Health Letter, March 2016
By Michael Carome, M.D.
If you’re not outraged,
you’re not paying attention!
Read what Public Citizen has to say about the biggest blunders and outrageous offenses in the world of public health, published monthly in Health Letter.
More than 25 years ago, the editors of The New England Journal of Medicine (NEJM) unambiguously articulated the journal’s commitment to publish research studies involving human subjects only if the studies adhered to the highest ethical standards. Those standards included ensuring that subjects are not exposed to unreasonable risks and that they provide informed consent.
Reflecting this long-standing commitment not to publish reports of unethical research, NEJM policies for manuscripts reporting data from human subjects research require that authors include, “[i]f applicable, a statement that the research protocol was approved by the relevant institutional review boards [IRBs] or ethics committees and that all human participants gave written informed consent.” (Although not always sufficient to guarantee that research is ethical, appropriate review of human research by an IRB or ethics committee and informed consent are cornerstones of the system for protecting human subjects.)
Disturbingly, the current NEJM editors showed a willingness to publish and vigorously defend research that was unethical and that violated the journal’s policies regarding the protection of human subjects when they released an online article presenting results of the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) trial.
In an apparent attempt to satisfy the NEJM’’s requirements regarding human subjects, lead FIRST trial researcher Dr. Karl Bilimoria from Northwestern University and his co-authors stated in their article that the FIRST “trial protocol was reviewed by the Northwestern University institutional review board office, which determined the trial to be non-human-subjects research.” Importantly, it was only the manager of the Northwestern University IRB that made this determination — the IRB itself did not review or approve the trial protocol.
Even a cursory review of the FIRST trial’s methods described in the NEJM paper makes it immediately obvious that thousands of general surgery residents and their patients were human subjects of the research. Residents across the U.S. were randomly assigned, in groups by hospital, to either a “usual care” control group that complied with all current Accreditation Council for Graduate Medical Education (ACGME) requirements — which include a work-shift cap of 16 consecutive hours for first-year residents — or to an experimental group with a less restrictive, “flexible” work-hour schedule, where some first-year residents were forced to work significantly longer shifts (28 or more hours) than permitted under current ACGME rules.
The researchers then measured the rates of death and serious complications in patients cared for by the residents, as well as the residents’ perceptions of their work schedules, education, quality of life and well-being. Significantly, the researchers convened a data safety monitoring board to monitor their trial, a procedure that would have been unnecessary if the research truly had not involved risks to human subjects.
Without IRB review, there was no independent ethical assessment of the risks posed to the subjects enrolled in the trial, whether those risks were reasonable and sufficiently minimized, or the plan not to obtain the informed consent of the (unrecognized) subjects.
The failures of the researchers to characterize their trial as one that involved human subjects research, to ensure that it had appropriate IRB review and approval, and to obtain the informed consent of all trial subjects represented egregious ethical lapses. Equally alarming is the NEJM editors and reviewers’ inexplicable acceptance of the researchers’ assertion that their trial did not involve human subjects research, despite the incontrovertible evidence to the contrary.
When pressed by a British Medical Journal reporter to explain why the NEJM published the article, a journal spokesperson said, “We believe the study was conducted in an ethical fashion. The investigators followed appropriate procedures, and the study protocol was reviewed by the institutional review board office at Northwestern University.” (The spokesperson notably failed to clarify that the IRB itself had not reviewed the protocol.)
By backsliding on long-standing ethical commitments and violating their own policy, which is intended to ensure that all human subjects research published by the journal meets high ethical standards, the NEJM editors have signaled to the research community that the ethical lapses made by the FIRST trial researchers were acceptable, effectively encouraging similar lapses by future researchers.
And the research community wonders why public confidence and trust in the clinical research enterprise is eroding.
Public Citizen’s prior work regarding the FIRST trial, as well as a related trial in internal medicine residents, the iCOMPARE trial.
 Lenzer J. Longer shifts don’t increase harm to patients, finds controversial study. BMJ. 5 February 2016;352. doi: http://dx.doi.org/10.1136/bmj.i719.