Compliance Challenges for Clinical Research Sites

By Beth Weinman, David Peloquin, and Jessica DeLalio  

I. Introduction

For healthcare providers who wish to participate in clinical research as part of their medical practice, the demands of clinical research regulatory requirements and sponsor obligations can be daunting. U.S. Food and Drug Administration (FDA) regulations require that physicians take responsibility for ensuring compliance with good clinical practice (GCP), human subject protection, and financial disclosure obligations for research studies in which they participate as clinical investigators. When research is funded by the federal government, there are additional obligations imposed by the Department of Health and Human Services’ Office of Human Research Protections. Those obligations may be unfamiliar and the consequences of non-compliance intimidating, especially for community-based physicians. As the demands for clinical trial diversity increase and emerging biotechnology companies engage in their own smaller studies, more clinical trial sites and community-based physicians are becoming involved in research. It is critically important for would-be investigators to understand the clinical research compliance landscape. Participating in research as an investigator opens exciting opportunities both for improving patient access to new treatments and for investigator professional development, but it is not without risk. This article focuses on compliance challenges for clinical investigators and recent trends in FDA regulation and enforcement of clinical trial obligations.

A common challenge for new researchers is appreciating the difference between clinical practice (i.e., the practice of medicine), which is not subject to federal regulation, and clinical investigations of FDA-regulated products, which is subject to FDA’s jurisdiction. Consequently, well-intentioned medical practitioners run the risk of unknowingly violating research requirements while trying to provide the best patient care. Non-compliance with research requirements can lead to the collection of poor-quality data, which undermines the research enterprise, and other unwelcome consequences, including potentially an FDA Warning Letter directed to the investigator, the rejection of data from a clinical site, dissatisfied research sponsors, reputational harm, delays in patient access to new drugs, disqualification from handling investigational drugs and devices altogether, and state medical board enforcement actions. However, missteps in navigating the clinical research requirements are avoidable; by engaging experienced regulatory legal counsel, sponsors and clinical investigators can avoid common pitfalls, better facilitate interactions with FDA, and mitigate regulatory, litigation, and other enforcement risks.  

II. Regulatory Requirements and Market Changes are Impacting the Clinical Research Landscape

In June 2024, FDA issued highly anticipated draft guidance on the submission of Diversity Action Plans (DAPs) to help sponsors meet new requirements of the Federal Food, Drug, and Cosmetic Act (FDCA).[1] The goal of requiring sponsors of certain clinical studies to submit DAPs to FDA is to improve enrollment of participants from historically underrepresented populations in clinical studies. In the draft guidance, FDA provides examples of clinical study enrollment and retention strategies, including, among other things, “implementing sustained community engagement” and “selecting clinical study site locations that would facilitate enrollment of a representative study population.”[2] To do so, FDA recommends tactics like engaging community health workers and local health care providers and conducting studies at sites that serve demographically diverse populations.[3] As sponsors implement these strategies, clinical trials will bring more local doctors and historically overlooked research sites into the research community.  

Simultaneously, small and mid-sized biotechnology companies are steadily comprising more of the industry’s clinical research pipeline, replacing traditional, large-scale pharmaceutical players. The top 15 pharmaceutical companies’ share of the industry’s clinical pipeline halved from roughly 40% in 2011 to 20% in 2021,[4] and emerging biotechnology companies’ spending on research and development that leads to increased clinical work is anticipated to grow.[5] Such companies may cast a wider net with respect to clinical sites, but may have fewer resources to monitor compliance, thereby depending on those sites to know and comply with the applicable rules.

III. FDA’s Bioresearch Monitoring (BIMO) Program

FDA’s Bioresearch Monitoring (BIMO) program is the vehicle through which FDA evaluates the conduct of FDA-regulated clinical and pre-clinical trials and any required reporting pursuant to such trials. Among other oversight activities, the program entails on-site inspections, data audits, and remote regulatory assessments, both domestically and internationally.[6] The program aims to protect the rights, safety, and welfare of human research subjects and ensure the quality and integrity of data used to support marketing applications submitted to FDA.[7]

At the conclusion of an inspection, the FDA investigator issues a Form 483 when he or she has observed any conditions that, in his or her judgment, may constitute violations of the FDCA. The investigator will read and discuss each observation on the last day of the inspection at the closeout meeting with firm management. While the close out meeting serves as an opportunity to ask questions, request clarifications, and inform the FDA investigator of any corrective actions implemented during the inspection process, it is generally advisable to acknowledge the issues and address them in the written response to the Form 483. Responding timely (within 15 business days) and effectively to the Form 483 is critical to reducing the likelihood of receiving an FDA Warning Letter or being the target of an enforcement action. In a Form 483 response, FDA expects to see a robust description of the site’s plans for prompt and effective corrective and preventive action, and confirmation of any corrective or preventive actions that have been completed. It is generally best practice to provide status updates to FDA after the initial Form 483 response to keep the agency informed of progress and to demonstrate compliance.

IV. Common Trends in FDA BIMO Warning Letters

From fiscal year (FY) 2019 through End of Year (EY) 2024, FDA conducted nearly 72,000 inspections,[8] approximately 5,600 of which were conducted at clinical and pre-clinical sites as part of FDA’s BIMO program. Approximately 1.7% of these BIMO program inspections were classified as Official Action Indicated, a classification signifying that the compliance state of the site is unacceptable and that regulatory or administrative action is recommended. Roughly 22% of the BIMO inspections were classified as Voluntary Action Indicated (VAI), signifying that objectionable conditions or practices were identified and remediation expected, but no agency administrative or regulatory action is recommended.[9] A review of FDA Warning Letters issued to clinical trial sponsors and investigators pursuant to BIMO program inspections from FY2019 through EY2024 reveals common challenges faced by those conducting FDA-regulated research and lessons on how to potentially avoid them in the future.

Protocol Non-Compliance

The most frequently cited noncompliance in BIMO-related Warning Letters (25 of 42 Warning Letters) from FY2019 through EY2024 was failing to ensure that the clinical investigation was conducted according to the investigational plan, as required by 21 C.F.R. § 312.60. Investigators were often cited for failing to ensure that all subjects met all inclusion and exclusion criteria before their enrollment in the study and for deviating from protocol-specified requirements (e.g., failing to administer protocol-required assessments, failing to perform required analyses, or administering the investigational drug improperly). These types of deviations often occur when the staff and investigator at a clinical site are not sufficiently familiar with the protocol requirements, are eager to help their patients get access to investigational drugs even when they do not qualify, or do not prioritize the importance of assessments that in their view are not critical to patient care. Regardless of the reason for occurrence, failing to comply with the clinical trial protocol can lead the study sponsor to suspend research at the site. Protocol noncompliance can significantly undermine the usefulness of data collected from clinical sites even when it does not pose a subject safety risk. When sponsors are looking for clinical investigator sites, they typically ask whether the site has received a Form 483 or Warning Letter, or whether the site has ever been subject to a research suspension. Evidence of noncompliance may make sponsors reluctant to conduct research at the site.

Failure to Submit IND

FDA also often cited investigators for failing to submit an Investigational New Drug application (IND) pursuant to 21 C.F.R. § 312.20 (13 of 42 Warning Letters) prior to commencing research. In seven of these cases, investigators acted as “sponsor-investigators”[10] pursuing their own research, rather than that of a third-party sponsor responsible for regulatory filings. Reasons for failing to submit an IND varied; most commonly, investigators argued that they were not obligated to submit an IND because the test article being studied was a food or dietary supplement, not a drug. In such letters, FDA consistently noted the regulatory definition of a “drug,” which relies on the intended use of the investigational article rather than its chemical structure, and its applicability to the investigation at issue. Others argued that they misunderstood their relevant obligations, believing that approval of the protocol by an Institutional Review Board (IRB) negated the need for an IND or meant that the IND was approved.[11]

The Warning Letters also described instances in which the clinical investigator asserted that the research subject to the Warning Letter was not FDA-regulated, but rather constituted medical practice for which submission of an IND prior to drug administration was not needed. FDA regulation defines a clinical investigation as “any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects.”[12] However, for the purposes of FDA’s requirements governing the use of investigational new drugs (including the submission of an IND under Part 312 of the FDCA), “an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.”[13] FDA’s guidance on determining whether human research studies can be conducted without an IND notes that “a randomized trial evaluating an unapproved use of a lawfully marketed drug is a clinical investigation and may require an IND. In contrast, use of a lawfully marketed drug for an unapproved use in the course of medical practice is not a clinical investigation and does not require an IND because it involves the use in an individual patient where the primary intent is to treat the patient.”[14] It is not uncommon for researchers to fail to appreciate the significant differences between clinical practice and clinical research. This may be especially true for health care providers and sites with little previous experience in conducting clinical research. Physician investigators that wish to compare patient treatments using marketed drug products may not recognize that their research could be subject to FDA oversight.

For example, in a Warning Letter issued to a sponsor-investigator at a Minneapolis county-level medical center, FDA described its long-held view “that when an investigator limits his choices, his patients’ choices, and the choices of the people working for him in the treatment of those patients, then he is conducting a clinical investigation,” which “is different from the practice of medicine, where the primary intent is to treat the individual patient.”[15] The investigator had claimed that an IND was not needed for the clinical investigation because, among other reasons, the administering physicians were free to use their professional medical judgment to choose whichever standard of care therapy they thought most appropriate, but also to choose not to enroll any particular subject in the investigation.[16] FDA explained, however, that the use of the drug products was not “in the course of medical practice” because the protocol pre-specified the drug intervention to be administered to certain subjects during specified time periods, and because the sponsor-investigator instructed the administering physicians regarding the specific drugs that were to be administered on a given day.[17]

In a Warning Letter issued to a sponsor-investigator and owner of a private anesthesia practice,[18] FDA rejected the argument that the test article was not an investigational drug and did not require an IND because it incorporated three approved and long-marketed drugs commonly used for sedation.[19] FDA explained that the protocol pre-specified the drug intervention to be administered to subjects according to a randomization schedule, thereby limiting clinical judgment and the interventions available for administration to each subject.[20] FDA also noted that just because individual drugs are considered part of a standard of care does not render them “noninterventions in a study setting.”[21]

Determining whether clinical research requires the submission of an IND or investigational drug exemption (IDE) can be tricky, especially when the research involves the use of marketed drugs or devices or when the research does not have a commercial purpose. Consulting with experienced FDA counsel can be critical in determining whether a submission is warranted or an exemption from submission may apply.

Inadequate IRB oversight

A select number of investigator Warning Letters involved a lack of sufficient IRB oversight. FDA cited investigators under 21 C.F.R. § 312.66 (for drug studies) and 21 C.F.R. § 812.40 (for device studies) for failing to ensure approval and continuing review by a compliant IRB. In these instances, FDA observed that once the investigators obtained initial IRB approval (for those that did), they neglected to monitor the status of the approval. Not only did the investigators inadvertently allow the IRB approval to lapse, but they also failed to halt the conduct of the study until any such lapse was remedied. In these Warning Letters, FDA emphasized that the failure to ensure continuing IRB review raises concerns regarding the protection of the safety, rights, and welfare of human research subjects.

V. Mitigating Post-Inspection Warning Letter Risk

To guard against the issuance of a Warning Letter or FDA enforcement action, it is critical to prepare for BIMO inspections and respond to any issued Form 483 comprehensively, explaining any missteps that occurred, why they occurred,, and why the proposed remediation will be effective. In a June 2024 draft guidance entitled “Processes and Practices Applicable to Bioresearch Monitoring Inspections,” FDA emphasizes best practices for communication between FDA and industry in advance of, during, and after an inspection.[22] FDA stresses that a response should acknowledge FDA’s observations and demonstrate a commitment from senior leadership to address the observations. Experienced counsel can help sponsors and investigators craft a clear, concise, comprehensive, and respectful Form 483 response within the recommended timeframe.

 Well-written responses should:

• Address each observation separately;
• Correct misinformation and express any disagreement in a respectful manner;
• Explain defensible missteps;
• Summarize completed actions and planned corrective and preventive actions in a logical format with related timelines;
• Provide evidence in well-organized attachments that demonstrate completion of actions or progress towards completion, or that clarify or provide context for any potential misunderstandings;
• Detail a method for verifying or monitoring the effectiveness of the proposed corrective actions;
• Commit to future status updates; and
• Invite FDA’s feedback.

It is important that communications to FDA demonstrate an appropriate “tone from the top” and avoid common pitfalls, such as being overly argumentative or self-critical. A response should acknowledge FDA concerns when they are supported by the evidence and propose reasonable remedial action that is tailored to the specific concerns noted in the Form 483. When reporting on remedial action taken, the response should include evidence of the remedial action as an attachment. The response should also include a timeline for when any remaining remedial action will be complete, reflecting reasonable, attainable dates.

FDA has found 483 responses to be inadequate, as reflected in the review of BIMO inspection Warning Letters, when they 1) do not provide details on completed or proposed training on compliance with FDA laws and regulations governing the conduct of clinical investigations; and 2) where respondents promised to implement training or procedures, but the response did not provide sufficient detail to show how the training or procedures would remedy the deficiency and prevent repeat conduct in the future. The BIMO inspection Warning Letters also found unsatisfactory any attempts to 1) blame deficiencies on contract research organizations or other third parties involved in or running investigations on a sponsor’s behalf; and 2) brush off the need for corrective action by simply stating that the investigator is no longer conducting any studies and does not intend to do so in the future. FDA emphasized that it is the clinical investigator who is ultimately responsible for complying with applicable FDA regulations governing the conduct of clinical investigations and protection of human subjects, regardless of whether deficiencies may be attributed to actions of third parties. Additionally, even when a clinical investigator noted his or her intent to avoid conducting research in the future, FDA expected the investigator to describe plans for preventing similar violations from recurring in the event that he or she changes course and decides to participate in a future clinical study.

Moreover, the evidentiary bar appeared higher in connection with clinical studies where there were more egregious objectionable conditions observed by FDA and with clinical studies that enrolled pediatric subjects, which is perhaps unsurprising given the vulnerability of the patient population. For example, FDA’s November 2024 Warning Letter issued to a company studying a rare disease investigational drug product in pediatric patients raised serious concerns about the validity and integrity of clinical trial data after a third-party vendor deleted electronic clinical outcome assessment data for all subjects without the company’s approval, some of which were unrecoverable by the company.[23] Despite the company’s reporting of corrective actions taken to prevent further data deletion and back up existing data, as well as its detailing of preventive actions the company plans to take, FDA noted that the company’s response to the inspection 483 “did not provide sufficient details regarding the procedures being implemented to prevent similar violations in the future.” The deficiencies in the trial ultimately led to the company’s receipt of a complete response letter delaying any approval of its investigational drug product until identified deficiencies are addressed.[24]

VI. FDA Enforcement Tools

Beyond issuing Warning Letters to investigators, FDA can disqualify investigators for repeatedly or deliberately failing to comply with FDA’s GCP regulations or repeatedly or deliberately submitting false information to FDA or to a study sponsor.[25] Disqualification renders the investigator ineligible to receive investigational products, thereby preventing an investigator from conducting any clinical investigation that supports an application for the research or marketing of any FDA-regulated product. Disqualification can jeopardize patients’ continued and reliable access to the investigational product. It also subjects submissions that contain data reported by a disqualified investigator to additional FDA scrutiny.[26] Moreover, the results of disqualification proceedings are publicly available through FDA’s online disqualification proceedings database,[27] which poses risks of reputational harm. Even if proceedings conclude favorably for an investigator, the fact of such proceedings can undermine sponsor confidence in the investigator’s ability to conduct compliant research.

Enforcement for non-compliant clinical research sometimes goes beyond FDA. The Department of Justice’s (DOJ’s) Consumer Protection Branch (CPB) also pays close attention to research misconduct and data integrity issues. Clinical investigators may face criminal prosecution by DOJ, which continues to emphasize the powerful enforcement tools it has at its disposal to pursue clinical trial fraud. In March 2021, for example, a licensed physician who served as the primary investigator for clinical trials at a clinical research site and the clinical trial site director were sentenced to 63 months and 30 months in prison, respectively, based on fraud charges related to fabricating clinical trial data in a pediatric study for an asthma medication.[28] Similarly, in October 2022, a lead study coordinator and a research assistant for a clinical research firm were sentenced to 40 months and 24 months in prison, respectively, and ordered to pay approximately $2.1 million in restitution for, among other things, falsifying trial data to make it appear as though subjects were participating in the trial when they were not.[29]

In 2022, DOJ’s Deputy Assistant Attorney General identified clinical trial fraud as a key DOJ enforcement focus,[30] and in January 2023, CPB’s Assistant Director emphasized his office’s interest in prosecuting research fraud.[31] CPB’s Assistant Director noted that even in cases where an FDA inspection results in a VAI or No Action Indicated classification, DOJ may still decide to investigate and employ its more expansive toolkit to uncover fraudulent activity.[32]  

When research is funded by the U.S. Department of Health and Human Services (HHS), the research will be subject to oversight by the HHS Office for Human Research Protections (OHRP). Like FDA, OHRP may initiate investigations of non-compliant research and conduct not-for-cause compliance evaluations.^[33] When a particular study involves both an FDA-regulated product and HHS funds, it may be subject to concurrent oversight and enforcement by both FDA and OHRP. 

If the research study involves the billing of certain standard of care services to third-party payors such as Medicare or Medicaid, the submission of such claims will be subject to Medicare and Medicaid program rules, as well as fraud and abuse laws such as the federal Anti-Kickback Statute. Violation of Medicare or Medicaid program requirements and/or the federal fraud and abuse laws may give rise to False Claims Act liability. Recent years have seen enforcement actions based on the False Claims Act involving institutions that allegedly billed the Medicare program and other federal health care programs for certain services rendered in industry-sponsored research studies that should have been billed to the study sponsor.[34]

VII. Conclusion

Clinical research is distinct from patient treatment and typically includes assessments and recordkeeping that are essential to drug or device development but not necessarily to patient care. The requirements to ensure timely and appropriate informed consent, strict protocol compliance, careful recordkeeping, and appropriate reporting of adverse events or other problems may seem onerous, but they exist for good reason. Clinical research regulations are designed both to ensure subject safety and the collection of high-quality data that can be used to inform product development and approval decisions. Establishing appropriate training and procedures to govern the conduct of clinical research, hiring diligent and qualified staff to whom tasks can be delegated, and having an experienced staff member conduct regular audits to identify areas for improvement will ease the compliance burden. It is equally important that investigators familiarize themselves with the research protocol’s requirements and implement the protocol, as written, with minimal deviations. Strict compliance with GCPs, including with respect to recordkeeping and reporting, are also critical to limiting FDA inspectional observations and further enforcement risk. If a BIMO program inspection leads to a Form 483, however, it is important to call in experienced counsel, as needed, and be mindful of best practices and recommended time frames for responding.

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[1] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies Draft Guidance for Industry (June 2024), https://www.fda.gov/media/179593/download [hereinafter FDA, Diversity Action Plans]. Congress granted FDA new authority to require Diversity Action Plans for certain clinical studies through enactment of the Food and Drug Omnibus Reform Act of 2022, as part of the Consolidated Appropriations Act (Dec. 2022) (P.L. 117-328). See Ropes & Gray Insights, FDA Takes Next Step In Advancing Diversity in Clinical Studies (July 8, 2024), https://www.ropesgray.com/en/insights/alerts/2024/07/fda-takes-next-step-in-advancing-diversity-in-clinical-studies.
[2] FDA, Diversity Action Plans, supra note 1.
[3] Id.
[4] McKinsey & Company, CROs and Biotech Companies: Fine-tuning the Partnership (2022), https://www.mckinsey.com/industries/life-sciences/our-insights/cros-and-biotech-companies-fine-tuning-the-partnership.
[5] Biotech Companies to Increase R&D Spend but Highlight Complexity of Clinical Trials – ICON (2024), https://investor.iconplc.com/news-releases/news-release-details/biotech-companies-increase-rd-spend-highlight-complexity.
[6] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Bioresearch Monitoring Program Information (Aug. 2022), https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/fda-bioresearch-monitoring-information/bioresearch-monitoring-program-information.
[7] Id.
[8] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, FDA Data Dashboard- Inspections (last visited Sept. 30, 2024), https://datadashboard.fda.gov/ora/cd/inspections.htm.
[9] Id. See also U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Inspection Classifications, https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-basics/inspection-classifications.
[10] 21 C.F.R. § 312.3(b) defines “sponsor-investigator” as “an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. The term does not include any person other than an individual. The requirements applicable to a sponsor-investigator under this part include both those applicable to an investigator and a sponsor.”
[11] In the case of medical devices, FDA requires the submission and FDA approval of an investigational device exemption application (IDE) prior to using a significant risk device in an investigation pursuant to 21 C.F.R. § 812.20. Although the medical device-related warning letters reviewed did not cite investigators for failure to submit an IDE, one can imagine the reasons for investigators failing to do so in the drug context summarized above to be equally applicable in the device context.
[12] 21 C.F.R. § 312.3(b).
[13] Id. The practice of medicine exception also appears in Section 1006 of the FDCA, under which FDA cannot “limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship.”
[14] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Guidance for Clinical Investigators, Sponsors, and IRBs: Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted Without an IND (Sept. 2013), https://www.fda.gov/files/drugs/published/Investigational-New-Drug-Applications-%28INDs%29-Determining-Whether-Human-Research-Studies-Can-Be-Conducted-Without-an-IND.pdf.
[15] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Warning Letter to Lauren R. Klein, Ref: 21-HFD-45-04-02 (May 6, 2021), https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/lauren-r-klein-md-ms-605544-05062021.
[16] Id.<
[17] Id.
[18] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Warning Letter to Maggie Jeffries, M.D. / Avanti Anesthesiology, LLC, Ref: 23-HFD-45-03-01 (Mar. 3, 2023), https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/maggie-jeffries-md-avanti-anesthesiology-llc-646498-03032023.
[19] Id.
[20] Id.
[21] Id.
[22] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Processes and Practices Applicable to Bioresearch Monitoring Inspections Guidance for Industry (June 2024), https://www.fda.gov/media/179027/download.
[23] U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Warning Letter Issued to Issued to CEO & Founder of Applied Therapeutics, Inc. (Nov. 27, 2024), https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/applied-therapeutics-inc-696833-12032024.
[24] See U.S. Securities and Exchange Commission, Applied Therapeutics, Inc., Form 8-K (Dec. 2, 2024), https://www.sec.gov/ix?doc=/Archives/edgar/data/1697532/000095017024132306/aplt-20241202.htm.
[25] See 21 C.F.R. §§ 312.70, 812.119. FDA can also debar clinical investigators, but debarment can only occur after a felony or misdemeanor conviction related to the development, approval, or regulation of drug products. See 21 U.S.C. § 335a(a), (b). For the purposes of this article, we focus on the potential for disqualification.
[26] Id.
[27] See U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Clinical Investigators – Disqualification Proceedings, https://www.accessdata.fda.gov/scripts/SDA/sdNavigation.cfm?sd=clinicalinvestigatorsdisqualificationproceedings&previewMode=true&displayAll=true.
[28] U.S. Department of Justice, Office of Public Affairs, Medical Doctor and Study Coordinator Sentenced to Prison in Scheme to Falsify Clinical Trial Data (2021), https://www.justice.gov/opa/pr/medical-doctor-and-study-coordinator-sentenced-prison-scheme-falsify-clinical-trial-data.
[29] U.S. Department of Justice, Office of Public Affairs, Two Florida Medical Study Coordinators Sentenced in Connection with Scheme to Falsify Clinical Trial Data (2022), https://www.justice.gov/opa/pr/two-florida-medical-study-coordinators-sentenced-connection-scheme-falsify-clinical-trial.
[30] Ropes & Gray, DOJ Increases Focus on Clinical Trial Fraud (Feb. 2022), https://www.ropesgray.com/en/insights/alerts/2022/02/doj-increases-focus-on-clinical-trial-fraud.
[31] Sue Sutter, Data Integrity Fallout: Sponsors Risk Reputational Damage, Negative Impacts on Other Research (Jan. 2023), https://pink.citeline.com/PS147456/Data-Integrity-Fallout-Sponsors-Risk-Reputational-Damage-Negative-Impacts-On-Other-Research.
[32] Sue Sutter, Clinical Data Integrity: Clean US FDA Inspection No Guarantee That DoJ Won’t Investigate (Nov. 2022), https://pink.citeline.com/PS147279/Clinical-Data-Integrity-Clean-US-FDA-Inspection-No-Guarantee-That-DoJ-Wont-Investigate.
[33] Public Health Service Act § 289, 42 U.S.C. § 289; OHRP’s Compliance Oversight Assessments (2024), https://www.hhs.gov/ohrp/compliance-and-reporting/evaluating-institutions/index.html. 
[34] See, e.g., U.S. Department of Justice, Florida Research Hospital Agrees to Pay More than $19.5 Million to Resolve Liability Relating to Self-Disclosure of Improper Billing for Clinical Trial Costs (Jan. 4, 2024), https://www.justice.gov/opa/pr/florida-research-hospital-agrees-pay-more-195-million-resolve-liability-relating-self.