Race With a Killer
Connie Jimmerson remembers that her daughter Tashica was a bit more attached to home than usual on that Friday seven years ago. She remembers it clearly.
"She was fine," Jimmerson says. "She was just all up under me all that Friday. She wouldn't go play with the kids...I couldn't get rid of her," Jimmerson says.
The next morning Tashica awoke with what Jimmerson thought was stomach flu.
"She was running a temperature and throwing up. I just took it to be a little stomach virus, you know. I went to the store. I got her some soup, 7Up and aspirin," Jimmerson recalls while sitting at her home in Longview. "She just kept laying around. She didn't seem to be getting any better."
Tashica's condition rapidly worsened. She could barely stand. She was becoming incoherent, asking for water and forgetting that she asked. Then she didn't recognize her mother.
Although Jimmerson didn't know it then, Tashica was fighting for her life. A lethal bacterium was rapidly multiplying in her body, causing an illness known as meningococcemia or meningococcal sepsis, a severe blood infection that often mimics flu symptoms in its early stages. Meningococcal sepsis is caused by the same bacterium that causes bacterial meningitis, but, while frequently mistaken, the two illnesses differ greatly. Meningitis, an infection of membranes lining the spine and brain, is much easier to treat. Meningococcal sepsis is both difficult to treat and often deadly. Those who survive the disease are frequently left maimed.
Within hours, Jimmerson would be in an emergency room watching helplessly as Tashica hemorrhaged from her internal organs.
Each year, about 3,000 to 4,000 young Americans are infected with meningococcal disease, which encompasses both meningitis and meningococcal sepsis. Outbreaks have occurred among freshmen living in college dormitories and children in day care. The disease appears among those who have been in close contact, but it is selective, striking some and leaving others who are exposed unharmed. The disease terrifies parents and confounds doctors, who have a small arsenal of medicines for treatment. About 60 percent of the cases of meningococcal disease are meningococcal sepsis.
Antibiotics, even if started early, are often ineffective at preventing the devastating effects of the blood infection. In just a few hours, children such as Tashica can die, bleeding from every orifice while vital organs shut down in an unstoppable cascade. Those not dead within the first few hours have a better chance of living, but their limbs often turn blue because toxins released by the bacteria cause blood to clot, slowing circulation to the extremities. Frequently, hands, feet, arms and legs are amputated from gangrene that sets in as a result of small blood vessel damage.
At the small East Texas hospital where Jimmerson first took Tashica, doctors gave the 7-year-old a spinal tap, a procedure in which fluid is extracted from the spine and tested. Jimmerson says she was told to wait outside the examining room.
"They took so long until I just walked in on them. Just then they told me that they had to Careflight her to Children's in Dallas," she says. "The doctor came out and told me that they were going to have to Careflight her and that they had to sedate her...They stopped her from breathing and a machine was going to be breathing for her."
Doctors put Tashica on a helicopter ambulance for a flight to Children's Medical Center of Dallas, about 150 miles away. They estimated her chances at "50-50," Jimmerson says. But in those early-morning hours, a study team of nearly two dozen doctors, nurses and therapists headed by Dr. Brett Giroir, now chief medical officer at Children's and then director of critical care medicine, was about to test something new, a cloned human protein called BPI.
Giroir, a Harvard graduate and acting chairman of pediatrics at University of Texas Southwestern Medical Center at Dallas, believed the drug, named Neuprex by its maker, could give the body a powerful natural weapon to fight the onslaught of meningococcal sepsis.
When Tashica arrived at Children's Medical Center, she didn't appear to have much of a chance. Her heart had stopped three times before she arrived, twice in the helicopter. It was risky to infuse the potentially revolutionary treatment into Tashica. She might die, threatening more than two years of work leading up to that moment.
"By any rights she was supposed to die," Giroir says. "If you give her the drug and she dies, it might have killed the drug forever. The first person that gets it dies. That's not usually a good thing, but we gave it to her anyway."
"If you ever want a time you will remember, try taking a 7-year-old kid who's gotten three CPRs before she got here and you're giving her a drug that no sick person has ever gotten before. Pretty dramatic...It's subject to bias, but she stabilized essentially as soon as she got the drug," Giroir says. "You kind of say, 'I think something just happened here.'"
Tashica became the poster child for the initial BPI study and its almost miraculous-seeming success in 1995. Eventually 25 others would have similarly positive outcomes after being treated with Neuprex. A second clinical trial started in 1996. Those treated with Neuprex also seemed to be doing better than those who received a placebo. Researchers attempting to gauge the drug's effectiveness, however, faced a difficult roadblock: The disease is both rare and dangerously swift, overwhelming a child's natural defenses in just hours. Even finishing the paperwork in time to get subjects enrolled in the study before they died became a problem.
As a result, the second trial could not scientifically repeat the initial success of Neuprex. In fact, by the time the $10 million trial ended, the effect of Neuprex on mortality rates for meningococcal sepsis victims was inconclusive, federal officials said when they decided not to approve the drug.
Government rejection was devastating to advocates such as Giroir and to XOMA, the small California pharmaceutical company that took on the risky and expensive attempt to win approval for Neuprex. Because the disease is so rare, neither XOMA nor any other pharmaceutical company could have expected a big payoff just from a meningococcal treatment even if Neuprex were approved. For XOMA, the second clinical trial was a losing gamble that would have to be explained to stockholders.
Freshly rejected, the company isn't in a position to risk another study of Neuprex as a treatment for meningococcal sepsis. A partnership with a larger pharmaceutical company has opened the possibility that Neuprex could be approved to fight other illnesses, but approval is at least five years off, a XOMA representative says.
Giroir, the first to propose using Neuprex to battle meningococcal sepsis, and his peers don't deny the second clinical trial failed to show a significant reduction in mortality or that the study had problems. Yet they all remain convinced Neuprex could be a powerful weapon to fight deaths related to meningococcal sepsis right now if they could just get it into patients during the first critical hours of the infection. Not only that, but the study showed that a large number of infected children treated with Neuprex went home with hands, feet, arms and legs they might otherwise have lost, Giroir and his colleagues say.
"It reduced amputations. There was a 25 percent risk reduction in mortality and a highly significant improvement in overall functional outcome," Giroir says. "Although it was--quote--a negative study by narrow definition, reducing amputations by two-thirds is pretty positive."
Doctors such as Giroir say that while they wait five years or more for another costly and lengthy study to be completed--if one even happens--more children who could benefit from Neuprex will be maimed or killed.
"It's not available now," says Giroir, a clearly dedicated physician and just as clearly a frustrated one. "When it reduces amputations by two-thirds, and I can't even get it for compassionate use, then it's a big deal."
As a pediatrician in the early 1990s, Giroir says he found that medicines available to help children survive a battle with meningococcal sepsis were not doing the job and cases of the disease in Texas were climbing.
According to the Centers for Disease Control and Prevention, the leading cause of meningitis before the 1990s was Haemophilus influenzae, but now children are protected from that as part of their routine childhood vaccinations. Today, the CDC says that Neisseria meningitidis is a leading cause. A vaccine is available for many strains of Neisseria meningitidis (the bacteria that causes meningitis and meningococcal sepsis), too, but it is expensive, only lasts about three years and there are questions about whether it can increase susceptibility to infection after repeated use. As a result, disagreement exists in the medical community about widespread and routine use of vaccinations in the absence of a specific outbreak.
Without reliable vaccines, fighting outbreaks and treating children have been an ongoing struggle for doctors. About 1993, Giroir came across what he thought might be a powerful weapon against meningococcal sepsis. While in Santa Fe, New Mexico, during a meeting of what's known as the "Shock Society," a group of physicians that studies treatments for sepsis, Giroir saw a medical abstract on a poster for a substance called bactericidal/permeability-increasing protein, or BPI.
"It was a normal, human protein that had been cloned and had a variety of interesting properties," he says. "Basically, this was a drug that had not been tried in clinical trials before. They'd done some safety testing in humans. It had a variety of properties which made it seem to be very potentially applicable particularly to meningococcal disease which we were seeing."
It is difficult as a doctor, he says, to have so little at hand to help him stop the effects of the ravaging disease, especially in otherwise healthy children and young adults. About the time he attended the Santa Fe conference, Giroir had been seeing a typically inexplicable increase in the number of meningococcal sepsis cases at Children's Medical Center.
"We had normally, before that time, potentially been seeing two to three cases, four cases a year in the ICU. We were seeing 20 to 25 cases a year in the ICU of very bad disease, extremely bad disease," he says. "The cases were increasing mostly in East Texas...basically we were at the end of the funnel, so that all of the cases that were occurring we got all the sick patients and the patients who were really critically ill."
Bacteria associated with meningitis are easily killed with antibiotics, but endotoxin, a poisonous byproduct, is unaffected by antibiotics. A small amount of endotoxin is not harmful to the body. You remove endotoxin from your gums in very small amounts when you floss your teeth. With meningococcal sepsis, an overwhelming amount of endotoxin floods a victim's blood, and the body's natural defenses cannot react fast enough to fight off the effects.
"This bacteria has endotoxin in 100- to 1,000-fold greater excess than other bacteria of its similarity," Giroir says. "It is really the toxin that is produced that causes this horrendous shock state and clotting and heart dysfunction and everything else. It affects all the organs, including the heart and its ability to pump."
What Giroir saw in BPI was a substance that the body already produces to fight infection. It stops bacteria and neutralizes endotoxin.
"What you are really doing is augmenting the body's own ability to deal with disease. Normally you can deal with these things because your body has defensive mechanisms, but when you have such an overwhelming kind of infection, particularly in children, you cannot match the onslaught," Giroir says.
BPI had been in development for 20 years when Giroir saw the poster. Eventually, he would make contact and befriend the man who discovered BPI, Peter Elsbach, a clinical professor at New York University School of Medicine.
Elsbach says early research showed that the white blood cells that help humans fight infection do "subtle damage" to bacteria. Between 1973 and the early 1990s, Elsbach and his colleagues tried to find out what part of a white blood cell actually damaged bacteria. What they eventually found led to their discovery of BPI.
"That was a long time ago, and that search led to the isolation of the single protein," he says.
They cloned the protein, establishing its complete amino acid sequence and demonstrating that one-half of the protein carried all of the anti-bacterial properties.
"That half of the protein, and that is now Neuprex, that half of the protein has the ability to block the activity of what is the main component...that causes many of the symptoms of sepsis, not just sepsis from meningococcemia but sepsis from other causes," he says.
Giroir says what he saw in BPI was a substance that could flood the body with a weapon to attack the poisons produced during the rapid progression of meningococcal sepsis.
"BPI had properties of endotoxin binding and neutralization. It was a protein that your body normally made and circulated and, of course, it made me feel better that it was much less likely to cause a lot of bad effects because you normally run around with it," Giroir says. "So, basically from that moment I made a commitment, and certainly my group made a commitment, to try to get this involved in pediatric trials."
That commitment led Giroir and the staff at UT Southwestern to embark on the study that started with Tashica Jimmerson.
Three years ago, an outbreak of meningococcal disease occurred in a rural area north of Houston, spreading fear. It is often a mystery why outbreaks occur where they do. The disease just shows up in the population without warning or predictable pattern. Certain areas in Texas and certain parts of Oregon appear particularly susceptible to outbreaks, research shows.
Between 300 and 400 children or young adults die, and about the same number lose extremities to meningococcal sepsis-related gangrene annually. Some also suffer strokes, which cause "neurologic devastation" and "take out half their brain," Giroir says.
Harley Beaty was just shy of her third birthday when the 1999 outbreak struck. Her case is similar to those that doctors such as Giroir must contend with once meningococcal sepsis is diagnosed. Even with good medical treatment, there is often little doctors can do to stop the ferociously rapid progression of the disease. On May 2, 1999, a Sunday, Harley and her family had an outing at Lake Livingston, near their home in Shepherd.
"We were Jet Skiing, boating, swimming. The whole family was there," says Donna Brock, Harley's grandmother and caregiver. "All my nieces, nephews, brothers, sisters were there. Harley was fine."
The next day, Brock says, she woke up at about 5 a.m. and got dressed and ready for work. Harley called to her.
"I went and got her something to drink, and she laid back down and went back to sleep. I thought nothing of it," Brock says. "I went to work."
At the time, Brock worked in Houston, about an hour away. She probably got home about 10 hours later, she says.
"My husband greeted me at the car and I asked him what he was doing at home. He told me that Harley was real sick and he decided to stay home in case she had to go to the hospital. He said she'd been running a fever and been throwing up and had diarrhea. I went into the house and she was lying on the couch," Brock says.
Harley's fever had been going up and down all day, according to Earl Brock, Donna's husband, who had been giving Harley cold baths and fever medicine during the day. She began complaining that her arm hurt, and what looked like a little bruise appeared on her hip, Brock says.
"I took and raised the sleeve of her shirt, and she cringed. It looked like someone took two fingernails and clawed...her arm. I was thinking, 'What is that?' And then I took and moved the shirt off of her shoulder. I pulled the shirt down off of her shoulder, and on her shoulder she had what looked like a silver dollar," she says. "What it looked like to me or reminded me of was like she had fallen on concrete and skinned it. It was scabbed over. I was thinking, 'What is this?'"
Brock had seen Harley in a bathing suit the day before, and she hadn't noticed anything on her skin like the bruises. She called her sister, a paramedic. The sister said she needed to get Harley to an emergency room.
"I walked back over to Harley and her lips were starting to turn blue," Brock says. "I called 911."
Once she arrived at the local hospital, doctors started Harley on antibiotics. They quickly decided to get her to Texas Children's Hospital in Houston, Brock says. They wanted to send her by a helicopter ambulance, but none was available, Brock says. So, they sent her by ambulance. Donna and Earl Brock followed.
"When the ambulance left, they were doing the speed limit. Then they got to where they were going 60, 65, 70, 75, 80. We were doing almost 100 before we got there," she says. "My son was in the ambulance. He saw them mashing on her stomach."
They got to the hospital and went to the back of the ambulance, but the attendants would not let them near it, she says. One of them put his hand on the back of the ambulance door so they couldn't open it, she says.
"It seemed like forever before they really opened the ambulance, and then when they opened it and pulled her out, she was hemorrhaging from the nose, the mouth; I mean, she just had blood everywhere," Brock says, pausing. "The only thing I remember after seeing her was I remember them telling the hospital that they had a code blue. That meant she was dead on arrival."
She was close to it. The purplish "rashes" and bruises from the destruction of blood vessels now seemed to cover her entire body. As meningococcal sepsis took over, doctors treated her with drugs designed to keep her vital organs from shutting down.
Harley spent two weeks in a coma and on life support and about three months in the hospital.Relatives watched as Harley's body changed in her struggle to live.
"In the beginning, both hands were black. Both feet were black, and I'm not talking just feet. It went almost to her knees. She swelled up so big that her ears started folding out," Brock says, pushing her ears outward to demonstrate. "You couldn't even tell she had a neck. She was on life support. She had these lesions everywhere."
When she was finally released, Harley's hearing was badly damaged, and her hands and feet were black. "When she came home, these fingers were totally shriveled," Brock says, raising her hands. "They looked like a prune.
"Her left foot was totally black. It felt like ceramic," she says, rapping her knuckles on the table to produce what she says sounds the same as knocking on the blackened foot.
Before amputating, doctors wanted to wait to see if any of her extremities would regain blood circulation, so they sent Harley home with her ruined foot still attached, Brock says.
"The doctor said, 'Are you prepared? You may be home putting her sock on and her foot might fall off in your hand.' How do you prepare yourself for something like that? The tip of her thumb fell off in my sister's hand and she about had a heart attack," she says.
"But it was sad after they amputated...I just couldn't tell her you don't have a foot. Of course, she didn't realize because she had a bandage," she says. "My sister was back there when they undid the bandages. My sister said Harley looked at her and said, 'They cut my foot off'...It just killed her when she said that."
The doctors did all they could with the treatments they had available. But, as Harley clearly proves, even those who survive the horrible disease can suffer its effects forever. Harley is not the same as she was before being stricken.
Now 6 years old, she is without her left foot and wears a prosthetic to school. She lost the tips of her first two toes on her right foot and three fingers. She wears hearing aids because her hearing, while at about 80 percent, is not complete. She was held back in kindergarten because she has a speech impediment now, Brock says. She has large, burnlike scars on her skin in places where Donna and Earl first saw what they thought was bruising on that afternoon three years ago. Besides all that, she still faces surgeries to correct problems with scarred bone growth plates. Her outcome is one that is considered relatively good for a patient who did not receive Neuprex.
Harley will have no finger for a wedding ring, but that's not important, Brock says.
"I just thank God every day that he let us keep her," Brock says.
By the time Neuprex was infused into Tashica, the "ramp up" effort to test its usefulness in fighting meningococcal sepsis had been significant, Giroir says. As many as four of Giroir's team would visit the tiniest of clinics in Texas to educate them about the study, he says. Getting a pharmaceutical company to agree to pay for the clinical trial was not easy because the ultimate payoff could be as small as the 300 to 400 cases per year.
But Berkeley, California-based XOMA agreed to take on the trial and collaborate with New York University in the development of Neuprex. XOMA banked on the possibility that Neuprex could have applications in other treatments for shock after it was approved to treat meningococcal sepsis.
After Tashica, the next seven patients who were given the treatment in subsequent months also responded well and they lived. Giroir expanded the study.
"The bottom line is that we started to have a study where we only wanted six to eight patients, but because everybody was living, we, with the approval of the FDA...extended the trial to 25 to 26 patients," he says.
The results were astonishing. Tashica was the cover girl for XOMA's 1995 annual report. "Tashica is Number One," the cover said beside a smiling and radiant Tashica. The treatment would be designated an orphan drug and put on the FDA's fast track for a second, much expanded and much more expensive trial. It seemed almost miraculous.
In 1996, XOMA started what was called "Phase III" of Neuprex trials. Jack Castello, chairman, president and chief executive officer, says his company is ultimately a business, a publicly traded company, that needs to make money, but that doesn't mean it isn't interested in finding effective treatments for rare diseases. In the case of the Neuprex trials for meningococcal sepsis, it just made good emotional and economic sense, he says.
"We were approached by people like Brett Giroir who knew of the characteristics of the drug who said two things: One, there is a real need," he says. "There are children, even babies, dying horrible deaths of this disease every day, every year. When we get into it, it's probably one of the most horrible ways to die of any that you could ever dream of, and certainly for a child it's got to be just devastating, the amputations, the limbs turning gangrenous, the horrible eruptions, 20 different fluid lines into a baby. There's a lot of emotional reason to do it."
From a drug-development standpoint, he says, both the massive endotoxin production and the relative predictability of the disease helped make meningococcal sepsis an excellent testing ground to help determine the ability of Neuprex to treat sepsis that resulted from other causes, such as a blood infection from a gunshot wound. It was a bit of a tough sell, but Castello eventually prevailed and received approval to proceed.
The second trial employed what is known as "double-blinded, placebo-controlled" methods. That meant that neither doctors nor patients knew who got the drug. Doctors such as Giroir were so convinced that Neuprex helped that they did not want to even use a placebo on any children, but the government requires it.
In the case of Neuprex, XOMA set out to prove the drug reduced deaths. Once the study started, however, it became clear that proving a mortality reduction would be a problem. The rapid progression of the disease made it terribly difficult to transport study subjects to participating hospitals before they died.
During the first Neuprex study, which Giroir set up himself, hospitals all over Texas were notified, and transportation by Careflight was arranged. Giroir could get the patients to his door or to the door of a hospital such as Texas Children's Hospital in Houston quickly. That wasn't the case this time around. The entire United States and Canada and the United Kingdom were included, and both transportation and education were problematic. Patients were dying before they could be included in the study.
"All the cases of meningococcal sepsis don't occur in convenient places. They occur in Oshkosh, and they occur in Greenville, South Carolina. They don't always occur in Dallas, Texas, and San Francisco and New York City where all the big hospitals are," says Patrick Scannon, chief scientific and medical officer for XOMA, who keeps a photograph of a child stricken with meningococcal sepsis over his desk as a reminder of his mission.
Not only did it take time for doctors to identify the condition and get patients to a hospital participating in a study, but most patients often had already wasted many valuable hours at home dealing with what seemed like the flu.
"The average time to getting into the study was six hours from the time of first antibiotics to the time they got the study drug," Giroir says. "The issue was that two-thirds of the patients that were going to die, died by that six-hour time period."
Scannon says despite the lack of proof that Neuprex was having a significant impact on the number of deaths, their trial was showing Neuprex had a benefit to what is known as "morbidities," or other ill effects of the disease.
"We also showed a very substantial reduction in quantity and quality of amputations, of gangrene and amputations," he says.
So, during the course of the study, XOMA convinced the FDA to change the end point of the study from mortality rate to a combination of possible benefits from the drug.
"During a trial, lots of things happen that are beyond people's control or expectations. Patients might not be as sick; the natural history of the disease may change. There are established procedures whereby people who are conducting the study can actually look at certain kinds of events," says Karen Weiss, director of the division of clinical trial design and analysis in the FDA's Center for Biologics Evaluation and Research. "This is a fairly unusual and extraordinary situation...We went to the effort and agreed with the company to discuss actually changing the end point."
When the study was over, the FDA agreed that it appeared Neuprex might have benefits. But, the agency said, the study (which took three years to include 400 patients) did not scientifically demonstrate what it needed to for approval.
"What happened was that on that agreed-upon end point, which was a composite of not only looking at survival but other morbidities, on that agreed-upon outcome, there still wasn't a difference. There wasn't evidence that it was effective based on that," Weiss says.
In 2000, the results of the study were made public. The report on Neuprex was far less glowing than it had been five years before when Tashica was number one. The disease itself seemed to have beaten the study's effort to succeed. The FDA's failure to approve the drug for any kind of use was devastating to XOMA and Giroir's team.
"Of course, we were very, very disappointed. We had done everything that we thought we could do, and I think the FDA didn't disagree with us," Scannon says. "They just felt that on top of everything we had done, that to convince them that the product was suitable for approval we needed more information."
Once death was eliminated as proof of the value of Neuprex, the stamp of approval had relied entirely on whether the secondary end point, the "composite," could show that Neuprex had a significant effect on meningococcal sepsis patients. Unfortunately, that composite was designed between the FDA and XOMA without Giroir's input or the input of any investigators. As a result, the composite secondary outcome was flawed and ultimately meant Neuprex would be rejected by the FDA.
The dramatic reduction in amputations among those treated with Neuprex was obvious to doctors looking at the research results, but final results were lumped with many minor effects. The huge reduction in amputations was so buried by irrelevant conditions that the important benefit ultimately became statistically insignificant, Giroir says.
"This is the essence of it. This is why the drug didn't get approved. Because the composite variable, the way they structured it, if you had knee pain and you had four extremity amputations, you were put in the same bucket, the same category," he says. "There was death, life and this intermediate category that lumped all kinds of things together.
"If you look at the whole trial, we had a 68 percent reduction in amputations," he says. "Four kids with four extremity amputations in the placebo group. No kids with four extremity amputations in the BPI group. That's pretty compelling."
Connie Jimmerson sits on her couch, rubbing her now 14-year-old daughter's bare feet. Tashica lost half of her left foot, the toes on her right foot and the tips of her fingers, but she escaped meningococcal sepsis in comparatively good shape. If anyone believes in Neuprex and Dr. Brett Giroir, it's this mother and daughter. Jimmerson says when she first talked to Giroir on that night in 1995 about allowing Tashica into the study, to possibly save her daughter's life, she had no hesitation. Then, Jimmerson saw the blackness in her daughter's limbs stop spreading as soon as Tashica got Neuprex, she says.
"At first it was just at the tip of her toes, and then it started going on up, but after she got the medication, it stopped. I keep God first, but I really think it helped her."
Those involved in the failed efforts to get Neuprex to others who were in Tashica's position all similarly remain convinced the drug reduces amputations and that it could be proven to reduce death if it didn't take so long to get into doctors' hands.
"It's rather frustrating," says Elsbach, the researcher who is at the end of a career spent working on BPI. "I would agree with the FDA that they felt more information was necessary. But, you know, that is complicated by the fact that from what I could see looking at the data that if the agent had been available right on admission without delay, and I think Brett Giroir feels that way, that the results would have been quite convincing."
Scannon says he feels the same but concedes that launching a study that could get the drug to more patients is just too expensive to get funded. Even if it were funded, the speed of the disease competes with the time it takes to fill out paperwork to make the study valid.
"We felt, and continue to feel, that to do another study of meningococcemia would be very, very difficult to do because frankly there was nothing we could have done to accrue patients more quickly," Scannon says. "In other words, there is just a certain amount of paperwork it takes to legally conduct a proper clinical trial, and so it wasn't as if looking back on it we hit our hand on our forehead and said, 'Oh, my God, we could have done this better.'
"When the drug is approved and you don't have all this paperwork, it can be used as soon as the person hits the door. In fact, it could be used before they left Tyler, Texas, because it could be in Tyler, Texas, too," Scannon says. "In a clinical trial setting, we couldn't put Neuprexeverywhere in the world. We had to take our best guesses and put it wherever we thought it should go."
Sitting in his office almost two years to the day since the final results of the study were made public, Brett Giroir recounts the efforts to get Neuprex into the hands of doctors everywhere. He is clearly just as convinced that Neuprex has a profound effect on meningococcal sepsis now as he was after Tashica was infused with Neuprex seven years ago.
"There were people who believed that based on those data the drug should have gotten some kind of approval," he says. "You have a drug that may or may not work, but it has no side effects and the alternative is no arms or no legs or a dead child? Yeah, I'll take that compared to all the other really experimental things we do in the ICU to try to rescue these kids."
Get the This Week's Top Stories Newsletter
Every week we collect the latest news, music and arts stories — along with film and food reviews and the best things to do this week — so that you'll never miss Observer's biggest stories.