# Presentation: 845962

## Immunization Safety Review Committee:  or Everything I’ve Learned about Immunization Trustbusters and Strategies to Enhance that Trust

**Marie C. McCormick, Committee Chair**
**Harvard School of Public Health**
**National Vaccine Advisory Committee**
**June 3, 2003**

**Notes:**
This talk represents a modification of a talk that I gave at a continuing education symposium at the Harvard School of Public Health on the public’s trust in medicine and public health.  As you will see later from the selection criteria for the committee, the title is very accurate.

## Trustbusters: Formulation of Vaccine Policy

- Recent rapid expansion of the childhood vaccine schedule not well explained to the public
- Apparent abrupt changes in vaccine policies for “safety” reasons: thimerosal and rotavirus
- Perceived conflict of interest on official panels making recommendations for the vaccine schedule

**Notes:**
Among the reasons for public wariness about childhood vaccines are a number of issues that involve vaccine policy formulation, the handling of adverse events, and incomplete or inaccurate science.  
Issues in vaccine policy formulation include the rapid expansion of the childhood schedule over the past ten years or so without clear explanations to the public.  In a recent publication, about 25% of parents believe that their children are getting too many shots, and they could clearly stratify vaccines in terms of the degree of risk they thought the wild-type disease presented.  Thus, measles was considered a high-risk disease, but not rota virus.  And in developed countries, that is probably a fair assessment.
Secondly, the past few years have seen relatively abrupt changes in vaccine policy, again not well communicated to the public.  Examples include the removal of thimerosal from vaccines and the introduction and removal of rota virus vaccine from the schedule.  While there may have been very good reasons for this, in the eyes of the public, policy makers are seen as saying that procedures were safe one year and not the next.
Finally, there is a perceived conflict of interest in the composition of the official panels making policy recommendations.  Such panels may include those who developed the vaccine and the manufacturers.  Such expertise is needed for the development of vaccine policy on the uses and distribution of vaccines, but skeptical public may also see a certain lack of objectivity.

## Trustbusters: Adverse Events

- Exposing one’s child to a governmentally “mandated” risk
- Perceived exemption from legal recourse, i.e. suits
- Adverse event reporting system seems unresponsive
- The same agency sets the policy and examines the adverse event
- Context of lack of experience with the wild type disease

**Notes:**
The risk and handling of adverse events or perceived adverse reactions to vaccines also may lead to distrust.
We should acknowledge that we are exercising a powerful public health tool in requiring children to undergo a small but finite risk of an adverse event to protect the public’s health.  While exceptions are possible, many parents see this risk as a government mandate.  This, by the way, is not unique to childhood vaccines.  The Prevention Board of the IOM also oversees studies of Agent Orange and Gulf War Syndrome which are other “government mandated exposures”.
However, the childhood vaccines are exempt from the American way of dealing with adverse events, I.e. suits.  Thus, not only is the exposure seen as mandated, but recourse is seen as limited.
Third, we have heard that the adverse event reporting system seems unresponsive.  With limited resources, those overseeing VAERS and other activities must triage which events to pursue.  Indeed, the addition of the Vaccine Safety Datalink project is a major contribution to surveillance for adverse events.  However, if no one responded to your complaint, you may be unaware of the activities to examine the issue.
No matter what the internal administrative arrangement, from the outside, the same agency sets policy and examines adverse events, CDC.  Again, a wary public may perceive this as a conflict of interest.
Finally, there is very limited experience in the current population of parents, and even grandparents, with the diseases being prevented.  Thus, they are not able to place the risk of adverse events from the vaccines in the context of the risks of wild type disease.  Whenever I talk to reporters about MMR, the adverse event that always catches their attention is Dawson’s encephalitis, and the image of an adolescent dying demented.

## Trustbusters: Incomplete Science

- Poorly designed studies
- Premature conclusions without timely follow-up by other authoritative researchers
- Lack of study  and publication
- Reasoning by analogy

**Notes:**
We have to add that professionals are not blameless in generating concern.
For example, one web site asserts that vaccines are responsible for increasing the cases of Type 1 diabetes based on an ecological study published as a letter to the editor.
Secondly, the studies done by Dr. Wakefield regarding measles virus are examples of premature conclusions based on observations that needed much more assessment.  His concern about the bowel problems of individuals with neurodevelopmental disabilities is laudable.  His observations of the persistence of measles virus particles in the lymphoid tissue of the intestines of some individuals with these conditions is a provocative one, and is worthy of further investigation.  However, the linkage between that observation and autism is certainly not supported even by his own case series which includes individuals with conditions other than autism.
The Committee has also encountered vaccine issues which have received little scientific attention.  For example, even basic information on the pharmacokinetics of thimersol had not been published when the committee addressed this issue.  Likewise, some publications from the VSD project have been slow to reach publication in peer-reviewed literature, thus diminishing their usefulness in assessing vaccine safety.
Finally, some linkages between vaccines and adverse events have been argued through analogy between the adverse event and known toxic effects of components of vaccine, notably the analogy between symptoms of mercury toxicity and autism.  This latter issue has been addressed by Dr. Karin Nelson in a recent issue of Pediatrics.  However, the comparison of mercury and autism is in the peer-reviewed literature.

## Enhancing Trust

- Enlisting respected, neutral agencies

**Notes:**
So, how do you go about enhancing trust?  One way is to enlist the assistance of agencies which are respected for their science and not seen as having a vested interest in the results.

## Getting Outside Assistance

- Institute of Medicine
- Medical Academy of the National Academy of Sciences (1863)
- Founded in 1970
- (At least) five prior vaccine safety reports

**Notes:**
In this case, it was the Institute of Medicine which is part of the National Academy of Sciences.  The latter was founded in 1863 by Congress to provide authoritative scientific advice to the government and other agencies.  The IOM, the medical branch, was founded in 1970, and since then has released at least five vaccine safety reports prior to the institution of our committee. 

## Criteria for Committee Selection

- No financial ties with vaccine manufacturers or their parent companies
- No past or present service on vaccine advisory committees
- No expert testimony, publications on issues of vaccine safety
- No current or recent funding from CDC on vaccine issues

**Notes:**
The second way is to set stringent criteria for the membership of the committee to avoid the appearance of conflict of interest.  The criteria were:

## Rationale for These Criteria 

- An _objective and independent _committee that would not be subject to criticisms of conflict of interest
- Given the uncertainty surrounding the hypotheses that would come before the committee in the future, the IOM wanted to _ensure consistency in the committee membership _

**Notes:**
The rationale for these criteria are noted here.  As one of our observers commented in print, it meant a committee which knew nothing about vaccines!  However, it did have the epidemiologic, immunologic, and clinical expertise to assess the literature and presentations to the committee.  I would also note that this has been a very hard-working committee.  We have had at least one, and often, two three-ring binders of material for each meeting, and I can assure that the members have read this material.  We have also had expert staffing from the IOM to facilitate the rapid production of reports.

## Enhancing Trust

- Enlisting respected, neutral agencies
- More pro-active approach to assessing adverse events

**Notes:**
Another strategy to enhance trust is a more pro-active approach to assessing adverse events.  In this regard, we think that the recent establishment of clinical assessment centers is a very positive step in getting more standardized information.  The committee has reviewed VAERS reports, and the unevenness of the information limits their utility.

## Enhancing Trust

- Enlisting respected, neutral agencies
- More pro-active approach to assessing adverse events
- Improving access to correct information

**Notes:**
We also think that more needs to be done to improve access to correct information.  This involves two steps.  The first is having a better idea of what the concerns are influencing the public, and the second is to develop strategies to address these concerns.  In one of our reports we comment on a mini-study done by one of the members of the ease or lack of it in getting information on the topic of the report.  

## Enhancing Trust

- Enlisting respected, neutral agencies
- More pro-active approach to assessing adverse events
- Improving access to correct information
- Early identification of emerging concerns, of the dimensions of the concern, and of strategies to allay concerns

**Notes:**
Clearly, it would also help guide the research and communications response if there were earlier identification of emerging concerns.  For example, some of the concern about thimerosal is driven by the lack of information about the metabolism of thimerosal by infants and the potential for the mercury to accumulate in the body.  Such concerns would have been allayed by adequate pharmacokinetic studies now in the press and underway.  The survey of parents mentioned earlier is also a helpful approach to identifying the dimensions of concerns, but more is needed.  Some of you may know that my husband does public opinion polling on the public’s views on issues of health and health policy.  His recent work on the public’s knowledge about small pox and use of the vaccine indicates a rather broad gulf between the public and professional views.

## Enhancing Trust, contin.

- Nature of the recommendations made by review panels.

**Notes:**
I would note that I think one of the aspects of our committee’s work that has been seen very positively is our ability to make recommendations beyond the assessment about whether an adverse event is associated with a vaccine.  One of the concerns of at least some of the public is that the assessment of causality only means that no further attention will be paid to the issue.  To be able to make recommendations about needed research or other strategies to address the concern helps in addressing this concern.

## Issues Needing Further Attention

- Communication about the introduction of or changes in vaccines to the childhood schedule to professionals and the public
- Composition and rationale of federal policy-making committees
- Broaden the policy framework to include  ethical and economic issues

**Notes:**
Clearly the foregoing indicates that there needs to be attention to the way that communication about the changes in vaccine schedule for children occurs both to professionals and the public.  Second, the process of federal policy making about vaccines deserves a review and a clear rationale.  Finally, as future vaccines come on line, the policy framework may need to be more inclusive, as illustrated by a recent thoughtful discussion by Feudtner and Marcuse in Pediatrics.

## Implications for Public Health

- Case study for other “government mandated” exposures
- Natural history
- Sources of discontent
- Earlier intervention points
- Role of communication of risk

**Notes:**
As I mentioned earlier, the childhood vaccine schedule is not the only example for public health in which controversy has occurred.  Agent Orange and the Gulf War Syndrome share some features.  Perhaps if we conducted case studies of these controversial issues we might learn more about the natural history of the emergence of these controversies, and what the sources of discontent are.  These findings, in turn, may suggest earlier intervention points to preserve trust and better strategies for the communication of risk.

## Next Steps

- Report on influenza vaccine under preparation
- One additional meeting to be held in fall, 2003
- Preparation of manuscripts for publication in professional journals
- Preparation of an all-encompassing summary written for the lay public

## Immunization Safety Review

- www.iom.edu/imsafety
- Imsafety@nas.edu
- 202/334-1342