Elsevier

Vaccine

Volume 26, Issue 20, 12 May 2008, Pages 2466-2470
Vaccine

Impact of different case definitions for acute otitis media on the efficacy estimates of a pneumococcal conjugate vaccine

https://doi.org/10.1016/j.vaccine.2008.03.013Get rights and content

Abstract

Considerably higher vaccine efficacy estimate for clinical acute otitis media (AOM) has been obtained for the 11-valent pneumococcal conjugate vaccine with protein D of Haemophilus influenzae as a carrier (PncPD11) in the POET study than for the 7-valent pneumococcal conjugate vaccine (PncCRM7) in the Finnish Otitis Media (FinOM) Vaccine Trial. We recalculated PncCRM7 efficacy from the FinOM data using a case definition for AOM very close to the POET definition and a definition giving an incidence for AOM in the control group comparable to that obtained in the POET study. The different case definitions had only a slight impact on the vaccine efficacy estimates compared to the original case definitions. We were not able to show that the differences between the study results would be due to the case definitions used.

Introduction

Acute otitis media (AOM) is the most common cause of children's office visits in developed countries and also the most common indication for antibiotic prescription and surgical intervention [1], [2]. Streptococcus pneumoniae, or pneumococcus (Pnc) is the most frequent cause of AOM being responsible for up to a third of cases [3], [4].

Prevention of otitis media would be of great importance in reducing the morbidity, suffering, antibiotic consumption and costs of treatment. The advent of pneumococcal conjugate vaccines has shown promise in these regards. They have proven efficacious against invasive disease and pneumonia caused by pneumococcal serotypes covered by the vaccine [5]. In the Finnish Otitis Media (FinOM) Vaccine Trial [6], the protective vaccine efficacy (VE) of the 7-valent pneumococcal conjugate vaccine (PncCRM7, Prevenar by Wyeth) against culture confirmed pneumococcal AOM caused by vaccine serotypes was 57%. On the other hand, the VE was only 6% against all clinical AOM episodes. In the Northern California Kaiser Permanente (NCKP) study [5] the efficacy of the PncCRM vaccine against clinical AOM episodes was 7%. After introduction of the vaccine in the national program, otitis media office visits may have decreased as much as 20% [7].

Recently efficacy results of a novel 11-valent pneumococcal conjugate vaccine with protein D of Haemophilus influenzae as a carrier (PncPD11, GlaxoSmithKline Biologicals) against AOM were reported from the POET study [8]; the VE estimates were considerably higher (34% with 95% CI 21–44) against clinical AOM compared to those of the currently available 7-valent pneumococcal conjugate vaccine. On the contrary, the VE estimates of the two vaccines against AOM caused by the pneumococcal vaccine serotypes were similar (57% for both vaccines), but the 11-PncPD also reduced AOM due to non-typable Haemophilus influenzae (NTHi) by 35% (95% CI 2–57) while PncCRM7 did not, VE estimate being −11 (95% CI −34 to 8). It is noteworthy that the observed incidence of AOM episodes in the control group of the POET study (0.13 episodes/person year) was only about one-tenth of the incidence rates seen in children less than 2 years of age in the FinOM (1.24 episodes/person year [6]) and NCKP (1.72 episodes/person year [9]) control groups.

In addition to varying epidemiological circumstances and the vaccine effect per se, differences in the study methodology could account for the observed differences in the efficacy of the two vaccines. We therefore further analyzed the data of the FinOM Vaccine Trial to see whether vaccine efficacy would depend on the case definition used. Our specific aim was to make the results comparable to the POET study by applying the definition used in that study.

Section snippets

Subjects

Two thousand four hundred and ninety-seven subjects were enrolled in the FinOM Vaccine Trial at the age of 2 months [6], [10] conducted by the National Public Health Institute, Finland (KTL) in Tampere region in southern Finland from December 1995 to March 1999. The FinOM Vaccine Trial was a randomized, controlled double-blind efficacy study. The primary objective was to assess the efficacy of each of two 7-valent pneumococcal conjugate vaccines (PncCRM7 and PncOMPC7) against AOM caused by the

Results

Of the 1662 children randomized to the PncCRM and control arms, 1632 entered the PP follow-up period starting 2 weeks after the third vaccination at 6 months of age and altogether 1580 (95%) completed the follow-up at 24 months of age according to the protocol.

The children in the treatment groups were similar in regard to demographic characteristics and risk factors for AOM (for details, see [6]).

No major differences were seen between the vaccine efficacy estimates obtained using different case

Discussion

The PncCRM vaccine efficacy against AOM was not significantly affected by the case definition used. The PncCRM vaccine efficacy estimates against clinical AOM remained well below the estimates presented for 11-PnPD when we used the POET study case definition for AOM or a case definition giving similar incidence for AOM in the control arm as in the POET study. Thus, our results do not support the conclusion that the difference in the efficacy estimates would be solely explained by the case

Acknowledgements

The FinOM Studies were supported by Aventis Pasteur, Merck & Co. Inc., and Wyeth.

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