Description
The purpose of this guidance is to assist sponsors in prospectively assessing the occurrence of treatment-emergent suicidal ideation and behavior in clinical trials of drug and biological products.2 The focus of this guidance is on clinical trials conducted under investigational new drug applications, or trials that are intended for submission in a new drug application or a biologics license application. Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the importance of assessment of suicidal ideation and behavior in psychiatric and nonpsychiatric drug trials falling under the authority of the FDA, and the general principles for how best to accomplish this assessment during drug development. This guidance is not intended to give advice on how best to screen patients for entry into clinical trials, even though instruments used for assessing patients during the conduct of trials can also be used for screening patients. Making decisions about which patients to enter into a particular trial is a separate matter that is determined largely by the questions that the trial is intended to address.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
5Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH
Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition
Class of drugs with reports of suicidal ideation
Class of drugs with reports of suicidal ideation
Used in microdose trials for receptor occupancy
Stakeholders
2Entity responsible for submitting applications under section 524B
Possible to conduct the FIH trial in healthy volunteers
Regulatory Context
Regulatory Activities
6IND for treatment use; Regulatory submission required for clinical trials and expanded access.
Rule does not apply to products marketed under an NDA
BLA for biological products
Development program for drugs intended for sGERD treatment
Conducted to assess pharmacokinetics and safety
Large simple trials for which data collection is minimized
Document Types
4The nature of the document regarding plant-based food labeling
Recommended documentation to be included in a thorough fatality investigation report.
Source of information for C-SSRS integration
Defines the standard of veterinary practice and limits for anesthetic regimens
Attributes
4Psychometric property of the C-SSRS
Evidence that the individual intended to kill him- or herself, at least to some degree.
Methods used for standardizing inter- and intra-rater reliability
Central nervous system activity in neurologic drugs
Technical Details
Substances
6Controlled antidepressant trials revealed a signal for drug-related suicidal ideation
Meta-analysis of trials revealed a signal for suicidal ideation; Drug class requiring regular assessment
establishing a causal association for a human teratogenic exposure; recognized human teratogen cited in references; Known teratogen cited in literature
Pharmacologic class for heart failure; Drug class used in heart failure treatment
Drug with reports of treatment-emergent suicidal ideation
Drug class requiring regular assessment
Testing Methods
5C-CASA categories used for classification of events
C-SSRS is a prospective assessment instrument that directly classifies suicidal ideation and behavior
Columbia Suicide Severity Rating Scale
Electronic self-report version of the C-SSRS
Columbia Classification Algorithm of Suicide Assessment
Clinical Concepts
10This category can include anything beyond a verbalization or thought, but it stops short of a suicide attempt.
Superficial cuts or scratches, hitting or banging, or burns intended to relieve distress.
Self-injurious behavior associated with no intent to die.
The primary clinical focus of the prospective assessment in trials; Prospective assessment of occurrence in clinical trials
Important to distinguish from actions with suicidal intent
evaluation of a drug to treat symptoms of Alzheimer's disease
Population where assessment might be difficult
Patient population with higher odds ratio for suicidal ideation
A potentially self-injurious behavior, associated with at least some intent to die as a result of the act.
When the person is interrupted from starting a potentially self-injurious act.
Identified Hazards
Hazards
2Possible signal of risk identified for certain drugs
Potentially self-injurious behavior associated with intent to die or other reasons.
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- DSCSA Implementation: Product Tracing Requirements — Compliance Policy
- E6(R3) Good Clinical Practice: Annex 2
- Consumer Antiseptic Rub Final Rule Questions and Answers Guidance for Industry: Guidance for Industry
- Best Practices for Communication Between IND Sponsors and FDA During Drug Development
- Botanical Drug Development: Guidance for Industry
- Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry
- Reformulating Drug Products That Contain Carbomers Manufactured With Benzene
- ANDA Submissions -- Refuse-to-Receive Standards Rev.2