Miscellaneous Flashcards
By signing the 1572 the PI agrees to
1) Personally conduct or supervise the study
2) Protect the health and welfare of the subjects per 21 CFR 50
3) Report AEs to the sponsor
4) Ensure all staff on the study understand their obligations and commitments
5) Maintain adequate and accurate records and make them available for inspection
6) Ensure that an IRB compliant with 21 CFR 56 reviews the trial
7) Comply w/ requirements in 21 CFR 312 (Investigational new drug application)
What do sponsors do with completed 1572s?
Submit them to the FDA
What is 21 CFR 54 about?
Financial Disclosure
Per 21 CFR 54, what information must be reported by investigators to a company submitting a new drug application?
1) Compensation to the investigator in which the value of the compensation could affect the outcome of the study
2) A proprietary interest in the test product
3) Any equity interest in the sponsor of a covered study
4) Any equity interest in a publicly held company exceed $50K in value
What is the dollar limit for payments made to an investigator/institution a companies must disclose to the FDA when submitting a NDA?
$25,000 +
What is the time frame in which a sponsor is required to obtain financial disclosures from an investigator?
Before an investigator can participate in a trial until 1 year following completion of the trial
What is form FDA 3455 used for?
Disclosing financial interests
What is form FDA 3454 used for?
Certifying that there are no reportable financial interests
What is 21 CFR Part 11 about?
Electronic records - specifies processes that must be in place to ensure that electronic documents and signatures are equivalent to paper documents & handwritten signatures.
What are the requirements for a computer system to comply with 21 CFR Part 11?
- Computer systems with electronic records and signatures must ensure accuracy, reliability, and consistent performance
- Must use and maintain secure, computer-generated, time-stamped audit trails
- Include system checks so only authorized individuals have access to the system, can alter records, and perform operations
- Procedures must be established to ensure that records are retained for a period of time, in an appropriate format, and meet FDA requirements.
Required elements of a DOA?
- Names of study staff members and the responsibilities assigned to them
- Staff signatures w/ date
- PI initials and date
Form FDA 1572 is legally binding between the investigator and whom?
FDA
Which two CFRs cover informed consent?
21 CFR 50 and 45 CFR 46
Which CFR discusses broad consent?
45 CFR 46 (not included in 21 CFR 50)
Required elements for informed consent per 21 CFR 50 & ICH E6
1) The study involves research (purpose, duration, procedures, which procedures are experimental, group assignment)
2) Foreseeable risks, inconveniences and discomforts
3) Potential benefits
4) Alternatives procedures or treatments that may be advantageous (ICH E6 requires important risks/ benefits of the alternatives)
5) Confidentiality of records
6) Compensation for injury and access to medical treatments
7) Who to contact & contact details for more info
8) Voluntariness
9) ICH E6 (only; not FDA or HHS) requires outline of subject responsibilities
10) Subject payment
11) 21 CFR 50 (only) requires posting on clinicaltrials.gov
12) 45 CFR 46 (only) requires research collecting private health information or identifiable biospecimens to include either:
- statement that identifiers might be removed and data/samples used for future studies without further consent
- The samples, even with identifiers removed, will not be used or distributed for future research.
Additional required elements of consent if relevant
1) There may be risks that are unforeseeable
2) When participation may be terminated by the investigator
3) Additional costs to subject from participation
4) Consequences for withdrawal
5) Statement that significant new findings that may influence subject’s willingness to continue participation will be shared
6) Approximate number of subjects involved
For studies subject to HHS 45 CFR 46:
7) Biospecimens may be used for commercial profit and whether subject will share the profit
8) Statement re: whether clinically relevant research results will be shared and when
9) If study involves biospecimens, whether the research will or might include whole genome sequencing
Which regulatory body requires that the person obtaining consent sign and date the consent form?
ICH E6 (as opposed to HHS or FDA)
Which regulatory body/bodies require the subject/subject’s LAR receive a copy of the consent?
FDA requires they receive a copy. ICH E6 requires they be given a signed and dated copy.
If a consent is signed electronically which CFR should be considered?
The investigator must ensure the subject’s electronic signature fulfills the requirements of 21 CFR 11
The HHS and FDA issued joint guidance on the use of electronic systems for obtaining informed consent. What is one of the major topics made clear in this guidance?
That obtaining the subject’s informed consent ultimately lies with the investigator and cannot be delegated to an electronic system.
What is Form FDA 1571?
IND application
What form is used to apply for an IND?
Form FDA 1571
Which CFR/regulation/regulatory body requires a copy of a clinical trial’s consent form be posted publicly?
45 CFR 46. It is not required by the FDA or ICH E6
Which regulation requires the submission of a Form FDA 1572?
21 CFR 312. ICH does not require a document of this type.
Which regulation or regulatory body uses ALCOA-C?
ICH E6. It also requires that changes to source data be traceable, not obscure original entry, and should be explained if necessary.
What does ICH E6 require with regards to quality management?
ICH E6 requires that sponsors implement quality management system that uses a risk-based approach.
Which regulatory body addresses the role of a sponsor-investigator?
The FDA. ICH E6 does not directly address it.
