Exposing dangerous flaws in a clinical trial that put premature babies at risk

An unethical clinical trial exposed 1,316 premature infants to increased risk of blindness and death without parents being informed of the risks. Public Citizen alerted the world.

  • 1,316 Number of premature infants exposed to an increased risk of blindness, brain damage and death while in the SUPPORT trial.
  • 12 Number of weeks the premature infants could be enrolled in the life-threatening trial.
  • 23 Number of major academic medical centers involved in the SUPPORT trial.

In 2013, Public Citizen learned of a highly unethical federally funded clinical trial that took place throughout the country between 2005 and 2009 involving premature babies. Determined to ensure that similar failings couldn’t occur again, Public Citizen rang alarm bells.

On April 10, 2013, Public Citizen contacted media nationwide about the trial, which had been funded by the National Institutes of Health (NIH). We told reporters how the Surfactant, Positive Pressure and Oxygenation Randomized Trial (SUPPORT) tested two experimental strategies for managing oxygen treatment in premature babies, with one group maintained at a low blood oxygen level and the other at a high level. The trial exposed 1,316 premature infants to increased risk of blindness and death without parents of the babies being informed of the risks to their babies or the true nature and purpose of the research.

The trial

Premature babies usually require treatment with oxygen. As part of routine care, the amount of oxygen given to such babies is adjusted based on a measure of blood oxygen level called oxygen saturation, which can be continuously checked with a probe placed on the skin.

For the medical centers participating in the SUPPORT study, routine care of premature infants not in the study typically involved giving enough oxygen to maintain oxygen saturation levels between 85 and 95 percent. The exact oxygen target level for a particular infant at any particular time would be based on the baby’s individual medical needs and the wishes of the baby’s parents.

In contrast to usual clinical care, the extremely premature infants enrolled in the SUPPORT study were randomly put in two groups that each received a different experimental target range of oxygen saturation: a low range (85-89 percent) and high range (91-95 percent). The researchers primarily wanted to see whether the babies were more likely to die or suffer retinal damage, which can lead to blindness, if their oxygen levels were targeted to the low or high range. It has long been known that, in general, giving high levels of oxygen to premature infants can lead to retinal damage, blindness and lung injury, while giving too little oxygen can cause brain damage and death.

Lack of consent

As documented in a March 7, 2013, letter from the Office for Human Research Protections (OHRP) in the Department of Health and Human Services (HHS) to the University of Alabama at Birmingham, one of the lead institutions for the SUPPORT study, the consent forms for the study did not disclose to the babies’ parents any of the risks of the experimental oxygen management interventions, including risks of severe retinal damage, possible blindness, neurologic injury and death. The consent forms also failed to address two other critically important pieces of information:

  • That one purpose of the research was to determine whether extremely premature infants were more likely to die if treated with the higher versus lower oxygen target; and
  • An explanation of how the infants would be treated if they weren’t in the study compared to how they would be treated by participating in the study.

What we did

Public Citizen called on HHS to:

  • Apologize to the parents;
  • Ensure that participating institutions take corrective action to avoid such serious deficiencies in the consent process for future research;
  • Launch an independent investigation into how the HHS system for review and oversight of clinical trials failed so miserably.
  • Determine what systemwide actions are necessary to prevent similar future failures; and
  • Identify and suspend any similarly unethical ongoing research involving premature infants that is funded by NIH or any other HHS agency.

What happened next

Public Citizen’s letters – and the subsequent media attention – generated a heated debate in the medical research community over what constitutes informed consent. The debate was hugely important because of the impact it could have on ethical and regulatory standards for clinical trials.

Publicity over the SUPPORT trial also sparked an unusual HHS public forum on August 28, 2013. The meeting gave the public the rare opportunity to comment about the adequacy of protection of human subjects in clinical trials. Public Citizen’s experts testified on the gravity of the ethical breaches of the SUPPORT trial. Parents of babies enrolled in the trial also spoke out and joined Public Citizen in a press conference outside HHS.

 

We want you to explain why the intent of study was not originally provided to us as it was envisioned by DHHS. We want to know why the risks and intent of the study were not clear. Why was our child a subject in a medical experiment without our knowledge or permission? Carrie Pratt, parent of a DHHS SUPPORT participant

In October 2014, OHRP confirmed that parents of premature infants enrolled in the government-funded SUPPORT trial were not given adequate notice of the trial’s risks. The agency simultaneously released a guidance document, “Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care.”

Since Public Citizen unveiled the trial’s risks in 2013, we have continued monitoring the study. In 2017, Public Citizen uncovered new information on the SUPPORT trial that revealed additional major ethical lapses and failures to comply with key requirement of federal regulations for the protection of human subjects. Public Citizen’s request that the OHRP immediately expand its ongoing compliance oversight investigation in the SUPPORT trial is still awaiting answer.

The word ‘unethical’ doesn’t even begin to describe the egregious and shocking deficiencies in the informed-consent process for this study. It is highly likely that had they been appropriately informed about the nature of the research and its risks, many, if not most, parents would not have allowed their babies to be in this study. Dr. Michael Carome, director of Public Citizen’s Health Research Group

Highlights

  • The SUPPORT trial endangered premature infants by randomly assigning them to high- or low-oxygen groups, causing those in the low-oxygen group to be exposed to hypoxia (blood oxygen levels below the range considered to be safe).
  • Researchers primarily wanted to see whether the babies were more likely to die or suffer retinal damage, which can lead to blindness, if their oxygen levels were targeted to the low or high range.
  • It has long been known that, in general, giving high levels of oxygen to premature infants can lead to retinal damage, blindness and lung injury, while giving too little oxygen can cause brain damage and death.
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