November 18, 2014 | By Márcio Barra
Pharmupdates is back! After a hiatus, I felt the time was right to resume updating once again, this time with an emphasis on the Portuguese side of news. So, enjoy the first article, part 1 of a new series detailing the new clinical research Law in Portugal, Law 21/2014. Please be mindful of typos, as the bulk of my writing is now done in a foreign keyboard.
Up until April 2014, the procedure for submitting and requesting an approval of a clinical trial in Portugal was governed by Law 46/2004 of 19 August 2004. This law was revoked by Law 21/2014, of 16 April 2014, which introduced some new considerations that sponsors have to be aware when seeking to conduct clinical trials in Portugal. Both laws incorporate the principles of the Clinical Trials Directive 2001/20/EC. It is worth noting that while Law 21/2014 introduced new procedures for submitting a clinical trial authorization request, some of the procedures are still not fully operational. Thus, some of the principles of previous law are still in use.
Concerning the approval of a clinical trial, according to law 21/2014, like the law before it, an approval request has to be sent to the Portuguese National Competent authority (INFARMED), under Article 26. º for clinical trials with experimental drugs. The new law has some changes on the way each chapter is organized. While in the previous law, the entire range of available procedure is detailed in chapter III and IV, in the new law, the content is more spread out, making for a more complex read.
Under the new law, the sponsor is to request permission to INFARMED through the RNEC (RNEC – National Clinical Trials Registry). Within 30 business days, the governing board of the INFARMED has to issue an opinion. However, the RNEC is still not in operations as of this moment, and so the submission procedure is still conducted under Law 46/2004. The same holds true under law 21/2014 for CEIC’s (the Portuguese National Ethics Committee for Clinical Research) approval procedure, with the sponsor having to request an opinion through the RNEC. The CEIC, or a designated CES (local Committees for Health Sciences), then has 30 business days to issue their opinion on the ethical aspects of the trial. However, this period can be extended for 20 days if the intervention in question is a genetic therapy, a somatic cell therapy, or an intervention that contains genetically modified organisms. If the CEIC or CES has to resort to outside expert opinion, the timeline can be extended for an additional 50 days. Xenogeneic therapies have no set deadline for a statement to be issued. INFARMED enjoys the same extended time frames for the same special cases. As for the National Committee for Data Protection, the committee has a 30 day timeline to issue a statement.
The CEIC is still to publish more in-depth guidance for submission of a clinical trial authorization request under law 21/2014. According to the Law 46/2004 and the guidance published by CEIC, the approval request has to comply with Annex I of CEIC’s guidance note (found here: http://goo.gl/w5fz08 ).
A more in-depth look will be now provided at each article of the now governing law, highlighting the differences between the previous version.
A noticeable difference compared to the previous law of clinical trials is that the new law applies to all clinical research conducted in humans. This includes observational studies, which are now too encompassed in Law 21/2014, and studies which use individual health data (such as registries).
The new law further emphasizes the importance that is to be given to the clinical trial participant. Article 3 introduces a new statement, highlighting that “in clinical studies, all precautions must be taken to respect the privacy of the individual and minimize any damage to their rights of personality and their physical and mental integrity.”
Article 4, on the evaluation of risk/benefit by the national competent authority, now includes a short statement, declaring that the experimental therapy risk/benefit can be reviewed at any time during the trial, if new evidence appears or through interim analyses of the study itself. This highlights the growing trend in clinical trial design of adopting interim analysis in their statistical analysis plan.
Article 6, which deals with the topic of financial compensation of patients in clinical trials, introduces some new points. Patients are not to be granted any financial incentives or benefits, save for expenses reimbursement expenses and compensation for damage suffered from clinical trial participation. Some minimum requirements for the protection of participants are also more fleshed out and detailed in comparison to the previous law. The assigned ethic committee (either the CEIC or a CES) is also provided with the authority to, in non-interventional studies and exceptional situations, remove the need for explaining to the participant what the trial is about and attaining informed consent.
Specific provisions are established for clinical trial participants, including the minimum requirements for the protection of participants, specific provisions regarding the participation of minors and disabled individuals in clinical trials, as well as provisions related to obtaining informed consent (Articles 6 to 8).
The procedure for attaining consent on minors too has been more detailed. Alongside the other requirements, a clinical trial can only be performed on minors when it has been obtained the informed consent of a minor aged above 16 years and his legal representative. If the minor has less than 16 years, the representative is the sole responsible for grating informed consent, although it must reflect the presumed will of the minor. The assigned ethic committee again is given the right, under exceptional circumstances, to waive the requirements of informed consent and informing the minor patients in clinical studies without intervention. The assigned ethic committee is given the same right for participants of age unable to provide informed consent.
Part 2 is coming next
Lei n.º 21/2014, de 16 de abril