Preemie study sparks debate on research risk disclosures

WASHINGTON, Sept. 5, 2013 — Dagen Pratt's parents enrolled their tiny premature baby in a study of oxygen treatment believing she'd get the best possible care. They didn't understand it was an experiment to test what dose works best. No one mentioned any risks.

Now 6, Dagen struggles with cerebral palsy, and they wonder: Is that long-ago study to blame?

"Tell
me that the Support study did not hurt Dagen in any way," her father,
Shawn Pratt, challenged a U.S. government panel on Wednesday as his
daughter, dressed in a bright sundress, stood quietly by.

A major
controversy has erupted over what sounds like a straightforward
question: How much should patients be told about the potential risks
before they're enrolled in certain kinds of medical research?

The
issue isn't about how to study a brand-new, unapproved therapy. All
sides agree that those studies must fully inform participants that
there's no guarantee the experiment will work, or even be safe.

Instead,
the debate is about one of modern medicine's dirty little secrets:
Doctors frequently prescribe one treatment over another without any
evidence to know which option works best. There's no requirement that
they tell their patients when they're essentially making an educated
guess, or that they detail the pros and cons of each choice. Researchers
are supposed to outline all the risks when they study which commonly
used option is best. But could that mislead patients into thinking
research is riskier than their own doctor's best guess?

U.S.
federal health officials put that question to the public Wednesday, as
they debate how strictly to regulate this type of research — a debate
sparked by that study of premature babies who included Dagen Pratt of
Kingwood, W.Va.

The tiniest preemies face serious risks, including death and disabilities.

Oxygen
has been a mainstay of treating them, but doctors didn't know just how
much to use. Too much causes a kind of blindness called retinopathy of
prematurity. Too little can cause neurologic damage, even death. So
hospitals used a range of oxygen, with some doctors opting for the high
end and some for the low.

The Support study, conducted between
2005 and 2009, aimed to settle which end of that range was the best
dose. It randomly assigned about 1,300 preemies at 23 hospitals to a
lower or higher oxygen dose. To researchers' surprise, slightly more
babies who got the lower dose died, a finding that has led to new
standards for the care of preemies.

The problem: A government
watchdog agency last spring ruled that researchers violated federal
regulations that required them to spell out the risks of the study for
parents. Nowhere in the consent forms that parents had to sign was death
mentioned.

"This was a very, very important study to do," Dr.
Jerry Menikoff, head of the Office for Human Research Protections,
stressed Wednesday. "All we were asking for is a couple of sentences to
say there were risks," he added.

He agreed with consumer
advocates that a similar study in New Zealand phrased the issue more
appropriately, saying the question is whether the lower dose "is safe
and effective in reducing serious vision and lung problems without
increasing mortality or neurodevelopmental disability."

But
critics, including the head of the National Institutes of Health, argued
that back in 2005, doctors didn't think the lower dose really posed a
survival risk — the question was more about which dose did a good-enough
job at saving their vision.

In fact, preemies who didn't enrol
in the study — and got whatever range of oxygen their doctors deemed
best — turned out to have a higher risk of death, said NIH Deputy
Director Kathy Hudson.

Dr. John Lantos, a bioethicist at
Children's Mercy Hospital in Kansas City, Mo., knows that firsthand. His
twin grandsons were born during the Support study but weren't given an
opportunity to enrol. One died soon after birth. The other today is
thriving but suffered severe retinopathy and has poor vision.

"Nonvalidated
therapy is often more dangerous than careful research," Lantos said,
adding that the consent forms should make that clear as well. "Doctors
just hate to say they don't know something. When they do say it, we
should listen."

While the experts debated how to explain research
risks, two families who travelled to Washington for the unusual meeting
outlined a bigger hurdle: Reeling from the stress of having a
vulnerable preemie, they simply didn't understand that they were
participating in an experiment. And they still haven't been told what
dose of oxygen their children received, and it's impossible to say
whether lingering health problems are a consequence of the study or of
being extremely premature.

Yet, they now wish they hadn't participated.

"I
unknowingly placed my son in harm's way," said Sharissa Cook of
Attalla, Ala., who wonders if vision problems experienced by her
6-year-old, Dreshan Collins, were caused by the study or from weighing
less than two pounds at birth. "The only thing a mother wants is for her
baby to be well."

Dagen's mother, Carrie, was more blunt with
reporters: "Why is omitting information not considered lying?" she said.
"We were told they would give her the best care every day."