In her article for BMJ titled “What use is mass flu vaccination?”, Dr. Margaret McCartney asks “why are we vaccinating so many people in whom we have no proof that it works?” Systematic reviews of influenza vaccine clinical trials have highlighted that few randomized controlled clinical studies with currently available vaccines have been conducted in adults, however estimates of vaccine efficacy in adults by these systematic reviews have differed (1-4). Some have included as negative studies those that were underpowered. Others have not included more recent trials that have been carried out for the purpose of licensure (5, 6).
In the article, McCartney conflates limited randomized clinical trial data with lack of data. It also assumes that valuable data can only come from clinical trials, which require considerable resources to conduct. With the current positive data on vaccine efficacy in younger individuals (1, 3, 7), many feel that a placebo-controlled trial in the elderly would be unethical. Well-designed, observational studies confirm influenza vaccine effectiveness in adults against influenza virus infection in the community as well as against more severe influenza disease (8, 9), however vaccine effectiveness depends on many factors including the population understudy, the degree of match between vaccine and circulating viruses, and the study endpoint chosen.
Fewer influenza vaccine clinical trials have been conducted in the elderly, and available data indicate that vaccine effectiveness is likely lower in this group than among healthy adults. More effective vaccines for elderly populations are clearly needed, and it is encouraging that research is ongoing (5). However, the high rates of influenza-associated hospitalizations and mortality in adults and elderly populations justifies the use of influenza vaccines (even if only moderately effective) to reduce this large burden of disease (10, 11).
References
1. Breteler JK, Tam JS, Jit M, Ket JC, De Boer MR. Efficacy and effectiveness of seasonal and pandemic A (H1N1) 2009 influenza vaccines in low and middle income countries: a systematic review and meta-analysis. Vaccine. 2013;31(45):5168-77.
2. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. The Cochrane database of systematic reviews. 2014;3:CD001269.
3. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. The Lancet Infectious diseases. 2012;12(1):36-44.
4. Darvishian M, Gefenaite G, Turner RM, Pechlivanoglou P, Van der Hoek W, Van den Heuvel ER, et al. After adjusting for bias in meta-analysis seasonal influenza vaccine remains effective in community-dwelling elderly. Journal of clinical epidemiology. 2014;67(7):734-44.
5. DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. The New England journal of medicine. 2014;371(7):635-45.
6. Jain VK, Rivera L, Zaman K, Espos RA, Jr., Sirivichayakul C, Quiambao BP, et al. Vaccine for prevention of mild and moderate-to-severe influenza in children. The New England journal of medicine. 2013;369(26):2481-91.
7. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. The Cochrane database of systematic reviews. 2012;8:CD004879.
8. McNeil S, Shinde V, Andrew M, Hatchette T, Leblanc J, Ambrose A, et al. Interim estimates of 2013/14 influenza clinical severity and vaccine effectiveness in the prevention of laboratory-confirmed influenza-related hospitalisation, Canada, February 2014. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2014;19(9).
9. Thompson MG, Sokolow LZ, Almendares O, Openo K, Farley MM, Meek J, et al. Effectiveness of nonadjuvanted monovalent influenza A(H1N1)pdm09 vaccines for preventing reverse transcription polymerase chain reaction-confirmed pandemic influenza hospitalizations: case-control study of children and adults at 10 US influenza surveillance network sites. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013;57(11):1587-92.
10. Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng P-Y, Steiner C, et al. Hospitalizations Associated With Influenza and Respiratory Syncytial Virus in the United States, 1993–2008. Clinical Infectious Diseases. 2012;54(10):1427-36.
11. Centers for Disease Control and Prevention. Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morbidity and mortality weekly report. 2010;59(33):1057-62.
Rapid Response:
In her article for BMJ titled “What use is mass flu vaccination?”, Dr. Margaret McCartney asks “why are we vaccinating so many people in whom we have no proof that it works?” Systematic reviews of influenza vaccine clinical trials have highlighted that few randomized controlled clinical studies with currently available vaccines have been conducted in adults, however estimates of vaccine efficacy in adults by these systematic reviews have differed (1-4). Some have included as negative studies those that were underpowered. Others have not included more recent trials that have been carried out for the purpose of licensure (5, 6).
In the article, McCartney conflates limited randomized clinical trial data with lack of data. It also assumes that valuable data can only come from clinical trials, which require considerable resources to conduct. With the current positive data on vaccine efficacy in younger individuals (1, 3, 7), many feel that a placebo-controlled trial in the elderly would be unethical. Well-designed, observational studies confirm influenza vaccine effectiveness in adults against influenza virus infection in the community as well as against more severe influenza disease (8, 9), however vaccine effectiveness depends on many factors including the population understudy, the degree of match between vaccine and circulating viruses, and the study endpoint chosen.
Fewer influenza vaccine clinical trials have been conducted in the elderly, and available data indicate that vaccine effectiveness is likely lower in this group than among healthy adults. More effective vaccines for elderly populations are clearly needed, and it is encouraging that research is ongoing (5). However, the high rates of influenza-associated hospitalizations and mortality in adults and elderly populations justifies the use of influenza vaccines (even if only moderately effective) to reduce this large burden of disease (10, 11).
References
1. Breteler JK, Tam JS, Jit M, Ket JC, De Boer MR. Efficacy and effectiveness of seasonal and pandemic A (H1N1) 2009 influenza vaccines in low and middle income countries: a systematic review and meta-analysis. Vaccine. 2013;31(45):5168-77.
2. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. The Cochrane database of systematic reviews. 2014;3:CD001269.
3. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. The Lancet Infectious diseases. 2012;12(1):36-44.
4. Darvishian M, Gefenaite G, Turner RM, Pechlivanoglou P, Van der Hoek W, Van den Heuvel ER, et al. After adjusting for bias in meta-analysis seasonal influenza vaccine remains effective in community-dwelling elderly. Journal of clinical epidemiology. 2014;67(7):734-44.
5. DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. The New England journal of medicine. 2014;371(7):635-45.
6. Jain VK, Rivera L, Zaman K, Espos RA, Jr., Sirivichayakul C, Quiambao BP, et al. Vaccine for prevention of mild and moderate-to-severe influenza in children. The New England journal of medicine. 2013;369(26):2481-91.
7. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. The Cochrane database of systematic reviews. 2012;8:CD004879.
8. McNeil S, Shinde V, Andrew M, Hatchette T, Leblanc J, Ambrose A, et al. Interim estimates of 2013/14 influenza clinical severity and vaccine effectiveness in the prevention of laboratory-confirmed influenza-related hospitalisation, Canada, February 2014. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2014;19(9).
9. Thompson MG, Sokolow LZ, Almendares O, Openo K, Farley MM, Meek J, et al. Effectiveness of nonadjuvanted monovalent influenza A(H1N1)pdm09 vaccines for preventing reverse transcription polymerase chain reaction-confirmed pandemic influenza hospitalizations: case-control study of children and adults at 10 US influenza surveillance network sites. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013;57(11):1587-92.
10. Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng P-Y, Steiner C, et al. Hospitalizations Associated With Influenza and Respiratory Syncytial Virus in the United States, 1993–2008. Clinical Infectious Diseases. 2012;54(10):1427-36.
11. Centers for Disease Control and Prevention. Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morbidity and mortality weekly report. 2010;59(33):1057-62.
Competing interests: No competing interests