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PLoS One. 2017 Jan 27;12(1):e0163586. doi: 10.1371/journal.pone.0163586. eCollection 2017.

Influenza Vaccination of Healthcare Workers: Critical Analysis of the Evidence for Patient Benefit Underpinning Policies of Enforcement.

Author information

Institut national de santé publique du Québec, Quebec City, Quebec, Canada.
Laval University, Quebec City, Quebec, Canada.
British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.
University of British Columbia, Vancouver, British Columbia, Canada.
Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
University of Toronto, University Health Network, Toronto, Ontario, Canada.
McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
Australian National University, Acton, Australia.
Canberra Hospital, Garran, ACT, Australia.
Institut National de la Santé et de la Recherche Médicale, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Sorbonne Universités, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Unité de Santé Publique, Paris, France.



Four cluster randomized controlled trials (cRCTs) conducted in long-term care facilities (LTCFs) have reported reductions in patient risk through increased healthcare worker (HCW) influenza vaccination. This evidence has led to expansive policies of enforcement that include all staff of acute care hospitals and other healthcare settings beyond LTCFs. We critique and quantify the cRCT evidence for indirect patient benefit underpinning policies of mandatory HCW influenza vaccination.


Plausibility of the four cRCT findings attributing indirect patient benefits to HCW influenza vaccination was assessed by comparing percentage reductions in patient risk reported by the cRCTs to predicted values. Plausibly predicted values were derived according to the basic mathematical principle of dilution, taking into account HCW influenza vaccine coverage and the specificity of patient outcomes for influenza. Accordingly, predicted values were calculated as a function of relevant compound probabilities including vaccine efficacy (ranging 40-60% in HCWs and favourably assuming the same indirect protection conferred through them to patients) × change in proportionate HCW influenza vaccine coverage (as reported by each cRCT) × percentage of a given patient outcome (e.g. influenza-like illness (ILI) or all-cause mortality) plausibly due to influenza virus. The number needed to vaccinate (NNV) for HCWs to indirectly prevent patient death was recalibrated based on real patient data of hospital-acquired influenza, with adjustment for potential under-detection (5.2-fold), and using favourable assumptions of HCW-attributable risk (ranging 60-80%).


In attributing patient benefit to increased HCW influenza vaccine coverage, each cRCT was found to violate the basic mathematical principle of dilution by reporting greater percentage reductions with less influenza-specific patient outcomes (i.e., all-cause mortality > ILI > laboratory-confirmed influenza) and/or patient mortality reductions exceeding even favourably-derived predicted values by at least 6- to 15-fold. If extrapolated to all LTCF and hospital staff in the United States, the prior cRCT-claimed NNV of 8 would implausibly mean >200,000 and >675,000 patient deaths, respectively, could be prevented annually by HCW influenza vaccination, inconceivably exceeding total US population mortality estimates due to seasonal influenza each year, or during the 1918 pandemic, respectively. More realistic recalibration based on actual patient data instead shows that at least 6000 to 32,000 hospital workers would need to be vaccinated before a single patient death could potentially be averted.


The four cRCTs underpinning policies of enforced HCW influenza vaccination attribute implausibly large reductions in patient risk to HCW vaccination, casting serious doubts on their validity. The impression that unvaccinated HCWs place their patients at great influenza peril is exaggerated. Instead, the HCW-attributable risk and vaccine-preventable fraction both remain unknown and the NNV to achieve patient benefit still requires better understanding. Although current scientific data are inadequate to support the ethical implementation of enforced HCW influenza vaccination, they do not refute approaches to support voluntary vaccination or other more broadly protective practices, such as staying home or masking when acutely ill.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

GDS, MG, CL and AY have been engaged (with or without remuneration) to provide expert testimony during legal challenges against enforced healthcare workers influenza vaccination policies in Canada. GDS has received grants from GSK and Pfeizer and travel reimbursement to attend an ad hoc advisory board meeting of GSK. BJW has participated in clinical trials and ad hoc advisory boards with several vaccine manufacturers as well as receiving occasional speaker's fees. He has held or holds research grants with GSK and Medicago. He is medical officer for Medicago Inc. and has served as an expert witness for US and Quebec vaccine injury compensation programs. MK has received research grants from Roche, Merck, Siemens, Hologic, and Boerhinger Ingelheim for unrelated studies. FC has received personal fees from AstraZeneca and GlaxoSmithKline for consultancy on influenza epidemiology outside the submitted work. DMS, DMP, ML and PC have no competing interests to report. There are no patents, products in development or marketed products to declare. This does not alter the authors adherence to PLOS ONE policies on sharing data and materials.

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