Its an incredibly stressful time: Your child has just been born weeks premature and is raced to intensive care.
By ALAN BAVLEY
The Kansas City Star
Suddenly, youre asked to let your fragile new child become part of a research study.
How much should you be told about the studys potential risks or benefits? How much should any patient be told before agreeing to become a research subject? That question has the medical community embroiled in a heated debate.
Dozens of prominent scientists and ethicists have been taking sides, some insisting on transparency, others saying some kinds of information may actually mislead and could scare people off from volunteering as subjects.
It all started early this year when a federal watchdog agency accused leaders of a major national preemie study of bungling the issue of informed consent. The agency said parents werent advised that their babies faced potential risks of blindness, neurological damage or death.
Now a patient advocacy group has broadened the debate by raising similar questions about a second preemie study. This time, Childrens Mercy Hospital is among as many as 20 research centers participating.
It may all come to a head today in Washington at a Health and Human Services public meeting on how federal informed-consent regulations should be applied to studies such as these that try to fine-tune accepted medical practices.
Informed consent is central and crucial, but its not handled well, said John Lantos, a pediatrician and director of the bioethics center at Childrens Mercy. Lantos plans to attend the HHS meeting today.
The system is broken, Lantos said. I hope what comes out of these meetings is an acknowledgment that it needs to be fixed and a clear statement of how to fix it.
He spoke confidently that Childrens Mercy is doing right by its patients, even as he argued for more clarity in the federal rules for explaining the risks and benefits of research studies to potential participants.
In March, the current controversy arose after the HHS Office of Human Research Protections determined that a federally financed study of about 1,300 preemies at such prominent research centers as Yale, Stanford, Duke and Emory had broken rules by not advising parents of reasonably foreseeable risks to their babies.
The Surfactant, Positive Pressure and Oxygenation Randomized Trial, or SUPPORT, study looked at how much supplemental oxygen preemies should receive. Doctors have known for a generation that giving these infants oxygen can save their lives or prevent brain damage, but that too much can lead to blindness. While an acceptable range of oxygen levels had been established, doctors werent sure if they should stick to the higher or lower ends of the range.
Preemies in the SUPPORT study, which ran from 2004 to 2009, were selected at random to receive higher or lower amounts of oxygen. Ultimately, the study found that babies who got the higher amounts were more likely to suffer severe eye damage, but they also were less likely to die.
It would have been appropriate for the consent form to explain that the study involves substantial risks (and) that by participating in this study, the level of oxygen an infant receives would in many instances be changed from what they would have otherwise received, HHS said.
The parents of five of the children in the SUPPORT study sued the University of Alabama-Birmingham, where the study was based.
And Public Citizen, a Washington-based patient advocacy group, pounced on the HHS findings. It called the SUPPORT studys informed-consent process unethical and demanded that HHS Secretary Kathleen Sebelius apologize to the parents of the children in the study. It also asked the agency to suspend enrollment in another half-dozen studies by the same consortium of research centers until its informed-consent procedures could be scrutinized.
Meanwhile, 45 prominent ethicists and physicians signed a letter to the New England Journal of Medicine saying that SUPPORTs informed-consent documents were seriously inadequate.
A similar number of prominent experts, including Lantos and Francis Collins, director of the National Institutes of Health, defended SUPPORT. Several even invoked the preemie son of John and Jacqueline Kennedy who died shortly after his birth 50 years ago as a reason to maintain the research.
When babies like Patrick Bouvier Kennedy are born today, they wrote, their chances of survival to adulthood are greatly improved, thanks to research made possible by thousands of parents and their children.
Public Citizen upped the ante last week by releasing its analysis of another federally funded study, the Transfusion of Prematures, or TOP, trial now underway. TOP assigns groups of preemies to receive transfusions on either a restrictive basis or a liberal basis determining at what point a blood transfusion is ordered.
Public Citizen found that generally, the TOP consent forms made no mention of potential risks.
This study does not carry any additional risks to your baby if you choose to take part, the Childrens Mercy consent form obtained by Public Citizen says.
We believe that is simply misleading, said Michael Carome, a physician and director of Public Citizens Health Research Group. The researchers should be fully transparent.
A preemie who receives too little blood runs the risk of heart stress, brain injury, even death, according to Carome. But frequent transfusions can delay the maturation of the infants bone marrow or lead to serious damage in the colon.
I believe that if parents were fully informed, few would choose to participate, Carome said.
Standard care for preemies allows doctors to tailor transfusions and other treatments to babies individual conditions, Carome said. TOP doesnt allow doctors much leeway to vary from the study except in emergencies.
Each baby is unique and the factors vary from baby to baby, Carome said. You dont want to wait until a baby is at the cliffs edge.
Lantos, the Childrens Mercy ethicist, scoffed at what he called Caromes beautiful and romantic view of decisions made in an intensive care unit.
Because infants are monitored around the clock, they may be seen by a dozen doctors, Lantos said, each making judgments on factors that may or may not be grounded in scientific evidence. That being the case, regular care may be just as random as being assigned to one or another group in a research study, he said.
Lantos said the consent forms that research institutions such as Childrens Mercy prepare are based on their best guess of the federal regulations, which can be ambiguous.
HHS should insist that potential study subjects are given accurate information about the relative risks and benefits of both research and non-validated therapy, Lantos says in a statement he plans to deliver today. That is the only way to insure that choices be truly informed choices.
In June, HHS reacted to the SUPPORT controversy by putting its compliance action on hold while it studied the informed-consent process. That process begins with todays meeting.
Lantos plans to present his own story, as a grandfather. Seven years ago, his twin grandsons were born prematurely. One died of respiratory failure. The other is thriving but has poor vision.
We didnt know about the SUPPORT study, Lantos says. I wonder how our family would feel if the twins had been enrolled.
To reach Alan Bavley, call 816-234-4858 or send email to firstname.lastname@example.org.