By Sue Coons
The Government Accountability Office (GAO) agreed to “investigate the operations” of commercial IRBs at the request of U.S. Sens. Elizabeth Warren, D-MA, Sherrod Brown, D-OH, and Bernie Sanders, I-VT. “GAO accepts your request as work that is within the scope of its authority. Consistent with GAO Congressional Protocols, given broad congressional interest in these issues, and upon agreement with your staff, we will allow other congressional committees of jurisdiction and interested members of Congress to become co-requesters of this work,” Orice Williams Brown, GAO managing director for Congressional Relations, wrote in a letter released on Aug. 10.1
The senators did not say how the topic of commercial IRBs became a focus of their attention. On Nov. 19, 2019, the senators released a letter saying they had sent letters to the large private equity-owned IRBs, WIRB-Copernicus Group (WCG) Clinical and Advarra. This letter raised questions about whether for-profit IRBs “are vulnerable to conflicts of interest that could inhibit their ability to protect research subjects, and whether the two companies are maintaining appropriate ethics standards.” The lawmakers also requested information on the IRBs’ approvals, processes, policies, and quality metrics.2
“The recent trend of private equity ownership is especially troubling, given the pressures to reduce costs and ramp up profits that often accompany private equity’s entry into a field,” the senators wrote. “If managers see their primary responsibility as generating returns for their investors, they may emphasize speed over thoroughness in the review process, creating risks for patients.”2
The senators also said they were concerned about reports of “pay to participate” clinical trials, where patients must pay for the opportunity to enroll in a research study. “These studies may take advantage of vulnerable patients and their families, restrict access to treatment to those who can afford to pay, create incentives to oversell the potential benefits of the trial, and potentially compromise the design of the clinical trial,” they wrote.2 The Food and Drug Administration (FDA) and the National Institutes of Health (NIH) also have said they are asking committees to consider how these scenarios should be handled.
In a report from Aug. 19, 2019, Michele Russell-Einhorn, JD, chief compliance officer for Advarra, talked about the increasing number of protocols that ask for participants to pay to be in the study. She mentioned one that was $7,000 to enroll, and another requested “upward of $250,000.” There were “serious concerns about how ethical it was to charge people to participate in the research — and whether it was absolutely necessary,” she said.3
However, comments on Twitter pointed out that Advarra had approved such a study for the Lung Institute in Dallas (ClinicalTrials.gov Identifier: NCT03040674). The informed consent form for this study indicated there is no cost to participate in the data collection and investigation of the patient’s response to study treatment. However, it continues, “[a]t this time, insurance companies are not covering the cost of cellular therapy for chronic pulmonary diagnosis; therefore, the cost of study treatment is the responsibility of the participant.”
Questions from Senators
In the letters to Advarra and WCG, the senators requested information regarding approvals, processes, policies, and quality metrics for each of the past five years. Former Advarra CEO Patrick K. Donnelly wrote extensive comments to the senators, defending the company’s procedures and its commitment to excellence. “Advarra IRB conducts high-quality review of research, which is guided by a talented team well-versed in the regulatory and ethical standards governing human subjects research, as well as a robust internal compliance program, and written policies and procedures.” Donnelly said Advarra had reviewed only a relatively small number of “pay to participate” protocols. Some were disapproved; others were pended for more information. For each of these studies that was approved, the IRB required the study sponsor to make “significant revisions” to the original study proposal, he said, “as well as materials provided to the prospective human subject participants before the study could be approved.”4
In a follow-up letter to the Senators on April 8, 2020, Advarra President and Chief Research Services Officer Scott Uebele gave additional data, including more on “pay to participate” protocols. He said, to the best of his information, Advarra had reviewed only nine studies that met this criterion. Four were disapproved, three were withdrawn or tabled, and two were approved.5
WCG’s Donald A. Deieso, executive chairman and CEO, responded similarly to the senators. “Our practices make certain that we scrupulously adhere to all regulatory requirements, that no panelist has any financial interest in any study that they review, and that there are no conflicts of interest in our mission to protect human subjects.”6
The senators told the GAO they were not satisfied with the responses. The companies responded with generalities, they said, with assurances their review process was thorough and high-quality but provided few data to corroborate these claims. “WCG’s response failed to address key concerns about conflicts of interest, ‘pay for participation’ trials, and quality metrics,” they wrote. “Advarra provided some information about its conflict of interest policies and the number of ‘pay to participate’ trials it has reviewed, but did not provide specific data or examples.”7
The senators asked the GAO to address these questions:
- What is the current market structure for IRBs? To what extent has the use of commercial IRBs increased relative to the use of academic or other nonprofit IRBs? What has driven the market consolidation of for-profit IRBs? What role does private equity play in this process? How does it affect the ability of IRBs to appropriately review research proposals and protect patients and scientific integrity?
- Have commercial IRBs established appropriate protections to address the inherent conflicts of interest posed by their profit-seeking mission? Have they created appropriate procedures to address and ensure transparency regarding conflicts of interest among panel members who may have industry ties?
- Have commercial IRBs established appropriate processes and procedures to protect patients and ensure the scientific integrity of “pay-for-participation” studies?
- Do existing standards of quality, efficiency, and effectiveness provide adequate protection for participants in IRB-approved clinical trials? How can IRBs, the FDA, and the Department of Health and Human Services address any shortcomings in the system to improve quality and patient outcomes?
- How do procedures and outcomes differ between academic and commercial IRBs?
In the GAO response, Williams Brown said the investigation would begin in about six months, which should be February or March 2021. She gave no indication of how long the investigation may take.1
- Letter from GAO to Senator Elizabeth Warren, Aug. 10, 2020. https://www.warren.senate.gov/imo/media/doc/20-0731%20Warren%20GAO%20reponse.pdf
- Letters from Senators Warren, Brown, and Sanders to WCG Clinical and Advarra, Nov. 19, 2019. https://www.warren.senate.gov/oversight/letters/senators-warren-brown-and-sanders-investigate-inherent-conflicts-of-interest-of-private-equity-owned-institutional-review-boards
- Robbins R. Amid rising concern, pay-to-play clinical trials are drawing federal scrutiny. Stat, Aug. 6, 2019. https://www.statnews.com/2019/08/06/amid-rising-concern-pay-to-play-clinical-trials-are-drawing-federal-scrutiny/
- Response to letter requesting information on Advarra IRB, Dec. 12, 2019. https://www.warren.senate.gov/imo/media/doc/Advarra%20response%20.pdf
- Letter from Scott E. Uebele, CEO of Advarra, to Sens. Warren, Brown, and Sanders, April 8, 2020. https://www.warren.senate.gov/imo/media/doc/Advarra%20response%20.pdf
- Letter from WCG to Senators Warren, Brown, and Sanders, Dec. 12, 2019. https://www.warren.senate.gov/imo/media/doc/WCG%20Response.pdf
- Senators Warren, Brown, and Sanders call for the government watchdog to investigate for-profit institutional review boards (IRBs), June 18, 2020. https://www.warren.senate.gov/oversight/letters/senators-warren-brown-and-sanders-call-for-the-government-watchdog-to-investigate-for-profit-institutional-review-boards-irbs