Introduction
Research misconduct in a clinical trial may first come to light through a whistleblower, a monitoring visit, an audit, an inspection, or an internal review of study records.
Imagine an investigator reviewing a participant’s file after a study visit. The investigator discovers that the participant experienced an adverse event. The investigator sees this documented in the clinical notes. However, when reviewing the case report form (CRF), the investigator notices that the incident was not recorded. Was this mere oversight from the research coordinator or something that requires a closer look?
An omission from a CRF can be more than a paperwork problem. Incomplete safety data may affect sponsor oversight, participant protection, and the reliability of information used in regulatory decision-making. Significant or systemic data-integrity problems may cause the U.S. Food and Drug Administration (FDA) to question whether affected data are reliable enough to support regulatory decisions. Depending on the facts, the matter may also require review by the sponsor, the Institutional Review Board (IRB), clinical research leadership, institutional compliance, legal counsel, or the research integrity office.
Understanding What Counts as Research Misconduct
Under 42 CFR 93, research misconduct means fabrication, falsification, or plagiarism in proposing, performing, or reviewing research or in reporting research results. A finding requires more than an inaccurate record. The conduct must represent a significant departure from accepted practices of the relevant research community; must have been committed intentionally, knowingly, or recklessly; and must be established by a preponderance of the evidence. The Office of Research Integrity’s (ORI) State of Mind Guidance explains how institutions should evaluate whether a respondent (meaning any individual(s) alleged to have committed research misconduct) acted intentionally, knowingly, or recklessly.
Research misconduct does not include honest error or differences of opinion. ORI’s Honest Error Guidance assists institutions in evaluating that distinction. This is especially important in clinical trials, where a transcription mistake, protocol deviation, or erroneous adverse event coding error does not necessarily indicate wrongdoing. At the assessment stage, the institution considers whether the allegation falls within the definition of research misconduct, appears to involve a covered Public Health Service (PHS)-supported activity, and is sufficiently credible and specific to identify potential evidence.
When does 42 CFR 93 apply?
The revised ORI 2024 Final Rule on PHS Policies on Research Misconduct became effective January 1, 2025, and applies to allegations received on or after January 1, 2026. The regulation applies to research misconduct involving PHS-supported biomedical or behavioral research, research training, or related activities. It does not automatically govern every clinical trial. Even when 42 CFR 93 does not apply, institutional policies, sponsor requirements, U.S. Food and Drug Administration (FDA) regulations, contractual obligations, or other legal processes may still require action. Institutions subject to the rule were required to submit the updated annual report and assurance for the 2025 reporting year by April 30, 2026.
How FDA Oversight Differs from a Research Misconduct Proceeding
When 42 CFR 93 applies, it governs how institutions assess and address an allegation of research misconduct. The FDA operates under separate statutory and regulatory authorities focused on clinical-trial conduct, data reliability, and participant protection. FDA action can proceed independently of an institutional research misconduct review and may serve a different purpose. Institutions therefore should not treat FDA noncompliance and PHS research misconduct as interchangeable findings.
When an FDA inspection identifies conditions that may violate the Food, Drug, and Cosmetic Act and related acts, the agency issues a Form FDA 483 to the institution at the close of the inspection. The form lists the investigator’s observations and is discussed directly with institutional leadership, but it is no a final agency determination that a violation occurred. The FDA encourages the institution to respond in writing with a corrective action plan and to implement it promptly.
The FDA has several distinct tools that may be relevant, depending on the facts and the applicable legal criteria. These tools should not be understood as automatic stages in a single escalation sequence. The FDA may issue a Warning Letter; initiate proceedings to disqualify a clinical investigator who has repeatedly or deliberately violated applicable requirements or repeatedly or deliberately submitted false information; or impose a full or partial clinical hold when the legal standard for a hold is met.
In the context of investigator misconduct, FDA guidance explains that a hold may be appropriate when credible evidence of serious regulatory violations or false reporting indicates that participants are or would be exposed to an unreasonable and significant risk of illness or injury. Examples may involve falsified eligibility information, falsified consent documentation, or fabricated participants, but the controlling issue is the risk to participants.
A clinical hold runs on its own timeline, separate from any institutional misconduct inquiry, as it is meant to protect study participants immediately. Since the same conduct that draws FDA scrutiny can also be the subject of an institution’s own misconduct inquiry, the IRB, clinical research office, compliance personnel, and legal counsel should share relevant information promptly. The FDA and an institution may reach different conclusions because they are applying different authorities, criteria, and purposes.
Closing Thoughts
Meeting the April 2026 reporting and assurance deadline does not by itself establish operational readiness. ORI’s Writing Policies and Procedures and Sample Policies and Procedures guidance documents remain useful references for institutions revisiting their policies. Additionally, staff handling allegations should understand that the assessment phase from ORI’s Assessments Guidance is distinct from a formal inquiry. An early review of a discrepancy, such as a missing CRF entry, should not be mistaken for or substituted for a process required by the regulation.
A clinical trial’s data serves more than the institution that generated it. It informs FDA’s approval decisions, shapes clinical practice, and depends on the trust of the study participants who voluntarily agreed to take part. Institutions can protect that trust by distinguishing error from possible misconduct, addressing immediate risks, preserving evidence, and coordinating parallel reviews without prejudging their outcomes.
References and Resources
- Financial Disclosure by Clinical Investigators, 21 CFR § 54 (1999).
- Investigational New Drug Application, 21 CFR § 312 (2023).
- Mohseni, Tasha. 2026. “Modernizing the Handling of Research Misconduct: What Institutions Need to Know.” ACRP Blog, January 20. Accessed September 16, 2026.
- Public Health Service Policies on Research Misconduct, 42 CFR § 93 (2024).
- The Office of Research Integrity (ORI). 2024. “ORI Final Rule.” Accessed September 16, 2026.
- The Office of Research Integrity (ORI). 2025a. “Guidance for Public Health Service Policies on Research Misconduct 42 CFR Part 93 (2024) Honest Error.“ Accessed September 16, 2026.
- The Office of Research Integrity (ORI). 2025b. “Guidance for Public Health Service Policies on Research Misconduct 42 CFR Part 93 (2024) Institutional Assessments.” Accessed September 16, 2026.
- The Office of Research Integrity (ORI). 2025c.”Guidance for Public Health Service Policies on Research Misconduct 42 CFR Part 93 (2024) Writing Policies and Procedures for Addressing Allegations of Research Misconduct.” Accessed September 16, 2026.
- The Office of Research Integrity (ORI). 2025d. “Sample Policies and Procedures for Addressing Allegations of Research Misconduct for Public Health Service Policies on Research Misconduct 42 CFR Part 93 (2024).” Accessed September 16, 2026.
- The Office of Research Integrity. 2026. “Guidance for Public Health Service Policies on Research Misconduct 42 CFR Part 93 (2024) State of Mind.” Accessed September 16, 2026.
- U.S. Department of Justice (DOJ). 2026. “Doctor and Staff Charged with Falsifying Data in Clinical Drug Trials.” Accessed September 16, 2026.
- U.S. Food and Drug Administration (FDA). 2004. “Guidance for Industry and Clinical Investigators: The Use of Clinical Holds Following Clinical Investigator Misconduct.” Accessed September 16, 2026.
- U.S. Food and Drug Administration (FDA). 2020. “FDA Form 483 Frequently Asked Questions.” Accessed September 16, 2026.
