin coordinated manuscript development.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2023.2262571.

Additional information

Funding

This manuscript was funded by GlaxoSmithKline Biologicals SA which took responsibility for all costs associated with the development and publishing of the present manuscript.