For the Record: Dr. Judy Stone - UMN's Clinical Research Practices -- Far From "Beyond Reproach"

See no, hear no, speak no evil

 – Inge Vandormael on Deviant Art

Dr. Judy Stone, not just another wacko,

 writes:

 Leaders at the University of Minnesota seem to living in a parallel universe to many of us, fervent in their delusion that all is well at the state’s flagship institution of higher learning. It is they who are not learning. Last week, the Accreditation of Human Research Protection Programs (AAHRPP) came out with a sharply critical report on the state of research practices at the U. Many of us were surprised, having suspected that the report would be another whitewash, as it was bought and paid for by the UMN, and also because of conflicts of interest, with AAHRPP also accrediting⁠ the UMN program.

Given President Kaler’s repeated goal (and seeming belief) of a research program that is “beyond reproach,” it is particularly damning that the AAHRPP concluded, “the University’s efforts with regard to human subjects protections do not consistently reflect “best practices” and are not, at this point, even remotely “beyond reproach.”

The report came out of a long-standing controversy over the death of Dan Markingson, a psychotic young man who committed suicide while participating in an Astra-Zeneca trial. Dan had been offered a “choice” of involuntarily commitment or obeying the recommendations of his psychiatrist, Dr. Stephen Olson, Director of the UMN’s schizophrenia research. This prompted considerable questions about research practices at the UMN, particularly on studies involving vulnerable populations. Dr. Carl Elliott, a bioethicist at UMN has written extensively about this⁠, as have I, including: Lack of an informed consent, investigator’s shirking their responsibilitiesand serious conflicts of interest among the investigators and Institutional Review Board (IRB) charged with overseeing the trial.

AAHRPP critical findings

A few of the damning findings include (page numbers refer to this pdf⁠):

—“inadequate and inconsistent attention to the process of consent, capacity to consent, the use of surrogate decision-makers, and general efforts to address vulnerability of potential research subjects to coercion and undue influence” p 9

—“Most striking was the commonly conveyed sense of doubt in leadership’s commitment to human subjects protection. The widespread characterization of a few researchers in the Department of Psychiatry as ‘untrustworthy’ and as creating a ‘culture of fear’ in relation to efforts to enhance the protection of research subjects was of major concern to the external review team.” p 10

—In regards to the University’s Research Strategic Plan, “there is a notable absence of specific objectives relevant to human subject protections or research ethics more broadly.” p 23

Education and Training

—“Beyond the basic CITI requirements, though, there are currently no human subjects protections training requirements for investigators, including those working with high-risk or vulnerable populations.” p 42

—“One recent change in practice implemented pursuant to this initiative is the reported elimination of the ‘Responsible Conduct of Research’ (RCR) continuing education course requirement for faculty, resulting in 3,900 hours in total annual time savings.”8 “It was hard for the external review team to understand why researcher education in ethics and responsible conduct of research would be considered an ‘administrative burden,’ especially at a time when the University’s leadership should be signaling its intention to strengthen its protections for research subjects.” p 24

Dr. Charles Schulz is the chair of the Department of Psychiatry. Yet in his testimony in the wrongful death suit brought by Dan Markingson’s mother, Mary Weiss (p. 156),Schulz said that he hadn’t even read the consent form for a study in which he was a co-investigator (and was listed on the FDA Form 1572 as being a responsible party). Further, Schulz, a leading schizophrenia researcher, was not aware that informed consent requires disclosure of financial COIs⁠, arguing that disclosing information about his financial ties to the study sponsor could “confuse” the situation.

Scientific Review of Proposals

—Noted an “apparent lack of rigor and consistency in departmental-level scientific review” p 50

—“there was only a single documented scientific reviewer for five studies, in clear violation of the University’s policy.” p 48

—“cases were identified where the scientific review was completed by a subordinate faculty member for research in which a department chair was the principal investigator. In these cases, a conflict of interest exists” p 51

IRB:

—“evidence of weak and often inadequately expert review of research” (by the IRB) p 9

—“The failure to have either adequate number of IRB members, or adequate expertise, during IRB deliberations raises profound questions about the IRB’s ability to conduct a robust and reliable protocol review.” p 27

—“The Medical IRB does not routinely have the requisite number of members or expertise at its meetings to properly handle the number of studies it reviews.” p 31

—“the team found little discussion of the risks and benefits to subjects.” p 33

—“the length of time allotted for IRB review was alarmingly inadequate given the number of complex items scheduled for review.” (Ave time for review was 3-5 minutes) p 34

—“The review process, as documented in the minutes, does not reflect a meaningful discussion of the risks and benefits of research protocols and the necessary steps taken to protect human subjects in the face of scientific or ethical concerns.” p 35

—“the IRB review process may be unacceptable, and that it often contravenes the IRB’s own policies and procedures.” p 35

— Several Department of Psychiatry protocols “did not appear to give serious consideration to evaluating the risks involved” p 67

—“University policy, which assumes capacity to consent to research absent ‘substantial evidence’ to the contrary, is inconsistent w OHRP (Office of Human Research Protections) guidance p 68

—The new Human Research Protections Plan does not address “whether or how the recruitment or consent process would introduce safeguards to protect against the inherent coercion of being held for involuntary treatment” and only a single instance where consideration of the dual and potentially conflicting role of treating psychiatrist/investigator was addressed. p 72

—“the current human subjects protection program as it involves psychiatric research does not reflect the best efforts of a University of this caliber.” p 83

Dr. Teri Caraway, a political science professor, assessed the AAHRPP consultants: “The written report was much harder hitting than the verbal responses given by panelists during the question and answer period. It seemed to me that the panelists bent over backwards to put the most positive spin possible on rather shocking findings, and they refused to draw conclusions about whether they found evidence of violations of state or federal regulations, such as Dan’s law, even though the report raised concerns that researchers at the U are still recruiting their own patients.”

It is unfortunate that, in presenting their report to the UMN Faculty senate, the AAHRPP consultants refused to make any statements critical to the UMN, undermining faculty demands for real reform.

In Part 2 on the UMN review, tomorrow, I address what the AAHRPP reviewers missed–or ignored–in their reporting.