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Session IV. Ethical, liability and regulatory issues
Vaccine 21 (2003) 3501–3502
Commentary
Session IV. Ethical, liability and regulatory issues W. Paul Glezen∗ Molecular Virology, Microbiology and Pediatric Influenza Research Center, Baylor College of Medicine, One Baylor Plaza Suite 221 D, Houston, TX 77030, USA
Neonatal tetanus has, in the past, been responsible for a quarter of neonatal deaths in developing countries. Immunization of pregnant women with tetanus toxoid is an important component of the worldwide program to eliminate neonatal and puerperal tetanus [1]. This practice has been free of any serious reactions or complications and is accepted in most cultures [2]. Other life-threatening events of the perinatal period such as sepsis with group B streptococcus (GBS) or pneumococci could be prevented by maternal immunization [3]. Despite the experience with tetanus toxoid and extensive use of other inactivated vaccines during pregnancy, a sense of uneasiness pervades discussion of expanding this practice. This is evident from the poor uptake of influenza vaccine for pregnant women in the US. Few events are more tragic than the fulminating pneumonia death of a previously healthy woman near parturition caused by a preventable influenza virus infection [4]. Fortunately, such deaths are rare, but hospitalization of pregnant women near term with pneumonia is not rare and occurs at the same rate as that for women the same age with chronic underlying conditions [5]. The only way to prevent serious morbidity in pregnant women is to administer the vaccine in the second or third trimester of pregnancy, because the vaccine formula is updated each year and the newly formulated vaccine is not available until September before the influenza season. This means that the women at risk will already be pregnant by the time that the relevant vaccine is available. One of the reasons for poor uptake of influenza vaccine may be the failure of the manufacturer to sufficiently document the safety and efficacy in this population to allow extension of the indication for pregnancy. The attitude of the manufacturers seems counter to the 17 January 2001 amendment to 45 CFR 46 that encourages clinical research in pregnant women by promoting a policy of presumed inclusion (not automatic exclusion because of a vulnerable state—the previous assumption), and by ∗
Tel.: +1-713-798-4469; fax: +1-713-798-6802. E-mail address: [email protected] (W.P. Glezen).
permitting the pregnant woman to be the sole decision maker with regard to her participation in research. Compliance with this regulation, at least in spirit, would require that sufficient data be submitted to the FDA to allow for extension of the indications printed in the package insert to match the current recommendations for use during pregnancy. The safety record of influenza vaccine merits this extension. Preparation for the next influenza pandemic dictates inclusion of this indication to prevent the high mortality in pregnant women of a completely na¨ıve population. Current regulatory action is guided by the “precautionary principle” [6]. An example of the precautionary principle in action is the elimination of thimerosal from vaccines supplied in multiple dose vials. This action has significantly increased the cost of vaccines that now must be packaged as single dose preparations. The potential benefits of proposed vaccines far outweigh the risks that have been magnified by these restrictions [7]. Imposition of the precautionary principle gone awry is one of the major factors threatening the vaccine supply and smothering vaccine development. Litigation is another factor threatening the supply of licensed vaccines and the development of new vaccines. In the US, the safety of vaccines is highly regulated, and monitoring is effective in detecting rare adverse events when they do occur. In the present climate, the exposure to litigation is great for vaccine programs, in general, and for any perinatal event—even in the absence of real injury. Therefore, it must be acknowledged that giving vaccines to pregnant women will expose the system to litigation. With the slim profit margin attained by vaccine production, it is unlikely that manufacturers will be willing to produce vaccines for administration to pregnant women even if they are proven to be safe. Therefore, the only possibility for progress will be the extension of programs like the US Vaccine Injury Compensation Program to cover vaccines recommended for delivery to pregnant women [8]. This system stabilized the supply of routine childhood vaccines when it was enacted in 1986. The model must be amplified to include all vaccines for persons of all ages.
0264-410X/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0264-410X(03)00398-0
3502
W.P. Glezen / Vaccine 21 (2003) 3501–3502
Limited opportunities are available for delivery of preventive services to patients—particularly adults. Prenatal care visits represent such an opportunity that should not be missed. The health care system is under pressure to reduce costs. Vaccines have proven cost effectiveness and, in some circumstances, are cost saving. Used responsibly, maternal immunization is a safe procedure that should become a routine part of health care. References [1] Glezen WP. Editorial: prevention of neonatal tetanus. Am J Public Health 1998;88:871–2.
[2] Heinonen OP, Slone D, Shapiro S. Immunizing agents. Birth defects and drugs in pregnancy. Littleton (MA): Publishing Sciences Group, Inc.; p. 314–21. [3] Glezen WP. Maternal vaccines. Primary Care: Clin Office Pract 2001;28:791–806. [4] Shahab SZ, Glezen WP. Influenza virus. In: Gonik B, editor. Viral diseases in pregnancy. New York: Springer-Verlag; 1994. p. 215–23. [5] Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094–102. [6] Miller HI, Conko G. Precaution (of a sort) without principle. Priorities for Health 2001;13:5–39. [7] Michaud CM, Murray CJL, Bloom BR. Burden of disease— implications for future research. JAMA 2001;285:535–9. [8] Duranson E. Protection of newborns through maternal immunization. Session IV. Ethical, liability and regulatory, this issue.
Commentary
Session IV. Ethical, liability and regulatory issues W. Paul Glezen∗ Molecular Virology, Microbiology and Pediatric Influenza Research Center, Baylor College of Medicine, One Baylor Plaza Suite 221 D, Houston, TX 77030, USA
Neonatal tetanus has, in the past, been responsible for a quarter of neonatal deaths in developing countries. Immunization of pregnant women with tetanus toxoid is an important component of the worldwide program to eliminate neonatal and puerperal tetanus [1]. This practice has been free of any serious reactions or complications and is accepted in most cultures [2]. Other life-threatening events of the perinatal period such as sepsis with group B streptococcus (GBS) or pneumococci could be prevented by maternal immunization [3]. Despite the experience with tetanus toxoid and extensive use of other inactivated vaccines during pregnancy, a sense of uneasiness pervades discussion of expanding this practice. This is evident from the poor uptake of influenza vaccine for pregnant women in the US. Few events are more tragic than the fulminating pneumonia death of a previously healthy woman near parturition caused by a preventable influenza virus infection [4]. Fortunately, such deaths are rare, but hospitalization of pregnant women near term with pneumonia is not rare and occurs at the same rate as that for women the same age with chronic underlying conditions [5]. The only way to prevent serious morbidity in pregnant women is to administer the vaccine in the second or third trimester of pregnancy, because the vaccine formula is updated each year and the newly formulated vaccine is not available until September before the influenza season. This means that the women at risk will already be pregnant by the time that the relevant vaccine is available. One of the reasons for poor uptake of influenza vaccine may be the failure of the manufacturer to sufficiently document the safety and efficacy in this population to allow extension of the indication for pregnancy. The attitude of the manufacturers seems counter to the 17 January 2001 amendment to 45 CFR 46 that encourages clinical research in pregnant women by promoting a policy of presumed inclusion (not automatic exclusion because of a vulnerable state—the previous assumption), and by ∗
Tel.: +1-713-798-4469; fax: +1-713-798-6802. E-mail address: [email protected] (W.P. Glezen).
permitting the pregnant woman to be the sole decision maker with regard to her participation in research. Compliance with this regulation, at least in spirit, would require that sufficient data be submitted to the FDA to allow for extension of the indications printed in the package insert to match the current recommendations for use during pregnancy. The safety record of influenza vaccine merits this extension. Preparation for the next influenza pandemic dictates inclusion of this indication to prevent the high mortality in pregnant women of a completely na¨ıve population. Current regulatory action is guided by the “precautionary principle” [6]. An example of the precautionary principle in action is the elimination of thimerosal from vaccines supplied in multiple dose vials. This action has significantly increased the cost of vaccines that now must be packaged as single dose preparations. The potential benefits of proposed vaccines far outweigh the risks that have been magnified by these restrictions [7]. Imposition of the precautionary principle gone awry is one of the major factors threatening the vaccine supply and smothering vaccine development. Litigation is another factor threatening the supply of licensed vaccines and the development of new vaccines. In the US, the safety of vaccines is highly regulated, and monitoring is effective in detecting rare adverse events when they do occur. In the present climate, the exposure to litigation is great for vaccine programs, in general, and for any perinatal event—even in the absence of real injury. Therefore, it must be acknowledged that giving vaccines to pregnant women will expose the system to litigation. With the slim profit margin attained by vaccine production, it is unlikely that manufacturers will be willing to produce vaccines for administration to pregnant women even if they are proven to be safe. Therefore, the only possibility for progress will be the extension of programs like the US Vaccine Injury Compensation Program to cover vaccines recommended for delivery to pregnant women [8]. This system stabilized the supply of routine childhood vaccines when it was enacted in 1986. The model must be amplified to include all vaccines for persons of all ages.
0264-410X/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0264-410X(03)00398-0
3502
W.P. Glezen / Vaccine 21 (2003) 3501–3502
Limited opportunities are available for delivery of preventive services to patients—particularly adults. Prenatal care visits represent such an opportunity that should not be missed. The health care system is under pressure to reduce costs. Vaccines have proven cost effectiveness and, in some circumstances, are cost saving. Used responsibly, maternal immunization is a safe procedure that should become a routine part of health care. References [1] Glezen WP. Editorial: prevention of neonatal tetanus. Am J Public Health 1998;88:871–2.
[2] Heinonen OP, Slone D, Shapiro S. Immunizing agents. Birth defects and drugs in pregnancy. Littleton (MA): Publishing Sciences Group, Inc.; p. 314–21. [3] Glezen WP. Maternal vaccines. Primary Care: Clin Office Pract 2001;28:791–806. [4] Shahab SZ, Glezen WP. Influenza virus. In: Gonik B, editor. Viral diseases in pregnancy. New York: Springer-Verlag; 1994. p. 215–23. [5] Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094–102. [6] Miller HI, Conko G. Precaution (of a sort) without principle. Priorities for Health 2001;13:5–39. [7] Michaud CM, Murray CJL, Bloom BR. Burden of disease— implications for future research. JAMA 2001;285:535–9. [8] Duranson E. Protection of newborns through maternal immunization. Session IV. Ethical, liability and regulatory, this issue.