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Letters |

Adverse Events and Quadrivalent Human Papillomavirus Recombinant Vaccine

Vicky Debold, PhD; Eric Hurwitz, PhD
JAMA. 2009;302(24):2657-2658. doi:10.1001/jama.2009.1880
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Published online

To the Editor: Dr Slade and colleagues1 evaluated reports submitted to the Vaccine Adverse Event Reporting System (VAERS) for quadrivalent human papillomavirus recombinant vaccine (qHPV). Federal officials have cited this study as evidence that qHPV “is a safe and effective vaccine.”2 However, we consider that conclusion to be unwarranted because the study draws inferences from data likely to be systematically biased, and because the design of the study cannot disprove causal associations at the individual level.

First, the significance of some adverse events, such as Guillain-Barré syndrome (GBS), was evaluated by computing proportional reporting ratios (PRRs) based on the number of acceptable reports and the number of qHPV doses distributed, which were then compared with background GBS rates for hospitalized persons of unknown vaccination status or to background GBS rates for VAERS reports submitted for different vaccines. Because GBS has been associated with both non-qHPV vaccines and natural infections,3 valid comparisons and proper interpretation of findings assumes knowledge of vaccine exposure histories.

In addition, because of systematic errors, the PRRs for adverse events following qHPV are likely to be much higher than calculated in the study by Slade et al. Underreporting of adverse events following vaccination is common,4 and as acknowledged by Slade et al, the reports that VAERS receives frequently are incomplete or inadequate to the point of not being analyzable. Poor report quality partly accounts for why only 8 of 42 reported GBS cases (19%) were included in the GBS PRR estimate. Moreover, using the total number of vaccine doses distributed (rather than administered) systematically inflates the ratio's denominator.

Second, even assuming that valid data would show no signal between receipt of qHPV and adverse events, epidemiologic studies of this type would not disprove a causal relationship between a specific individual's vaccination and an adverse health outcome.5 A vaccine regarded as safe at the population level is not necessarily safe for all individuals and subpopulations.

Federal policy makers are responsible for weighing a vaccine's benefits and harms at the general population level and determining whether it should be licensed and recommended. Physicians, on the other hand, are responsible for helping individual patients weigh the benefits and harms of each vaccine in light of the patient's unique circumstances. Despite reassurances to the contrary, this study's findings should not be interpreted as proof that qHPV's benefits outweigh its harms.

AUTHOR INFORMATION

Financial Disclosures: Dr Debold reported receiving honoraria from the US Food and Drug Administration, the Centers for Disease Control and Prevention, and the Department of Health and Human Services for work related to vaccine policy and serving without financial compensation as a director at the National Vaccine Information Center and SafeMinds. No other disclosures were reported.

REFERENCES

Slade BA, Leidel L, Vellozzi C,  et al.  Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine.  JAMA. 2009;302(7):750-757
PubMedCrossRef
 Gardasil vaccine safety: information from FDA and CDC on the safety of Gardasil vaccine. US Food and Drug Administration Web site. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm179549.htm. Accessed August 23, 2009
Legido A, Tenembaum SN, Katsetos CD, Menkes JH. Autoimmune and postinfectious diseases. In: Menkes JH, Sarnat HB, Maria BL, eds. Child Neurology. 7th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005:601
Rosenthal S, Chen B. The reporting sensitivities of two passive surveillance systems for vaccine adverse events.  Am J Public Health. 1995;85(12):1706-1709
PubMedCrossRef
Rothman KJ, Greenland S, Poole C, Lash TL. Causation and causal inference.  In: Rothman KJ, Greenland S, Poole C, Lash TL, eds. Modern Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:5-31

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Slade BA, Leidel L, Vellozzi C,  et al.  Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine.  JAMA. 2009;302(7):750-757
PubMedCrossRef
 Gardasil vaccine safety: information from FDA and CDC on the safety of Gardasil vaccine. US Food and Drug Administration Web site. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm179549.htm. Accessed August 23, 2009
Legido A, Tenembaum SN, Katsetos CD, Menkes JH. Autoimmune and postinfectious diseases. In: Menkes JH, Sarnat HB, Maria BL, eds. Child Neurology. 7th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005:601
Rosenthal S, Chen B. The reporting sensitivities of two passive surveillance systems for vaccine adverse events.  Am J Public Health. 1995;85(12):1706-1709
PubMedCrossRef
Rothman KJ, Greenland S, Poole C, Lash TL. Causation and causal inference.  In: Rothman KJ, Greenland S, Poole C, Lash TL, eds. Modern Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:5-31
December 23, 2009
John Iskander, MD, MPH; Claudia Vellozzi, MD, MPH; Barbara A. Slade, MD, MS
JAMA. 2009;302(24):2657-2658.
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