Description
This guidance describes the recommended content of the integrated summary of effectiveness (ISE) for inclusion in a new drug application (NDA) or biologics license application (BLA).2 Although there are no regulations requiring an ISE for BLA submissions, applicants are encouraged to provide an ISE because it represents an opportunity to present a coherent analysis and presentation of the drug’s benefits.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
2Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Class of drugs approved based on effects on blood pressure.
Stakeholders
2Entity submitting development data and knowledge; Entity performing the work process for change
Entities submitting supplements to BLAs
Regulatory Context
Regulatory Activities
3New Drug Application
Biologics License Application
Empiric strategies that provide predictive enrichment (e.g., studying known responders in a randomized withdrawal study).
Document Types
5A comprehensive integrated analysis of the effectiveness of a study drug.; The ISE is a self-contained, detailed analysis that comprehensively examines relevant data from multiple sources.; The ISE is a comprehensive summary of experience related to effectiveness required for drug approval.; The main document providing an integrated summary and analysis of clinical data.
Cybersecurity information should be included in device labeling
Section 2.7.3 of the CTD describing efficacy results; Data concerning tolerance should be summarized under section 2.7.3.5
eCTD specifications for regulatory submissions
Common Technical Document module containing clinical pharmacology summaries.
Attributes
5Legal standard for drug approval under the FD&C Act
Method of adjusting dosage for individualization.
Required description for maternal and offspring findings
A measure of the strength of evidence in meta-analysis results.; overall association... was not statistically significant in adult subjects
Assessment of the relevance of observed effect sizes and endpoints.
Technical Details
Substances
1High levels used as a blood marker for increased risk in CV disease.
Testing Methods
8PK data used for dose selection
plan for evaluating equivalent or improved performance
Random effects analysis using the DerSimonian and Laird method to estimate pooled resolution rates.
empirical approach reliant on data from reference population
Analytical method used to describe dose-response and subpopulation differences.
A statistical method for analyzing time-to-event outcomes.
Analyses of data from more than one study to provide insight into effectiveness.
Statistical method used to evaluate efficacy from various sources
Processes
2Analysis of data from more than one study.; The practice of combining subject-level data or outcomes from multiple studies.
Using the greater power of pooled analyses to gain insight into the nature of the drug's effectiveness.
Clinical Concepts
6Loss of therapeutic effects over time.
Safety findings including deaths and post-mortem examinations
Juveniles, geriatric animals, or animals with compromised organ function
Primary endpoints including cardiovascular death, nonfatal heart attack, and nonfatal stroke.
Relationships between dose and effectiveness, including age, sex, and race factors.
Study of how the body interacts with administered substances
Standards & References
Specifications
2Plain-text label used to describe the primary endpoint
Marker used to predict clinical benefit in accelerated approval
ICH References (6)
Choice of Control Group in Clinical Trials.
Ethnic Factors in the Accessibility of Foreign Clinical Data.
Evaluation of benefit/risk across regions or important subpopulations
document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.
Dose-Response Information to Support Drug Registration
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.
Related CFR Sections (2)
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 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 →
See Also (8)
- Study of Sex Differences in the Clinical Evaluation of Medical Products (Status: Draft)
- Format and Content of the Clinical and Statistical Sections of an Application (Status: Final)
- Clinical Studies Section of Labeling for Human Prescription Drug and Biological Products — Content and Format: Guidance for Industry (Status: Final)
- Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document (Status: Final)
- Low Sexual Interest, Desire, and/or Arousal in Women: Developing Drugs for Treatment Guidance for Industry (Status: Draft)
- 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)