- Email: [email protected]
A perfect storm
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A perfect storm Lessons from the vaccine controversy What of the tens of thousands of children who, ‘protected’ by their parents against a nonexistent risk, have been exposed to the very real risks of deafness, blindness, meningitis and death?
ast month a chill went down the collective spine of journal editors around the world. It was a month no one wants to repeat, but one we must not forget. For several years, there has been heated public debate over the possibility of a link between autism and the so-called three-in-one MMR vaccine, given in infancy to prevent the formerly ubiquitous childhood diseases of measles, mumps and rubella. Some parents became so concerned that they insisted on their children receiving the three constituent vaccines separately. Others skipped the immunizations altogether. The principal (some would say sole) scientific basis for the fear of MMR was an article by Andrew Wakefield M.D., and colleagues, published by The Lancet in 1998.1 The authors reported on a group of 12 children who had both a particular bowel disorder and neurological deficits. The authors speculated that both conditions could be due to the MMR vaccinations the children had received. Dr. Wakefield’s article, suggesting a hitherto unsuspected mechanism behind a serious and poorly understood disease, set in mo-
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MARJORIE K. JEFFCOAT, D.M.D. EDITOR E-mail: [email protected]
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tion an urgent worldwide research effort. In the United States alone, both the Centers for Disease Control and Prevention and the National Institutes of Health are studying large cohorts (100,000 or more) of children. Over time, these newer, larger and bettercontrolled studies came to the forefront and with remarkable unanimity left the Wakefield findings standing alone. To date, the conclusion of all this work is that there is no persuasive evidence that any vaccine can cause autism and that the MMR vaccination is, in this respect, safe.2 (For specific contraindications to vaccination in individual children, see the recommendations of the CDC’s Advisory Committee on Immunization Practices.2) Science is full of false starts and disappointing dead ends, and this story might not have been remarkable except for the unusual speed with which, and scale on which, it unfolded. But in February 2004, the editor of The Lancet, a medical journal of international repute, introduced a new dimension by announcing that, in hindsight, the Wakefield article should not have been published. In scientific circles, such a repudiation is a bombshell. A mere difference of opinion would not justify such a serious measure taken by The Lancet this month. After all, journals are an appropriate venue in which to debate new ideas. Science, as I often have said, is
JADA, Vol. 135, April 2004 Copyright ©2004 American Dental Association. All rights reserved.
V I E W S
self-correcting: research that can be repeated becomes part of our knowledge base, while the rest is discarded and forgotten. So why was the “Wakefield affair” so unusual? At least three forces conspired to make the Wakefield article more than just a collection of irreproducible results. First, by most standards, the work itself did not constitute first-rate science. It was a study of only 12 children, without a control group, and so in itself could not prove anything about the hundreds of thousands of children who receive the vaccine each year. It would be logical to expect a follow-up study, and one was indeed under way in 1998. Unfortunately, it too was seriously flawed by, among other things, using some of the same subjects who were studied in the initial group. Second, the MMR-autism link was seized on as a rallying point by advocates for autistic children and used as the basis for pressure aimed at eliminating the danger and compensating the injured. It’s understandable that a parent facing this mysterious condition would reach for an explanation, however tenuous, that might offer hope for a cure. It is equally understandable that the usual pack of lawyers would pick up the scent. In any case, a wellorganized pressure group, untroubled by scientific niceties, immediately took the Wakefield results as proven doctrine. The fact that Thimerosal, a preservative formerly used to stabilize the vaccine, contains a mercury compound was icing on the litigious cake. Finally—and this is what
provoked The Lancet’s extraordinary statement—it emerged that the principal author had at least the appearance of a serious conflict of interest. At the time of the study, Dr. Wakefield was being paid as a consultant by the British Legal Aid board to assess whether parents who claimed their children had been damaged by MMR had a legal case against manufacturers or providers. This connection was not disclosed to The Lancet, Dr. Wakefield maintaining to this
While a major conflict of interest may result in outright rejection, in general we believe that full disclosure is the best antidote to bias: armed with the information, our readers can decide for themselves whether an author’s employment or other activities affect the science.
day that it was irrelevant to the science presented. Any one of these factors might have led to an awkward but ultimately forgettable episode, but taken together they’ve had a massively destructive effect. Millions of dollars and thousands of research hours have been wasted chasing a chimera, but that’s the least of it. What of the tens of thousands of children who, “protected” by their parents against a nonexistent risk, have been exposed to the very real risks of deafness, blindness,
meningitis and death associated with the MMR diseases? JADA, like its peers (including The Lancet), does everything in its power to avoid being party to such a perfect scientific storm. Our policy requires every author to declare potential conflicts of interest; these are made known to the reviewers and included alongside the published article. While a major conflict may result in outright rejection, in general we believe that full disclosure is the best antidote to bias: armed with the information, our readers can decide for themselves whether an author’s employment or other activities affect the science. Of course, there is only so much we can do if the author chooses to conceal this crucial information. JADA is a special type of periodical. We recognize science is changing and challenging and, at times, controversial. Our reviewers and our readers are key to maintaining the standard of the science we publish here. Without your knowledge and vigilance, shabby work could creep in unchallenged, doing who knows what damage in the process. Nothing stems the spread of error like lively and critical discussion. If there’s any doubt that you’re up to the challenge, just pick up any issue and take a look at the Letters section. To all those who take the time to write, thanks for making our Journal better. ■ 1. Wakefield AJ, Murch S, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-41. 2. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Notice to readers: recommended childhood immunization schedule—United States, 1998. MMWR Morb Mortal Wkly Rep 1998;47(01):8-12.
JADA, Vol. 135, April 2004 Copyright ©2004 American Dental Association. All rights reserved.
403
I
E
W
S
A perfect storm Lessons from the vaccine controversy What of the tens of thousands of children who, ‘protected’ by their parents against a nonexistent risk, have been exposed to the very real risks of deafness, blindness, meningitis and death?
ast month a chill went down the collective spine of journal editors around the world. It was a month no one wants to repeat, but one we must not forget. For several years, there has been heated public debate over the possibility of a link between autism and the so-called three-in-one MMR vaccine, given in infancy to prevent the formerly ubiquitous childhood diseases of measles, mumps and rubella. Some parents became so concerned that they insisted on their children receiving the three constituent vaccines separately. Others skipped the immunizations altogether. The principal (some would say sole) scientific basis for the fear of MMR was an article by Andrew Wakefield M.D., and colleagues, published by The Lancet in 1998.1 The authors reported on a group of 12 children who had both a particular bowel disorder and neurological deficits. The authors speculated that both conditions could be due to the MMR vaccinations the children had received. Dr. Wakefield’s article, suggesting a hitherto unsuspected mechanism behind a serious and poorly understood disease, set in mo-
L E
MARJORIE K. JEFFCOAT, D.M.D. EDITOR E-mail: [email protected]
402
D
I
T
O
R
I
A
L
tion an urgent worldwide research effort. In the United States alone, both the Centers for Disease Control and Prevention and the National Institutes of Health are studying large cohorts (100,000 or more) of children. Over time, these newer, larger and bettercontrolled studies came to the forefront and with remarkable unanimity left the Wakefield findings standing alone. To date, the conclusion of all this work is that there is no persuasive evidence that any vaccine can cause autism and that the MMR vaccination is, in this respect, safe.2 (For specific contraindications to vaccination in individual children, see the recommendations of the CDC’s Advisory Committee on Immunization Practices.2) Science is full of false starts and disappointing dead ends, and this story might not have been remarkable except for the unusual speed with which, and scale on which, it unfolded. But in February 2004, the editor of The Lancet, a medical journal of international repute, introduced a new dimension by announcing that, in hindsight, the Wakefield article should not have been published. In scientific circles, such a repudiation is a bombshell. A mere difference of opinion would not justify such a serious measure taken by The Lancet this month. After all, journals are an appropriate venue in which to debate new ideas. Science, as I often have said, is
JADA, Vol. 135, April 2004 Copyright ©2004 American Dental Association. All rights reserved.
V I E W S
self-correcting: research that can be repeated becomes part of our knowledge base, while the rest is discarded and forgotten. So why was the “Wakefield affair” so unusual? At least three forces conspired to make the Wakefield article more than just a collection of irreproducible results. First, by most standards, the work itself did not constitute first-rate science. It was a study of only 12 children, without a control group, and so in itself could not prove anything about the hundreds of thousands of children who receive the vaccine each year. It would be logical to expect a follow-up study, and one was indeed under way in 1998. Unfortunately, it too was seriously flawed by, among other things, using some of the same subjects who were studied in the initial group. Second, the MMR-autism link was seized on as a rallying point by advocates for autistic children and used as the basis for pressure aimed at eliminating the danger and compensating the injured. It’s understandable that a parent facing this mysterious condition would reach for an explanation, however tenuous, that might offer hope for a cure. It is equally understandable that the usual pack of lawyers would pick up the scent. In any case, a wellorganized pressure group, untroubled by scientific niceties, immediately took the Wakefield results as proven doctrine. The fact that Thimerosal, a preservative formerly used to stabilize the vaccine, contains a mercury compound was icing on the litigious cake. Finally—and this is what
provoked The Lancet’s extraordinary statement—it emerged that the principal author had at least the appearance of a serious conflict of interest. At the time of the study, Dr. Wakefield was being paid as a consultant by the British Legal Aid board to assess whether parents who claimed their children had been damaged by MMR had a legal case against manufacturers or providers. This connection was not disclosed to The Lancet, Dr. Wakefield maintaining to this
While a major conflict of interest may result in outright rejection, in general we believe that full disclosure is the best antidote to bias: armed with the information, our readers can decide for themselves whether an author’s employment or other activities affect the science.
day that it was irrelevant to the science presented. Any one of these factors might have led to an awkward but ultimately forgettable episode, but taken together they’ve had a massively destructive effect. Millions of dollars and thousands of research hours have been wasted chasing a chimera, but that’s the least of it. What of the tens of thousands of children who, “protected” by their parents against a nonexistent risk, have been exposed to the very real risks of deafness, blindness,
meningitis and death associated with the MMR diseases? JADA, like its peers (including The Lancet), does everything in its power to avoid being party to such a perfect scientific storm. Our policy requires every author to declare potential conflicts of interest; these are made known to the reviewers and included alongside the published article. While a major conflict may result in outright rejection, in general we believe that full disclosure is the best antidote to bias: armed with the information, our readers can decide for themselves whether an author’s employment or other activities affect the science. Of course, there is only so much we can do if the author chooses to conceal this crucial information. JADA is a special type of periodical. We recognize science is changing and challenging and, at times, controversial. Our reviewers and our readers are key to maintaining the standard of the science we publish here. Without your knowledge and vigilance, shabby work could creep in unchallenged, doing who knows what damage in the process. Nothing stems the spread of error like lively and critical discussion. If there’s any doubt that you’re up to the challenge, just pick up any issue and take a look at the Letters section. To all those who take the time to write, thanks for making our Journal better. ■ 1. Wakefield AJ, Murch S, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-41. 2. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Notice to readers: recommended childhood immunization schedule—United States, 1998. MMWR Morb Mortal Wkly Rep 1998;47(01):8-12.
JADA, Vol. 135, April 2004 Copyright ©2004 American Dental Association. All rights reserved.
403