Report on Research Compliance 21, no. 8 (August, 2024)
◆ The Food and Drug Administration (FDA) has given Massachusetts Institute of Technology (MIT) 15 days from receipt of its June 21 warning letter to elaborate on corrective actions to address violations of federal requirements for informed consent and institutional review board (IRB) operations identified during a 2023 remote regulatory assessment. After their May 30 to June 9, 2023, assessment, agency officials shared with MIT various “observations” and asked MIT to address them, which occurred on June 30, 2023, FDA said. However, the responses are insufficient. FDA “determined that your IRB violated IRB regulations, as published in Title 21, Code of Federal Regulations (CFR) Part 56,” the letter said. “The applicable provisions of the CFR are cited for each violation listed below. The violations include, but are not limited to the following: failure to ensure that information given to subjects as part of informed consent is in accordance with 21 CFR 50.25 [21 CFR § 56.109(b)]” and “failure to prepare and maintain adequate documentation of IRB activities [21 CFR 56.115].”
FDA provided several examples related to informed consent failures. MIT’s IRB failed to ensure that a study’s informed consent documents “included a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject, as required by 21 CFR 50.25(a)(4).” Other informed consent forms for more than minimal-risk research failed to “include an explanation as to whether any compensation is available if injury occurs and, if so, what it consists of, or where further information may be obtained as required.” Some forms did not “include a statement that notes the possibility that the FDA may inspect the records.” Regarding IRB operations, FDA said some meeting minutes didn’t accurately track member participation and votes; member names weren’t always current and “lists did not include IRB members’ earned degrees, representative capacity, or indications of experience such as board certifications, licenses, etc., sufficient to describe each member’s chief anticipated contributions to IRB deliberations.” FDA said MIT needs to provide a “description of the standard of care approaches that will be added to the [consent forms] for the identified protocols” and recommended that “a roster of active members at the time of the meeting should be prepared and appended to the respective meeting minutes,” among the actions MIT should describe in its response. (7/25/2024)
◆ The National Science Foundation (NSF) on July 24 announced a five-year award to create the Safeguarding the Entire Community of the U.S. Research Ecosystem (SECURE) Center, which it said “will serve as a clearinghouse for information to empower the research community to identify and mitigate foreign interference that poses risks to the U.S. research enterprise.” The center “will share information and reports on research security risks, provide training on research security to the science and engineering community and serve as a bridge between the research community and government funding agencies to strengthen cooperation on addressing security concerns,” NSF said.
The center “will also serve as the nexus for five regional centers managed by six institutes of higher education: SECURE Northeast—Northeastern University; SECURE Southeast—Emory University; SECURE Midwest—University of Missouri; SECURE Southwest—The University of Texas at San Antonio and Texas A&M University; and SECURE West—University of Washington. Additionally, Mississippi State University, University of Michigan and Stanford University’s Hoover Institution “will provide expertise on sensitive research, threat types, geopolitical analysis and international collaboration. Participation by the College of Charleston and Mississippi State University, located in NSF Established Program to Stimulate Competitive Research jurisdictions, ensures that emerging research and minority-serving institutions are included in SECURE Center activities.” In terms of funding amounts, NSF said $50 million would go to University of Washington and $17 million to Texas A&M. (7/25/2024)
◆ Auditors for the HHS Office of Inspector General said the Agency for Strategic Preparedness and Response (ASPR)—the lead agency making awards for the development of COVID-19 therapies during the pandemic—“did not have an established process for reviewing or monitoring contract files for completeness and accuracy, and ASPR’s contractor failed to comply with the terms of its contract. Further, ASPR failed to adequately maintain oversight, did not finalize and obligate funds for another contract, and, while ASPR’s internal contract administration policies specified the documentation that should be maintained within a contract file, ASPR’s policies did not address the organization and maintenance of electronic records.” To complete their audit, officials “reviewed a judgmental sample of 28 research and development contracts (out of 235 unique contracts): 26 contracts were awarded by ASPR with contract actions from FYs [fiscal years] 2017 through 2020 and 2 contracts were awarded through the ASPR Next program.” They said that, “although this audit was not designed to focus on contract management specifically related to COVID-19 efforts, our audit period includes research and development contracts awarded through FY 2020, the first full year of the COVID-19 pandemic.”
“Of the 28 contracts reviewed, ASPR did not appropriately complete or was missing documentation for 8 different contracts. Specifically, three contracts were incorrectly reported within the Federal Procurement Data System (FPDS), three contracts were missing required documentation, and four contracts did not have technical evaluations appropriately completed or maintained,” auditors reported. Specifically, auditors found that a firm with a 10-year contract was sold four years into the agreement but neither the seller nor the new owner alerted ASPR until nearly two years later; notification is required within 30 days and new contracting arrangements are supposed to be made. But those took an additional seven months to finalize, auditors said. OIG did not specify the dollar amounts or contractors involved in this incident, but cited another in which an ASPR contracting officer inappropriately gave verbal authorization for the start of a $14,000 contract, which was later finalized and paid two years afterward, actions that violated several statutes. ASPR agreed to implement a series of recommendations auditors made, including developing training for contractors and new policies and procedures to strengthen oversight. (7/18/2024)
◆ A grand jury in Maryland indicted Hoau-Yan Wang, formerly a City University of New York (CUNY) neuroscientist, on one count of major fraud against the U.S., two counts of wire fraud, and one count of false statements, the Department of Justice (DOJ) recently announced. “The fraudulent grant applications to the NIH sought funding for scientific research of a potential treatment and diagnostic test for Alzheimer’s disease and resulted in the award of approximately $16 million in grants from approximately 2017 to 2021, part of which funded Wang’s laboratory work and salary,” DOJ said. “From approximately May 2015 through approximately April 2023, Wang allegedly engaged in a scheme to fabricate and falsify scientific data in grant applications made to the NIH on behalf of himself and the biopharmaceutical company.”
Science reported that Wang has been under investigation for more than two years related to his conduct of basic science studies supporting the drug simufilam being developed by Cassava Sciences, now in clinical trials. CUNY’s misconduct investigation was stymied because Wang refused to provide data, the publication said. “If convicted, he faces a maximum penalty of 10 years in prison for the count of major fraud, 20 years in prison for each count of wire fraud, and five years in prison for the count of false statements,” according to DOJ. (7/11/24)
◆ Staff at Emory University committed seven violations of the Animal Welfare Act (AWA) from July 2019 to May of last year that resulted in the death of research animals, triggering a $42,000 settlement, according to allegations in a recent agreement posted on the Animal and Plant Health Inspection Service (APHIS) website. APHIS said the incidents involved violations of requirements for housing, handling and water. In separate incidents, voles died from a variety of causes: dehydration, injuries suffered in a cage change and attacks by other voles after being placed in the “wrong cage with a different social group.”
Additionally, a staff member “found a dead vole in a freezer outside of a plastic bag. An investigation determined that, on a previous day, six voles had been through euthanasia procedures and placed in the freezer. The euthanasia procedures were incomplete and the animals were not handled properly.” A mouse died after being trapped in a defective feeder. A pair of two-year-old rhesus macaques died after becoming stuck in gaps in their enclosures. A gerbil had to be euthanized after becoming injured escaping from its cage during the performance of husbandry, according to the settlement. The agreement is not an admission of wrongdoing by Emory. (7/11/24)
◆ While U.S. researchers and those around the world scrambled to assemble facts about the spread of COVID-19 and develop vaccines and treatments, the Department of Defense (DoD) employed General Dynamics IT to develop “a combination of fake social media accounts on multiple platforms to spread fear of China’s vaccines among Muslims at a time when the virus was killing tens of thousands of people each day. A key part of the strategy: amplify the disputed contention that, because vaccines sometimes contain pork gelatin, China’s shots could be considered forbidden under Islamic law,” according to an investigation by Reuters published June 14. Reuters found “at least 300 accounts on X, formerly Twitter, that matched descriptions shared by former U.S. military officials familiar with the Philippines operation. Almost all were created in the summer of 2020 and centered on the slogan #Chinaangvirus—Tagalog for China is the virus.”
Although aimed at the Philippines to counteract what military officials said was China’s growing influence, the talking points they shared have been repeated by Americans and other skeptics. Daniel Lucey, M.D., an infectious disease specialist at Dartmouth’s Geisel School of Medicine, told Reuters the program was indefensible. “I’m extremely dismayed, disappointed and disillusioned to hear that the U.S. government would do that,” he said. A DoD official confirmed the existence of a program to spread “secret propaganda to disparage China’s vaccine in the developing world” but “declined to provide details.” According to Reuters, the program—begun under the Trump administration in spring 2020 and discontinued by President Joe Biden a year later—was implemented despite “strong objections from top U.S. diplomats in Southeast Asia at the time.” Reuters noted that research shows “when individuals develop skepticism toward a single vaccine, those doubts often lead to uncertainty about other inoculations.” It also warned that General Dynamics recently won a new DoD contract and that, although some policies about “psychological operations” have been tightened, they will continue. “Last year, top Pentagon generals wrote that the U.S. military could undermine adversaries such as China and Russia using ‘disinformation spread across social media, false narratives disguised as news, and similar subversive activities [to] weaken societal trust by undermining the foundations of government,’” Reuters reported. (6/27/24)
◆ An investigator continued providing treatment to one or more research participants after expiration of an investigational new drug (IND) application and IRB approvals, according to a June 7 warning letter posted on the FDA website. The letter to Angela D. Ritter, M.D., refers to three examples of failures to follow FDA regulations, but the circumstances are nearly identical, so it is not clear how many subjects the agency was concerned about. The study or studies involved protocols for individual patient expanded access for emergency use. In each instance, an IND allowed for subcutaneous administration of a drug—the name is redacted—for only two weeks, but administration continued for 50 additional doses. IRB approval, granted for two weeks of treatment, was not revised and renewed as required. FDA referenced previous correspondence from Ritter indicating she said she had “relied too much” on a contract research organization she thought was handling the IND and IRB approvals and that she had hired additional regulatory staff, among other changes.
FDA, however, is seeking more details. The agency requested that Ritter respond within 15 days with “the actions you have taken to prevent similar violations in the future” or to document compliance if she disagreed with the findings. The website for the Center for Advanced Research and Education in Gainesville, Ga., describes Ritter as director of its research. According to the website, she joined the center in 2018 and has researched an advanced form of nonalcoholic fatty liver disease, osteoporosis, diabetes, weight loss, high cholesterol, Alzheimer’s disease and COVID-19. (6/27/24)
◆ The HHS Office of Research Integrity (ORI) found that a former laboratory technician at Baylor College of Medicine engaged in research misconduct in research supported by two NIH grants. Darrion Nguyen, who formerly worked at Baylor’s Division of Pediatric Neurology and Developmental Neuroscience, falsified and/or fabricated experimental data and results that were included in a Public Health Service (PHS)-funded research project progress report, a presentation, a poster, six research records and two figures of a prospective manuscript, ORI said. Specifically, ORI found that Nguyen falsified and/or fabricated three separate measurements in three different types of mice by copying and pasting measurement values collected from the brain of a single mouse. He also misrepresented the social interaction behavior of one cohort of mice by copying and pasting the manually scored social interaction behavior of mice from a different cohort and misrepresented data in two additional measurements, ORI said.
In the voluntary settlement agreement, Nguyen agreed to have his research supervised for three years, during which a committee of two to three senior faculty members must review data and submit reports to ORI for any PHS-supported research in which Nguyen participates. In addition, during the three-year supervisory period, Nguyen agreed to ensure that any institution employing him submits a certification to ORI that the data provided are based on actual experiments or are otherwise legitimately derived and that the data, procedures and methodology are accurately reported and not plagiarized in the application, report, manuscript or abstract. If no supervision plan is provided to ORI, Nguyen agreed to provide certification to ORI at the end of the three-year supervisory period that his participation was not proposed in a research project for which an application for PHS support was submitted and that he has not participated in any capacity in PHS-supported research. Finally, Nguyen agreed that he would exclude himself voluntarily from serving in any advisory or consultant capacity to PHS, including, but not limited to, service on any PHS advisory committee, board and/or peer review committee. (6/20/24)
◆ A bipartisan group of 60 senators has asked Senate colleagues who control funding for NIH to maintain strong funding for the institution. In a letter addressed to the leaders of the Committee on Appropriations and its subcommittee on Labor, Health and Human Services, and Education, and Related Agencies, the group of lawmakers noted that sustained research investment has allowed NIH to advance biomedical innovation. However, “America has faced challenges in maintaining its position as the world leader in research and development, and many researchers have similarly struggled to secure funding. As NIH grants become more competitive, researchers can easily spend half their careers working before receiving a grant,” the letter said.
“It is essential to continue this federal support for the benefit of the American people and to ensure that our Nation remains at the forefront of medical research,” the lawmakers, led by Sens. Bob Casey, D-Pa, and Thom Tillis, R-N.C., wrote. “We recognize the difficult choices that need to be made with respect to the budget. If we are to continue grappling with emerging threats, as well as improve the health of Americans and the quality of their lives, we must continue to invest in biomedical research that has the potential to save and improve lives, as well as reduce long-term health care expenditures.” The senators asked their colleagues to include in the 2025 appropriations for the NIH “the full allocation of funding for the NIH that was provided by the 21st Century Cures Act.” The letter followed a similar effort in the House, in which 200 lawmakers asked their House Appropriations Committee colleagues to appropriate at least $51.3 billion for the NIH in fiscal year 2025. (6/20/24)
◆ Ivor Pritchard, senior advisor to the director of the HHS Office for Human Research Protections (OHRP) and a former acting director of OHRP, is retiring after 20 years with the agency, OHRP announced in an emailed newsletter. Pritchard joined OHRP in 2004, following 28 years with the federal Department of Education, where he was a senior research analyst. When he joined OHRP, Pritchard brought “a wealth of experience and expertise,” the agency said. Pritchard’s research interests are in research ethics and federal policy, moral and civic education research and practice and education policy, according to his HHS biography.
“As senior advisor to the director of OHRP, Dr. Pritchard spearheaded numerous initiatives aimed at protecting the rights, welfare, and well-being of subjects involved in research conducted or supported by HHS, as well as for upholding the highest ethical standards for our field,” OHRP said in its retirement announcement. “This has included support in the effort to revise the Common Rule, as well as issuing guidance and clarifications, providing direction in the development of educational products and programs, and maintaining regulatory compliance.” Pritchard also served as a mentor to junior staff, engaged frequently with stakeholders and the public and advocated for the ethical principles underpinning the work of OHRP, the agency said. (6/13/24)
◆ ORI has found that Shaker Mousa, former professor, chairman and executive vice president of the Albany College of Pharmacy and Health Sciences (ACPHS) Pharmaceutical Research Institute, engaged in research misconduct in research supported by PHS funds. Specifically, the fraud involved the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases grants, ORI said. Following a report from ACPHS and further analysis by ORI, the agency found that Mousa intentionally, knowingly or recklessly falsified or fabricated chick chorioallantoic membrane (CAM) assays used to determine angiogenesis activities in small molecules. Two studies, including a 2013 study in Nanomedicine and a 2005 study in the Journal of Cardiovascular Pharmacology, were impacted, ORI said. Specifically, ORI found that Mousa falsified seven micrograph panels in the two journals “by reusing CAM images from the same source and falsely relabeling them to report pro-angiogenic factors as alternate pro-angiogenic factors, anti-angiogenic drug treatments as alternate anti-angiogenic drug treatments, and control treatments and anti-angiogenic treatments as the same treatment.”
As part of a voluntary settlement agreement, Mousa agreed to have his research supervised over the next four years. For any research project requesting PHS support, Mousa will be required to submit a plan for supervision prior to submitting the application for PHS support. In addition, any institution employing him must certify to ORI that the research in which Mousa is involved is based on actual experiments and that the data, procedures and methodology are reported accurately. If Mousa does not participate in research over the next four years, he will need to certify that nonparticipation at the end of the four-year period. In addition, ORI said that the Journal of Cardiovascular Pharmacology has published a retraction of the study in question; as part of the voluntary settlement, Mousa will request that the study in Nanomedicine also be corrected or retracted. (6/13/24)
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