Guidance for Industry
Submission of Abbreviated Reports and
Synopses in Support of
Marketing Applications
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
August 1999
Clinical Guidance for Industry
Submission of Abbreviated Reports and
Synopses in Support of
Marketing Applications
Additional copies are available from:
The Drug Information Branch (HFD-210)
Center for Drug Evaluation and Research (CDER)
5600 Fishers Lane, Rockville, MD  20857 (Tel) 301-827-4573
http://www.fda.gov/cder/guidance/index.htm
or
Office of Communication
Training, and Manufacturers Assistance (HFM-40)
Center for Biologics Evaluation and Research (CBER)
1401 Rockville Pike, Rockville, MD  20852-1448
http://www.fda.gov/cber/guidelines.htm; (Fax) 888-CBERFAX or 301-827-3844
(Voice Information) 800-835-4709 or 301-827-1800
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
August 1999
Clinical    Table of Contents
I. INTRODUCTION.......................................................................................................................................................1
II. BACKGROUND.........................................................................................................................................................2
III. SUBMISSION OF STUDY REPORTS.....................................................................................................................3
A. CLINICAL EFFICACY AND SAFETY STUDIES............................................................................................................4
B. HUMAN PHARMACOKINETICS, BIOAVAILABILITY, AND CLINICAL PHARMACOLOGY STUDIES.............................6
IV. FORMAT OF AN ABBREVIATED CLINICAL REPORT......................................................................................8
A. CLINICAL EFFICACY STUDIES.................................................................................................................................8
B. HUMAN PHARMACOKINETICS, BIOAVAILABILITY, AND CLINICAL PHARMACOLOGY STUDIES.............................9
V. FORMAT OF A SYNOPSIS.......................................................................................................................................9
VI. RECOMMENDED PROCEDURES........................................................................................................................10 Guidance for Industry1
Submission of Abbreviated Reports and Synopses
in Support of Marketing Applications
I. INTRODUCTION
This document provides guidance to applicants on submitting abbreviated reports and synopses in
lieu of full reports for certain clinical studies, both in marketing applications for new drug and
biological products and in supplements to approved applications.  This guidance is intended to
meet the requirements of Section 118 of the Food and Drug Administration Modernization Act of
1997 (Modernization Act), which directs FDA to issue guidance on when abbreviated study
reports may be submitted in new drug applications (NDAs) and biologics license applications
(BLAs) in lieu of full reports. 
This guidance focuses on the circumstances when full study reports, abbreviated reports, and
synopses can be used to submit data concerning the effectiveness of new drugs and biological
products.  As discussed below, generally full reports on safety are required.  However, in some
instances, the safety data in a particular study may not be germane to the proposed use and a
complete discussion of safety may be unnecessary.  The guidance also describes the recommended
formats for abbreviated reports and synopses.  Applicants are urged to discuss the planned report
formats for a specific application with the appropriate review division prior to submission.
If additional guidance is needed, the applicant is directed to CDER=s guidance for industry,
Format and Content of the Clinical and Statistical Section of Applications (July 1988) and the
International Conference on Harmonisation (ICH) guidance, E3 Structure and Content of Clinical
Study Reports (July 1996), as well as to the appropriate review division within CDER or CBER.
                                               
1
This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) and the Center for
Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA).  This guidance represents the
Agency=s current thinking on the submission of full study reports, abbreviated reports, and synopses of information
related to effectiveness for new drugs and biological products.  It does not create or confer any rights for or on any
person and does not operate to bind FDA or the public.  An alternative approach may be used if such approach satisfies
the requirements of the applicable statutes, regulations, or both.
1 II. BACKGROUND
Section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act provides that full reports of the
investigations to demonstrate a product=s safety and effectiveness be submitted in an NDA. 
Similarly, for BLAs FDA often requires that a manufacturer submit full reports to demonstrate
that the biological product is safe, pure, and potent (21 CFR 601.2(a) and (c)(1)(i)).  The NDA
regulations at 21 CFR 314.50, which define what must be submitted in an application, do not
explicitly define a full report, but require, among other things, submission of  a Adescription and
analysis of each controlled clinical study pertinent to a proposed use of the drug@ and of  Aany
other data or information relevant to an evaluation of the safety and effectiveness of the drug
product@ (21 CFR 314.50(d)(5)). 
In 1988, FDA issued the Clin/Stat guidance, which called for full study reports only for studies
that contributed effectiveness data as well as safety information.  For other studies, applicants
were advised to submit abbreviated reports of the effectiveness results.  In 1996, ICH issued its
E3, which provided an updated description of the contents of a full study report and specific
provisions for submission of less-than-full study reports.  However, applicants have not used the
provisions to submit less-than-full study reports contained in both the Clin/Stat guidance and E3
as much as they could have because of difficulties deciding when a full study report is required by
the reviewing body.  For example, clinical drug and biological product development programs
often include numerous clinical studies and resulting data that are not intended to contribute to
the evaluation of the effectiveness of a product for a particular use and are not needed to support
information included in labeling.  Accordingly, such studies may be submitted as abbreviated
reports or synopses, and this guidance is intended to facilitate their submission.
This guidance addresses studies submitted in the following sections of an NDA or BLA:
!  human pharmacokinetics and bioavailability [21 CFR 314.50(d)(3) and 601.2, section 6 of
FDA 356h]
!  clinical data (including clinical pharmacology) [21 CFR 314.50(d)(5) and 601.2, section 8
of FDA 356h]
!  statistical [21 CFR 314.50(d)(6) and 601.2, section 10 of FDA 356h]
Clinical pharmacology studies are defined in the human pharmacokinetics, bioavailability, and
clinical pharmacology section of this guidance to include pharmacokinetics (i.e., absorption,
distribution, metabolism, and excretion C ADME) and/or pharmacodynamic studies (i.e., dose
and/or concentration/range and dose and/or concentration/response), including those performed in
special populations, drug-drug interaction studies, and population pharmacokinetics and/or
pharmacodynamic studies (PK/PD screens).  In addition, clinical pharmacology studies are defined
to include mass balance studies, other human pharmacology studies, studies in human tissues,
organs, cell cultures, and cellular and/or subcellular fractions, and any associated assay validation
studies, that is, studies needed to demonstrate the accuracy, reproducibility, sensitivity, and
specificity of a method used in measuring pharmacologic response(s) or chemical entity(s) in
2 biological samples.2  As defined in this guidance, biopharmaceutics studies include bioavailability,
bioequivalence, food effect studies, permeability studies, in vitro dissolution and solubility studies,
and associated assay validation studies.
III. SUBMISSION OF STUDY REPORTS
The information on clinical investigations required under 21 CFR 314.50 should be submitted in
one of three formats:  (1) full study reports, (2) abbreviated reports, or (3) synopses.
Full study reports (i.e., the complete E3 report) should be submitted for all clinical and human
pharmacology investigations that contribute to the evaluation of effectiveness for the proposed
indication, or that otherwise support information included in labeling.
During the development of a product, studies may be conducted that ultimately do not contribute
to the evaluation of the effectiveness of a product for a specific indication.  As discussed more
fully below, such studies should be submitted as either abbreviated reports or synopses. 
Abbreviated reports should be submitted for studies that are not intended to contribute to the
evaluation of product effectiveness or provide definitive information on clinical pharmacology, but
about which the reviewer needs sufficient information to determine that the study results do not,
in fact, cast doubt on the effectiveness claims or the description of the clinical pharmacology. 
Abbreviated reports should contain all the safety information included in a full report.
Synopses should be submitted for studies that are not relevant to the evaluation of product
effectiveness or clinical pharmacology, but that provide information the reviewer needs to
evaluate the safety data from the study.  Complete safety information from a study submitted in
synopsis format should be included in the Integrated Summary of Safety (ISS) [21 CFR
314.50(d)(5)(vi)(a)] for drug products and for biological products where an ISS is included in the
application.    For biological product applications not containing an ISS, the safety information for
studies submitted in synopsis format should be appended to the synopsis.
Clinical drug development programs vary widely in the number of studies performed and the
number of patients studied.  Development programs with many studies and many exposed patients
are likely to compile a substantial database from controlled trials, as well as from less relevant
trials that should be submitted in a less-than-full format.  In contrast, applications for products
that have undergone rapid development programs (typically for serious or life-threatening diseases
without adequate therapy), or products intended for orphan indications, may compile only a small
total database.  In such cases, detailed evaluation of all available information may be critical to
assessing the product=s safety and effectiveness.  Therefore, applicants should plan to file full
study reports for products that are the subject of very limited development programs (defined for
                                               
2 See Conference Report: Analytical Methods Validation: Bioavailability, Bioequivalence, and Pharmacokinetic
Studies, Pharmaceutical Research, Vol 9, No. 4, 1992, pp. 588-592.
3 the purposes of this guidance as fewer than six clinical trials, including dose-comparison trials,
designed to determine efficacy, but excluding bioavailability studies, bioequivalence studies,
biopharmaceutic and interaction studies, and other pharmacokinetic studies).  However, even in
small clinical development programs, it is possible that certain studies need not be submitted as
full reports, if there is agreement in advance with the relevant reviewing division on studies that
may be submitted as abbreviated reports or synopses. A general overview to help in determining
the types of studies to be submitted is presented in the attached decision tree (Attachment).
In general, because it may be difficult to distinguish among studies that require full reports,
abbreviated reports, or synopses, applicants should confer with the relevant reviewing division
prior to deciding the format in which studies will be reported. The goals of a consultation would
be to limit study reporting in applications to that which is essential to document the evidence of
effectiveness for Agency review, and to minimize the need for the Agency to request full study
reports for studies originally reported in abbreviated or synopsis format (see section VI). 
A. Clinical Efficacy and Safety Studies
1. Studies for which full reports should be submitted
Full study reports (i.e., the complete E3) should ordinarily be submitted for all
studies from clinical investigations of drugs or biological products that are the
subject of very limited clinical development programs (i.e., programs with a total
of fewer than six clinical trials from any phase of drug development designed to
determine effectiveness, including dose-comparison trials).
In addition, full study reports should be submitted for clinical effectiveness studies
that (a) evaluate a dose, regimen, patient population, and indication for which
marketing approval is sought, and (b) are capable by design, conduct, and
enrollment of assessing the effectiveness of the product.  Full study reports are
expected for these studies whether or not they demonstrate a treatment effect. 
Examples include:
!  Studies providing the basis for dose recommendations (e.g., dose-
comparison studies).
!  Controlled studies identified by the applicant as contributing directly to
substantial evidence of effectiveness.
!  Controlled studies that support an intended comparative claim.
!  Controlled studies considered supportive of effectiveness (e.g., studies
believed to show a favorable trend, possible effect in a subgroup).
4 !  Controlled studies of different indications (stages of disease, different study
populations) or dosage forms or regimens if they are intended to provide
support for approval.
!  Controlled studies evaluating effectiveness for the indication that failed to
show an effect.
2. Studies for which abbreviated reports should be submitted
Abbreviated reports should be submitted for studies that do not fall under A.1.,
and that meet the following conditions:   (1) The studies are not intended to
contribute to the evaluation of product effectiveness, and  (2) the reviewer needs
sufficient information about the studies to determine that their results do not, in
fact, cast doubt on the effectiveness claims for the product.  Abbreviated reports
should also be submitted for studies that do not fall under A.1., but that contribute
significantly to the safety database.  Abbreviated reports should contain a full
safety report.
Examples of studies that should be submitted as abbreviated reports include: 
!  Studies with active controls that do not provide the primary or
substantiating evidence of effectiveness  (e.g., active-controlled
equivalence trials from clinical development programs in which the primary
evidence of effectiveness is contributed by placebo-controlled, dose-
controlled, or other superiority designs).  Active-controlled trials in which
differences were observed or that support a claim in labeling should be
submitted as full study reports.
!  Studies of related indications for which marketing approval is not being
sought (unless they are intended to provide significant substantiating
evidence of effectiveness for the indications being sought).
!  Studies not designed as efficacy studies or designed as efficacy studies for
different indications that contribute significant information about product
safety (e.g., large, randomized or nonrandomized trials where enrollment
approached or exceeded the size of the efficacy trials, or expanded access
studies that collected information related to efficacy).
!  Studies of doses or dosage forms not intended for marketing (unless they
are intended to provide significant substantiating evidence of effectiveness).
!  Controlled (i.e., hypothesis testing) safety studies may be submitted as
abbreviated reports; however, as for all studies, adequate detail on study
5 design and conduct to permit complete analysis of safety should be
provided.
In some cases, with agreement from the relevant reviewing division, applicants
may file negative studies (studies failing to show a treatment effect) as abbreviated
reports if the efficacy trials proposed to be filed as full reports are judged adequate
for evaluation of effectiveness.  In such cases, the format for display of the efficacy
data (see Section IV. A) should be agreed upon in advance.
3. Studies for which synopses should be submitted
Some studies are generally only examined in sufficient depth to assess if they cast
doubt on the safety of the product for the proposed indication.  For these studies,
complete safety information should be included in the ISS or, for applications for 
biological products not containing an ISS, the safety information should be
appended to the synopsis.  Examples of studies that should be submitted as
synopses include:
!  Studies of unrelated indications for which marketing approval is not being
sought (unless they form a significant portion of the safety database, in
which case they should be submitted as abbreviated reports).
!  Studies evaluating routes of administration for which marketing approval is
not being sought.
!  Incomplete studies, defined for the purpose of this guidance as those
enrolling fewer than one-third of intended patients, unless stopped for
safety reasons or for futility (inability to show efficacy).  Those studies
stopped for safety reasons or due to futility should be submitted as
abbreviated reports.
!  Uncontrolled studies not specifically identified as needing abbreviated or
full study reports.
!  Early general phase-1 safety-tolerance studies, but not specific, required
toxicity studies (e.g., dermal irritation studies required for topical
products), which ordinarily should be submitted as full reports.
B. Human Pharmacokinetics, Bioavailability, and Clinical Pharmacology
Studies
Sponsors of products with very limited development programs should consult the relevant
review division prior to submitting less-than-full reports for studies in this section.
6 1. Studies for which full reports should be submitted:
!  Clinical pharmacology and biopharmaceutics studies that support labeling
statements.
!  The most relevant in a series of similar studies (e.g., for a series of three
food-drug interaction studies, only the most relevant study would be
submitted as a full report).  For the purposes of this guidance, most
relevant means the study with the best design, power, dose, or study
population to address the study question and the intended dose, indication,
and patient population.  When studies in a series are not in agreement, all
studies of that type should be submitted as full reports.
!  Dose ranging studies to determine the dose(s) for phase-2 and -3 studies.
!  Bioavailability and bioequivalence studies that compare performance of the
formulation or dosage form used in clinical trials to that intended for
marketing.
!  One representative assay validation study for each analytical method at
each analytical site.
2. Studies for which abbreviated reports should be submitted:
!  Less relevant studies in a series of similar studies (see above).
!  Bioavailability/bioequivalence studies not assessing performance of
material used in clinical trials relative to dosage forms intended for
marketing.
3. Studies for which synopses should be submitted:
!  Studies that have been shown to have defects in design, conduct, data
handling or analysis that render them incapable of supporting a useful
and/or relevant conclusion.
!  Bioavailability/bioequivalence studies not assessing performance of
material used in clinical trials relative to dosage forms intended for
marketing.
!  Studies evaluating dosage forms no longer under development.
!  Discontinued studies.
7 !  Studies from abandoned indications.
IV. FORMAT OF AN ABBREVIATED CLINICAL REPORT
A. Clinical Efficacy Studies
An abbreviated report should contain a full report of information related to safety and
enough information to allow the reviewers to fully assess whether the efficacy results, if
any, cast doubt on the effectiveness of the product for the proposed indication. As
described below, the abbreviated study report should contain only selected sections of E3.
An abbreviated report should include all safety information included in a full report,
whereas efficacy information should be concise and not as comprehensive as in a full
report.
The following sections should be included in an abbreviated study report (the numbered
sections are described in E3):
!  Section 1 - Title page
!  Section 2 - Synopsis
!  Section 3 - Table of contents for the individual clinical study report
!  Section 4 - List of abbreviations and definitions of terms
!  Section 9.1 - Overall study and design and plan: description
!  Section 9.8 - Changes in the conduct of the study or planned analyses
!  Section 10.1 - Disposition of patients
!  Section  12 - Safety evaluation
!  Section 13 - Discussion and overall conclusions
!  Section  14 - Tables, figures and graphs referred to but not included in the text
!  Section 16.1.1 - Protocol and protocol amendments
!  Section 16.1.2 - Sample case report forms (unique pages only)
!  Section  16.3.1 - Case report forms for deaths, other serious adverse events and
withdrawals for adverse events (submit under item 12 - FDA form 356h)
!  Section 16.4 - Individual patient data listings for safety data.  Individual patient
listings of efficacy data are not necessary.
!  A summary of the efficacy evaluation (suggested to be primarily in table form). 
The summary should contain enough information for the reviewer to determine
whether the study results are germane to the overall evaluation of effectiveness and
to use in review of the integrated analysis of effectiveness, if necessary (including
means, confidence, intervals, p-values, standard errors, etc.)  Section 11.4.1 of 
ICH E3 format may be used, if appropriate. 
!  Any additional information pertinent to the evaluation of safety should also be
included.
8 Section 12, Safety evaluation, should provide comprehensive safety information.  Other
sections should be concise and need not be as comprehensive as in a full report.
B. Human Pharmacokinetics, Bioavailability, and Clinical Pharmacology
Studies
The E3 guidance focuses on safety and efficacy trials, but notes that the basic principles
and format can be applied to other kinds of trials such as clinical pharmacology trials. 
Additional guidance on content and format for submission of pharmacokinetics and
biopharmaceutics studies is provided in CDERs Clin/Stat guidance.  FDA recommends
that the provisions of  the Clin/Stat guidance and E3 be applied as appropriate to clinical
pharmacology and biopharmaceutics studies.
The sections included in an abbreviated clinical pharmacology and biopharmaceutics study
report are the same as those described above for clinical efficacy studies.  For a study with
clinical pharmacology and biopharmaceutics data, the following should also be included:
!  Summary tables of mean values, standard deviations or coefficients of variation,
confidence intervals and observed ranges, along with sample size.
!  For assay validation studies, assay performance should be summarized in enough
detail for the reviewer to assess the adequacy of the assay performance including
standard curve results, quality control results, specificity, accuracy, and
reproducibility. There should be a reference to the full validation report for the
analytical method.
!  Formulation information including batch or lot numbers and qualitative and
quantitative composition, and relationship to use in studies.
Published literature may be submitted in lieu of the abbreviated report.  If the publication
does not contain all of the items listed above, an attachment including the missing items
should accompany the publication.
V. FORMAT OF A SYNOPSIS
A synopsis should contain sufficient information to allow the reviewer to assess if the results cast
doubt on the safety of the product for the proposed indication.  The synopsis should summarize
the study including sufficient data to illustrate results. One example of the structure and content of
a synopsis is described in E3 (section 2).  A study protocol and protocol amendments (Section
16.1.1 of E3) should be provided along with the synopsis.
Generally, a complete discussion of the safety data from these studies, including all information
from section 12 (Safety  Evaluation) as described in  E3, should be included with the synopsis
9 and/or in a separate section in the Integrated Summary of Safety.  In some cases, with the
agreement of the appropriate reviewing division, a complete discussion of safety may not be
necessary.
Published literature may be submitted in lieu of the synopsis with supplemental safety data as
appropriate.  If the publication does not contain all of the information provided in a synopsis, an
attachment including the missing information should accompany the publication.
VI. RECOMMENDED PROCEDURES
We encourage applicants to discuss with the Agency at the earliest possible time which studies
should be submitted as full study reports, abbreviated reports, or synopses.  Such discussions
should begin during pre-IND meetings when foreign clinical trials have been completed (and the
initial U.S. studies will be phase 3) and at all end-of-phase 2 and/or pre-NDA/BLA meetings for
all drugs or biological products.  Prior to submission of the application, a division director may
request any study to be submitted as an abbreviated or full study report if, in his or her opinion,
these reports will aid in evaluating the proposed claim.  In addition, division staff may request
additional study data (e.g., individual patient data listings for efficacy) during the course of a
review if the study has been submitted in an abbreviated or synopsis format.
If FDA and the sponsor have agreed upon the types of study reports needed and the application
has been submitted, but not yet filed, and the Agency determines that more extensive reports are
needed, the application will be filed (assuming no other refuse-to-file issues exist).  In this
instance, the additional abbreviated or full study report(s) requested should be submitted within
60 days (30 days for priority applications) of the request.  If the requested report(s) is not
submitted, and the information is needed for the determination of safety and effectiveness, this
deficiency may be a basis for not approving the application.
 
If no agreement on the types of study reports to be submitted has occurred prior to submission
and the Agency finds the information submitted to be insufficient on its face to evaluate safety
and/or effectiveness, this inadequacy may serve as a basis to refuse to file the application (21 CFR
314.101(d)(3)). 
Once the application is filed, requests for additional abbreviated reports or full study reports
should be authorized by the relevant division director.  Additional abbreviated study reports or full
study reports should be requested within the first six months of the review for standard
applications and within the first three months for priority applications.  Requests for additional
abbreviated or full study reports made beyond these times would be extremely unusual and should
be authorized by the office director.  If the applicant believes that a request for additional study
reports is inappropriate, the applicant should meet with the requesting official to discuss and
resolve the matter.  If the issues cannot be resolved at that level, an appeal may be made through
the dispute resolution process.
10 The applicant should submit a requested abbreviated or full study report within 60 days of
receiving a request (30 days for priority applications).  The submitted report may be considered a
major amendment for purposes of the user fee clock if submitted within 90 days prior to the user
fee action date.  If the requested study report is not submitted, and this information is needed for
the determination of  safety and effectiveness of the product,  this deficiency may be a basis for
not approving the application.
11 Attachment
Clinical Studies
Study Supports Proposed Labeling
Yes
No
Yes
Adequate and Well Controlled Trial
of Indication (Efficacy Trial)
or
Yes
Most Relevant Trial of Group ( Clin Pharm )
No
Full Study Reports
Full CRTs Abbreviated Report or Synopsis
Yes
Efficacy Study Conducted for the
Proposed Indication or Closely Related
or
Yes Less Relevant Clin Pharm Study
of Dose, Dosage Form
Abbreviated Reports No
and
Synopses
Safety Datasets
and
Safety Datasets
12 13