LMR Flashcards
If an investigator uses the test article in an emergency use situation, what must happen afterwards and in what time frame?
The investigator must have an independent physician review the reason for use within 5 working days of use. This documentation must be submitted to IRB within 5 working days of use.
How is the prospect of direct benefit to the subject determined?
1) Subject is facing life-threatening situation that necessitates intervention
2) Appropriate animal and other preclinical studies have been conducted, supporting potential for direct benefit
3) Risks associated with investigation are reasonable in relation to what is known about medical condition of potential class of subjects, and risks/benefits of standard therapy, and what is known about risks and benefits of proposed intervention or activity
What are examples of additional protections of rights and welfare provided to subjects?
5 examples
I) consultation with reps of communities in which investigation will be conducted
II) Public disclosure to communities in which investigation will be conducted
III) Public disclosure of sufficient information following completion of trial
IV) Establishment of an independent data monitoring committee
V) If obtaining informed consent is not feasible and a LAR is not reasonably available, the investigator will attempt to contact family member who is not a LAR; the investigator will summarize efforts made to contact family members and make this available to IRB at time of continuing review
Each IRB should have at least how many members?
5
Each IRB shall include:
1 member whose primary concerns are in the scientific area
1 whose primary concerns are in nonscientific areas,
1 who is not otherwise affiliated with the institution.
When must an IRB register/when does registration become effective?
Each IRB must submit an initial registration and must renew every 3 years. IRB registration become effective after review and acceptance by HHS/FDA.
How often does an IRB need to revise its registration information? (if changes are made)
must submit changes concerning main contact within 90 days. 30 days if disbanding, otherwise at time of registration renewal.
May a clinical investigator be an IRB member?
Yes except they can not participate in initial or continuing review of a study in which they have a conflicted interest.
The IRB regulations require an IRB to have a diverse membership. May one member satisfy more than one membership category?
Yes.
May the IRB use alternate members?
Yes, if they are formally appointed, listed on the IRB roster and proper IRB procedures are in place that describe their appointment and function.
Does a non-affiliated member need to attend every IRB meeting?
No.
What are examples of IRB members considered to be non-scientists?
FDA believes the intent of the requirement for diversity of disciplines was to include members who had little or no scientific or medical training or experience. In the past, lawyers, clergy and ethicists have been cited as examples of persons whose primary concerns would be in non-scientific areas.
The FDA regulations [21 CFR 56.104(c)] exempt an emergency use of a test article from prospective IRB review, however, “… any subsequent use of the test article at the institution is subject to IRB review.” What does the phrase “subsequent use” mean?
“Subsequent use” would be a second use with that subject or the use with another subject. FDA regulations allow for one emergency use of a test article in an institution without prospective IRB review, provided that such emergency use is reported to the IRB within five working days after such use.
What is IRB expedited review?
Procedure through which certain kinds of research may be reviewed and approved without convening a meeting of the IRB. The IRB may also use the expedited review procedure to review minor changes in previously approved research.
May informed consent be obtained by telephone from a legally authorized representative? (non-emergency)
No, A verbal approval does not satisfy the 21 CFR 56.109(c) requirement for a signed consent document. However, a consent form can be sent to the LAR and discussion can be conducted over the phone with the LAR signing the form and sending it back.
How long does an IRB retain its records? (And what happens when an IRB refuses to allow an inspection of records)
3 years
FDA may refuse to consider a clinical investigation in support of an application for a research/marketing permit if the institution or IRB that reviewed the investigation refuses inspection
Active Protocol
any protocol for which an IRB conducted an initial review or a continuing review at a convened meeting or under an expedited review procedure during the preceding 12 months
If an IRB changes information that is not contact/chair person or cessation of research, how long does it have to report such information?
Whenever the IRB renews it’s registration
Independent ethics committee (IEC)
a review panel that is responsible for ensuring the protection of the rights, safety, and well-being of human subjects involved in a clinical investigation and is adequately constituted to provide assurance of that protection.
FDA shall provide a written determination within ____ days after receiving IND application
30
Grounds for clinical holds on Phase I studies:
unreasonable risk
unqualified investigators
IB is misleading, inaccurate or incomplete
or IND doesn’t contain sufficient information to assess risk to subjects
Grounds for clinical holds on Phase II or III studies:
deficient protocol to meet stated objectives
When an ongoing study is on a clinical hold can new subjects be enrolled and what happens to subjects currently enrolled and on IP?
no new subjects,
subjects on IP have to stop unless specifically permitted by the FDA
Who can appeal the FDA’s decision for a clinical hold?
Sponsor
Under an IND, if no subjects are entered into a study for 2+ years or if all studies under an IND remain on clinical hold for 1 year+, the IND may be placed on “_____”
Inactive status
INDs that are “Inactive” for ___+ years may be terminated
5
For an IND, how soon should the sponsor report serious unexpected life-threatening safety events to FDA?
7 calendar days.
For an IND, how soon should the sponsor report serious unexpected safety events to FDA when not life-threatening?
15 calendar days.
For an IND, what form is used for the sponsor reporting serious unexpected safety events?
Form FDA 3500A
What does SUSAR stand for?
Suspected unexpected serious adverse reaction
For an IND, when do investigators report serious events to sponsors?
As soon as possible (typically stated in protocol). (15 Days)
For an IND, when is the annual report provided to the FDA by the sponsor?
60 calendar days from the anniversary of the IND becoming active.
True or False: Reactions which are serious but expected are subject to expedited reporting requirements
False. Reactions that are serious but unexpected are subject to expedited reporting.
For an IND, when do Investigator’s provide annual report to sponsor?
No time criteria, give to sponsor to submit to FDA.
For an IND, when does the Investigator need to submit the final report to the sponsor?
When the study site is finished with the investigation (no specified time constraints).
For emergency use of a drug, where immediate use of the product was required and the patient was not able to be consented, how long does the sponsor have to notify the FDA of the use of the product?
5 working days
Fatal or life-threatening unexpected adverse drug reactions are required to be reported no later than how many days after first knowledge? What about non-life-threatening unexpected ADRs?
Fatal unexpected ADRs: 7 calendar days after first knowledge
Non-fatal serious unexpected ADRs: 15 calendar days after first knowledge
When is unblinding inappropriate in the case of a fatal or serious adverse event?
If a fatal or serious outcome is the primary efficacy endpoint, the integrity of the clinical investigation may be compromised if the blind is broken. It may be advantageous to reach an agreement with regulatory authority not to unblind and expedite reporting.
What key data elements should be included in expedited reports for serious adverse drug reactions?
Patient details
Suspected medicinal product
Other treatments patient was receiving
Details of Suspected ADR
Reporter of the event
Sponsor details
Key aspects of Phase II studies:
o Initial demonstration of efficacy in patients, short-term safety information
o Conducted in a relatively limited number (100-300) patients who have the disease
o Often involve hospitalized patients who can be closely monitored
o Many focus on dose-response, dosing schedule, or other issues related to preliminary safety and efficacy
o Takes about 1 to 3 years to complete
Key aspects of Phase 1 studies:
o Small trials with healthy subjects, purpose is to determine pharmacokinetics and maximum tolerated dose
o Conducted to determine the appropriate dose range with regard to safety and toxicity (not to evaluate efficacy)
o Conducted in a limited number (20-80) of health volunteers or patients (cancer, AIDS)
o Many compounds are abandoned in this phase because of safety/toxicity problems
Key aspects of Phase III studies:
o Use in large numbers of patients, long-term safety data
o Conducted in larger (several hundred to several thousand) and more diverse groups for whom the drug is ultimately intended
o Make comparisons between new treatment and standard therapy or placebo
o Study drug used by practicing physicians in the same manner as it would be used after marketing
o Takes about 2 to 5 years to complete
Key aspects of Phase IV studies:
o Post-marketing, continue assessing therapeutic value and monitor less common adverse events
What does CAPA stand for?
Corrective and Preventative Action Plans
What is a significant risk device? (4)
A device that:
1) is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject.
3) is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject
4) Otherwise presented a potential for serious risk to the health safety, or welfare of a subject.
When a sponsor intends to conduct a clinical investigation with an exception from informed consent for emergency research, what must be done?
Sponsor shall submit a separate IND for such investigation.
The sponsors request for a regulatory hearing must be made within ___ of the sponsors receipt of FDA’s notification of nonacceptance
10 days
What are the responsibilities of Sponsors as outlined in 21CFR Part 812?
1) Gaining FDA and IRB approval before beginning the investigation
2) Selecting investigators and monitors
3) Informing investigators
4) monitoring investigations
5) Emergency Research
Can a sponsor make certain changes without prior approval of a supplemental application? If so what is the timeline? (812)
Yes – but the sponsor must notified the FDA within 5 days of the changes going in to effect.
Responsibilities of Investigators as outlined in 21 CFR Part 812
1) Awaiting approval.
2) Compliance.
3) Supervising device use.
4) Financial disclosure.
5) Disposing of device.
For IDE, when does a sponsor need to report an unexpected adverse device event?
10 working days.
For emergency use of a device, where immediate use of the product was required and the patient was not able to be consented, how long does the sponsor have to notify the FDA of the use of the product?
5 working days
