June 14, 2017

After Learning of Faulty Equipment That Could Endanger Babies, Clinical Trial Leaders Continued Experiment, Apparently Didn’t Alert Key Officials

Quotes From Emails: ‘This Is Very Worrisome’ and ‘We Are Now Well Over 1,100 Infants … So We Will No Doubt Continue’

WASHINGTON, D.C. – Lead investigators for a federally funded trial involving premature infants were alerted to serious problems with oxygen monitors used in the trial while it was ongoing — problems that could have endangered the infants — but decided to continue enrolling infants without correcting the problems and without notifying proper authorities or the infants’ parents, newly uncovered documents appear to show.

The federally funded U.S. SUPPORT trial, which began in 2005, involved 1,316 premature infants at nearly two dozen research institutions throughout the U.S. The infants were randomly assigned to receive different amounts of oxygen, either in a low or high range. The last baby was enrolled in 2009, but researchers continued to collect long-term follow-up data on a large group of the subjects until age 6-7.

In light of the information, Public Citizen and two renowned bioethicists, Ruth Macklin, Ph.D., and Lois Shepherd J.D., today sent a letter to the Office for Human Research Protections (OHRP) — an agency within the U.S. Department of Health and Human Services — calling on the office to investigate the findings, sanction the responsible parties and inform the parents of babies enrolled in the trial.

“What we discovered is extremely disturbing,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “It appears that the babies in the experiment were knowingly put in harm’s way, but that neither the parents nor the institutional review boards (IRBs) responsible for overseeing the experiment at the research institutions were notified. Such actions would have subverted the multi-layered safety net intended to protect the babies who were the subjects of this complex experiment.”

When Public Citizen in 2013 learned of the trial, the organization called on the government to notify parents about serious ethical lapses that had occurred during the trial. The organization said the trial had been highly unethical because parents had not been adequately notified of the risks; the infants had been exposed to an increased risk of blindness, brain injury and death. Public Citizen also highlighted the unethical use of oxygen monitors that purposely displayed inaccurate readings to prevent the babies’ medical teams from knowing to which trial group the babies were assigned. HHS acknowledged Public Citizen’s complaints, but so far has refused to take further action.

In April 2013, Public Citizen sought under the Freedom of Information Act all NIH records related to the review and oversight of the experiment. After much foot-dragging by NIH and incomplete releases of documents, Public Citizen sued HHS, prompting the release of tens of thousands of pages over the past year.

Emails reveal that in June 2008, while babies were still being enrolled in the SUPPORT trial, the lead SUPPORT trial investigators were informed about serious problems with the oxygen monitors being used in the trial. These problems involved a defect in the devices’ underlying calibration software that was uncovered by researchers in the U.K. who were conducting a trial nearly identical to the SUPPORT trial’s oxygen experiment. Of particular concern was the observation by the U.K. researchers that the defective monitors appeared to be causing some of the babies to be exposed unexpectedly to more time at oxygen levels below the range considered to be safe.

The emails show that Dr. Neil Finer, national principal investigator for the SUPPORT trial, notified several other SUPPORT trial investigators and the lead NIH staff member overseeing the trial. Finer said in one email that “This is very worrisome.” Finer also said in another, “We are now well over 1,100 infants on our way to 1,310 so we will no doubt continue as we are.”

Public Citizen found no evidence that the entities that should have been told — and that had the authority to halt the trial (the IRBs and the OHRP) — were ever told about the faulty oxygen monitors.

The ethically appropriate course of action for the investigators to take would have been to immediately suspend subject enrollment in the trial, promptly report the problems to the responsible IRBs and wait for the outcome of the IRBs’ review.

“The apparent course of action taken by the investigators, if confirmed, represented a reckless disregard for the safety of the babies in the trial and major breaches of fundamental ethical principles and regulatory requirements governing research involving human subjects,” added Macklin, distinguished university professor emerita, Albert Einstein College of Medicine.

Read the letter and emails, and view other materials.

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