Institutional Ethics Committees Move Too Slowly, Critics Say
On May 25, 2023, surgeons split open 39-year-old Jake Seliger’s chin and jaw bone and excised his entire tongue in an effort to remove a fast growing squamous cell carcinoma. They then removed some quadricep muscle, fat, and skin to create a flap in his mouth that acts as an incapacitated substitute, a journey Seliger has been documenting in a blog. But despite his doctor’s efforts to remove the cancer, a CT scan in July revealed new tumors in his neck, and possibly in his lungs.
Seliger’s prognosis at this point is terminal, though there are treatments that could possibly help him. He wants to enroll in one of two specialized clinical trials to target his quickly spreading cancer. But he may not have the opportunity to try. He told Undark by email that he’s frustrated that such trials can be delayed by bureaucratic hurdles.
Before medical research can take place, it has to be approved by an institutional review board. IRBs are ethics committees that review research proposals to protect participants and ensure their rights and well-being are protected. They also make sure the research is compliant with specific federal regulations, as well as any additional criteria the institution wants to add. There are about 2,300 IRBs in the U.S. While most IRBs are based at universities, the number of commercial for-profit IRBs has grown. In 2021 about half of those that reviewed medical studies were for-profit and serve private companies.
All human research is reviewed by an IRB — researchers submit proposals detailing the purpose of the investigation, the procedures, the risks and benefits, consent forms, and more. The committee decides whether or not the proposal is acceptable and may ask for revisions, which can take weeks or months depending on how often a given IRB convenes.
IRBs were officially codified in the National Research Act of 1974, after it became clear that more needed to be done to prevent unethical research. Among the most egregious examples was the Tuskegee Syphilis Study, in which researchers examined the effects of syphilis in Black men over the course of 40 years — and did not inform them when a treatment became available. More than 100 participants died as a result. And there are plenty of other examples from that era.
“Even well meaning people in that time found themselves doing things that undermined the public trust and harmed other people,” said Alex John London, a professor of philosophy at Carnegie Mellon University. In the absence of IRBs, London says it’s hard to imagine that researchers would write the same protocols and consent forms as they do knowing that a committee is going to be reviewing it.
“Even well meaning people in that time found themselves doing things that undermined the public trust and harmed other people.”
Although IRBs play an important role in protecting trial participants, critics say that the boards can also be overly cautious and protective of their institution, with consent processes that are intended more for shielding institutions from litigation or liabity.
IRBs also have “an element of paternalism,” said Holly Fernandez Lynch, an assistant professor of medical ethics at the University of Pennsylvania and co-chair of the Consortium to Advance Effective Research Ethics Oversight. “You could decide to ride a motorcycle or jump off a cliff with a parachute or whatever. You could do all of these things as a competent adult who is able to make decisions for yourself,” she said. “But you cannot just choose to participate in research that a researcher offers to you unless an IRB has said that that researcher can offer it to you.”
Since his surgery in May, Seliger often feels he is drowning in his own mucus, according to his blog. The damage to nerves means he can’t swallow properly, and without fully functional salivary glands, his mucus is thicker than it was, making it difficult to clear from his airway. He wrote that his “every breath enters my nose or mouth and triggers a Rube-Goldberg-like chain reaction of misery.” In September, in an effort to stop his cancer from spreading, he enrolled in a clinical trial of an antibody treatment, though it was not the trial he is hoping for. (He would have liked a personalized cancer vaccine currently in clinical trials, which showed good promise and minimal side effects.) The consent form he received, which Undark has reviewed, was approved by Advarra, a for-profit company that convenes IRBs, and is 23 pages long.
Drug companies and universities often want consent forms to be legal documents, said Robert Klitzman, a professor of psychiatry and director of the Master of Science in Bioethics program at Columbia University. Lengthy consent forms, he said, “for a patient with a serious disease who’s stressed and depressed or anxious, it’s just too much information.”
“From an ethical point of view,” he added, “it’s not designed to cover your butt but to actually have the person understand what they’re getting themselves into.”
The IRB process is “not a promise that you’re going to be protected against bad things happening,” said Fernandez Lynch. “It’s a promise that a group of reasonable people thought that this research study was an okay thing and acceptable thing to offer you as a research participant.”
As an example of how complicated consent can slow science, Simon Whitney, a physician, ethicist, and author, wrote of a heart attack study published in 1988 in his book “From Oversight to Overkill.” Before that point, it was up to a cardiologist’s discretion to treat patients after a heart attack. There were some experiments suggesting that the drugs aspirin or streptokinase, a treatment for inflammatory lung conditions, could be helpful, but individual physicians decided how to treat based on their own opinions about the research — no ethics committee required. (Whitney could not be reached for an interview due to ongoing illness, according to his publisher.)
However, the 1988 study, which was led by Rory Collins, currently a physician and epidemiologist at Oxford University, was designed to test the power of these drugs to save heart attack patients. The study launched in 16 countries, each with their own consent processes. The consent form approved by the IRB at Harvard University — one of the U.S. institutions engaged in the study — was four pages long and given to people while receiving emergency care for a heart attack. Though the U.S. had 20,000 eligible heart attack patients every month, on average only 12 were enrolled. In comparison, Britain enrolled 180 subjects a month, without a lengthy consent form. Collins concluded that the American consent process was responsible for about 10,000 unnecessary deaths.
The IRB process is “not a promise that you’re going to be protected against bad things happening.”
But, according to Whitney’s book, the IRB system was still more efficient before 1998, when a subcommittee of the Committee on Government Reform and Oversight met to investigate IRB performance after a report suggested that they were too overworked to serve as reliable protectors of human subjects. The committee concluded that the government could place sanctions on institutions that violated (or potentially violated) the regulations by suspending their authority to conduct federally funded research until further review. When that occurs, participants can’t receive treatments, enroll, or be recruited to studies, and results can’t be reported or analyzed. For researchers, it means losing months or years of work. For society, it means a delay of potentially helpful treatments.
Thousands of studies were halted in subsequent years. For instance, around 2000, a genetics researcher sent out a family history questionnaire to subjects in a study, after obtaining their consent. One of the participants’ fathers complained that he had not given consent to his genetic information being used for the study, so the government shut it down, along with more than a thousand other studies, some which had little or no connection to genetics. Before any of the studies could resume, they were subjected to additional review. Since those years of regulatory crackdown, Whitney writes in his book, IRBs have added more requirements for fear of being shut down by the Office for Human Research Protections, or OHRP, which provides federal oversight of IRBs.
Greg Koski, who became director of the OHRP in 2000, just after the shut-downs, wrote that “The suspensions created a crisis of confidence and a climate of fear, often resulting in inappropriately cautious interpretations and practices that have unnecessarily impeded research without enhancing protections for the participants.”
In their efforts to make sure that research meets all the requirements, IRB approval can be slow, delaying projects as simple as a survey for months. “IRBs are often under great strain and underfunded at universities,” said Klitzman, the Columbia psychiatrist. University IRBs may also be limited in their expertise — it’s possible that no one serving on the committee is in the field of a proposal that’s submitted. But half of all medical research as of 2021 was reviewed by for-profit companies owned by private equity firms. Those commercial IRBs tend to be faster, but some question their conflicts of interest.
Advarra and the Consortium of Independent Institutional Review Boards, a nonprofit professional group, did not immediately respond to requests for comment. But in an earlier interview with Undark about another aspect of their research review services, an Advarra executive disputed claims that their business model poses an inherent conflict of interest. “If anything, if there was pressure to rubber stamp or do anything inappropriate, it would ultimately hurt the reputation of Advarra, and compromise the value of the review that we perform,” said Daniel Eisenman, Advarra’s executive director of biosafety services, in 2021.
“The objective concern would be that private equity-owned IRBs would focus too much on speed and regulatory compliance and their customer,” said Fernandez Lynch, pointing out that their customers are the pharmaceutical or biotechnology companies that hire them to review research and not the people who volunteer to participate in research. (University researchers generally can’t use private IRBs.)
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In early 2023, a report from the U.S. Government Accountability Office (GAO) called for greater federal oversight of these commercial IRBs, noting that “the emphasis on profit or faster IRB protocol review may have resulted in independent IRBs with private equity investment being less focused on potential harms of research to human subjects.”
For a 2009 investigation, the GAO submitted a protocol for a fictitious medical device to three independent for-profit IRBs. The description of the device matched several examples of “significant risk” devices from FDA guidance, and it falsely presented it as cleared by the FDA. Two of the IRBs rejected it, citing safety concerns, but one of them, which has since closed, approved it.
Some experts see a possible solution to the problem of potentially lenient commercial IRBs, along with any underresourced university IRBs: a centralized government IRB. New Zealand and the United Kingdom both take this approach. “Legitimate centralization that’s done with integrity would solve a lot of problems,” Klitzman said.
But there may be some benefits to regional IRBs. “If I’m doing a project on something related to reproductive technology in Texas, versus Massachusetts, they might be really different considerations,” said Emma Tumilty, a bioethicist at the University of Texas Medical Branch. Whitney argues in his book for local IRBs to have more autonomy than they currently do, with less punitive government oversight.
“The emphasis on profit or faster IRB protocol review may have resulted in independent IRBs with private equity investment being less focused on potential harms of research to human subjects.”
Another way to streamline the process is to make guidelines clearer, according to Klitzman. If a project qualifies as minimal risk, it can get expedited review or be exempt from federal policy. Minimal risk is described in OHRP policy as “the probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” But IRBs disagree with what qualifies as “minimal risk,” Klitzman said, and there’s not a consensus as to whether even a simple procedure, like drawing blood, qualifies. He believes the regulations should spell out exactly what constitutes minimal risk so IRBs themselves don’t have to decide.
As for Seliger, he says he is now hopeful about his future despite his aggressive cancer. Because of the clinical trial he is in, he may have longer to live than doctors orginally forecasted — a CT scan in November revealed that some of the tumors in his neck and lungs have shrunk. But he is still dismayed by the system. In an email to Undark, Seliger wrote: “I do think we need *some* epistemic system for determining what medications/technologies are safe and effective. The average person, including me, is poorly equipped to wholly make that decision or those kinds of decisions for ourselves. At the same time, the IRB system as they exist now are way too decentralized, slow, and paternalistic.”
Christina Szalinski is a freelance science writer with a Ph.D. in cell biology based near Philadelphia.