Law No. 14874, enacted on May 28, 2024, establishes the principles and rules to be observed when conducting clinical trials on human beings; it also institutes the National System of Ethics in Research. It is essential to appreciate the importance of this historic milestone for the country. Among its objectives, besides reaffirming the precepts of Good Clinical Practices, it aims to simplify and streamline the ethical and regulatory analysis processes of research projects, fostering expectations within the research community of a significant increase in the number of clinical trials conducted in Brazil and attracting more international sponsors.
Naturally, the new law maintains in force fundamental precepts previously described in the Collegiate Board Resolution No. 466 of 2012 and in the Good Clinical Practices Guide. Additionally, regarding the ethical analysis of research involving human beings, the new law institutes the National System of Ethics in Research with human beings, composed of a national ethics body in research and satellite centers for ethical review, represented by Independent Ethics Committees. The national body is responsible for issuing regulations, evaluating the system’s effectiveness, accrediting and certifying Independent Ethics Committees, monitoring and training IEC members, as well as acting as an appellate body when necessary. The key change instituted by this law delegates exclusively to the Ethics Committees the responsibility to evaluate the qualifications of investigators and their scientific research projects, and monitor their execution and applicable regulatory requirements, thus eliminating the dual ethical approval process that was previously in place in Brazil.
Regarding the timelines established for ethical review, the acceptance or rejection of the complete research documentation must be carried out by the Independent Ethics Committee within 10 business days from the submission date, with the issuance of the project opinion within 30 business days from the receipt of the research project. If additional information or adjustments need to be requested before issuing an opinion, the deadline may be suspended for up to 20 business days. The sponsor or investigator then has up to 10 business days to respond to the queries received, with the possibility of extending this period with justification. If an appeal against an issued opinion is necessary, the investigator must submit the request within 30 business days, and the national ethics body will review the appeal within the same 30-day period. Moreover, prioritization is provided for the analysis of research of strategic interest to the Unified Health System and to respond to public health emergencies, in which case the Independent Ethics Committee must issue an opinion within 15 business days.
The wording of the new law maintains the prohibition on compensating subjects, with provisions for the necessary reimbursement of expenses such as transportation, meals, and other necessary costs. The national registry of healthy subjects in bioequivalence studies is also maintained, along with the prohibition on volunteers participating in more than one study simultaneously.
An important aspect of the law pertains to the use of placebos. Placebos are accepted when there are no proven methods of prophylaxis, diagnosis, or treatment for the disease targeted by the research, or when the harm from using a placebo does not outweigh the benefits of participating in the research. The law reaffirms the principle that the subject should not be deprived of receiving the best available treatment. Throughout the text of the new law, the responsibilities of the sponsor and investigator, as previously listed in Good Clinical Practices, are reaffirmed.
Regarding the provision of post-study medication, one of the most awaited aspects of the new legislation, there was a change from the understanding of the text previously approved by the National Congress. The provision that conditioned the supply of post-study medication to a maximum period of 5 years was initially vetoed by the acting president. It is worth noting that previously RDC No. 38/2013 regulated the free provision of medication to subjects in case of termination of the study. However, the newly enacted law details a series of criteria governing such a provision, establishing the requirement for a post-study access plan to be submitted by the sponsor and approved by the respective Ethics Committee, stating the need for free provision of the post-study experimental medication for a determined period, and it must be submitted for appraisal before the clinical research project begins. The request to the National Competent Authority must also be made to authorize the importation of the product, ensuring that the subject’s treatment is not interrupted. The new legislation emphasizes the importance of individualizing the analysis for each subject receiving the post-study medication, evaluating individual benefits, and considering the severity of the disease and the health risks, as well as the availability of satisfactory therapeutic alternatives.
In addition to the principles and rights of subjects already well described in the Good Clinical Practice Guide being reaffirmed in the new legislation, guidelines are set out regarding the storage of biological materials collected as part of clinical trials. It clarifies that human biological material stored in biobanks and biorepositories is the property of the subject under the custody of the responsible institution. This material must be used only for the purpose described in the protocol unless express consent is given for use in future research. In biobanks, the storage period is indefinite, and the management of human biological material is the responsibility of the institution. Regarding biorepositories, the storage period must be determined, and the management is the responsibility of the sponsor-investigator. At the end of the clinical trial, the biological material may continue to be stored (under the subject’s authorization), be transferred to another biobank, or be discarded.
Finally, the registration of the clinical trial will be carried out with the national ethics body and must be updated on a publicly accessible website. The obligation for the sponsor/investigator in charge to send an annual report on the progress of the study to the Ethics Committee remains, including reporting research protocol deviations and serious adverse events that have occurred, the latter of which must also be reported to Anvisa. In cases of interruption of the ongoing clinical trial, a technical-scientific rationale must be submitted to the Ethics Committee within 30 business days, along with a report on the results obtained up to the point of interruption, with additional communication to Anvisa.
The entire scientific community awaits the real impacts of the new law on the daily routine of research projects, as well as subsequent operational regulations. However, there is undoubtedly a positive expectation of increased competitiveness for the country and a reduction in bureaucratic processes in the future.
Comments