Return to Emily Friedman home page
First published in Hospitals & Health Networks OnLine, 2 February 2005
The flu vaccine crisis this winter has highlighted many soft spots in our health care system and in public health policy.
|I had a little bird,
Its name was Enza;
I opened the window
--Children's jump-rope rhyme from the influenza pandemic of 1918-1919
One of the difficulties in writing for publication, as opposed to writing for one's own amusement, is that there is a significant lag between the time a piece is written and the time it is published. Such is the case with this column; I am trying to tell a story that is still unfolding. By the time you read this, we will know much more than we knew when I wrote it. In the meantime, we can only watch and wait.
In the summer of 1918, two unusual health events were noted by many observers. The first was that the number of people falling ill with influenza seemed unusually high; the second was that many of those being infected were young and otherwise healthy--and they were dying of the disease. The flu pandemic that followed swept around the world, infecting 30 percent of the global population; 22 million people died in a year's time, many of them young. It killed more people than the Black Death of 1348-49 and is considered to have been the worst epidemic, in terms of deaths, in recorded human history.
This flu was thought to have originated in Spain, which was unlikely; but because Spanish news media were less muzzled than many in Europe (World War I was causing widespread censorship), they were able to report on it more fully. As a result, the pandemic became known as the Spanish flu or the "Spanish Lady."
Its origins were obscure, although it is now believed to have been caused by an unusually mutated virus that originated in China. One theory at the time held that it broke out at a U.S. military camp and was spread because infected bedding was burned and the virus became airborne. Another theory, which was more sound scientifically and has been widely accepted, was that this was an avian virus that had emerged in chickens, then jumped to domestic swine, and from there transferred to human beings.
As for its massive effect, it just happened to emerge at an opportune time: There was a world war on; millions of people had been dislocated; civilian and soldier alike were often underfed, underclothed and exposed to bitter weather; large numbers of young people were gathered together in confined spaces; and censorship made it impossible to warn the public of the danger in a timely manner.
Fortunately, by 1945, a vaccine to protect people against influenza was available. Making it has proved to be a time-consuming process, as influenza viruses are notorious for mutating, so the vaccine must be reconcocted and remanufactured every year. But development of the vaccine was a big step forward. And its use was relatively problem-free.
Until 1976, that is. That year, a young recruit at Fort Dix, N.J., died of a flu virus that seemed similar to the deadly one of 1918. Scientists advised then-President Gerald Ford that everyone in the United States should be inoculated against what quickly became known as the "swine flu." However, there was not enough time to fully test the new vaccine, and manufacturers feared lawsuits from adverse reactions. The government promised to take on liability for any problems, and the National Influenza Immunization Program (NIIP) began in October 1976. More than 40 million people were vaccinated by mid-December.
Unfortunately, by then there were reports from 10 states that some people receiving the vaccine had developed Guillain-Barré Syndrome, a severe and sometimes fatal neurological disorder. The NIIP was suspended. By January 1977, more than 500 people who had been vaccinated were reported to have contracted Guillain-Barré, and 25 had died. Only one person, the Fort Dix soldier, is known to have died of swine flu; the epidemic never materialized.
These cautionary tales remind us that there is a delicate balance between not doing enough and doing too much in the face of a possible epidemic. They are also useful in reminding us that, when it comes to public health policy, we haven't learned either lesson.
Just about everyone in health care knows that pharmaceuticals are a bit of a sore point these days. Among the issues being hotly debated are the safety and effectiveness of prescription drugs, whether the Food and Drug Administration (FDA) is too cozy with their manufacturers, and why the FDA is so dead set against the reimportation from Canada and European countries of pharmaceuticals that have been manufactured in the United States but are available at much lower cost in those nations. In the past decade, there has also been comment about growing consolidation in the pharmaceutical industry, which inevitably results in less competition and fewer sources for a given product.
These concerns became more than fodder for political debates when, on Oct. 5, the British government suspended the license of a Liverpool plant owned by Chiron, a U.S. biotech firm, which just happened to produce half of the entire U.S. flu vaccine supply.
This should not have come as a surprise. The FDA had inspected the plant in 1999, before Chiron acquired it, and found it had problems; Lester Crawford, acting director of the FDA, later said they had been "cleaned up." In 2000, the British government ordered a recall of a polio vaccine made in the plant because of fears it might be contaminated with the agent that causes bovine spongiform encephalopathy, or "mad cow" disease. In 2003, FDA inspectors again found contamination problems; some agency officials wanted the FDA to mandate changes, but it opted instead to accept Chiron's plan to tidy things up.
In August 2004, while conducting a final inspection of flu vaccine headed for the United States, Chiron found bacterial contamination. In late September, British inspectors were back at the plant and found worrisome evidence of more widespread contamination. Chiron president Howard Pien chose to keep this information private and a few days later assured U.S. officials that the vaccine supply would be delivered as promised.
On Oct. 5, the British government lowered the boom by lifting the plant's license. Then, and only then, did the FDA stop taking Chiron's word on the situation and conduct its own investigation, which confirmed the British findings. Nearly 50 million doses of vaccine were useless. Later in the year, the British government extended its ban on vaccine manufacturing at the plant, which meant that a sufficient supply of flu vaccine for the United States in 2005-2006 was also in doubt.
It is ironic that, in Greek mythology, Chiron was "the wounded healer."
Well, once the announcement was made, everybody swung into action. Health and Human Services Secretary Tommy Thompson issued a soothing press release saying that the 60 million doses of vaccine that were available "puts America in a strong position to keep people safe during the upcoming flu season." The same day, the federal Centers for Disease Control (CDC) issued recommendations governing who should have priority for getting the flu vaccine of which Thompson said there was enough.
A week after the announcement that the vaccine would be unavailable, Chiron reported that it had warned the FDA in mid-September that this was likely to happen; the FDA denied the claim, saying that it had relied on weekly reports from the firm that everything was going swimmingly.
As always happens once the horse is out of the barn, both the House and Senate duly held hearings, with various congressmen blaming everyone from Chiron to the FDA to the CDC. Rep. Henry Waxman (D-Calif.) accused the FDA of withholding information about problems at the Liverpool plant until after the presidential election. In response to evidence of the plant's ongoing problems, Lester Crawford responded that the problems had "resurfaced" after having been fixed. Then-candidates John Kerry and George W. Bush got into it, with Kerry accusing Bush of poor planning and deceiving the public, and Bush retorting that there aren't enough flu vaccine manufacturers because of the malpractice litigation system.
On Nov. 18, David Graham, an FDA official, testified before Congress that the agency was "feckless and far too likely to surrender to demands of drug makers." Three days later, Congress passed the omnibus federal spending bill for the 2004-2005 fiscal year; among its appropriations was $100 million to ensure an adequate future supply of flu vaccine. Virtually all of the money will go to drug manufacturers.
In December, HHS announced that it was going to purchase 1.2 million doses of vaccine from Germany under a loophole in federal law that allows the vaccines in as "experimental," which gets around the 12-month licensing process. Anyone receiving the inoculation, however, would have to sign a waiver releasing the manufacturer from any liability for adverse reactions. Thompson had explored a similar arrangement with Canada, but the Canadian health minister decided to hang onto his supply in case there was unexpected demand in his own country.
The same week, Thompson announced that he was delaying the release of a federal task force report on the safety of reimported drugs. This prompted Congressman Gil Gutknecht (R-Minn.) to observe, "Here we are buying flu vaccine from Germany, yet they're sitting on a report that probably says it is dangerous to purchase medicines from other countries. Why is it that the FDA can do this safely, but your local pharmacist can't?"
The governor of Illinois, a Democrat, announced that he was asking the federal government to allow his state to purchase flu vaccine from Europe for nursing home patients. The mayor of New York, a Republican, contracted with Illinois for 200,000 doses. New Mexico's Democratic governor signed up for 150,000 doses for patients in his state. The governor of Vermont, a Republican, sued the Bush administration in federal court for the right to legally import pharmaceuticals, including flu vaccine.
I think it is safe to say that what occurred here was a major public policy failure. In the first place, we are not talking about Nikes with faulty shoestrings or hairbrushes that might break; we are talking about a vaccine to prevent a disease that kills about 36,000 Americans every season, and that, as history tells us, can kill a whole heck of a lot more people than that.
In the second place, given the stakes, maybe the FDA should not be so trusting. This plant had documented problems going back to the Clinton administration, year after year, yet the FDA kept believing that the factory had cleaned up its act, year after year. Whether the agency knew that the crisis was likely before stuff hit the fan is irrelevant; when so much of the production of a needed vaccine is concentrated in one facility, it should be watched like a hawk. Happy phone calls from its owner do not constitute sufficient oversight.
Third, we should remember the proverb about the known enemy being preferable to the unknown one. In late 2004, President Bush signed into law Project Bioshield, which will spend $5.6 billion to protect Americans against bioterrorist attacks using anthrax, smallpox or other infectious agents. It will also fund research into botulism and effective treatments for the results of radiological and nuclear attacks (good luck on that last one).
No one, including me, opposes being prepared for such eventualities. But I must point out that we have known for hundreds of years that a mutated influenza virus will start infecting the human population in the autumn of every year, and that it will sweep around the globe for several months before burning out and getting ready to mutate for the next season. The phrase that kept surfacing during the angry debate over the flu vaccine situation was "caught by surprise." How could anyone have been caught by surprise? We knew that flu would strike. We knew that half of all vaccine production was concentrated in one plant. We knew the plant had problems. How could anyone have possibly been surprised?
Fourth, I am still waiting for the feds--any fed--to explain to me why it is OK to import from Germany an experimental vaccine, which has not been approved for use in the United States, and give it to people who are very young, very old or chronically ill, but it is not OK for people to buy licensed, approved drugs that were manufactured in this country and then sent to Canada or Ireland or Australia. I realize that this administration has a close relationship with the pharmaceutical industry--the Medicare Modernization Act demonstrated that in spades--but this dichotomy is indefensible.
And just wait: If people get sick from the German vaccine, some FDA official will undoubtedly hold a gleeful press conference and say, "See? We told you so!"
Meanwhile, Americans responded to the announcement that there would not be enough flu shots in the classic American way: Suddenly, everybody wanted one. It didn't matter if they had ever caught the flu, what their age was, if they had any underlying illness or even if they were afraid of needles: If there wasn't enough of it, we had to get it. Sort of the preventive medicine equivalent of Cabbage Patch Kids or Tickle Me Elmo. And so those at high risk and those at no risk at all started lining up at drug stores, grocery stores, hospitals, clinics and physicians' offices. In California, a 79-year-old woman died from injuries she sustained when she fell after standing in line for five hours.
The lucky ones got in early, in the right places. Professor Barbara Wolfe of the University of Wisconsin wrote in the Chicago Tribune that "a low-risk 49-year-old computer programmer in New York City strolled right into his doctor's Upper East Side clinic and easily got a flu shot, while my mother and hundreds of other seniors who live in retirement homes in Florida were told no flu shots were available." A physician friend of mine was threatened with a lawsuit by a perfectly healthy 45-year-old patient who did not want to be inconvenienced by catching the flu.
And then there was the usual array of crooks and frauds. An Internet ad for "Immuna-Flu" promised great results and "natural cherry juice" flavoring; you had to read the really teeny print to find the admission that "Immuna-Flu is not a substitute for flu shots." Another Internet ad suggested (I am not making this up) Ultramarine Shark Liver Oil as "the best flu shot alternative." A woman in Minnesota was arrested after giving "flu shots" to more than two dozen people for $20 each before fleeing as police closed in. It turns out that she was a nurse and was giving bona fide injections of vaccine, but she was not authorized to do so. Vendors started raising prices. Hospitals, pharmacies, physicians and individuals were solicited to purchase flu vaccine at prices double, triple, even 10 times the usual price. In Florida and Kansas, one firm, Med-Stats, offered pharmacies an $85 vial for $700 or more. The attorneys general of both states sued the company; Tommy Thompson vigorously supported the suits and wrote to every state attorney general, urging them to prosecute price-gougers. Hey, Secretary Thompson, if you're serious, there are a few other drugs whose prices I would invite you to investigate....
Inevitably, real dangers surfaced. To its great credit, Shore Memorial Hospital in New Jersey alerted the feds that it had been offered 8,000 doses of an unapproved vaccine; the shipment was seized.
And, in a peculiarly American touch, Iowa Electronic Markets, an online futures exchange, asked health care providers to predict when flu would crop up in Iowa. They called the effort the Influenza Prediction Market; it provided $100 to each trader. The money came from a grant by an unnamed pharmaceutical firm.
While all this was going on, there was the little problem of how to distribute what vaccine there was. The CDC guidelines targeted those most likely to be at risk of dire consequences from influenza: Everyone over 65, people aged 2 to 65 with chronic illness, pregnant women, nursing home patients, children who are taking aspirin, front-line health care workers, people who have close contact with infants, and babies aged 6 to 23 months. The total was approximately 95 million people, or about 30 million more than there were doses of vaccine.
CDC director Julie Gerberding asked for voluntary rationing by the public in the form of healthy people forgoing vaccinations. The CDC also arranged with Aventis Pasteur, now the supplier with the most flu vaccine, to redistribute planned shipments so that they went to providers caring for patients at the highest risk in areas with the most such patients.
Two weeks later, the CDC convened a panel of bioethicists who were charged with deciding how remaining flu vaccine supplies should be allocated. It was not known if their recommendations would be available and implemented before the flu season ends this year.
The CDC recommendations had the weight of clinical and practical validity. If you were not in one of the high-risk groups, you were asked to forgo vaccination. Many people did just that.
But, of course, not everybody did. Senate Majority Leader Bill Frist, M.D. (R-Tenn.), a healthy 52-year-old, got his shot before the announcement that the vaccine supply would be curtailed. Shortly thereafter, so did many people on Capitol Hill because anyone with a Hill credential was declared eligible; two days after the news came out about the shortage, Frist graciously opened his office as a makeshift clinic, and quite a few legislators and staffers, some not eligible under the CDC guidelines, received vaccinations there. They defended themselves by saying that Congress' official physician, John Eisold, M.D., told them they should be inoculated because they come in contact with many people and shake a lot of hands.
So do clergymen, business executives and members of wedding parties, Dr. Eisold; senators can learn to wash their hands, just like the rest of us.
Senator Evan Bayh (D-Ind.) refused the offer for himself and his family. As for other senators, he said, "That's a matter of conscience for them." Some of those who got shots later apologized. Frist did not, saying, "I think a case can be made that you don't want to be infecting other people."
Meanwhile, in sports-mad Chicago, after the shortage was announced, all members of the Bears professional football team were offered vaccinations, because, after all, there are things more important than fragile infants and seniors. It's hard to say how many of them took up the offer because the firestorm of publicity led the Bears to recant previous information and insist that only two asthmatic players got inoculated. Observers said more than two were so favored.
In Maricopa County, Ariz., and Bloomfield County, N.J., officials used lotteries to decide who in the high-risk groups would get the vaccine. In New Jersey, 1,100 residents signed up for 300 doses; in Arizona, 24,000 hopefuls were registered. Maricopa County then passed up a chance to buy 6,000 more doses, but, after being criticized by those who had entered the lottery, it bought the vaccine, so most lottery registrants got their shots.
Minnesota had some doses left over and sent them to Maryland. Urged by District of Columbia congressional delegate Eleanor Holmes Norton, Congress donated 3,000 of its personal supply of unused doses to the hard-pressed District public health department and 18 District hospitals.
In December, Secretary Thompson, who had assured the nation in October that there was plenty of vaccine, announced the "Give Others a Shot" campaign, designed to persuade those not at high risk to forgo flu shots for the season.
It wasn't just public officials who had to decide. It was individual physicians who had insufficient supplies; one wonders if they envied those who had none. "I feel like I have to play God," said family physician Ellen Brull in Illinois. And how were they to decide? Should extremely elderly nursing home patients, who are in a captive environment where infection could spread, be favored over infants whose lives are just beginning? What constitutes "chronic illness"? What if a patient threatened to sue? "This is one of the most significant overnight public health dilemmas we have faced in this country," said Charles Daschbach, M.D., of St. Joseph's Hospital and Medical Center in Phoenix. "In countries where social justice is the highest medical ethics priority, the culture accepts and understands rationing. Here in the United States, the autonomy of the individual patient is valued above the needs of society."
On Nov. 11, the World Health Organization convened an emergency summit on influenza, attended by pharmaceutical representatives and health officials from many nations. It was prompted by the U.S. flu vaccine crisis and the spread of often-fatal avian flu in Asia, a situation that has become endemic.
Tommy Thompson announced that the United States has launched a program to develop a vaccine for avian flu in the event that it mutates so that it can be spread from person to person, which it has not done so far (it can be caught only from birds--we think). Attendees agreed that too little was being done to prevent another worldwide flu pandemic. But pharmaceutical firms said that they will not conduct research on future flu vaccines unless the costs are underwritten by governments.
By the end of 2004, the CDC ethics task force on allocation of flu vaccine had decided that the chronically ill elderly should have first priority, but could not agree as to whether healthy seniors or young children should be second on the list. HHS announced that it was diverting money from a program to fund vaccinations for children in order to purchase the experimental German flu vaccine.
So many Americans did the right thing and passed up a chance to get a shot that suddenly there was a glut of vaccine. The CDC, while it was still running "Give Others a Shot" public service announcements, expanded the high-priority categories to include anyone in close contact with people at high risk and all adults over the age of 50. That was the good news. The bad news was that only an estimated 35 percent of Americans in high-risk categories had been vaccinated by mid-December.
Tommy Thompson, in announcing his resignation, warned about the likelihood of another global influenza pandemic.
And so we sit at the dark of the year, watching, waiting and hoping, in the shadow of the Spanish Lady.
First published in Hospitals & Health Networks OnLine, 2 February 2005
© Emily Friedman 2004, 2005
Return to Emily Friedman home page