or years, ethicist Arthur Caplan warned medical researchers that paying businesses to evaluate their clinical trials was a bad idea.
He condemned trials that didn’t rely on hospital or academic review boards — long the gold standard in science — and argued that for-profit review boards were out to make a buck, not protect patients.
Today, Caplan sits on the advisory board of WIRB-Copernicus Group, the largest commercial institutional review board, or IRB, in the country.
He says he had no choice.
“This shift to commercial IRBs is, in effect, over,” said Caplan, who heads the division of bioethics at New York University Langone Medical Center. “It’s automatic and it’s not going back.”
Institutional review boards — which review all research that involves human participants — have undergone a quiet revolution in recent years, with many drug companies strongly encouraging researchers to use commercial boards, considered by many more efficient than their nonprofit counterparts.
Commercial IRBs now oversee an estimated 70 percent of US clinical trials for drugs and medical devices. The industry has also consolidated, with larger IRBs buying smaller ones, and even private equity firms coming along and buying the companies. Arsenal Capital Partners, for example, now owns WIRB-Copernicus Group.
But even if the tide has already turned, the debate over commercial review boards — and whether they can serve as human subject safety nets, responsible for protecting the hundreds of thousands of people who enroll in clinical trials each year — continues to swirl.
The debate could also intensify. Late last month, the National Institutes of Health announced that US-funded trials that are carried out at multiple research centers must begin using a single IRB, with few exemptions possible. Because few universities or hospitals have the capacity to review study protocols and track adverse events for far-flung institutions, the new rule is expected to be a windfall for commercial IRBs.
The modern history of science is littered with studies in which participants were harmed because researchers failed to take necessary precautions. Tragic deaths in research studies at the University of Pennsylvania, University of Minnesota, Johns Hopkins University, and elsewhere have raised questions about the quality of review boards in general, even when they are overseen by universities and hospitals.
But some experts say the risks are far greater with commercial review boards, which often have harder-to-spot conflicts of interest and a profit motive.
The Food and Drug Administration reported twice as many violations and problems with commercial IRBs as with nonprofit boards from 2008 to 2014, according to preliminary findings in a recent study, conducted by Gabrielle Goldstein, an attorney and doctoral student at the University of California, Berkeley.
In one example, the agency disqualified a commercial review board known as Texas Applied Biomedical Services after the company repeatedly failed FDA inspections.
The agency found that the company, known as TABS, lacked a doctor who understood the study protocols well enough to determine if they posed a risk to participants in one trial, including children. In its decision to disqualify the firm, the FDA said the board claimed to have lost relevant records in a computer crash, which an agency official said “strains credibility.”
The board also reportedly failed to disclose that one of its members had a financial relationship with the company paying for the trial.
TABS did not return calls seeking comment.
Mark Schreiner, a medical school professor and vice chairman of the IRB at Children’s Hospital of Philadelphia, said he is uncomfortable outsourcing the evaluation of pediatric trials to commercial review boards.
“IRBs are hired by the sponsor,” Schreiner said. “They are paid by them. And so if they turn down the study, then I think they’re unlikely to get repeat business.”
Commercial IRBs, for their part, reject such assertions.
David Borasky, vice president of WIRB-Copernicus Group, said commercial IRBs, which the industry prefers to call “independent” IRBs, provide faster evaluation of proposed clinical trials than universities and hospitals can, without jeopardizing quality.
Borasky said they also tend to have more advanced technology, permitting better oversight of multisite trials that will have to be handled by a single IRB.
“This is what we were built to do,” Borasky said. “In this day and age you don’t have to be sitting in the same building as somebody to have good monitoring.”
Part of the problem with assessing the relative merits of different review boards is that their overall performance is hard to measure.
“These are black boxes,” said Dr. Steven Joffe, a pediatric oncologist and bioethicist of the University of Pennsylvania, who serves on the FDA’s Pediatric Ethics Committee. “IRBs as a rule are incredibly difficult to study. Their processes are opaque, they don’t publicize what they do. There is no public record of their decision or deliberations, they don’t, as a rule, invite scrutiny or allow themselves to be observed. They ought to be accountable for the work they do.”
Federal regulators at the FDA and the Department of Health and Human Service’s Office for Human Research Protections are charged with overseeing review boards. But they don’t have sufficient staff to monitor the thousands of IRBs and tens of thousands of studies conducted in the US and internationally.
The FDA, for example, has inspected WIRB-Copernicus only three times in the past five years, and in two of those inspections found “objectionable conditions or practices” that the company agreed to correct. Last year, the company handled reviews for 40 out of the 45 drugs that the agency approved. (In a statement, a spokeswoman for the agency said data for IRB inspections indicate the boards are “generally compliant.”)
“I think most ethical and other problems with IRBs and human subjects research oversight are not detected by FDA or OHRP,” said Dr. Michael Carome, a former senior official with the Office for Human Research Protections and now director of Public Citizen’s Health Research Group.
Against that backdrop, many experts are worried about the expansion of commercial IRBs.
Schulman Associates IRB, a well-known commercial board based in Ohio, has conducted reviews for hundreds of study protocols a year and has seen those numbers grow by double-digit percentages year over year, according to Sharon Nelson, who heads the firm’s consulting and compliance division. The business has trials covering about 15,000 individual sites. Two years ago, American Capital Equity III became the majority investor in the company.
“I think the test is in how the IRB or the organization manages either real or perceived or potential conflict of interest,” Nelson said. “In the case of Schulman and many strong commercial or independent IRBs, we are accredited. We have measures in place that are very clear to all of us. Those who sit in the business realm, or the ethical review board, are clear about lines that we don’t cross.”
Jennifer Miller, an assistant professor of bioethics at NYU’s medical school, who has studied the impact of private equity investment in commercial IRBs, thinks the model of private equity investing in scientific review boards, with their practice of buying a company, increasing its value, and reselling within three to five years for a profit, is worrisome.
“Private equity could help an IRB by allowing it to professionalize, better educate, and train its members and handle globalization of research,” Miller said. “But it could also put extra emphasis on cutting costs and boosting revenues. The main mission and reason for being of an IRB is to protect research subjects.”
Caplan, the NYU ethicist, said he joined the advisory board of WIRB-Copernicus Group to help ensure the commercial review board does its job responsibly.
“If you want to work in research ethics,” he said, “you work with them.’’
An earlier version of this story misstated the number of trials that are overseen by Schulman Associates IRB.