The trials among children, which will ultimately be conducted at five universities in the United States, will allow researchers to determine effective and safe dosing of the vaccine, which has been designed to prevent a strain of influenza that has already claimed more than 1,000 lives worldwide.
"There was a lot of thought and consideration about the safest but most expeditious way to proceed, and we have completed enrollment," said Dr. Karen Kotloff, lead investigator of H1N1 studies conducted at the University of Maryland School of Medicine, which is leading the trials. "This is a vaccine that is made in exactly the same way as the standard, licensed flu vaccine."
Roughly 600 children are enrolled in the National Institutes of Health's trials, she said. They are evenly divided into three age groups: 6 to 35 months, 3 to 9 years, and 10 to 17 years.
Children will receive two doses of vaccine, with half receiving 15 micrograms of antigens -- just as they would for each of the three strains in seasonal flu vaccine -- while others will receive30 micrograms to see if a higher dose is needed to protect against swine flu.
Younger children will undergo three blood draws to test vaccine effectiveness while children above the age of 10 will undergo five -- similar to adults -- a concession to the younger children's dislike of having blood taken.
"We try to spare children the anxiety and discomfort associated with blood-drawing," Kotloff said.
For the most part, children's trials are similar to the adult version, but with a few notable differences.
"The difference is we have to get consent from both the parents and the child," said Dr. Janet Englund, a pediatrician with Children's Hospital, Seattle, who is running one of the five branches of the study, explaining that any child 7 or older must give their own consent to participate in the trial. She said that about 2 percent of children do refuse to participate.
While some concerns have been raised about the speed of clinical trials in children for the flu vaccine, doctors cited both the concern of having vaccine available in time for flu season and the history of medications needed for adults and children as reasons for the child trial following so soon after the start of the adult one, which started on Aug. 7.
Not Just Smaller Adults
"The history of doing clinical trials in kids is an evolving one. We are now in the stage in our evolution where kids' trials start sooner than they used to," said Dr. Harley Rotbart, professor and vice chairman of pediatrics and microbiology at the University of Colorado Health Sciences Center at Denver and author of "Germ Proof Your Kids," who is not involved in the NIH's clinical trials.
He said that testing on children is often done quickly after testing in adults because pediatricians used to have difficulty knowing how to dose medications in children.
"When a pharmaceutical company would get approval in adults, they would never do [clinical trials] in children," he said. "We ended up treating children as mini-adults."
Side effects, said Rotbart, could present an issue.
"One issue is dosing, but the second issue is that adults and children have different rates of and types of side effects from vaccines," he said.
While local effects of the injection might be shrugged off in adults, they would be taken more seriously in children.
"Kids are not just little adults, and all the questions that we asked when we do adult trials have to be asked again, because kids are a different species," Rotbart said.
Kotloff noted that those concerns present themselves in swine flu vaccines, hence the separation by age group.
"There's different information that you get from each age group," she explained, although she noted that is most obvious with the oldest patients. "It does seem that people over about age 50 have some immunity to this H1N1 swine flu. Children have little or no immunity."
She noted that this might affect both the number of shots and dosing to provoke an immune response.
"The amount of vaccine for immune status may differ by age group," Kotloff said.
Swine Flu Vaccine Trial Enrollment Concerns
While some parents might worry about enrolling their children in a clinical trial, doctors said those concerns could be assuaged.
For one thing, noted Dr. Kathryn Edwards, the pediatrician running Vanderbilt's branch of the clinical trial for swine flu vaccine, no one in the study would be receiving a placebo.
"Everybody wants to get some protection; they don't really want to go through this process and get nothing," she said.
Additionally, she noted that all the adults vaccinated for swine flu at Vanderbilt have been followed up with and no adverse events have been reported.
"The other thing that gives us a lot of confidence is this vaccine is made the same way as the flu vaccine we make every year," she said.
Doctors also noted that they would have their own children participate, and many of them do.
"At this one site, of the first 50 people who signed up, most of them were actually the children of medical professionals," Kotloff said.
Englund noted that her own children, while now too old to participate in children's trials, had done so in the past.
"As someone who's been doing this for 30 years, I would never give a vaccine if I wouldn't give it to my own children or grandchildren," Edwards said. "There is a very sophisticated and integrated data safety and monitoring committee that includes experts in pediatric and adult medicine."
She said that one person who had gotten the adult vaccine came in complaining of muscle aches, but it was ultimately determined that the person got the aches from pulling weeds, not the vaccine.
"He couldn't move, but obviously he had another reason or another explanation," Edwards said. "The assessment of adverse events is taken very seriously."
Swine Flu Vaccine Safety Panels
Edwards also noted that safety was determined separately from efficacy.
"That data safety and monitoring team does not include any investigators," she said. "It is a totally independent group."
Ultimately, Edwards said, she believes that the trial for the vaccine would likely be not only safe, but effective.
"I spent about two days going through old freezers here to find blood from children who were in the 1976 vaccine trial," she said, referring to the last outbreak of swine flu in the United States.
She had those tested, and they were found to have responded to the vaccine. She said she sees this vaccine producing an immune response, unlike the avian flu vaccine.
"I think that from that experience, we would suggest that two doses likely will work," she said.