Essential documents are commonly referred to as regulatory documents. ICH GCP guidance defines essential documents as “those documents which individually and collectively permit evaluation of the conduct of the clinical trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor, and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements.” Show A trial master file should be established at the beginning of any research study and maintained throughout the study. This file aids in the management of the study and is often a piece that is audited by study monitors and FDA officials. Unless otherwise noted, copies of all documents should be placed in the master file at the site and with the study sponsor or Contract Research Organization (CRO). The following sections outline the required documents according to ICH E6 Guidance for Industry: Good Clinical Practice (GCP). Please note that all human subjects research should adhere to ICH GCPs regardless of the type of clinical study. In all United States (US) clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in 21CFR50, for Food & Drug Administration (FDA) regulated clinical trials, or the Pre2018-ComRule or the RevComRule for federally funded or sponsored clinical trials. Department of Health & Human Services (HHS)-funded or sponsored clinical trials must also comply with 45CFR46-B-E. The FDA has also adopted the US-ICH-GCPs as guidance. As per 21CFR50, the Pre2018-ComRule, the RevComRule, and the US-ICH-GCPs, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) (institutional review board (IRB) in the US) and provided to the FDA with the investigational new drug application (IND). (See the Required Elements section for ICF content details.) Per the RevComRule, which took effect January 21, 2019, for each clinical trial conducted or supported by a federal department or agency, one (1) EC-approved informed consent form used to enroll subjects must be posted by the awardee or the federal department or agency component conducting the trial on a publicly available federal website that will be established as a repository for such ICFs. According to USA-12, two (2) federal websites have been identified to meet this requirement: ClinicalTrials.gov (USA-78) and a docket folder on Regulations.gov (USA-79). According to the RevComRule, if the federal department or agency supporting or conducting the clinical trial determines that certain information should not be made publicly available on a federal website (e.g., confidential, commercial information), such federal department or agency may permit or require redactions to the information posted. The ICF must be posted on the federal website after the clinical trial is closed to recruitment and no later than 60 days after the last study visit by any subject, as required by the protocol. According to 21CFR50, the Pre2018-ComRule, the RevComRule, and the US-ICH-GCPs, the investigator must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). ICF content should be briefly and clearly presented orally and in writing, in a manner that is easy to understand and commensurate with the comprehension level of the research participants, and without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant and/or his/her legal representative(s) or guardian(s), should also be given adequate time to consider whether to participate. Additionally, per the RevComRule, participants must be provided with the information that a “reasonable person” would want to have in order to make an informed decision and an opportunity to discuss that information. Furthermore, the RevComRule requires that the informed consent, except for broad consent, must begin with a concise and focused presentation of the key information and organized to facilitate comprehension. Broad consent may be obtained in lieu of a full informed consent only with respect to the storage, maintenance, and secondary research uses of private identifiable information and identifiable biospecimens. See USA-54 and USA-60 for additional information regarding informed consent and broad consent requirements. In addition, per 21CFR50, the Pre2018-ComRule, and the RevComRule, the ICF may be presented as either a full length written ICF or as a short form stating the consent requirements have been presented orally. The full length written ICF may be presented orally but must then be provided to the participant and/or his/her legal representative(s) or guardian(s) to read before it is signed. See G-ElectronicIC for further guidance related to electronic informed consent. Re-Consent According to 21CFR50, the US-ICH-GCPs, and the G-IRBFAQs, the EC should determine the need to re-consent enrolled participants in the event of an ICF modification due to protocol changes or new information which may, in turn, affect the willingness of already enrolled participants to continue in the study. The communication of this information should be documented. The G-IRBFAQs indicates that the FDA does not require re-consenting of participants who have completed their active participation in the study, or of participants who are still actively participating when the change will not affect their participation. One such case is when the change will be implemented only for subsequently enrolled participants. Language Requirements 21CFR50, the Pre2018-ComRule, the RevComRule, and the US-ICH-GCPs state that any information provided must be in a language understandable to the participant and/or his/her legal representative(s) or guardian(s). As delineated in the G-ICInfoSheet, when non-English speaking participants are enrolled in a study, ECs and investigators must ensure that the information provided to prospective participants and/or their legal representative(s) or guardian(s) is in a language and at a level they can comprehend. The EC must review and approve all English and non-English language versions of consent documents. The FDA also recommends that whenever non-English speaking participants are enrolled in a study, appropriate interpreter services be made available. USA-63 also states that when an oral presentation of the ICF is provided, the witness present should be fluent in both English and the participant’s language, and the translator may serve as the witness. See the G-ICInfoSheet and USA-63 for detailed information. Documentation Copies As set forth in 21CFR50, the Pre2018-ComRule, and the US-ICH-GCPs, the participant and/or his/her legal representative(s) or guardian(s) must sign and date an EC-approved written ICF. The RevComRule explicitly allows electronic signatures for consent documentation. See G-ElectronicIC for further guidance related to electronic informed consent. A written copy of the form must be given to the participant and/or his legal representative(s) or guardian(s). Per the Pre2018-ComRule and the RevComRule, the EC may waive the requirement to obtain a signed ICF if it finds any of the following:
The RevComRule also adds that the EC may waive the requirements to obtain a signed ICF if the participants are part of a distinct cultural group or community in which signing the form is not the norm, the research presents minimal risk, and there is an alternative approach to document informed consent. Per 21CFR50, the Pre2018-ComRule, the RevComRule, and the US-ICH-GCPs, if the consent information is only presented orally using the short form, the participant and/or his/her legal representative(s) or guardian(s) must sign the form (if capable), the witness must sign both the short form and a copy of the summary once consent has been provided, and the person obtaining the consent must sign a copy of the summary. A copy of both the summary and the short form should be given to the participant and/or his/her legal representative(s) or guardian(s). According to the US-ICH-GCPs, where the participant is illiterate and/or his/her legal representative(s) and/or guardian(s) is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:
Before participating in the study, the participant or his/her legal representative(s) and/or guardian(s) should receive a copy of the signed and dated ICF. Per the G-RevComRule-FDA, the informed consent requirements of the RevComRule are consistent with FDA regulations. Therefore, there may not be a need for sponsors or investigators to develop, and have ECs review, two (2) separate ICFs for research that must comply with both the RevComRule and FDA regulations. Who approves a clinical trial?Before the U.S. Food and Drug Administration (FDA) approves a clinical trial to begin, scientists perform laboratory tests and studies in animals to test a potential therapy's safety and efficacy. If these studies show favorable results, the FDA gives approval for the intervention to be tested in humans.
Which approvals are required to conduct clinical trials in India?The Drugs Controller General of India (DCGI) is an official of the CDSCO who is the final regulatory authority for the approval of clinical trials in the country.
What essential documents are needed to conduct clinical trials?The essential documents for clinical trials are the following: Investigator's Brochure. Clinical Study Protocol. Subject Information and Informed Consent Form.
Who must approve a clinical trial in the United States before it can begin?FDA responds to IND applications in one of two ways: Approval to begin clinical trials. Clinical hold to delay or stop the investigation.
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