Preclinical and Clinical Trial Requirements
Preclinical and Clinical Trial Requirements in Chile – a legal guide. Prepared in association with Carey, a leading global law firm, this is an extract from The Pharma Legal Handbook: Chile, available to purchase here for USD 99.
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
No. Chilean legislation and regulations do not require for clinical trials to be conducted locally in order to file for or obtain a marketing approval, the ISP accepts clinical trials conducted abroad. These studies must demonstrate the safety and efficacy of the product.
2. How are clinical trials funded?
Clinical trials may be privately or publically funded. Good Clinical Practice guidelines, approved by Exempt Resolution N° 460 of the ISP in January of 2015 (hereinafter GCP guidelines”), defines as sponsor of a clinical trial any individual, company, institution or entity with domicile and legal representative in Chile, responsible of initiating, administrating/controlling and/or financing a biomedical investigation in human beings or clinical study. Additionally, the individual, institution, company or entity that, not financing directly the biomedical investigation, has performed concrete actions to obtain its financing shall also be considered as sponsor.
As set forth under article 99 of the Sanitary Code and under the provisions set forth in Law No. 20.120 –on Scientific investigation on the Human Being, its Genome and Prohibits Human Cloning– and its regulations –set forth in Decree No. 114 of 2011–, to perform a clinical trial in our country, all individuals or entities, whether public, private, national or foreign who are sponsoring the trial with a pharmaceutical product, must request prior approval from the relevant Scientific Ethics Committee, and from the ISP.
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
The GCP guidelines follow the guidelines of the ICH Guideline for Structure and Content of Clinical Study Reports. In this regard, GCP guidelines state that clinical trial protocols must generally include the following general content requirements:
- General information: (i) Title of the Protocol, identification number of the protocol and date (any amendment shall also include the number and date of the amendment); (ii) name and address of the sponsor and monitor (if different to the sponsor); (iii) name and title of the persons authorized by the sponsor to sign the protocols and its amendments; (iv) name, title, address and phone number of the medical expert of the sponsor for the study; (v) name and title of the investigators responsible for conducting the study and address and phone number of the site or sites in which the investigation will be conducted. Name, title, address and phone number qualified physicians responsible for medical decisions related to the investigation site (if different to the investigator); (vi) Name, address of the clinical laboratories and other medical or technical departments and or sites involved in the study.
- Background information: (i) Summary of the findings in non clinical studies with potential clinical significance and other clinical studies relevant for the investigation; (ii) Summary of known and potential risks and benefits, if available, for human beings; (iii) description and justification of the route of administration, dosage, dosage scheme and treatment schedule; (iv) statement that the study will be conducted in accordance to GCP, the protocol and applicable regulatory requirements; (v) description of the target population of the study.
- Detailed description of the objectives and purpose of the study.
- Study design: (i) description of the primary and secondary evaluation points, if included; (ii) description of the type of study design (e.g. double blind; placebo controlled; parallel) and a schematic diagram of the design procedures and study stages; (iii) description of the measures taken to minimize/avoid bias (e.g. randomization; blinding); (iv) Description of the study treatment, study product dosage and dosage scheme. Also a description of the dosage, packaging and labelling of the study products; (v) Expected time of participation of study subjects and sequence and duration of all periods of the study and study follow-up, if applicable; (vi) description of rules to suspend and discontinue the study, totally or partially and of individual participation of subjects; (vii) procedures for counting the study products including placebo and comparators, if available; (viii) procedures for maintaining codes for randomization and procedures to open codes; (ix) identification of any data to be recorded on the Case Report Forms to be considered as source documents.
- Criteria for Inclusion, exclusion and withdrawal of study subjects (including procedure for withdrawal, collected data, replacement and follow up for withdrawn subjects).
- Subject treatment: (i) name, dosage, dosage scheme; route/means of administration, and treatment period for all treatment to be provided and follow up period for the subjects for each treatment/ study group/study arm; (ii) allowed and non-allowed medication/treatment prior or during the study; (iii) procedures for the monitoring of subject compliance.
- Efficacy evaluation, including specifications of efficacy parameters the methods and timings for their evaluation, recording and analysis.
- Safety evaluation, including specifications of safety parameters the methods and timings for their evaluation, recording and analysis. Additionally, description of procedures to record and generate adverse event reports and intercurrent diseases and follow up of subjects.
- Statistics: (i) statistical methods to be implemented, including planned intermediate analysis; (ii) Number of subjects to be included (per site for multicentric investigations) and the reason for sample size, including study potency and clinical justification; (iii) significance level; (iv) criteria for termination of study; (v) procedure to explain missing; non used or false data; (vi) description of procedures to report and justify any deviation of the original statistical plan ; (vii) study subject selection for analysis.
- Direct access to data/source documents, permitting access, audit and monitoring by the Scientific Ethics Committee and regulatory inspections.
- Quality Control and Quality assurance.
- Ethics considerations for the study.
- Data management and records custody.
- Financing and insurance.
- Publication policy
Responsibility for the revision and approval of the trial protocols for clinical trial investigation carried out in Chile rely on the relevant Scientific Ethics Committee and additionally by the ISP. If the approved protocol is changed, the Scientific Ethics Committee and the ISP must be notified.
4. What are the requirements for consent by participants in clinical trials?
As per Law No. 20.120 and its regulations, the consent necessary for participants to enter the clinical trial must comply with the following requirements:
- The consent must be granted before the enrollment, shall be a clear, free and informed consent and must be granted in writing.
- The consent may be given by the study subject or by the person authorized by law to provide the consent on behalf of the study subject.
- The consent shall be evidenced in a written form, signed by the study subject, the responsible investigator and by the Director of the Institution (or its delegate) where the trial will be performed, who additionally will attest to the authenticity of the issuance of the consent (ministro de fe).
- The information provided to the subject about the investigation project shall be adequate, sufficient and easy to understand and shall be previously approved by the corresponding Scientific-Ethics Committee as an official document included in the protocol of the scientific investigation.
- Additionally, the subject shall be expressly informed of his/her right to not authorize the investigation or of his/her right to revoke his/her consent at any moment or by any means without any liability, sanction or loss of benefits which will be recorded in the medical record and in the corresponding document of the investigation protocol.
- The consent shall be requested every time the terms and conditions of the investigation are substantially modified (except when such modifications are considered as minor modifications by the Scientific-Ethics Committee).
It is important to note that any mentally disabled individual who cannot express his/her will, shall not be able to participate in scientific investigations. In the case of scientific investigations in which a mentally disabled person who can express his/her will is participating, the approval of the Scientific Ethics Committee is required and, additionally, the approval of the relevant Sanitary Authority, plus the express consent of the study subject and his/her legal representative.
5. May participants in clinical trials be compensated?
Payment or compensation to participants of clinical trials is allowed, as they are there are no provisions under Chilean legislation and regulations prohibiting this kind of compensation.
In this regard, the GCP guidelines indicate that, “neither the investigator nor the staff should oblige, coerce or unduly influence a subject to participate or continue her participation in a study”. The parties involved may determine an amount of compensation as long as such agreement has been fully and clearly informed to the patient. In this regard, the following information must be provided to the participant:
- The pro-rated advanced payment to the subject for participating in the study, if applicable.
- The payment of the anticipated expenses to the subject for participating in the study, if applicable.
Compensation cannot be a donation of pharmaceutical products.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
Law No. 20.850 on 2015, also known as Ley Ricarte Soto, amended Chilean Sanitary Code regarding clinical trials. This law included a set of rules to specifically regulate circumstances of damages to patients due to their participation in clinical trials.
The holder of the provisional use authorization will be liable for any damage caused during the investigation, even if it could not have been foreseen or prevented according to the state of science at the time the damage occurred, stating that once the damage is proven, it will be presumed that this occurred as a result of the study.
Furthermore, the holder of the provisional authorization must also have civil liability insurance, which is also required for the execution of clinical studies under Law No. 20.120, its regulations and GCP guidelines.