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Vaccine Side Effects: Separating Mirage From Reality
Vaccine Side Effects: Separating Mirage From Reality John D. Grabenstein
Question: My patients are asking me about vaccine side effects they heard about on television or in the newspaper. What should I tell them? Answer: Vaccines recently have been the focus of unusually pointed criticism. It is easy to accuse a medication of causing harm. But a methodical review of available data shows that current vaccine recommendations are appropriate. Indeed, abstaining from vaccination is a more risky course of action. Modem vaccines are extraordinarily safe and reliable, offering some of the best
value of our pharmacopeia. Vaccines recently have been accused of causing multiple sclerosis, inflammatory bowel syndrome, autism, diabetes, and other serious conditions. While critics can paint compelling stories of how someone's life went bad shortly after a vaccination, objective analyses rarely show any elevated risk of harm resulting from vaccination. When tens of millions of people get vaccinated, random bad events will often be temporally associated with vaccination, by chance alone. Vac-
cination are memorable even and are ea ily blamed when trying to explain inexplicable illne e. 1-4 Then how do we eparate mirage from reality? How do we know if we are ob erving a coincidence or if a vaccine i cau ing harm? The an wer i found by measuring whether the ri k in the vaccinated group ignificantly greater than that among the unvaccinated group. Special team of epidemiologist at the Center for Di ease Control and Prevention (CDC) and at the Food and Drug Administration (FDA) meet weekly to monitor vaccine safety. Each question of vaccine-induced harm i rigorously investigated. They consider patterns in reports to the Vaccine Adverse Event Reporting System (VAERS), as well as conducting proactive studies. For example, CDC sponsors the Large Linked Database project with the assistance of several large managed care plans on the
We t a t. 12.4 Pe pI ha e bj ted to accinati n ince th day f Jenner' mallp x accine ver 200 year ago. 1,4-6 It i unreali tic to expect unanirnou approval of the nation ' vaccine policie . But pharmaci ts have a profe ional duty to advi e people on the be t u e of medication . Vaccine are ju t another kind of medication. Table 1 provide orne reaoned re pon es to general question about vaccine afety that the public may have. 1,2,4 Table 2 Ii ts telephone and Internet re ources about vaccine safety. In dealing with criticism of any medication, it is wise to a k some fundamental questions. 7 For example, does the source of the critici m take respon ibility for the information it relays? Doe the information stand up to critical appraisal? Does the information come from credible, referenced sources? Are the author of the tudie named?
Table 1. Inquiries about Vaccine Safety and Pharmacists' Potential Responses Inquiry
Response
"Getting vaccinated worries me."
"l'm glad you're asking questions about using medicines. Let's talk about how vaccine safety is monitored."
"I've heard about dangerous side effects from vaccines. How can the government allow these vaccines to be used?"
"I checked into how the CDC and FDA watch for vaccine side effects. They use several different monitoring programs and work with manufacturers to ensure production quality. Also, these vaccines have been used for many years with great success and with a solid track record."
"Isn't it terrible that vaccines harm people?"
"No drug is perfect. Every drug has side effects. The key question is whether this vaccine's side effects are outweighed by the dangers of the infection. Your risk of a bad event after vaccination is far less than your risk if you stay vulnerable to this infection." Or: "The inconvenience of vaccination is more than balanced by the benefit of staying healthy, rather than being hospitalized with the infection."
"Who decides which vaccines to use?"
liThe nation's experts at the CDC, the national societies of physicians, and authorities at major universities agree that this vaccine is worthwhile in cases like yours. The CDC wrote this Vaccine Information Statement (VIS) about this vaccine. Would you like me to explain what any of this means or help you find more information?"
" WOUld you take this vaccine? Would you let one of your kids get it?"
"I got this vaccine a few years ago, and my kids will get it when they reach the right age."
Vol. 39, No.3 May/June 1999
Journal of the American Phannaceutical Association
417
VACCINE UPDATE
Table 2. Resources for Vaccine Safety Information www.cdc.gov
Centers for Disease Control and Prevention Vaccine Information Hotlines
800- CDC- SHOT, 800-232-2522
Fax Information Service
888- CDC-FAXX
Vaccine Safety: What You Need to Know
www.cdc.gov/nip/vacsafe
Six Common Misconceptions About Vaccination and How to Respond to Them
www.cdc.gov/nip/publications/6mishome.htm www.immunize.org
Immunization Action Coalition
www.immunize.org/stories/unprot.htm
Stories of Victims of Vaccine-Preventable Diseases
Infectious Disease Society of America Vaccine Initiative
www.idsociety.org/vaccine/index.html
Institute for Vaccine Safety at Johns Hopkins School of Public Health
www.vaccinesafety.edu
Canadian Immunization Guide, 5th ed. Health Canada; 1998.
www.hc-sc.gc.ca/hpb/lcdc/publicat!immguide/index.html
Update: Vaccine-Preventable Diseases
www.hc-sc.gc.ca/hpb/lcdc/publicat!vacprev/index.html
Comparison of Effects of Diseases and Vaccines
www.hc-sc.gc.ca/hpb/lcdc/publicat/immguide/comp_e.html
Table 3. False Allegations About Vaccine Side Effects and Rejoinders Allegation
Rebuttal and Conclusion
Hepatitis B vaccine causes multiple sclerosis.
Rebuttal: No objective evidence supports this claim. Accusation based on anecdotes. World Health Organization and National Multiple Sclerosis Society agree that there is no evidence of a link.
Hepatitis B vaccine causes newborn deaths.
Rebuttal: Critics analyzed VAERS reports incorrectly, failing to note that the VAERS database can contain multiple reports of the same adverse event. Also failed to acknowledge that the current level of newborn deaths is comparable to level before this vaccine was used in infants.
Hepatitis B vaccine is not needed by children not at risk.
Rebuttal: All children are vaccinated against polio and other preventable infections, although only a fraction of children are likely to be infected. We cannot predict who will be infected with hepatitis B virus during their lifetime, so universal vaccination is prudent for all children. Conclusion: Hepatitis B vaccine is 95% effective at preventing infection. Vaccination prevents liver disease and hepatocellular cancer.
Whole-cell pertussis vaccine causes brain damage.
Rebuttal: Independent panels found that brain damage after whole-cell pertussis vaccine is either nonexistent or so rare that it is hard to distinguish from the background rate of neurologic problems that have always affected certain children. Conclusion: Pertussis vaccine prevents a dangerous respiratory infection of children.
Measles and measles-mumps-rubella vaccines cause inflammatory bowel disease and autism.
Rebuttal: Studies claiming associations are flawed by selection bias and biological inconsistencies. Conclusion: Vaccination against measles, mumps, and rubella prevents three dangerous infections.
Vaccination early in life predisposes children to diabetes.
Rebuttal: Claim based on simplistic "ecological" comparison of one country to another, without adjusting for multiple alternative explanations. Conclusion: Childhood immunization has added many years to a person's life expectancy. Vaccination is beneficial both to individuals and to communities.
VAERS = Vaccine Adverse Event Reporting System.
418
Journal of the American Pharmaceutical Association
May/June 1999
Vol. 39, No.3
VACCINE UPDATE
Bave the limitation of the tuclie been acknowledged? Could it be that detail are cited out of context? Are conspiracy theories claimed, especially claims that the truth is being suppressed? What are the motives of the information source? An old adage suggests that "if it's too good to be true, it probably isn't." The opposite often holds as well: If it seems so bad you wonder how we tolerate the problem, it probably isn't a real problem. Some of the specific recent complaints about vaccine safety appear in Table 3, matched with brief answers to explain the considered opinions of the nation's vaccine experts. 1- 3,5,6,8,9 I have never met a vaccine expert who did not readily seek vaccination, personally or for his or her family. Teasing questions like "Are
vaccine for your children afe? Tune in at eleven ... " attract an audience. But hallow new torie do a di ervice to the public. The journalistic tradition of balancing pro and con viewpoints may not be the best way to present opposing views that have differing degrees of factual ba i . The public needs help in separating the wheat from the chaff. They need help discerning when an allegation is premature, incorrect, or blown out of proportion. 3 Understanding the facts about vaccine safety is the first step in explaining how benefits outweigh risks. Lt. Col. John D. Grabenstein, MS Pharm, EdM, FASHP, is pharmacoepidemiologist, Army Medical Department, University.of North Carolina, Chapel Hill.
u.s.
References 1. Chen RT, DeStefano F. Vaccine adverse events: Causal or coincidental? Lancet. 1998;351:611-3. 2.
Ball LK, Evans G, Bostrom A. Risky business: challenges in vaccine risk communication. Pediatrics. 1998;101:453-8.
3.
Chen RT, DeStefano F. Vaccine safety [letter]. Lancet. 1998;352:63-4.
4.
Grabenstein JD, Wilson JP. Are vaccines safe? Risk com munication applied to vaccines. Hosp Pharm. In press.
5.
Gangarosa EJ, Galazka AM, Wolfe CR, et al. Impact of antivaccine movements on pertussis control: the untold story. Lancet. 1998;351:356-61.
6.
Nicoll A, Elliman 0, Ross E. MMR vaccination and autism 1998: Deja vu-pertussis and brain damage 1974 [editorial]? BMJ. 1998;316:715-6.
7.
Pless R. Do vaccines cause chronic illness?: assessing and responding to uncon firmed allegations. Update: Vaccine Prev Dis. 1998;6. Available at: http//www.hcsc.gc.ca/hpb/lcdc/publicat/vac p rev/voI6 - 2/i n d ex. htm I. Accessed March 30, 1999.
8. Jefferson T. Vaccination and its adverse effects: real or perceived [editorial]. BMJ. 1998;317:159-60.
9. Metcalf J. Is measles infection associated with Crohn's disease? The current evidence does not prove a causal link [editorial]. BMJ. 1998;316:166.
Send your immunization questions to Lt. Col. John D. Grabenstein, EdM, MS, FASHP, U.S. Army Medical Department, c/o University of North Carolina, Chapel Hill, NC 275997360; grabenstein @unc.edu. The assertions contained herein are the private views of the author. They should not be construed as official or reflecting the views of the U.S. Department of Defense or the Department of the Army.
FR OM THE LITERA TURE
Panel Counters Reports of a Vaccine-Diabetes Link Proceedings from a March 1998 meeting of the Diabetes Workshop Panel of the Institute for Vaccine Safety trongly contradict mass-media reports that immunizations increase the risk of acquiring diabetes. The panel concluded: • Genetic and environmental factors contribute to diabetes risk. • Selective infections are protective against type 1 diabetes in predisposed animal . • Other infections may increase the risk of diabetes mellitus in animals and human . • While selective vaccines are protective against type 1 diabetes mellitu in animal data in human are inconclusive. • No vaccines increase the risk of type 1 diabetes mellitus in humans. Source: Institute for Vaccine Safety Diabetes Workshop Panel. Childhood immunizations and type 1 diabetes: summary of an Institute for Vaccine Safety Workshop. Pediatr Infect Dis J. 1999;18:217- 22. Reprints: N. A. Halsey, Inst. for Vaccine Safety, Johns Hopkins School of Public Health, 615 N. Wolfe St., #5515, Baltimore, MD 21205; info@ vaccinesafety.edu.
L. Michael Posey, pharmacy editor, Journal of the American Pharmaceutical As ociation.
VOl. 39, No.3
May/June 1999
Journal of the American Phannaceutical Association
419
Question: My patients are asking me about vaccine side effects they heard about on television or in the newspaper. What should I tell them? Answer: Vaccines recently have been the focus of unusually pointed criticism. It is easy to accuse a medication of causing harm. But a methodical review of available data shows that current vaccine recommendations are appropriate. Indeed, abstaining from vaccination is a more risky course of action. Modem vaccines are extraordinarily safe and reliable, offering some of the best
value of our pharmacopeia. Vaccines recently have been accused of causing multiple sclerosis, inflammatory bowel syndrome, autism, diabetes, and other serious conditions. While critics can paint compelling stories of how someone's life went bad shortly after a vaccination, objective analyses rarely show any elevated risk of harm resulting from vaccination. When tens of millions of people get vaccinated, random bad events will often be temporally associated with vaccination, by chance alone. Vac-
cination are memorable even and are ea ily blamed when trying to explain inexplicable illne e. 1-4 Then how do we eparate mirage from reality? How do we know if we are ob erving a coincidence or if a vaccine i cau ing harm? The an wer i found by measuring whether the ri k in the vaccinated group ignificantly greater than that among the unvaccinated group. Special team of epidemiologist at the Center for Di ease Control and Prevention (CDC) and at the Food and Drug Administration (FDA) meet weekly to monitor vaccine safety. Each question of vaccine-induced harm i rigorously investigated. They consider patterns in reports to the Vaccine Adverse Event Reporting System (VAERS), as well as conducting proactive studies. For example, CDC sponsors the Large Linked Database project with the assistance of several large managed care plans on the
We t a t. 12.4 Pe pI ha e bj ted to accinati n ince th day f Jenner' mallp x accine ver 200 year ago. 1,4-6 It i unreali tic to expect unanirnou approval of the nation ' vaccine policie . But pharmaci ts have a profe ional duty to advi e people on the be t u e of medication . Vaccine are ju t another kind of medication. Table 1 provide orne reaoned re pon es to general question about vaccine afety that the public may have. 1,2,4 Table 2 Ii ts telephone and Internet re ources about vaccine safety. In dealing with criticism of any medication, it is wise to a k some fundamental questions. 7 For example, does the source of the critici m take respon ibility for the information it relays? Doe the information stand up to critical appraisal? Does the information come from credible, referenced sources? Are the author of the tudie named?
Table 1. Inquiries about Vaccine Safety and Pharmacists' Potential Responses Inquiry
Response
"Getting vaccinated worries me."
"l'm glad you're asking questions about using medicines. Let's talk about how vaccine safety is monitored."
"I've heard about dangerous side effects from vaccines. How can the government allow these vaccines to be used?"
"I checked into how the CDC and FDA watch for vaccine side effects. They use several different monitoring programs and work with manufacturers to ensure production quality. Also, these vaccines have been used for many years with great success and with a solid track record."
"Isn't it terrible that vaccines harm people?"
"No drug is perfect. Every drug has side effects. The key question is whether this vaccine's side effects are outweighed by the dangers of the infection. Your risk of a bad event after vaccination is far less than your risk if you stay vulnerable to this infection." Or: "The inconvenience of vaccination is more than balanced by the benefit of staying healthy, rather than being hospitalized with the infection."
"Who decides which vaccines to use?"
liThe nation's experts at the CDC, the national societies of physicians, and authorities at major universities agree that this vaccine is worthwhile in cases like yours. The CDC wrote this Vaccine Information Statement (VIS) about this vaccine. Would you like me to explain what any of this means or help you find more information?"
" WOUld you take this vaccine? Would you let one of your kids get it?"
"I got this vaccine a few years ago, and my kids will get it when they reach the right age."
Vol. 39, No.3 May/June 1999
Journal of the American Phannaceutical Association
417
VACCINE UPDATE
Table 2. Resources for Vaccine Safety Information www.cdc.gov
Centers for Disease Control and Prevention Vaccine Information Hotlines
800- CDC- SHOT, 800-232-2522
Fax Information Service
888- CDC-FAXX
Vaccine Safety: What You Need to Know
www.cdc.gov/nip/vacsafe
Six Common Misconceptions About Vaccination and How to Respond to Them
www.cdc.gov/nip/publications/6mishome.htm www.immunize.org
Immunization Action Coalition
www.immunize.org/stories/unprot.htm
Stories of Victims of Vaccine-Preventable Diseases
Infectious Disease Society of America Vaccine Initiative
www.idsociety.org/vaccine/index.html
Institute for Vaccine Safety at Johns Hopkins School of Public Health
www.vaccinesafety.edu
Canadian Immunization Guide, 5th ed. Health Canada; 1998.
www.hc-sc.gc.ca/hpb/lcdc/publicat!immguide/index.html
Update: Vaccine-Preventable Diseases
www.hc-sc.gc.ca/hpb/lcdc/publicat!vacprev/index.html
Comparison of Effects of Diseases and Vaccines
www.hc-sc.gc.ca/hpb/lcdc/publicat/immguide/comp_e.html
Table 3. False Allegations About Vaccine Side Effects and Rejoinders Allegation
Rebuttal and Conclusion
Hepatitis B vaccine causes multiple sclerosis.
Rebuttal: No objective evidence supports this claim. Accusation based on anecdotes. World Health Organization and National Multiple Sclerosis Society agree that there is no evidence of a link.
Hepatitis B vaccine causes newborn deaths.
Rebuttal: Critics analyzed VAERS reports incorrectly, failing to note that the VAERS database can contain multiple reports of the same adverse event. Also failed to acknowledge that the current level of newborn deaths is comparable to level before this vaccine was used in infants.
Hepatitis B vaccine is not needed by children not at risk.
Rebuttal: All children are vaccinated against polio and other preventable infections, although only a fraction of children are likely to be infected. We cannot predict who will be infected with hepatitis B virus during their lifetime, so universal vaccination is prudent for all children. Conclusion: Hepatitis B vaccine is 95% effective at preventing infection. Vaccination prevents liver disease and hepatocellular cancer.
Whole-cell pertussis vaccine causes brain damage.
Rebuttal: Independent panels found that brain damage after whole-cell pertussis vaccine is either nonexistent or so rare that it is hard to distinguish from the background rate of neurologic problems that have always affected certain children. Conclusion: Pertussis vaccine prevents a dangerous respiratory infection of children.
Measles and measles-mumps-rubella vaccines cause inflammatory bowel disease and autism.
Rebuttal: Studies claiming associations are flawed by selection bias and biological inconsistencies. Conclusion: Vaccination against measles, mumps, and rubella prevents three dangerous infections.
Vaccination early in life predisposes children to diabetes.
Rebuttal: Claim based on simplistic "ecological" comparison of one country to another, without adjusting for multiple alternative explanations. Conclusion: Childhood immunization has added many years to a person's life expectancy. Vaccination is beneficial both to individuals and to communities.
VAERS = Vaccine Adverse Event Reporting System.
418
Journal of the American Pharmaceutical Association
May/June 1999
Vol. 39, No.3
VACCINE UPDATE
Bave the limitation of the tuclie been acknowledged? Could it be that detail are cited out of context? Are conspiracy theories claimed, especially claims that the truth is being suppressed? What are the motives of the information source? An old adage suggests that "if it's too good to be true, it probably isn't." The opposite often holds as well: If it seems so bad you wonder how we tolerate the problem, it probably isn't a real problem. Some of the specific recent complaints about vaccine safety appear in Table 3, matched with brief answers to explain the considered opinions of the nation's vaccine experts. 1- 3,5,6,8,9 I have never met a vaccine expert who did not readily seek vaccination, personally or for his or her family. Teasing questions like "Are
vaccine for your children afe? Tune in at eleven ... " attract an audience. But hallow new torie do a di ervice to the public. The journalistic tradition of balancing pro and con viewpoints may not be the best way to present opposing views that have differing degrees of factual ba i . The public needs help in separating the wheat from the chaff. They need help discerning when an allegation is premature, incorrect, or blown out of proportion. 3 Understanding the facts about vaccine safety is the first step in explaining how benefits outweigh risks. Lt. Col. John D. Grabenstein, MS Pharm, EdM, FASHP, is pharmacoepidemiologist, Army Medical Department, University.of North Carolina, Chapel Hill.
u.s.
References 1. Chen RT, DeStefano F. Vaccine adverse events: Causal or coincidental? Lancet. 1998;351:611-3. 2.
Ball LK, Evans G, Bostrom A. Risky business: challenges in vaccine risk communication. Pediatrics. 1998;101:453-8.
3.
Chen RT, DeStefano F. Vaccine safety [letter]. Lancet. 1998;352:63-4.
4.
Grabenstein JD, Wilson JP. Are vaccines safe? Risk com munication applied to vaccines. Hosp Pharm. In press.
5.
Gangarosa EJ, Galazka AM, Wolfe CR, et al. Impact of antivaccine movements on pertussis control: the untold story. Lancet. 1998;351:356-61.
6.
Nicoll A, Elliman 0, Ross E. MMR vaccination and autism 1998: Deja vu-pertussis and brain damage 1974 [editorial]? BMJ. 1998;316:715-6.
7.
Pless R. Do vaccines cause chronic illness?: assessing and responding to uncon firmed allegations. Update: Vaccine Prev Dis. 1998;6. Available at: http//www.hcsc.gc.ca/hpb/lcdc/publicat/vac p rev/voI6 - 2/i n d ex. htm I. Accessed March 30, 1999.
8. Jefferson T. Vaccination and its adverse effects: real or perceived [editorial]. BMJ. 1998;317:159-60.
9. Metcalf J. Is measles infection associated with Crohn's disease? The current evidence does not prove a causal link [editorial]. BMJ. 1998;316:166.
Send your immunization questions to Lt. Col. John D. Grabenstein, EdM, MS, FASHP, U.S. Army Medical Department, c/o University of North Carolina, Chapel Hill, NC 275997360; grabenstein @unc.edu. The assertions contained herein are the private views of the author. They should not be construed as official or reflecting the views of the U.S. Department of Defense or the Department of the Army.
FR OM THE LITERA TURE
Panel Counters Reports of a Vaccine-Diabetes Link Proceedings from a March 1998 meeting of the Diabetes Workshop Panel of the Institute for Vaccine Safety trongly contradict mass-media reports that immunizations increase the risk of acquiring diabetes. The panel concluded: • Genetic and environmental factors contribute to diabetes risk. • Selective infections are protective against type 1 diabetes in predisposed animal . • Other infections may increase the risk of diabetes mellitus in animals and human . • While selective vaccines are protective against type 1 diabetes mellitu in animal data in human are inconclusive. • No vaccines increase the risk of type 1 diabetes mellitus in humans. Source: Institute for Vaccine Safety Diabetes Workshop Panel. Childhood immunizations and type 1 diabetes: summary of an Institute for Vaccine Safety Workshop. Pediatr Infect Dis J. 1999;18:217- 22. Reprints: N. A. Halsey, Inst. for Vaccine Safety, Johns Hopkins School of Public Health, 615 N. Wolfe St., #5515, Baltimore, MD 21205; info@ vaccinesafety.edu.
L. Michael Posey, pharmacy editor, Journal of the American Pharmaceutical As ociation.
VOl. 39, No.3
May/June 1999
Journal of the American Phannaceutical Association
419