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Differences on display on US informed-consent rules

Was it enough for doctors to tell the parents of extremely premature infants that there was “no additional risk” to their babies if they enrolled them in a randomized trial?  One treatment group, in which the preemies were maintained with higher blood oxygen, risked eye damage.  The other kept the babies at lower oxygen levels, risking brain damage and perhaps death.  Both were within the range of care that the babies would have received anyway.

That’s one of the loaded questions that senior US health officials grappled with today at an unusual public meeting convened by the National Institutes of Health (NIH) and the Office for Human Research Protections (OHRP), which polices the ethics of NIH-funded clinical trials.

The meeting was called after OHRP set off a firestorm this spring when it told investigators from the multi-site, NIH-funded SUPPORT trial that its consent forms failed to describe “the reasonably foreseeable risks of blindness, neurological damage and death” to the 1,316 infants that participated. (SUPPORT stands for ‘surfactant, positive pressure, and oxygenation randomized trial’, and the paper that resulted from the trial is here.)

At today’s meeting, officials heard from a parade of highly educated speakers, but perhaps the most moving testimony came from the parents of two infant participants in the study.

“They should have conveyed to me the effect of my son’s oxygen level being too high or too low,” said Sharissa Cook, an Alabama mother whose son was born weighing 765 grams (1 pound and 11 ounces). “Had I known the full extent of this study I would not have given my consent.”

Shawn Pratt, a West Virginia man, brought his pig-tailed six-year-old daughter, Dagen, to the meeting. She  was born 15 weeks early and had early surgery to correct eye damage, which is a common side effect of high levels of oxygen therapy. She also has cerebral palsy, which can result when premature infants get too little oxygen.

“Why was our child a subject in a medical experiment without our knowledge or permission?” Pratt asked. “We want to understand why the intent of the study was not originally provided to us, as it was envisioned by its designers.”

After the OHRP criticized the study’s consent forms in March, a string of reaction followed from the highest research echelons. They included this commentary in the New England Journal of Medicine by NIH director Francis Collins and his policy deputy, Kathy Hudson. Most of the responses defended the trial and the forms, arguing that the babies were put at no additional risk. But a vocal minority of physicians and bioethicists and the advocacy group Public Citizen have loudly disagreed. So did this Nature editorial, published last week.

Today’s meeting was an effort, in part, to keep the two sides talking — and listening to one another — as the OHRP sets about clarifying the rules for informed consent when treatments that are already in use are being studied. (And studied they will be, in increasing numbers, because the health care reform law of 2010 — otherwise known as Obamacare — has mandated such work.)

The unusual format of the meeting had speakers testifying before three senior officials — Jerry Menikoff, the OHRP director, the NIH’s Hudson, and Robert Temple, who directs the US Food and Drug Administration Center for Drug Evaluation and Research.

It was clear that views remain polarized.

“Randomization to the extremes of a usual care range has very real risks that need to be understood … and disclosed to patients,” argued Robert Danner, a critical care physician at the NIH Clinical Center. (Danner was speaking for himself, and not for the agency.)

“Making the research sound riskier than it really is is problematic,” said David Magnus, a bioethicist at Stanford University in California who spearheaded this letter to the New England Journal of Medicine, criticizing the OHRP for overreaching.

The OHRP’s Menikoff, for his part, said that the two sides are closer than the volume of the recent controversy might indicate. Rather than taking issue with the trial as a whole, he said, “What the Department [of Health and Human Services] was concerned about was the risks, and that those risks were not disclosed.” A couple of sentences in the SUPPORT consent form laying them out plainly would have done the trick, he said.

But Edward Campion, a senior deputy editor of the New England Journal of Medicine, noted that the SUPPORT study consent form was already long, at seven single-spaced pages. “Whether an extra paragraph would have created one more iota of patient understanding is problematic,” he said. “The need for better education and transparency is not accomplished by the consent form.”

A spokeswoman said that the Department of Health and Human Services “will thoughtfully review” the comments it has collected on a public docket that remains open until 9 September. It has no set  timetable set for releasing the updated guidance.


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