Around the Globe: US
Clinical Research Misconduct: Changes in US Clinical Trial Agreements May Be Necessary
Darshan Kulkarni
Kulkarni Law Firm

n October 6, 2023, the US Department of Health and Human Services, in conjunction with the Office of Research Integrity (ORI), proposed updates to revise the Public Health Service Policies on Research Misconduct. The proposal primarily focused on clinical research sites and did not specify how clinical trial agreements would need to be updated. Nevertheless, Clinical Research Organizations (CROs) and Sponsors must pay heed to site-level changes and update their contracts in light of their own exposure to avoid being caught flat-footed or surprised when the changes are confirmed.

Additionally, in line with previous changes, ORI is likely to allow for modest modifications in light of feedback but is unlikely to make significant changes to their proposals—as dramatic as the proposed changes are.

  1. Confidentiality Clauses: The proposed policies primarily affect Sites. However, it may be important to update confidentiality clauses to align with ORI’s stance. Additionally, sponsors may consider requiring sites to notify the sponsor in addition to appropriate regulatory authorities in the context of research misconduct.
  2. Site Audit Rights: Clinical trial agreement research site audit clauses should be reviewed to ensure appropriate and adequate access to not only site policies but also site training. This process should go beyond just financials and data integrity to encompass a thorough review of compliance with the new misconduct guidelines, institutional responsibilities, and ethical standards. The agreement should specify the scope, frequency, and methodology of these audits, as well as outline the actions to be taken in case of noncompliance. By doing so, sponsors can proactively ensure that research sites are adhering to the updated ORI guidelines, thereby minimizing risks and enhancing the integrity of the trial.
  3. Data Integrity: The new ORI proposal incorporates specific requirements related to data integrity and data storage. While these requirements are generally aimed at ensuring consistency, traceability, and integrity in research practices, they hold particular significance for sponsors involved in clinical trials. Given the critical nature of data in research, sponsors would be well-advised to explicitly reiterate these data storage requirements in their agreements and protocols. This becomes especially crucial if study results are called into question due to allegations of research misconduct. By clearly defining, emphasizing, and verifying stringent data storage practices in line with ORI’s updated guidelines, sponsors can safeguard the validity of their trials and mitigate risks associated with potential misconduct.
  4. Timelines: ORI’s recent proposal also introduces a range of specific timelines that govern various aspects of the process of investigating and remediating the research misconduct. These timelines include, but are not limited to, stipulations on when an investigation must be initiated following an allegation, deadlines for submitting reports to ORI, and timeframes within which appeals must be filed. Given the critical importance of timeliness in addressing allegations of research misconduct, it becomes increasingly vital for sponsors of clinical trials to be vigilant.

    Sponsors should take proactive measures to ensure not only that they are aware of these timelines, but that they also receive timely notifications at each critical juncture of the process of investigating and confirming the misconduct. Existing agreements should therefore be updated to establish new communication protocols with research institutions to guarantee that all relevant information is promptly relayed.

  5. Reporting Requirements: The newly proposed ORI guidelines include explicit stipulations concerning the reporting requirements and timelines that must be adhered to during the assessment phase of a research misconduct investigation. Given the critical nature of these timelines and reporting protocols, it is imperative that they are fully integrated into the clinical trial agreements between sponsors and research sites. This integration serves a dual purpose: First, it helps ensure that research sites are contractually obligated to follow the appropriate timelines as laid out by ORI, thereby protecting the integrity of the research process. Second, it makes it far more likely that sponsors are systematically notified about any updates or allegations of misconduct in a timely manner. This could be particularly crucial for sponsors to manage risks and make informed decisions in real time. By incorporating these ORI-specified reporting requirements and timelines into the agreement, sponsors can establish a robust framework for oversight and communication, thereby safeguarding the integrity and credibility of the clinical trial. Furthermore, contracts may choose to specify what sponsors can do in the event of alleged or confirmed research misconduct.
  6. Public Disclosure: Given that the new ORI guidelines enable significant public disclosure of research misconduct proceedings, it becomes increasingly crucial for clinical trial agreements, or SOPs that are incorporated by reference, to include detailed clauses that address the handling of public relations and disclosures pertinent to the trial. These clauses should consider delving into the specifics of how both sponsors and research institutions will manage communications, both internally and externally, in the event that aspects of the trial become publicly disclosed due to research misconduct allegations or findings. This might include protocols for issuing press releases, guidelines for social media communications, and procedures for informing stakeholders such as investors or board members. Additionally, the clinical trial agreement may outline the responsibilities of each party in managing public perception and legal obligations related to such disclosures. By incorporating these comprehensive clauses, sponsors and research institutions can better prepare for and manage the complexities and potential reputational risks associated with increased public disclosure, as mandated by the updated ORI guidelines.
  7. Financial Implications: In light of the proposed ORI policies, sponsors may choose to add comprehensive clauses that address the financial ramifications associated with halting or invalidating trials as a result of research misconduct allegations or findings. These clauses may not only add cursory statements but also provide an in-depth framework that delineates the financial responsibilities and liabilities of each party involved. This could include, for example, the allocation of costs for additional investigations, penalties for noncompliance with ORI guidelines, and the potential forfeiture of funds allocated for the trial. Additionally, the clauses may specify the conditions under which a trial may be halted or invalidated and the subsequent financial procedures that would be triggered in such scenarios. By clearly outlining these financial implications, sponsors and research institutions can establish a mutual understanding that safeguards both parties and ensures a level of fiscal responsibility and accountability in the unfortunate event that research misconduct occurs.

The newly proposed ORI guidelines bring with them a host of complexities that clinical trial sponsors and research institutions must navigate carefully. From the intricacies of data storage and reporting timelines to the nuanced financial and public relations implications of research misconduct, these updates necessitate a thorough reevaluation and likely revision of existing clinical trial agreements. By proactively addressing these changes—whether it’s enhancing audit rights, specifying new reporting timelines, or outlining procedures for public disclosure—both sponsors and sites can mitigate risks and uphold the integrity of their clinical trials. Acknowledging and acting on these updates should be viewed as a strategic imperative for ensuring compliance, managing reputational risks, and ultimately, safeguarding the scientific and ethical rigor of clinical research.