Safety Reporting and AEs
Defined in ICH E6(R3), this term describes a serious, unexpected adverse event or suspect adverse reaction where the nature or severity of the event is not consistent with the applicable product information (e.g., the Investigator’s Brochure or package insert).
What is a Suspected Unexpected Serious Adverse Reaction, or SUSAR?
Under 21 CFR 56.110 and 45 CFR 46.110, an IRB may use this review procedure only for research involving no more than minimal risk, or for minor changes in previously approved research during the period of authorization.
What is Expedited Review?
This is an individual or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research.
Who is a Legally Authorized Representative?
Formulated in response to the 1940s Nuremberg Trials, this foundational international document established the absolute essential requirement of voluntary consent for human experimentation, stating that the person involved must have legal capacity and be able to exercise free power of choice.
What is the Nuremburg Code?
This is the IRB's primary goal.
What is the protection of human subject rights and safety?
Under FDA IND regulations (21 CFR 312.32), a sponsor must notify the FDA of an unexpected, fatal or life-threatening suspect adverse reaction no later than this many calendar days after initial receipt of the information.
What is 7 calendar days?
Per ICH E6(R3) Section 1.4.7, an investigator may depart or deviate from a trial protocol without prior IRB/IEC approval or sponsor agreement under this single specific condition
What is to eliminate an immediate hazard to trial subjects?
These two entities are responsible for determining the appropriate age of assent for a given study.
Who are the state legislation and the IRB?
Under 45 CFR 46 Subpart D, this affirmative agreement to participate in research is required from a minor who is capable of providing it, in addition to parental permission.
What is Assent?
This finding most strongly suggests a protocol deviation with impact to subject safety.
Proceed for multiple choice options.
What is?
A. A visit window was missed by 2 days for a questionnaire
B. Study drug dosing occurred before safety labs review
C. A patient arrived late to a follow up visit
D. The CRC hasn't documented training on the newest eCRF completion guidelines
A subject enrolled in an oncology trial experiences an episode of severe neutropenia requiring hospitalization. The investigator notes that this is a expected, known adverse reaction listed in the Investigator’s Brochure (IB). Because it is an expected reaction, the investigator files a routine quarterly progress report instead of an expedited report to the Sponsor. Under standard FDA regulations (21 CFR 312.32) and ICH E6 GCP guidelines, this investigator made a critical reporting error for this specific reason.
What is - hospitalization makes the event a Serious Adverse Event (SAE), which requires expedited reporting to the Sponsor regardless of whether it is expected or unexpected?
Defined in ICH E6(R3) Section 3.9.7, this independent committee may be established by the sponsor to evaluate the progress of a trial, assess safety data, and analyze critical efficacy endpoints at interval periods to advise whether to continue, modify, or terminate the trial.
What is the DSMB, or Data Safety Monitoring Board?
or
What is the IDMC, Independent Data Monitoring Committee?
Under 21 CFR 50.27, if an illiterate or visually impaired subject agrees to participate in a clinical trial using a short-form consent process, FDA regulations require that this specific individual be present to observe the entire oral presentation and sign the consent documentation.
Who is an Impartial Witness?
In the Belmont Report, the mandate that the selection of research subjects must be fair and equitable—ensuring that burdens and benefits of research are distributed without bias toward particular socio-economic classes—falls under this core ethical principle.
What is the principle of justice?
A subject meets all inclusion criteria except one borderline lab value. The investigator asks to enroll the subject anyway and documents “clinically acceptable.” on the lab result. What should the CRC do next?
Proceed for multiple choice options.
A. Accept the investigator judgment and enroll the patient
B. Confirm whether the protocol allows investigator discretion
C. Delete the lab result from source review
D. Phone call the patient family and confirm they are not eligible for the study
DAILY DOUBLE!
In order for an adverse event to be classified as a SUSAR—requiring expedited 7- or 15-day reporting to regulatory agencies—it must satisfy these three specific criteria simultaneously.
What are:
Under 21 CFR 812.150(a)(3), investigational device investigators must submit regular progress reports at least once a year to both of these entities—
What are Sponsors and IRBs?
Per 45 CFR 46 Subpart C, when an IRB reviews a protocol involving prisoners as research subjects, at least one member of the IRB board must meet this specific qualification requirement.
What is a prisoner representative?
This ethical principle from the Belmont Report is primary when establishing additional safeguards against coercion and undue influence for decisionally impaired or economically disadvantaged subjects.
What is Respect for Persons?
A patient in a clinical trial experiences severe nausea (Grade 3 CTCAE) that prevents them from eating for two days, but it resolves with oral antiemetics at home without hospitalization or long-term damage. Explain why this event is classified as Severe, but NOT Serious.
What is "Severe" measures intensity/grade, whereas "Serious" is a regulatory legal term based on specific patient outcomes (such as death, hospitalization, or life-threatening risk)?
Under FDA Guidance on Data Monitoring Committees (DMCs), a DSMB/DMC recommendation to terminate a clinical trial early due to futilities is primarily driven by this determination.
What is the likelihood that the study will fail to demonstrate the intended therapeutic benefit even if continued to completion?
This type of protected population would have either a psychiatric disorder, an organic impairment, or a development disorder that affects cognitive or emotional functions to the extent that capacity for judgment and reasoning is significantly diminished, requiring special considerations for research consents.
What is cognitively impaired?
In 2015, the FDA’s Pediatric Ethics Subcommittee agreed that non-therapeutic procedural sedation requires careful evaluation of high-risk children and must be performed at a high-volume facility with this dedicated service.
What is a dedicated pediatric sedation service?