Correspondence
Comparative Efficacy of Influenza Vaccines
N Engl J Med 2010; 362:179-181January 14, 2010
- Article
To the Editor:
In their study comparing the efficacy of two vaccines against influenza types A and B, Monto et al. (Sept. 24 issue)1 report that the absolute efficacy against both types of influenza was 68% for the trivalent inactivated vaccine and 36% for the live attenuated vaccine. The term “absolute” is misleading, since the authors used it to mean the relative reduction in incidence in the vaccinated group, as compared with placebo. In the placebo group, the baseline risk, which was 9.5% for influenza A and 1.2% for influenza B, should have been reported in an accessible manner, along with the relative risks. Without this information, the absolute risk is not easily accessible, and the reader's perception of benefit or harm may be exaggerated.2 Since the trial included a diverse population in terms of age, sex, and ethnic background, results on heterogeneity of effect across these variables and the presence or absence of coexisting illnesses (e.g., diabetes and renal and cardiovascular disease) would be helpful to know. This is especially important because the cost-effectiveness of influenza vaccination for various subgroups remains uncertain.3 Full transparency of results is needed for informed health education and policy decisions.4,5
K.M. Venkat Narayan, M.D.
Carlos del Rio, M.D.
Emory University Rollins School of Public Health, Atlanta, GA
knaraya@emory.edu Dr. del Rio reports receiving research support from Merck and Sanofi Pasteur, lecture fees from Merck, and consulting fees from Bristol-Myers Squibb. No other potential conflict of interest relevant to this letter was reported.
5 References1
Monto AS ,Ohmit SE ,Petrie JG , et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med 2009;361:1260-1267
Full Text | Web of Science | Medline2
Schwartz LM ,Woloshin S ,Dvorin EL ,Welch HG . Ratio measures in leading medical journals: structured review of accessibility of underlying absolute risks. BMJ 2006;333:1248-1248
CrossRef | Web of Science | Medline3
Newall AT ,Kelly H ,Harsley S ,Scuffham PA . Cost effectiveness of influenza vaccination in older adults: a critical review of economic evaluations for the 50- to 64-year age group. Pharmacoeconomics 2009;27:439-450
CrossRef | Web of Science | Medline4
Zwarenstein M ,Treweek S ,Gagnier JJ , et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ 2008;337:a2390-a2390
CrossRef | Web of Science | Medline5
Fahey T ,Griffiths S ,Peters TJ . Evidence based purchasing: understanding results of clinical trials and systematic reviews. BMJ 1995;311:1056-1059
CrossRef | Web of Science | Medline
To the Editor:
In the article by Monto and colleagues, there is a disconnect between microbiologic efficacy and clinical effectiveness. What patients really want to know is, “Is this shot going to keep me from getting sick?” In the supplementary materials, the authors note that 1366 specimens were collected from 970 symptomatic participants (50% of the total). In turn, 119 participants (6% of the total and 12% of those with symptoms) had laboratory-confirmed influenza. Do the authors have data about the incidence of symptomatic illness in the vaccine and placebo groups? Do they have data showing whether the cases of laboratory-confirmed influenza were more severe than the unconfirmed, symptomatic illnesses?
Without more clinically relevant outcomes, we might be overselling vaccine effectiveness in avoiding illness. This microbiologic–clinical disconnect is one of several explanations for the oft-heard “I got the flu shot, but I got the flu anyway” from the patient who is reluctant to receive an influenza vaccine in subsequent years.
Jeffrey Linder, M.D., M.P.H.
Brigham and Women's Hospital, Boston, MA
jlinder@partners.org Dr. Linder reports receiving research funding from Roche. No other potential conflict of interest relevant to this letter was reported.
Author/Editor Response
We agree that the information requested by Narayan and del Rio is important, and all of it is found in various parts of our article. However, the correspondents are incorrect in describing our study population as diverse and then requesting stratified analyses on the basis of this diversity and the presence or absence of coexisting illnesses. Subjects who were eligible for our study were healthy men and women between the ages of 18 and 49 years, the only adult population for which the live attenuated vaccine is licensed and the only population without a vaccination recommendation.1 The makeup of this young, racially homogeneous population (78% of the subjects were 18 to 24 years of age, and 84% were white) reflects the fact that the study was carried out at four university campuses in Michigan.
Influenza surveillance was carried out from November through April. Illnesses that were characterized by at least one respiratory symptom and at least one systemic symptom during the period of surveillance-defined influenza activity were defined as symptomatic influenza-like illnesses. Of 1952 subjects, 600 (30.7%) had an symptomatic influenza-like illness during the study period, including 254 of 814 (31.2%) who received the live attenuated vaccine, 225 of 813 (27.7%) who received the inactivated vaccine, and 121 of 325 (37.2%) who received placebo. A subgroup of subjects with symptomatic influenza-like illness (119 of 600, 19.8%) had laboratory-confirmed influenza type A or B.
Significant absolute vaccine efficacy in reducing the risk of symptomatic influenza-like illness (whether laboratory-confirmed or not) was shown for the inactivated vaccine (26%; 95% confidence interval [CI], 11 to 38) but not for the live attenuated vaccine (16%; 95% CI, 0 to 30). Respiratory illness is common during the winter season, and even during periods of known influenza circulation, other viral agents are present.2 Since influenza vaccines can be expected to reduce the risk of illness caused only by influenza viruses, the examination of efficacy with the use of laboratory-confirmed outcomes is the only way to consistently evaluate these vaccines. We did not examine whether laboratory-confirmed cases were more severe than symptom-eligible but unconfirmed cases, but we3 and other investigators have examined this question previously.
Arnold Monto, M.D.
Suzanne E. Ohmit, Dr.P.H.
University of Michigan School of Public Health, Ann Arbor, MI
asmonto@umich.edu Since publication of their article, the authors report no further potential conflict of interest.
3 References1
Fiore AE, Shay DK, Broder K, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. Atlanta: Centers for Disease Control and Prevention. (Accessed December 21, 2009, at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm.)
2
Monto AS ,Sullivan KM . Acute respiratory illness in the community: frequency of illness and the agents involved. Epidemiol Infect 1993;110:145-160
CrossRef | Web of Science | Medline3
Ohmit SE ,Monto AS . Symptomatic predictors of influenza virus positivity in children during the influenza season. Clin Infect Dis 2006;43:564-568
CrossRef | Web of Science | Medline
