Off-label use of vaccines.
This article reviews the off-label recommendations and use of vaccines, and focuses on the differences between the labelled instructions on how to use the vaccine as approved by the regulatory authorities (or "label"1), and the recommendations for use issued by public health advisory bodies at national and international levels. Differences between public health recommendations and the product label regarding the vaccine use can lead to confusion at the level of vaccinators and vaccinees and possibly result in lower compliance with national vaccination schedules. In particular, in many countries, the label may contain regulatory restrictions and warnings against vaccination of specific population groups (e.g. pregnant women) due to a lack of evidence of safety from controlled trials at the time of initial licensure of the vaccine, while public health authorities may recommend the same vaccine for that group, based on additional post-marketing data and benefit risk analyses. We provide an overview of the different responsibilities between regulatory authorities and public health advisory bodies, and the rationale for off-label use2of vaccines, the challenges involved based on the impact of off-label use in real-life. We propose to reduce off-label use of vaccines by requiring the manufacturer to regularly adapt the label as much as possible to the public health needs as supported by new evidence. This would require manufacturers to collect and report post-marketing data, communicate them to all stakeholders and regulators to extrapolate existing evidence (when acceptable) to other groups or to other brands of a vaccine (class effect3). Regulatory authorities have a key role to play by requesting additional post-marketing data, e.g. in specific target groups. When public health recommendations for vaccine use that are outside labelled indications are considered necessary, good communication between regulatory bodies, public health authorities, companies and health care providers or vaccinators is crucial. Recommendations as well as labels and label changes should be evidence-based. The rationale for the discrepancy and the recommended off-label use of a vaccine should be communicated to providers.
Independent Regulatory Consultant, Vaccine Advice BVBA, 281 Sint Antoniusbaan, 2980 Zoersel, Belgium; University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium; University of Antwerp, Department of Vaccinology, 13 Prinsstraat, 2000 Antwerpen, Belgium. Electronic address: pieter.neels@vaccine-advice.be.
Pieter
P
Neels
Medicines Control Council South Africa, PO Box 622, Simons Town 7995, South Africa. Electronic address: jamess@icon.co.za.
James
J
Southern
Department of Pediatrics at Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: jabrams@wakehealth.edu.
Jon
J
Abramson
World Health Organization, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. Electronic address: duclosp@who.int.
Philippe
P
Duclos
World Health Organization, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. Electronic address: hombachj@who.int.
Joachim
J
Hombach
World Health Organization, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. Electronic address: martim@who.int.
Melanie
M
Marti
Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario M5T 3M7, Canada. Electronic address: alanna.fitzgerald-husek@medportal.ca.
Alanna
A
Fitzgerald-Husek
World Health Organization, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. Electronic address: fourniercaruanaj@who.int.
Jacqueline
J
Fournier-Caruana
University of Antwerp, Department of Vaccinology, 13 Prinsstraat, 2000 Antwerpen, Belgium; Independent Consultant, 64 Avenue de Jette, 1081 Brussels, Belgium. Electronic address: ghanquet@skynet.be.
Germaine
G
Hanquet
D017277:Drug Approval; D006801:Humans; D056687:Off-Label Use; D011358:Product Surveillance, Postmarketing; D014612:Vaccines / Q000008:administration & dosage* / Q000009:adverse effects
D014612:Vaccines
Off-label use; Regulatory authority; Safety; Vaccination