IOM: Set trigger before a vaccine death occurs
CDC urged to track reactions, explain liability
With its smallpox immunization plan now under way in the nation’s hospitals, the Centers for Disease Control and Prevention (CDC) must decide how many adverse reactions and deaths are acceptable before modifying or halting the program, told a special smallpox review panel formed at the Institute of Medicine (IOM) in Washington, DC.
The CDC should develop and communicate criteria — such as a threshold number of adverse events — that would trigger midcourse changes to the agency’s current guidance on issues such as screening, contraindications, and administrative leave policies, the IOM panel recommended.
"It is not an easy decision, that it why we are saying it should be made [beforehand]. It should not be made in the heat of battle," says Brian L. Strom, MD, MPH, chairman of the IOM panel and director of the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania School of Medicine in Philadelphia.
The IOM report was sponsored by the CDC, which is taking the suggestions seriously and reviewing its smallpox plans.
"Obviously, there has been a decision that [approximately] one per million deaths and 40 per million serious side effects is tolerable, given the risk seen by the government," Strom says. "Presumably, if you were talking about one per hundred deaths, it would not be tolerable. Where is the boundary in between? Decide that up front, not after the first or second death comes in. Then it is going to be under a political microscope, and it is going to be very hard to make a decision."
The CDC is addressing such concerns with the formation of a Data Safety Monitoring Board, which consists of experts who will assess the program as it goes forward.
"We have made a commitment to monitor this program in real time so that we can detect at the earliest possible moment any emerging, unexpected, or expected-but-rare problem," says Julie Gerberding, MD, MPH, CDC director. "Keep in mind that we used this vaccine for decades successfully. This is the vaccine that was involved in eradicating smallpox. And so I don’t think we anticipate we’ll be finding unusual complications, but we are very concerned that the program is administered safely, and so in real time, we’ll be watching very carefully. We are also working very carefully with the Department of Defense so that we can understand any complications that are occurring there [in military personnel], and we’ll be able to use that information as well."
The IOM committee commended plans to establish the safety monitoring board, but questioned the board’s independence if it is too closely tied to government. Fail-safe mechanisms for independent review, analysis, and reporting should be established or the proposed organizational arrangement should be reconsidered, the IOM advised.
Estimating that about 30% of the population is contraindicated for the smallpox vaccine due to various conditions, the IOM panel questioned whether the CDC will catch all reactions and adverse events using the existing Vaccine Adverse Event Reporting System (VAERS).
"It serves a critical role, but its purpose is not to quantify adverse reactions," Strom says. "Its purpose is to discover new reactions that we might not otherwise know about. There is vast underreporting. People don’t report their reactions to VAERS."
Instead, the committee strongly urged the agency to use a "pre-event vaccination system" to actively collect information on adverse events. Under that plan, adverse reactions would be reported into a secure data system by every immunization site.
"Then we will truly have definitive information — yes or no — about whether a person had an adverse reaction. I know CDC is, in fact, making that change because [the agency] asked us specifically about the program it is implementing," Strom says.
There was some confusion when the IOM report recently was released, with initial reports suggesting the panel was asking the CDC to stop the immunization effort until concerns are addressed. "Proceed with caution" is more to the point of the IOM’s recommendations.
"We never said they should not move ahead," Strom says. "What we said was that it shouldn’t be implemented until it can be done safely. Recognize that this is a national campaign being done locally. So CDC can implement nationally, but the real question is when it is implemented by each locale; it shouldn’t be initiated until the [local] programs think they are ready."
The CDC has clarified that each vaccination site should move ahead only when everything is in place to safely provide immunizations. This caution is important because any complications experienced during the initial phase of the immunization campaign could lessen willingness to participate in the program, the IOM stressed.
In that regard, the panel did ask for a pause in the process after the smallpox care teams are immunized in hospitals. The data collected from that effort should be thoroughly analyzed before the vaccine is offered to other health care workers, first responders, and public safety officials.
"The second phase shouldn’t be mounted until the analysis of the first phase is done," Strom says. "The decisions made in the first phase are based on data that are decades old. That needs to updated and corrected on a real-time basis. . . ."
It goes without saying that cumulative data should be scrutinized before the so-called "third phase" begins by offering the vaccine to the general public. In all cases, the process should be paused and restarted based on collected data rather than an arbitrary time line, Strom adds.
Liability issues clouded
Currently, some health care workers and many members of the public understandably are confused about several aspects of the program, the IOM noted. For example, many potential vaccine recipients may falsely assume that the provisions of the Homeland Security Act of 2002 would reimburse them for medical expenses or lost income resulting from complications of vaccination. However, the act covers only injuries that result from vaccine that was negligently manufactured or administered, the IOM panel reminded.
Other vaccine injuries might be covered under workers’ compensation laws, which vary by state, and by individuals’ health insurance plans. However, without clear means of compensation for losses that may occur even if the vaccine was carefully administered, some — perhaps many — health workers may decline vaccination, which would undermine the program’s effectiveness, the committee warned.
"[Liability issues] need to be made transparent, and that has to be part of the informed consent," Strom says. "Otherwise it is not truly voluntary. People need to know the medical and economic risk they are taking, given that there is limited liability or injury protection now build in. That is going to require the CDC working with the state health departments on a state-by-state basis because there are relying to a substantial degree on workers’ compensation, and that varies from state to state."
Gaps in coverage
For example, one of the current "gaps in coverage" concerns adverse reactions in contacts of people who volunteer for vaccination, Gerberding concedes. A number of steps are being taken by the CDC and other government agencies to clarify the situation, she says. "We’ve advised the states to get a very firm assessment of what workers’ compensation programs in their state will and will not cover, and we’re advising that various employers collaborate in this process," she says.
That said, the CDC is determined to move forward and clarify the issues as the program proceeds. "Even though the states may vary in the kinds of coverage or the programs that are available, we are certainly not going to delay this program because of concerns about compensation," Gerberding says. "The president’s decision to recommend this vaccine to the response teams was really based on the fact that we need urgent and efficient action. We live in a dangerous world these days, where a terrorist attack with smallpox is possible. Even though the president reassured us that an attack was not imminent, we all know that this is now a possibility, and we must be prepared," she adds.
Indeed, the risk of a vanquished disease being intentionally loosed on a largely vulnerable population is the great unknown that makes this the most unusual vaccine campaign in history.
"Presumably [the risk of an attack] is not zero, or the campaign wouldn’t have been done to begin with," Strom says. "Basically, our judgment was we don’t have that information; we can’t have that information; and to some degree, it is probably not even knowable even from a [government] security point of view. The central issue is: This is not the normal public health vaccine campaign. You normally would not give a vaccine that will kill people for a disease that doesn’t exist," he adds.
(Editor’s note: The complete IOM report is available at http://national-academies.org.)
With its smallpox immunization plan now under way in the nations hospitals, the Centers for Disease Control and Prevention (CDC) must decide how many adverse reactions and deaths are acceptable before modifying or halting the program, told a special smallpox review panel formed at the Institute of Medicine (IOM) in Washington, DC.
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