Considerations for unblinding individual study participants during vaccine trials

Neal Halsey; Stephen Evans; Mathuram Santosham; Adam Hacker; Kathryn M Edwards; Rebecca E Chandler; Matthew Z Dudley; Cornelia L Dekker; members of the SPEAC meta-DSMB; Seif Al-Abri; Narendra Arora; Jim Buttery; Alex Dodoo; Juhani Eskola; Ulrich Heininger; Youngmee Jee; Najwa Khuri; Stephen Obaro; Walt Orenstein; Punnee Pitisuttithum; Marco Safadi; Cynthia G Whitney; Steve Black

doi:10.1016/j.vaccine.2023.04.033

Considerations for unblinding individual study participants during vaccine trials

Vaccine. 2023 May 22;41(22):3399-3402. doi: 10.1016/j.vaccine.2023.04.033. Epub 2023 Apr 28.

Authors

Neal Halsey¹, Stephen Evans², Mathuram Santosham³, Adam Hacker⁴, Kathryn M Edwards⁵, Rebecca E Chandler⁴, Matthew Z Dudley³, Cornelia L Dekker⁶; members of the SPEAC meta-DSMB; Seif Al-Abri⁷, Narendra Arora⁸, Jim Buttery⁹, Alex Dodoo¹⁰, Juhani Eskola¹¹, Ulrich Heininger¹², Youngmee Jee¹³, Najwa Khuri¹⁴, Stephen Obaro¹⁵, Walt Orenstein¹⁶, Punnee Pitisuttithum¹⁷, Marco Safadi¹⁸, Cynthia G Whitney¹⁶, Steve Black¹⁹

Affiliations

¹ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States. Electronic address: [email protected].
² London School of Hygiene and Tropical Medicine, United Kingdom.
³ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.
⁴ Coalition for Epidemic Preparedness Innovations, Norway.
⁵ Vanderbilt University, United States.
⁶ Stanford University School of Medicine, United States.
⁷ Directorate General for Disease Surveillance and Control, Muscat, Oman.
⁸ Executive Director of The INCLEN Trust International, India.
⁹ University of Melbourne, Australia.
¹⁰ University of Ghana, Ghana.
¹¹ National Institute for Health and Wellfare, Helsinki, Finland.
¹² University of Basel Children's Hospital, Switzerland.
¹³ Institut Pasteur Korea, Republic of Korea.
¹⁴ University of Jordan, Jordan.
¹⁵ University of Nebraska Medical Center, United States.
¹⁶ Emory University, United States.
¹⁷ Mahidol University, Thailand.
¹⁸ São Paulo School of Medical Sciences, Brazil.
¹⁹ Global Vaccine Data Network, Auckland, New Zealand.

PMID: 37121805
DOI: 10.1016/j.vaccine.2023.04.033

Abstract

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Keywords: Adverse events; Regulatory guidance; Unblinding; Vaccine; Vaccine safety; Vaccine trials.

Publication types

Review

MeSH terms

Humans
Vaccination* / adverse effects
Vaccines* / adverse effects

Substances

Vaccines