Study Guide Flashcards
What are the basic elements of informed consent? (8)
- A statement that the study involves research and the purpose, duration and procedures to be done and identification of any procures which are experimental
- Any reasonable foreseeable risks or discomforts
- A description of any benefits
- A disclosure of appropriate alternative procedures
- A statement describing how the confidentiality or records will be maintained (possibility for the FDA to review records)
- For research involving more than minimal risk, an explanation as to whether any compensation or medical treatments are available in injury occurs
- Who to contact for questions about the research or who to contact in the event of research related injury
- Participation is voluntary and subject may discontinue at anytime
Are applicable clinical trials required to have a statement in their consent regarding ‘clinicaltrials.gov’?
Yes. The specific statement is “A description of this clinical trial will be available on ‘clinicaltrials.gov’ as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time”
Can the sponsor provide sample consent forms?
Yes. Although IRBs often have their own standard language.
Who has the final say to approve/disapprove consent forms
IRB
A short form
A document that states the elements of informed consent have been presented orally to and understood by the participant (or their LAR)
A written summary
The written oral summary of what is to be said to the participant and LAR which is IRB approved
Who signs the short form?
The subject (or LAR) and the witness
Who signs the written summary?
The consenter and the witness
What situations may an investigator use short form consent document?
- When a potential subject does not understand English and the investigator does not have an IRB-approved consent document translated into appropriate language
- When the window of opportunity for a subject to benefit from research participation is brief, and the IRB finds that by use of short form consent document is appropriate
Informed consent serves as a proof of the subjects _______________ in a clinical trial.
authorization to participate
When reviewing the informed consents a CRC or clinical research associate (CRA) should ensure
- The subject signed the most recent IRB approved version
- The subject signature is present in addition to the subject’s name
- The subject dated for themselves and the date is correct (verify against date of visit and date/time of study procedures on medical records)
- An error was corrected by drawing a single line through the error
- All pages of the informed consent document are present
What is source data verification (SDV)?
The process where data within the case report form (CRF) or other data collection systems are compared to the original source of information to confirm data accuracy
What is source data review (SDR)?
A review of source documentation to check quality, review protocol compliance and ensure compliance
What are case report forms (CRFs)?
A paper or electronic document designed to record all of the protocol required information to be reported to the sponsor.
What should one consider when reviewing/verifying information on a CRF?
- Compare the data recorded on the CRF against the data from the source documents
- Where source data was entered directly into the CRF, the signature (or initials) of the person recording and date should be present
- Additional - matches what is specified in the protocol
What adverse events need to be documented and where?
All adverse events (unrelated or related to the study) need to be documented in the AE page of the CRF and the patient’s medical records
What should be considered when reviewing/verifying AEs on the CRF
- Ensure all AEs are recorded on both the CRF and in the patient’s medical chart
- Ensure proper protocol procedures were followed for AEs
- Check that responsible person (investigator or designee) assessed AEs for seriousness, causality, and expectedness
Per CRF 312 when should investigators report SAEs, to who and what should be included in report?
Immediately - To sponsor
Promptly - To IRB
An assessment of whether there is a reasonable possibility that the drug caused the event
Per CRF 312 when should sponsors report SAEs, to who, under what circumstances?
ASAP, but no later than 15 calendar days
To the FDA and all participating investigators
After the sponsor determines that the information qualifies for reporting as:
1. Serious and unexpected suspected adverse reaction (i.e., SAEs)
2. Findings from other studies (e.g., pooled analysis of multiple studies)
3. Findings from animal or in-vitro testing (e.g., reports of organ toxicity near the expected human exposure)
4. Increased rate of occurrence of serious suspected adverse reactions
What is an unanticipated adverse device effect (UADE)?
- Any serious adverse effect on health or safety
- Life-threatening problem or death (caused by or associated with device)
- If that effect, problem or death was not previously identified in nature, severity, or degree of incidence in the application
- Any other unanticipated serious problems associated with a device that relates to the rights, safety or welfare of subjects
Per CRF 812 when should investigators report UADE and to who?
ASAP, but no later than 10 working days after learning of effects
To the sponsor and IRB
Per CRF 812 when should sponsors report UADE and to who?
10 working days
FDA and to all reviewing IRB’s and participating investigators
45 CRF 46 Part A pertains to:
Informed consent/common rule
45 CRF 46 Part B pertains to:
Pregnant women
45 CRF 46 Part C pertains to:
Prisoners
45 CRF 46 Part D pertains to:
Children
Consent needs to be obtained from the pregnant woman and father if…
If research may only benefit the fetus
*Not necessary from father if unable to obtain father’s consent for appropriate reasons
What are the reasons a father’s consent wouldn’t need to be obtained
- Unavailability
- Incompetence
- Temporary incapacity
- Pregnancy resulted from rape or incest
Can research offer to terminate a pregnancy?
No. No inducements, monetary or otherwise will be offered to terminate a pregnancy. Individuals engaged in research will have no part in any decision as to the timing, method or procedures used to terminate a pregnancy or determining the viability of neonate.
True or False: Federal regulations require IRBs to classify research involving children into one of four categories?
True
What are the IRB classifications for research involving children?
- Research not involving greater than minimal risk
- Research involving greater than minimal risk (direct benefit)
- Research involving greater than minimal risk (no direct benefit)
- Research that is not otherwise approvable, but presents an opportunity to understand, prevent or alleviate a serious problem affecting the health or welfare of children.
How is consent for minors determined?
The overseeing IRB will determine whether informed consent from one or both parents is needed based on the risk to subjects (children/minors) involved. Additionally, the asssent of the child may be required.
What should the IRB consider when determining assentment requirements?
- Nature of the research
- Child’s age, status and condition
- Whether all or some of the children are capable of assenting to participate
What happens if a child reaches the legal age of consent while enrolled in a study?
The child should be re-consented for ongoing continuation in research unless the IRB determines that the requirements for obtaining informed consent can be waived
What is an additional federal protection for wards of the state when research involves greater than minimal risk with no direct benefit to subjects?
The research must be either related to the children status as wards or be conducted in settings where majority of children involved are not wards
Wards of the state must be appointed
An advocate
True or False: In general 18 years of age is the legal age of adulthood, but this can vary from state to state
True
Four examples of disclosable financial interests in arrangements
- Significant payments of other sorts 25,000+ from the sponsor to the investigator or institution
- Any stock that exceeds 50,000 during the time or the study and up to one year afterwards
- Any equity interests (e.g., stocks) in any sponsor of the clinical trial
- Proprietary interest in the tested product (e.g., patent, trademark, copyright)
When is financial disclosure for an investigator required?
During the course of the study (agreement with sponsor) and for one year after completion of the study (all subjects have been rolled and follow-up of primary endpoint data is completed)
What are the three primary responsibilities of an investigator?
- Oversee the conduct of the trial under appropriate regulations
- Protect the rights, safety, and welfare of subjects
- Control the use of investigational product
What does Form 1572 state?
- Conduct study according to the current protocol
- Personally conduct or supervise the studies
- Obtain informed consent
- Report adverse event (AE)
- Properly train staff and employees
- Maintain adequate and accurate records
- Ensure that an IRB complies with federal regulation and oversees the study
- Comply with all other requirements CRF 312
What investigator form is used for IND?
Statement of Investigator Form (form 1572)
What investigator form is used for IDE?
Investigator Agreement not 1572
Form 1572 is a declaration of the ______ to comply with _______
Investigator
FDA regulations
Per FDA regulations, when do non-serious AEs need to be reported by the investigator?
No specific dateline for FDA. They should be recorded and reported to the sponsor following the description in the protocol.
True or False: The FDA does not provide specific dateline (e.g., number of days) for investigators in reporting SAEs
True. They only state “immediately” when reporting to the sponsor and “promptly” when reporting to the IRB
Per Federal Regulations, how long do investigators have to report serious adverse events to the sponsor and to the IRB?
No specific dateline for IND SAE for investigators. They should be reported “immediately” to the sponsor and “promptly” to the IRB.
True of False: The FDA does not provide specific dateline (e.g., number of days) for investigators in reporting unanticipated adverse device effects
False. The investigator should report the UADE to the sponsor and IRB ASAP but no later than 10 working days.
Per Federal Regulations, how long do investigators have to report unanticipated adverse device effects to the sponsor and to the IRB?
ASAP but no later than 10 working days to the sponsor and IRB
Do federal regulations limit who has access to an investigational product?
Yes. Regulations require an investigator to limit access to investigational products to only usage under the trial.