10 May (AHRP) – Newly obtained documents from the oxygen experiment (SUPPORT) reveal far more extensive medical ethics violations than those specified in the March 7, 2013 letter by the Office of Human Research Protection to the University of Alabama. On May 8, 2013, Public Citizen submitted a follow-up letter to Secretary of Health and Human Services Kathleen Sebelius and detailed analysis (31 pages) of the SUPPORT research protocol and consent forms approved by each of the 23 IRBs at the participating medical centers at which the experiment—Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) had been conducted on more than 1,300 extremely premature babies.
The review of 22 IRB-approved consent forms for the SUPPORT trial reveals that NONE complied with mandatory Federal disclosure requirements:
- NONE of the 22 consent forms explained that death was a risk—especially for babies randomized to low oxygen levels.
- Only two of 22 consent forms disclosed that babies randomized to high oxygen levels were at increased risk of retinopathy or blindness.
- NONE of the 22 consent forms disclosed that the pulse oximeter readings—that neonatologists rely on to determine an infants’ need for supplementary oxygen—were intentionally altered to provide the treating medical teams with either false high or false low oxygen saturation values (SOP2).
The IRB-approved consent forms falsely assured parents that the study posed no risk:
“Because all of the treatments proposed in this study are standard of care, there is no expected increase in risk for your infant.”
In fact, the primary purpose of the experiment—as stated in the protocol —was to assess the effects of two experimental strategies for managing oxygen and two strategies of ventilation therapy in extremely premature babies; the primary endpoints being: death vs. retinopathy (or blindness). But lacking a comparator group of babies who received standard-of-care which is, individually titrated oxygen, the experiment could not inform physicians whether either of the experimental groups compared favorably or worse than standard-of-care in terms of deaths and rate of retinopathy.
The parents from who consent was obtained were mostly young single mothers [indeed, the authors noted that “guardians” gave consent in some cases.] They were educationally and economically disadvantaged, had little understanding about the complexities of standard care provided to extremely premature babies whose survival depends on carefully calibrated life-support interventions such as oxygen supplementation and intubation (an invasive procedure involving insertion of a tube in to the trachea, the main airway leading to the lungs). Nor did they have any understanding that experimental treatments posed increased risks for the babies. The deceptive consent documents provided no clue about the true nature, purpose or risks involved.
The young mothers trusted the doctors and—as the editor of the NEJM suggested in an editorial defending the dubious consent process for SUPPORT—the mothers were
“reassured that giving birth at an academic medical center with a sophisticated nursery for premature newborns and with physicians who have extensive experience with very preterm infants” will provide the best care for their tiny, fragile premature infants.
But, as the protocol and consent documents demonstrate, the mothers (or parents) who consented to entrust the care of their baby to the doctors in this Federally-sponsored trial were badly deceived—they were not infomed about the increased risk of death for babies assigned to the low-oxygen group, and not told that the risk for eye disease (potential blindness) might be increased in babies assigned to the high oxygen grooup–their consents are, therefore, invalid.
In standard care, each baby’s individual needs is assessed by a skilled neonatologist whose professional judgment determines if and when an intervention is necessary. In randomized medical research, individual patients’ needs are subordinated to the requirements of the research protocol, which is one important reason why ethical standards and legal statutes require that “the voluntary informed consent of the human subject is absolutely essential.” [Nuremberg Code, Code of Federal Regulations]
For complete article go to AHRP.
For more on this subject also see Crucial Studies, Fragile Subjects and Neonates sought as Guinea Pigs.