Description
The purpose of this guidance is to inform industry of the Food and Drug Administration’s (FDA’s) current thinking regarding appropriate clinical trial designs to evaluate antibacterial drug products, and to provide an opportunity for sponsors to amend ongoing or completed trials accordingly. This guidance is in response to a number of public discussions in recent years regarding the use of active-controlled trials designed to show noninferiority (NI) as a basis for approval of antimicrobial drug products. These discussions initially focused on the indications acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and acute bacterial otitis media (ABOM). However, the science of active-controlled trials designed to show NI and the selection of appropriate NI margins in circumstances where an activecontrolled trial designed to show NI is an appropriate trial design has been a focus of recent discussions in other antimicrobial drug product indications and in other therapeutic areas as well.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
1superseded guidance topic
Stakeholders
1Entity responsible for submitting applications under section 524B
Regulatory Context
Regulatory Activities
3IND for treatment use; Regulatory submission required for clinical trials and expanded access.
repeat-dose toxicity studies that support a carcinogenicity Special Protocol Assessment (SPA)
Rule does not apply to products marketed under an NDA
Document Types
1Defines the standard of veterinary practice and limits for anesthetic regimens
Attributes
1critical to have an adequately justified NI margin and to use appropriate efficacy endpoints
Technical Details
Testing Methods
3other trial designs (i.e., superiority designs) will be needed
active-controlled trials designed to show noninferiority
Clinical trial design used to support approval
Clinical Concepts
7The disease previously referred to as ABECB; The primary disease state being studied in the clinical trials.; Patients with greater severity of ABECB-COPD should be offered treatment with an antibacterial drug.
Example of a clinical indication for an antibacterial drug
Example of infection where disease process may be similar between adult and pediatric populations.
Example of a serious bacterial disease; Example of serious bacterial disease in labeling language
Indication where NI margin definition is challenging; indications such as ABOM where data will not support the use of an NI design
Indication where NI margin definition is challenging
Indication where NI margin definition is challenging; indications such as ABS where data will not support the use of an NI design
Standards & References
Specifications
1Justification provided in the appendix for trial design.; Justification for a noninferiority margin for diabetic foot infections; Determining an NI margin for patients with DFIs
ICH References (1)
Choice of Control Group in Clinical Trials.
Related CFR Sections (1)
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Rare Diseases: Natural History Studies for Drug Development: Draft Guidance for Industry (Status: Draft)
- Upper Facial Lines: Developing Botulinum Toxin Drug Products (Status: Draft)
- Adverse Reactions Section of Labeling for Human Prescription Drug and Biological Products — Content and Format (Status: Final)
- Format and Content of the Clinical and Statistical Sections of an Application (Status: Final)
- Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products. (Status: Final)
- Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (Status: Draft)
- Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications (Status: Final)
- Clinical Studies Section of Labeling for Human Prescription Drug and Biological Products — Content and Format: Guidance for Industry (Status: Final)