Sens. Warren, Brown, Sanders Call for Government Watchdog to Investigate For-Profit Institutional Review Boards

WASHINGTON, June 19 -- Sen. Elizabeth Warren, D-Massachusetts, issued the following news release:

United States Senators Elizabeth Warren (D-Mass.), Sherrod Brown (D-Ohio), Ranking Member of the Senate Banking Committee, and Bernie Sanders (I-Vt.), Ranking Member of the Senate Budget Committee, requested that the Government Accountability Office (GAO) study for-profit Institutional Review Boards (IRBs), which review clinical research proposals to ensure that participant rights are protected and the research is conducted ethically. They are asking GAO to evaluate whether existing standards of quality, efficiency, and effectiveness provide adequate protection for participants in IRB-approved clinical trials, and to examine whether commercial IRBs have appropriate protections in place to address conflicts of interest and "pay to participate" clinical trials.

Their request follows inadequate responses they received to their initial investigation in 2019 by the two largest for-profit IRBs, WCG Clinical and Advarra. Both firms are owned by private equity investors, raising questions about whether they are under pressure to reduce costs and ramp up profits, trends that often accompany private equity's entry into a market. Commercial, for-profit IRBs now oversee approximately 70% of all drug and medical device trials in the United States.

"This private, for-profit model creates an inherent conflict of interest for IRBs, which may incentivize them to approve as many studies as they can as rapidly as possible. The urgency of the COVID-19 pandemic may further increase pressure for IRBs to provide rapid approvals that may be inadequate or incomplete," the senators wrote.

WCG Clinical and Advarra responded to the senators' initial questions with generalities, assuring them that their review process is thorough and high-quality, but provided little data to corroborate these claims. WCG's response failed to address key concerns about conflicts of interest, "pay for participation" trials, and quality metrics. Advarra provided some information about its conflict of interest policies and the number of "pay for participation" trials it has reviewed, but did not provide specific data or examples. The senators are releasing WCG and Advarra's responses publicly for the first time.

"Our preliminary investigation, opened in November 2019, raises questions about whether the commercial IRBs' reviews of these studies have significant vulnerabilities that may leave patients exposed to unnecessary risks during their participation in clinical trials," wrote the senators. "To address these unanswered questions, we request a GAO investigation of the operation of commercial IRBs."

Senator Warren has conducted a series of investigations into private equity abuses in health care and other industries throughout her time in the Senate and is fighting for reforms that protect students, workers, communities, and investors:

* Senators Warren, Brown and Tammy Baldwin (D-Wis.), along with Representatives Mark Pocan (D-Wis.), and Pramila Jayapal (D-Wash.), introduced the Stop Wall Street Looting Act, a comprehensive bill to fundamentally reform the private equity industry and level the playing field by forcing private equity firms to take responsibility for the outcomes of companies they take over, empowering workers, and protecting investors.

* Senators Warren, Brown, and Representative Pocan wrote to four private equity firms that currently invest or have recently invested in companies providing nursing home care and other long-term care services, citing reports that show private equity investment has played a role in the declining quality of care in nursing homes and requesting information about each firms' management of this sector.

* Senator Warren, Representatives Pocan, and Lloyd Doggett (D-Texas) wrote last month to five private equity firms with investments and physician staffing and emergency transport companies, questioning the role these companies play in patients receiving exorbitant surprise bills for out-of-network medical treatment.

* * *

June 16, 2020

To: Gene L. Dodaro, U.S. Comptroller General, Government Accountability Office, 441 G St. NW, Washington, D.C. 20548

Dear Mr. Dodaro:

We write to request a Government Accountability Office (GAO) investigation of the operation of commercial Institutional Review Boards (IRBs), the private, for-profit entities that approve drug research and other studies involving human subjects. As clinical trials related to the coronavirus disease 2019 (COVID-19) pandemic accelerate, ensuring that IRBs are providing adequate patient protection is more important than ever. Our preliminary investigation, opened in November 2019, raises questions about whether the commercial IRBs' reviews of these studies have significant vulnerabilities that may leave patients exposed to unnecessary risks during their participation in clinical trials.

In 2009, GAO released a study that exposed alarming vulnerabilities in human subject research reviews./1

In an undercover investigation, GAO was able to obtain IRB approval for a fictitious test of a medical device that met the Food and Drug Administration's (FDA) guidelines for "significant risk." The for-profit IRB that approved the fictitious device, Coast IRB, closed after the GAO investigation was made public./2

The report concluded that "the IRB system is vulnerable to unethical manipulation, particularly by companies or individuals who intend to abuse the system or to commit fraud, or who lack the aptitude or qualifications to conduct and oversee clinical trials. This vulnerability elevates the risk that experimental products are approved for human subjects testing with little or no substantive due diligence."/3

In the decade since this GAO investigation, the IRB landscape has shifted in several significant ways. First, while the 2009 GAO study noted "IRBs were historically located at academic institutions," it found that commercial IRBs "are playing an increasingly prominent role in the protection of human research subjects."/4

That trend has continued in the intervening decade, and commercial, for-profit IRBs now oversee approximately 70% of all drug and medical device trials in the United States./5

This is a particular concern because this private, for-profit model creates an inherent conflict of interest for IRBs, which may incentivize them to approve as many studies as they can as rapidly as possible./6

The urgency of the COVID-19 pandemic may further increase pressure for IRBs to provide rapid approvals that may be inadequate or incomplete. Though conflicts of interest are common among individual IRB reviewers, including at academic IRBs,/7 the profit motive and lack of transparency at commercial IRBs make potential conflicts especially worrisome. Furthermore, over the last decade, more than a dozen independent IRBs of all sizes have merged or been acquired to form two major firms, WCG Clinical and Advarra./8

Both IRBs are owned by private equity investors, raising questions about whether they are under pressure to reduce costs and ramp up profits, trends that often accompany private equity's entry into a market./9

In addition, recent reports have identified a growing trend of "pay to participate" trials, in which patients are asked to pay fees of thousands of dollars in order to participate in clinical research./10

In one particularly egregious example, a Florida physician proposed patient fees as high as $285,000 for participants in a study of plasma infusions to prevent aging./11

Another trial asked parents of autistic children to pay over $20,000 in enrollment, travel, and other expenses to participate in a trial of stem cell therapy./12

These practices, by definition, restrict access to clinical trials and risk taking advantage of vulnerable patients and their families. In addition, they create strong incentives for sponsors to oversell the potential benefits of the research, despite the high failure rate of early-stage trials./13

Furthermore, these studies' scientific validity is potentially compromised because in many cases, they forego a control group, since participants are unlikely to be willing to pay if they are not actually receiving a treatment./14

In response to these troubling trends, in November 2019 we asked the two largest for-profit IRBs, WCG Clinical and Advarra, for information on their policies and procedures for reviewing human subjects research, including information about how they ensure that reviews are thorough and high-quality, how and whether they prevent and disclose panel members' conflicts of interest, and how they identify and review "pay to participate" clinical trial proposals./15

We also asked for data to substantiate each of these procedures and to understand the scope of each IRB's responsibility. WCG Clinical and Advarra responded in generalities, assuring us that their review process is thorough and high-quality, but provided little data to corroborate these claims. But their responses - which we have attached to this request - failed to address many of our key concerns or questions with appropriate detail and specificity. Concerns that were not appropriately addressed in these responses included:

* Conflicts of interest. Advarra provided helpful guidance, indicating that the company's policies require disclosures of conflicts, examples of relationships that would constitute a conflict, and a requirement that individuals with conflicts "recuse themselves from participation in the review of any project for which they have a conflict of interest."/16

But the company provided no further details on the number of panel members who have recused themselves over conflicts in the past. WCG Clinical provided no details whatsoever on how they identify, address, and prevent undue influence from panel members' conflicts of interest.

* "Pay for participation" trials. We asked a series of questions about how the two largest IRBs protect patients and scientific integrity in "pay for participation" trials. Again, WGC ignored these questions, raising concerns about the company's approach to review of these ethically questionable studies. Advarra provided more helpful information, indicating that "these types of research proposals are still relatively rare."/17

They reported that they have reviewed nine such proposals to date, of which four were disapproved, three were withdrawn or tabled permanently, and two were approved.

* Quality Metrics. Neither IRB provided the specific metrics we sought in order to evaluate the quality, efficiency, and effectiveness of the review process and determine whether these for-profit IRBs had appropriate processes and procedures in place to protect patients and ensure the scientific integrity of human-subject studies. Advarra reported only that 80% of their proposals are approved with modifications and "a small percentage" are approved with no modifications.

To address these unanswered questions, we request a GAO investigation of the operation of commercial IRBs. We ask that this investigation address the following questions:

1. 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 non-profit IRBs? What has driven the market consolidation of for-profit IRBs, what role does private equity play in this process, and how does it affect the ability of IRBs to appropriately review research proposals and protect patients and scientific integrity?

2. Do commercial IRBs have appropriate protections in place to address the inherent conflicts of interest posed by their profit-seeking mission? Do they have appropriate procedures in place to address and ensure transparency regarding conflicts of interest among panel members that may have industry ties?

3. Do commercial IRBs have appropriate processes and procedures in place to protect patients and ensure the scientific integrity of "pay for participation" studies?

4. 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 current system to improve quality and patient outcomes?

5. How do procedures and outcomes differ between academic and commercial IRBs?

Thank you for your attention to this matter. We are happy to provide additional details regarding our concerns about commercial IRBs and about this request.

Sincerely,

Elizabeth Warren, United States Senator

Bernard Sanders, United States Senator

Sherrod Brown, United States Senator

See footnotes here: https://www.warren.senate.gov/imo/media/doc/2020.06.16%20Letter%20to%20GAO%20request%20on%20for-profit%20IRBs%20.pdf