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E3 Structure and Content of Clinical Study Reports

FinalCenter for Drug Evaluation and Research07/01/1996
Data Quality AssuranceProtocol DeviationStudy BlindingQuality AssuranceTreatment ComplianceGood Clinical PracticeBlindingRandomization

Description

The objective of this guideline is to facilitate the compilation of a single core clinical study report acceptable to all regulatory authorities of the ICH regions. The regulatory authority-specific additions will consist of modules to be considered as appendices, available upon request according to regional regulatory requirements.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

3
Investigational Product

Synonymous with drugs, medicines, medicinal products, vaccines, and biological products.; Product intended to benefit population groups once authorized; The product being tested in the clinical trial.; The product being studied in the clinical trial.; monitoring extent based on the nature of the investigational product; Management, storage, and accountability of the product being tested.; management should be arranged and conducted in accordance with applicable regulatory requirements; The produ

Drug Product

RTRT and CTD sections apply to drug products

Biological Product

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

Stakeholders

10
Independent Ethics Committee

Responsible for submission and communication oversight; Safeguard the rights, safety and well-being of trial participants; Reviewing trial conduct and records

Statistical Reviewer

The regulatory authority representative who verifies the results.

Regulatory Authority

Bodies that accept clinical trial data and grant marketing authorizations.

Applicant

Entity submitting development data and knowledge; Entity performing the work process for change

Data Monitoring Committee

Safety oversight body for interpreting adverse events; Safety oversight body for study design

Institutional Review Board

Governs top dose in clinical studies

Investigator

Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining

Sponsor

Entity responsible for submitting applications under section 524B

Principal Investigator

Responsible for reviewing case report forms

Biostatistician

DMC member knowledgeable about statistical methods and sequential analysis

Regulatory Context

Regulatory Activities

3
Marketing Application

Submission for product approval

Registration Application

data which should be presented in a registration application

Historically Controlled Trial

For a historically controlled trial, it is important to explain how the particular control was selected.

Document Types

9
Clinical Study Report

CSR supported by ADaM datasets; Contains analysis results and animal listings

Appendix 16.1.9

Contains details of the statistical analysis performed on each primary efficacy variable.

Informed Consent

Process by which a subject voluntarily confirms his or her willingness to participate in a particular trial; Integral feature of the ethical conduct of a trial

Case report tabulations

Regulatory authorities may require all individual data in archival case report tabulations.

Protocol Amendment

A document describing changes made to the original clinical trial protocol.

Protocol

Defines the standard of veterinary practice and limits for anesthetic regimens

Case Report Form

collect on the case report form (CRF) the Investigator's clinical interpretation

Audit certificates

Documentation of quality audits performed; Audit certificates, if available, should be provided in the same appendix.; Audit certificates should be included in the appendix if available.

Informed Consent Form

Document used to obtain and record participant consent; Document used to obtain and document participant consent.; Documents confirming participants' informed consent was appropriately obtained.; written, signed and dated form documenting the process of informed consent

Attributes

10
Sample Size

statistically justified calculation required in the plan

Confidence Intervals

Constructed using statistical methods to estimate effects.

P-value

Statistical parameter for genes of interest

Batch Number

Test product, dose, and mode of administration, including batch number.

Dose

Product characteristic evaluated alongside name similarity.

Severity

Seriousness of the effects of a hazard

Causality Assessment

Determination of the relationship between a product and an adverse event

Duration of Exposure

Factor to consider in risk assessment (one-time, constant, or intermittent).

Type I Error

Trial design should provide strong control of Type I error

Demographic Data

Patient characteristics such as age, sex, and race.

Technical Details

Substances

3
Investigational Product

Pharmaceutical form of an active ingredient or placebo being tested; Product being tested in the clinical trial; Pharmaceutical form of an active ingredient being tested in a trial

Active control

Comparison between the test drug and the active control.; Comparator drug used in the study; Used as a comparator in the efficacy analysis.

Placebo

Accountability procedures for the investigational product including placebo; used as a reference in a clinical trial

Testing Methods

10
Statistical Methods

Analysis of test data and rationale for sample sizes

Subgroup Analysis

Statistical considerations in clinical trials

Analysis of Variance

The validity of the assumptions for an experiment can be examined using analysis of variance (AOV).

Two-sample t-test

Example of a statistical test requiring specific documentation.

Exercise test

Functional assessment in the study design

Physical examination

Clinical assessment of the patient

ECG

Monitoring required when concomitant use is unavoidable.

Life Table Analysis

Informative analysis for reporting adverse event rates

Cox regression

Supportive information for covariate adjustment.

ANCOVA

Analysis of covariance used to test differences in slopes and intercepts; Analysis of covariance used in stability data analysis

Processes

8
Blinding

Manufacturing and handling should maintain blinding

Multicenter Study

Studies analyzed by analysis of variance techniques.

Crossover Design

A study design requiring specific documentation of sequences and washouts.

Clinical Laboratory Evaluation

Evaluation of safety-related laboratory tests

Safety Analysis

Assumes all patients who received at least one dose are included

Randomization

Process of assigning trial participants to treatment or control groups using an element of chance; Process of assigning participants to treatment groups.; Process of assigning participants to groups using chance to reduce bias.

Clinical Pharmacology Study

Basic principles of the guideline can be applied to these trials

Washout Period

required before baseline assessments for prior hormonal therapy

Clinical Concepts

10
Inclusion Criteria

Criteria for participant enrollment in the trial.; Characteristics that every potential participant must satisfy to qualify for trial enrollment.

Primary Efficacy Variable

The main variables subject to statistical analysis.

Efficacy Analysis

Analysis from which certain patients and observations may be excluded.

Medical history

Baseline assessment

Protocol Deviations

Patient data listings include protocol deviations.

Vital Signs

Includes fever, tachycardia, bradycardia, hypertension, hypotension, and respiratory rate

Deaths

Safety data that should generally be collected under all circumstances

Treatment Emergent Signs and Symptoms

Events not seen at baseline and events that worsened even if present at baseline

Primary Endpoint

The main outcome measure in a clinical trial

Concomitant Medication

Medications taken by patients during the study that may affect response.; Other drugs taken by the patient during the study

Standards & References

External Standards

6
Vancouver Declaration

References should be given in accordance with the 1979 Vancouver Declaration.

NCI

Toxicity grading scales

WHO

World Health Organization recommendations for mAb cocktails

CIOMS format

Format for reporting outcomes in adverse event listings

61 FR 37320

Federal Register publication citation for the guideline

Declaration of Helsinki

Ethical principles that are the origin of GCP standards.; Ethical principles for medical research involving human subjects

Specifications

5
Inclusion Criteria

Subject inclusion criteria for selection and withdrawal.

Normal Laboratory Ranges

Reference criteria for laboratory analysis

Primary Efficacy Variable

The primary measurements and endpoints used to determine efficacy should be clearly specified.

Surrogate Endpoint

Marker used as a substitute for a direct measure of clinical benefit

Exclusion Criteria

Subject exclusion criteria for selection and withdrawal.

ICH References (3)

ICH E3

document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.

Clinical Safety Data Management: Definitions and Standards for Expedited Reporting

Defines serious adverse events for clinical study reports

Dose-Response Information to Support Drug Registration

Further guidance on the design and analysis of studies exploring dose-response.

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

E3 Structure and Content of Clinical Study Reports | Guideline Explorer | BioRegHub