Description
The purpose of this guidance is to assist sponsors in the clinical development of drugs for the monotherapeutic, combination, and adjunctive treatment of major depressive disorder (MDD). Specifically, this guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs for antidepressant drug products. This draft guidance is intended to serve as a focus for continued discussions among the Division of Psychiatry Products (the Division), pharmaceutical sponsors, the academic community, and the public.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
2The class of products for which development programs are described.
clinical trial design issues and regulatory considerations may differ from previously approved drugs
Stakeholders
7The specific division within CDER preparing the guidance.
Entity responsible for submitting applications under section 524B
relevant age groups to study in drug development
Defined as persons who have not attained the legal age for consent; Patient population from whom assent may be required for biopsies
relevant age groups to be adolescents (ages 13 through 17)
Subjects less than 28 days old
Subpopulation with potentially different metabolism
Regulatory Context
Regulatory Activities
4Sponsors seeking to include a biomarker should request a guidance meeting
Phase 4 safety considerations mentioned in the table of contents.
Sponsors encouraged to consult FDA early
FDA typically requests a postmarketing commitment to conduct this
Document Types
2include the overall strategy for handling different intercurrent events... in the statistical analysis plan
Protocols for adaptive trials should include pre-specified criteria
Attributes
1Justification essential for trials using a noninferiority design
Technical Details
Substances
3A conventional class of antidepressants mentioned.
A conventional class of antidepressants mentioned.
found to cause Olney lesions
Testing Methods
5thorough evaluation of at least seven slices of the brain
accepted as primary endpoint in phase 3 studies
accepted as primary endpoint in phase 3 studies
accepted as primary endpoint in phase 3 studies
Supplementary juvenile animal studies may be needed
Processes
1to integrate information obtained in early phase clinical trials
Clinical Concepts
10The primary disease state addressed by this guidance.; diagnosis should be confirmed via a semi-structured interview; low prevalence of MDD in this age range
A specific clinical condition and potential indication.; patients who have not responded to more than one prior antidepressant
vacuoles that may precede the onset of permanent injury in the form of neuronal cell death
patients with renal insufficiency should be included in trials
Co-morbid condition in the general population
patients with chronic pain should be included in trials
patients with hepatic impairment should be included in trials
patients with human immunodeficiency virus should not be excluded
patients with hepatitis C should not be excluded
Patients with a history of substance abuse should also be considered
Standards & References
External Standards
1Used to define symptoms of MDD.
ICH References (4)
Statistical Principles for Clinical Trials; Discourages deterministic procedures due to high risk of bias; Notes that the use of Bayesian methods in clinical trials may be considered.
Choice of Control Group in Clinical Trials.
Guidance on when particular studies can be abbreviated or deferred for life-threatening diseases
The Extent of Population Exposure to Assess Clinical Safety: For Drugs Intended for Long-term Treatment of Non-Life-Threatening Conditions
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