Clinical Trial Inspections: The Legal Risks Revealed by ANVISA’s Findings. Risk Management and Good Clinical Practices
The new Clinical Research Law (“Law No. 14,874/2024”) has been the almost exclusive focus of the debate over the past two years regarding the development of clinical research in Brazil. Although the regulations still require adjustments, and the implementation of the new law presents its own challenges, other weaknesses—notably operational ones—equally impact the conduct of studies, exposing research centers, sponsors, and investigators to legal risks. These aspects, therefore, also merit attention for the sector’s proper development.
The second Report on Good Clinical Practice Inspection Metrics, published by the National Health Surveillance Agency (“Anvisa”), in May of this year—based on the ICH E6 (R2) Guidelines, RDC No. 945/2024, Law 14,874/2024, and other rules related to clinical research—provides a wealth of information for improving the management of research centers.
The inspections conducted by Anvisa were aimed at verifying the degree of compliance of research centers (which, ultimately, are intended to protect clinical trial participants), but they are not limited to a formal oversight exercise. In practice, they consist of a structured review of documents, facilities, and records, with the immediate potential to result in significant legal consequences.
The logic behind oversight is based on an obvious premise: a clinical research center is, essentially, a healthcare facility. As such, it has the same organizational and control obligations inherent in the healthcare activities of any clinic, which are carried out through robust Standard Operating Procedures (“SOPs”), rigorous traceability controls for documents, medications, and medical equipment; and the maintenance of complete, consistent, and up-to-date medical records, without which the center’s very ability to demonstrate the quality of its reports is compromised.
If the records are flawed, incomplete, or inconsistent, it is presumed that not only the reliability of the research is compromised, but also the center’s ability to demonstrate that it has adopted the required care and safety measures for the participant’s benefit. In the event of a claim for damages, the absence of contemporaneous, complete, and consistent records may hinder the demonstration of proper clinical conduct, effectively reversing the burden of proof and significantly increasing the exposure of those involved to civil liability.
Although the report in question warrants a full reading, some relevant nonconformities are examined below.
- The Informed Consent Form (“ICF”).
The ICF provides ethical and legal legitimacy to individuals’ participation in clinical trials. From the perspective of civil liability, it plays a significant role as a protective measure, not only for the participant, but especially the researcher and the sponsor, insofar as documentation regarding its proper execution demonstrates that the participant was previously and sufficiently informed, in a clear and effective manner, about the risks, benefits, and alternatives of the research, in compliance with the duty to inform and in respect for the participant’s autonomy as a research participant.
The findings consolidated in the ANVISA Report reveal significant shortcomings regarding the TCLE: lack of control over the signing of versions approved by the Research Ethics Committee (“CEP”); lack of re-consent (or renewal of consent) when applicable; and insufficient records regarding the conduct of the informed consent process, including data on the need for a witness, when applicable.
With regard to the management of participant data, the Report highlights a number of non-conformities, such as non-contemporaneous data entry, with sample collection and investigational product administration times lacking supporting evidence; gaps or discrepancies in study instruments; and inconsistencies between source documents, medical records, protocols, and the sponsor’s systems.
In the event of a legal dispute, a well-structured and properly formalized informed consent form helps to refute allegations of inadequate information, narrows the scope of liability for risks inherent in the medical procedure, and reinforces the argument that the patient consciously assumed the risks to which he or she would potentially be exposed.
Flaws in the consent process, such as those highlighted in the ANVISA Report, undermine this protective effect, weakening the defense and increasing liability. A lack of care in handling such an important document can be disastrous for the research itself—and especially for those involved (the centers, the investigator, and ultimately, the sponsor)—particularly considering that these non-compliances may even impact risk coverage under the contracted insurance policy.
A compliance analysis cannot ignore the research participant’s position, which is often asymmetrical (at a disadvantage) relative to the site and the researcher: disorganization, data inconsistencies, and the difficulty of proving that study findings were properly recorded undermine the defense of the research site and the researcher, particularly in civil liability lawsuits.
Another critical issue involves study documentation, in the broadest sense: the inspections identified contracts that were improperly drafted or drafted late, delays in reporting serious adverse events (SAEs) to the CEP, and a lack of staff training records; expired laboratory accreditation certificates, inconsistencies in electronic medical records, failures in inventory control and storage of medications, lack of adequate temperature control in the storage of the investigational product, and expired medications that were not segregated.
In legal disputes, such failures are usually interpreted against those responsible for addressing them; they complicate the allocation of liability in cases of protocol deviations and serious adverse events, and they jeopardize the potential exercise of the right of recourse.
Furthermore, structural, documentation, and informed consent failures are not limited to regulatory noncompliance: they directly impact the scientific quality of the study by compromising the reliability of the data generated and, consequently, the very utility of the research.
When research methodology is compromised, the consequences can be substantial: either the data indicate a lack of efficacy or safety of the product, or, conversely, suggest positive results that would not hold up under normal conditions; in either case, such a situation compromises the quality and safety of the investigational drug, with significant repercussions for the consumer market.
Law No. 14,874/24 assigns direct responsibilities to the investigator for conducting the study: for data integrity, for the safety of participants, and for the proper documentation of the activities carried out. Failure to comply with these duties not only constitutes a public health violation (Law No. 6,437/1977) but also subjects the responsible party and the research institution to sanctions that include warnings, fines, suspension or cancellation of studies, as well as the closure of the center, without prejudice to civil liability and, in more serious situations, criminal liability.
The commendable increase in clinical research in the country and the growing complexity of regulatory requirements necessitate that operational structures be prepared to respond adequately to this new reality; otherwise, without due care, the consequences could extend far beyond the administrative sphere, reaching contractual, litigation, and reputational dimensions.
Preventive measures and the early identification of vulnerabilities, a critical review of processes and contractual instruments, and the proper preparation of infrastructure are essential elements in conducting clinical trials. The ability of institutions to recognize their limitations, structure their growth, and manage their risks consistently—in line with current regulatory expectations—is imperative: a thorough evaluation of the ANVISA Report, with its advisory nature, is a good start!
This material is for informational purposes only and should not be used in isolation for decision-making. Specific legal advice may be provided by one of our attorneys. Copyright is reserved by KESTENER VIEIRA TORRONTEGUY SPEGIORIN ADVOGADOS.
