**Guidance for Industry**

**Information Program on Clinical Trials for Serious or Life-Threatening
Diseases and Conditions**

***DRAFT GUIDANCE***

**This guidance document is being distributed for comment purposes
only.**

Comments and suggestions regarding this draft document should be
submitted within 60 days of publication in the *Federal Register* of the
notice announcing the availability of the draft guidance. Submit
comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All
comments should be identified with the docket number listed in the
notice of availability that publishes in the *Federal Register*.

For questions regarding this draft document, contact Terry Toigo,
301-827-4460.

**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)**

**January 2004**

**Procedural**

**Revision 1**

**Guidance for Industry**

**Information Program on Clinical Trials for Serious or Life-Threatening
Diseases and Conditions**

*Additional copies are available from:*

*Office of Training and Communication*

*Division of Drug Information, HFD-240*

*Center for Drug Evaluation and Research*

*Food and Drug Administration*

*5600 Fishers Lane*

*Rockville, MD 20857*

*(Tel) 301-827-4573*

*http://www.fda.gov/cder/guidance/index.htm*

*and/or*

*Office of Communication, Training and*

*Manufacturers Assistance, HFM-40*

*Center for Biologics Evaluation and Research*

*Food and Drug Administration*

*1401 Rockville Pike, Rockville, MD 20852-1448*

*http://www.fda.gov/cber/guidelines.htm.*

*(Tel) Voice Information System at 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)**

**January 2004**

**Procedural**

Revision 1

# I. INTRODUCTION [1](#i.-introduction) {#i.-introduction-1 .TOC-1}

# II. BACKGROUND [1](#ii.-background) {#ii.-background-1 .TOC-1}

# III. REQUIREMENTS UNDER SECTION 113 OF THE MODERNIZATION ACT FOR IND SPONSORS [3](#iii.-requirements-under-section-113-of-the-modernization-act-for-ind-sponsors) {#iii.-requirements-under-section-113-of-the-modernization-act-for-ind-sponsors-3 .TOC-1}

## A. What information must I submit to the Clinical Trials Data Bank? [3](#a.-what-information-must-i-submit-to-the-clinical-trials-data-bank) {#a.-what-information-must-i-submit-to-the-clinical-trials-data-bank-3 .TOC-2}

## B. When should I begin submitting clinical trial information? [4](#b.-when-should-i-begin-submitting-clinical-trial-information) {#b.-when-should-i-begin-submitting-clinical-trial-information-4 .TOC-2}

## C. Can I submit my information at specified intervals rather than on a rolling basis? [5](#c.-can-i-submit-my-information-at-specified-intervals-rather-than-on-a-rolling-basis) {#c.-can-i-submit-my-information-at-specified-intervals-rather-than-on-a-rolling-basis-5 .TOC-2}

## D. What is a trial for a serious or life-threatening disease or condition? [5](#d.-what-is-a-trial-for-a-serious-or-life-threatening-disease-or-condition) {#d.-what-is-a-trial-for-a-serious-or-life-threatening-disease-or-condition-5 .TOC-2}

## E. What is a trial to test effectiveness? [6](#e.-what-is-a-trial-to-test-effectiveness) {#e.-what-is-a-trial-to-test-effectiveness-6 .TOC-2}

## F. Which trials are provided to the public through the Clinical Trials Data Bank? [6](#f.-which-trials-are-provided-to-the-public-through-the-clinical-trials-data-bank) {#f.-which-trials-are-provided-to-the-public-through-the-clinical-trials-data-bank-6 .TOC-2}

## G. Must I include information about foreign trial sites? [7](#g.-must-i-include-information-about-foreign-trial-sites) {#g.-must-i-include-information-about-foreign-trial-sites-7 .TOC-2}

# IV. IMPLEMENTATION ISSUES [7](#iv.-implementation-issues) {#iv.-implementation-issues-7 .TOC-1}

## A. How do I submit information to the Clinical Trials Data Bank? [7](#a.-how-do-i-submit-information-to-the-clinical-trials-data-bank) {#a.-how-do-i-submit-information-to-the-clinical-trials-data-bank-7 .TOC-2}

## B. What information about trial sites must be included? [7](#b.-what-information-about-trial-sites-must-be-included) {#b.-what-information-about-trial-sites-must-be-included-7 .TOC-2}

## C. How long does it take for information to be made available on ClinicalTrials.gov? [7](#c.-how-long-does-it-take-for-information-to-be-made-available-on-clinicaltrials.gov) {#c.-how-long-does-it-take-for-information-to-be-made-available-on-clinicaltrials.gov-7 .TOC-2}

## D. How long will information about studies remain available through ClinicalTrials.gov? [8](#d.-how-long-will-information-about-studies-remain-available-through-clinicaltrials.gov) {#d.-how-long-will-information-about-studies-remain-available-through-clinicaltrials.gov-8 .TOC-2}

## E. Can information be transferred from a sponsor computer to the PRS? [8](#e.-can-information-be-transferred-from-a-sponsor-computer-to-the-prs) {#e.-can-information-be-transferred-from-a-sponsor-computer-to-the-prs-8 .TOC-2}

## F. Can intermediaries acting on behalf of a sponsor submit data? [8](#f.-can-intermediaries-acting-on-behalf-of-a-sponsor-submit-data) {#f.-can-intermediaries-acting-on-behalf-of-a-sponsor-submit-data-8 .TOC-2}

## G. Can sponsors designate multiple individuals to be data providers? [8](#g.-can-sponsors-designate-multiple-individuals-to-be-data-providers) {#g.-can-sponsors-designate-multiple-individuals-to-be-data-providers-8 .TOC-2}

## H. What happens to the information submitted to the Clinical Trials Data Bank? [8](#h.-what-happens-to-the-information-submitted-to-the-clinical-trials-data-bank) {#h.-what-happens-to-the-information-submitted-to-the-clinical-trials-data-bank-8 .TOC-2}

## I. Can I submit other information to the Clinical Trials Data Bank? [8](#i.-can-i-submit-other-information-to-the-clinical-trials-data-bank) {#i.-can-i-submit-other-information-to-the-clinical-trials-data-bank-8 .TOC-2}

## J. Should I continue submitting information to the ACTIS and PDQ databases? [9](#j.-should-i-continue-submitting-information-to-the-actis-and-pdq-databases) {#j.-should-i-continue-submitting-information-to-the-actis-and-pdq-databases-9 .TOC-2}

## K. Are there exemptions for submitting clinical trials information? [9](#k.-are-there-exemptions-for-submitting-clinical-trials-information) {#k.-are-there-exemptions-for-submitting-clinical-trials-information-9 .TOC-2}

## L. Is Institutional Review Board preapproval of the protocol listing required? [9](#l.-is-institutional-review-board-preapproval-of-the-protocol-listing-required) {#l.-is-institutional-review-board-preapproval-of-the-protocol-listing-required-9 .TOC-2}

## M. Will FDA monitor compliance? [10](#m.-will-fda-monitor-compliance) {#m.-will-fda-monitor-compliance-10 .TOC-2}

## N. What information about protocol exceptions, single-patient use, and expanded access protocols must I include? [10](#n.-what-information-about-protocol-exceptions-single-patient-use-and-expanded-access-protocols-must-i-include) {#n.-what-information-about-protocol-exceptions-single-patient-use-and-expanded-access-protocols-must-i-include-10 .TOC-2}

#####  {#section .TOC-5 .unnumbered}

**Guidance for Industry**[^1]

**Information Program on Clinical Trials for Serious or Life‑Threatening
Diseases and Conditions**

This draft guidance, when finalized, will represent the Food and Drug
Administration\'s (FDA\'s) current thinking on this topic. It does not
create or confer any rights for or on any person and does not operate to
bind FDA or the public. You can use an alternative approach if the
approach satisfies the requirements of the applicable statutes and
regulations. If you want to discuss an alternative approach, contact the
FDA staff responsible for implementing this guidance. If you cannot
identify the appropriate FDA staff, call the appropriate number listed
on the title page of this guidance.

# I. INTRODUCTION 

This guidance is intended to assist sponsors who will be submitting
information to the Clinical Trials Data Bank. The data bank was
established as required under section 113 of the Food and Drug
Administration Modernization Act of 1997 (Modernization Act). This
guidance updates and replaces the March 2002 guidance for industry of
the same title to include assistance for sponsors who will be submitting
information required by the Best Pharmaceuticals for Children Act
(Public Law 107-109) (BPCA). Additional updates on procedural issues not
related to the BPCA will be discussed in future revisions to this
guidance.

FDA\'s guidance documents, including this guidance, do not establish
legally enforceable responsibilities. Instead, guidances describe the
Agency\'s current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited. The use of the word *should* in Agency guidances means that
something is suggested or recommended, but not required.

# II. BACKGROUND

Section 113 of the Modernization Act creates a public resource for
information on studies of drugs, including biological drug products, to
treat serious or life-threatening diseases and conditions conducted
under FDA\'s investigational new drug (IND) regulations (21 CFR part
312). Section 113 of the Modernization Act, enacted November 21, 1997,
amends section 402 of the Public Health Service Act (42 U.S.C. 282). It
directs the Secretary of Health and Human Services, acting through the
Director of the National Institutes of Health (NIH), to establish,
maintain, and operate a data bank of information on clinical trials for
drugs to treat serious or life-threatening diseases and conditions. The
Clinical Trials Data Bank is intended to be a central resource,
providing current information on clinical trials to individuals with
serious or life-threatening diseases or conditions, to other members of
the public, and to health care providers and researchers. Specifically,
section 113 of the Modernization Act requires that the Clinical Trials
Data Bank contain (1) information about Federally and privately funded
clinical trials for experimental treatments (drug and biological
products) for patients with serious or life-threatening diseases or
conditions, (2) a description of the purpose of each experimental drug,
(3) patient eligibility criteria, (4) a description of the location of
clinical trial sites, and (5) a point of contact for patients wanting to
enroll in the trial. Section 113 of the Modernization Act requires that
information provided through the Clinical Trials Data Bank be in a form
that can be readily understood by the public. 42 U.S.C. 282(j)(3)(A).

The BPCA, signed by the President on January 4, 2002, requires a
description of whether, and through what procedure, the manufacturer or
sponsor of an IND will respond to requests for protocol exception, with
appropriate safeguards, for single-patient and expanded access use of
the investigational drug, particularly in children.

The NIH, through its National Library of Medicine (NLM) and with input
from the FDA and others, developed the Clinical Trials Data Bank. The
first version of the Clinical Trials Data Bank was made available to the
public on February 29, 2000, on the Internet.[^2] At that time, the data
bank included primarily NIH-sponsored trials.

In response to the Modernization Act\'s requirements for a data bank,
FDA made available two draft guidances and a final guidance. The first
draft guidance provided recommendations for industry on the submission
of protocol information to the Clinical Trials Data Bank.[^3] It
included information about the types of clinical trials for which
submissions are required under section 113 of the Modernization Act, as
well as the content of those submissions.

The second draft guidance addressed procedural issues, including how to
submit required and voluntary protocol information to the Clinical
Trials Data Bank, as well as issues related to submitting certification
to the Secretary that disclosure of information for a particular
protocol would substantially interfere with the timely enrollment of
subjects in the clinical investigation[^4] The second draft guidance
also proposed a time frame for submitting the information. A final
guidance, made available on March 18, 2002,[^5] combined the two draft
guidances into a single guidance.

This updated guidance includes new recommended procedures for submitting
details, as required by the BPCA, about single-patient use and expanded
access use.

# III. REQUIREMENTS UNDER SECTION 113 OF THE MODERNIZATION ACT FOR IND SPONSORS

## A. What information must I submit to the Clinical Trials Data Bank?

Section 113 of the Modernization Act requires you to submit information
to the data bank about a clinical trial conducted under an
investigational new drug (IND) application if it is for a drug to treat
a serious or life-threatening disease or condition and it is a trial to
test effectiveness (42 U.S.C. 282(j)(3)(A)). If you wish, you can also
provide information on trials not designed to assess effectiveness or
for drugs to treat conditions not considered serious or
life-threatening.

Section 113 of the Modernization Act requires that you submit a
description of the purpose of each experimental drug, patient
eligibility criteria for participation in the trial, a description of
the location of clinical trial sites, and a point of contact for those
wanting to enroll in the trial. Section 113 requires that the data bank
provide this information in a form that can be readily understood by
members of the public (42 U.S.C. 282(j)(3)(A)).

The BPCA amended 42 U.S.C. 282 (j)(3)(A) to require that you submit a
description of whether, and through what procedure, you (the
manufacturer or sponsor of a clinical investigation of a new drug) will
respond to requests for protocol exception, with appropriate safeguards,
for single-patient and expanded access use of the investigational drug,
particularly in children.[^6]

To ensure that information available through the Clinical Trial Data
Bank is in a form that is readily understood, we have established four
data elements, which are listed below. The data elements are made up of
the following data fields: (1) descriptive information, (2) recruitment
information, (3) location and contact information, and (4)
administrative data. We have established the Protocol Registration
System (PRS), a Web-based data processing program, to facilitate
collection of this information for the data bank. The four data
elements, which are listed below, as well as definitions applicable to
the PRS, can be viewed at
[*http://prsinfo.clinicaltrials.gov/*](http://prsinfo.clinicaltrials.gov/).

> **1.** **Descriptive Information**
>
> Brief Title (in lay language)
>
> Brief Summary (in lay language)
>
> Study Design/Study Phase/Study Type
>
> Condition or Disease
>
> Intervention
>
> Single-patient/expanded access use
>
> **2. Recruitment Information**
>
> Study Status Information including

-   Overall Study Status (e.g., recruiting, no longer recruiting)

```{=html}
<!-- -->
```
-   Individual Site Status

> Eligibility Criteria/Gender/Age
>
> **3. Location and Contact Information**

::: Definition-Term
Location of Trial
:::

Contact information (includes an option to list a central contact person
for all trial sites)

> **4.** **Administrative Data**
>
> Unique Protocol ID Number
>
> Study Sponsor
>
> Verification date

To verify the existence of an IND and to assist in administrative
tracking, we ask that you also include in your submission the IND number
and serial number and designate whether the IND is located in the Center
for Drug Evaluation and Research (CDER) or the Center for Biologics
Evaluation and Research (CBER). This administrative information is in a
separate data field and will not be made public.

## B. When should I begin submitting clinical trial information?

Section 113 of the Modernization Act requires that sponsors submit
information no later than 21 days after the trial is opened for
enrollment[^7] (42 U.S.C. 282(j)(3)). Section 113 does not specify when
sponsors must submit information about clinical trials that are existing
and ongoing. To provide a transitional period for sponsors of clinical
trials that are currently ongoing and expected to continue enrolling
patients for more than 45 days, we ask that you submit information
within 45 days after this guidance is made available through the
*Federal Register*. We encourage you to submit information through the
PRS for inclusion in the data bank as soon as possible.[^8]

## C. Can I submit my information at specified intervals rather than on a rolling basis?

As discussed above, you must submit information about new protocols open
for enrollment within 21 days after the trial is open for enrollment (42
U.S.C. 282(j)(3)), and we request that you submit information about
existing ongoing trials within 45 days after this guidance is published.
Supplemental information can be submitted at 30-day intervals. Such
information includes amendments to the protocol with respect to one of
the data elements, or interruptions, continuations, or completion of
enrollment for a study. Protocol changes related to eligibility or
status information, such as routine opening and closing of trial sites,
can be made at 30-day intervals. FDA strongly encourages you to update
information about trials that are unexpectedly closed (e.g., clinical
hold) within 10 days after the closing or sooner if possible.

To ensure that the information available through the data bank is timely
and accurate, FDA also encourages you to review, verify, and update all
active protocol records on a semi-annual basis, at a minimum.

## D. What is a trial for a serious or life-threatening disease or condition? 

FDA has defined serious and life-threatening diseases and conditions in
previous documents. Most recently, FDA discussed issues related to
products intended to treat serious or life-threatening diseases and
conditions in the guidance for industry on *Fast Track Drug Development
Programs - Designation, Development, and Application Review* (November
1998).[^9] In that guidance, we stated that all conditions meeting the
definition of life-threatening, as set forth at 21 CFR 312.81(a), would
also be serious conditions. The term *life-threatening* is defined as
(1) diseases or conditions where the likelihood of death is high unless
the course of the disease is interrupted and (2) diseases or conditions
with potentially fatal outcomes, where the endpoint of clinical trial
analysis is survival (21 CFR 312.81(a)). All references in this document
to serious diseases or conditions include life-threatening diseases and
conditions.

As FDA reiterated in the *Fast Track Guidance*, the seriousness of a
disease is a matter of judgment, but generally is based on such factors
as survival, day-to-day functioning, and the likelihood that the
disease, if left untreated, will progress from a less severe condition
to a more serious one. For example, acquired immunodeficiency syndrome
(AIDS), all other stages of human immunodeficiency virus (HIV)
infection, Alzheimer\'s disease, angina pectoris, heart failure, cancer,
and many other diseases are clearly serious in their full
manifestations. Furthermore, many chronic illnesses that are generally
well managed by available therapy can have serious outcomes. For
example, inflammatory bowel disease, asthma, rheumatoid arthritis,
diabetes mellitus, systemic lupus erythematosus, depression, psychoses,
and many other diseases can be serious in some or all of their phases or
for certain populations.

Any investigational drug that has received fast track designation would
be considered a drug to treat a serious disease or condition.[^10]
Information on effectiveness trials for drugs that have received fast
track designation would qualify for submission to the Clinical Trials
Data Bank.

## E. What is a trial to test effectiveness? 

Not all trials carried out under 21 CFR part 312 are trials to test
effectiveness. FDA considers all phase 2, phase 3, and phase 4 trials
with efficacy endpoints as trials to test effectiveness.[^11]

## F. Which trials are provided to the public through the Clinical Trials Data Bank?

Section 113 of the Modernization Act requires sponsors to submit
information about clinical trials of experimental treatments for serious
or life-threatening diseases and conditions when conducted under the IND
regulations (42 U.S.C. 282(j)(3)(A)). Such information can be submitted
at any time with the consent of the protocol sponsor, and must be
submitted within 21 days after a trial to test effectiveness begins. In
addition, section 113 of the Modernization Act states that information
on all treatment IND protocols and all Group C protocols[^12] must be
included in the Clinical Trials Data Bank.

There are situations in which there may be patients with the disease or
condition for which the drug is being developed who are not adequately
treated by existing therapy, who do not meet the eligibility criteria
for enrollment, or who are otherwise unable to participate in a
controlled clinical study. In these situations, you may have initiated
an expanded access protocol or be willing to provide the drug to an
individual patient through a single-patient IND or protocol
exception.[^13] The BPCA requires that you submit a description of
whether, and through what procedure, you will respond to requests for
protocol exception for single-patient and expanded access use of the
investigational drug, particularly in children.

For protocols not specifically mentioned above, sponsors should review
each protocol submitted to an IND to determine if the protocol is for a
serious disease or condition and if it is a trial to test effectiveness.
If the protocol meets these criteria, the sponsor must submit
information about the trial to the Clinical Trials Data Bank,
***unless*** the sponsor provides detailed certification to FDA that
such a disclosure would substantially interfere with the timely
enrollment of subjects in the investigation (42 U.S.C. 282(j)(3) and
(j)(4)). Sponsors with questions on whether protocols meet the criteria
for submission to the Clinical Trials Data Bank are encouraged to
contact the appropriate review division for additional guidance.

## G. Must I include information about foreign trial sites?

Yes, you must include information about foreign trials when those trials
are conducted under an IND submitted to FDA and the trial meets the
criteria for submission to the Clinical Trials Data Bank. Section 113 of
the Modernization Act requires sponsors to submit information about
specified clinical trials that are \"under regulations promulgated
pursuant to section 505(i) of the Federal Food, Drug, and Cosmetic
Act,\" which are FDA\'s IND regulations (42 U.S.C. 282(j)(3)). Sponsors
may voluntarily conduct a foreign trial under the IND regulations.
Sponsors are not required to submit information to the Clinical Trials
Data Bank when a foreign trial is not conducted under an IND.

# IV. IMPLEMENTATION ISSUES

## A. How do I submit information to the Clinical Trials Data Bank?

To facilitate the submission process, we have established the Web-based
PRS at *ClinicalTrials.gov.* The system allows for entry of required and
voluntary information about clinical trials. You or your designee can
initiate submission of clinical trial information to
*ClinicalTrials.gov* by completing a registration form at
*<http://prsinfo.clinicaltrials.gov/>.*

After you have entered the data, the PRS generates a receipt for use by
sponsors. An electronic copy of the receipt will be sent to the FDA.

## B. What information about trial sites must be included?

Section 113 of the Modernization Act requires sponsors to submit a
description of the location of trial sites and a point of contact. To
ensure an adequate description, we recommend that you provide for each
individual trial site the full name of the organization, city, state,
postal code, and country where the protocol is being conducted; and a
central contact name and phone number. You can also provide the names
and phone numbers of individual site contacts.

## C. How long does it take for information to be made available on ClinicalTrials.gov?

Studies will be made available to the public through
*[ClinicalTrials.gov](http://ClinicalTrials.gov/)* within 2 to 5 days
after submission by the sponsor.

## D. How long will information about studies remain available through ClinicalTrials.gov?

NLM intends to maintain the Data Bank as a long-term registry of
clinical trials. Therefore, in addition to information about open
trials, information about closed trials will also be available through
*ClinicalTrials.gov,* even after accrual and analysis are completed and
the product is approved.

## E. Can information be transferred from a sponsor computer to the PRS?

Yes. Information can be transferred according to the format specified by
the PRS. The PRS has a mechanism for uploading and downloading
XML-formatted protocol records. Instructions for transferring
information are provided at
[*http://prsinfo.clinicaltrials.gov/*](http://prsinfo.clinicaltrials.gov/)

## F. Can intermediaries acting on behalf of a sponsor submit data?

Yes. For example, in some cases a sponsor might want to contract with an
information management company to serve as an intermediary in preparing
data for inclusion in
[*ClinicalTrials.gov*](http://ClinicalTrials.gov/). The information
management company, when authorized by the sponsor, could act on behalf
of the sponsor for this purpose.

## G. Can sponsors designate multiple individuals to be data providers?

Yes. When sponsors register to become a PRS data provider, they will be
given information, including instructions, for creating additional users
for their accounts. A sponsor can control access to the account by
designating users and administrators for the account.

## H. What happens to the information submitted to the Clinical Trials Data Bank?

Except for the IND number, serial number, and FDA center designation,
all information submitted through the PRS is made available to the
public at *[http://clinicaltrials.gov](http://clinicaltrials.gov/).*

## I. Can I submit other information to the Clinical Trials Data Bank?

Yes. PRS is designed to permit you to submit more detailed information
about a protocol. Additional data fields (e.g., projected enrollment)
and their definitions are included in the PRS. You also can submit
protocol information about other clinical trials under IND, including
trials for a disease or condition that is not serious or any trial that
is not designed to test effectiveness. Finally, you can submit
information about results of a trial*.* This information, which,
according to the structure of the Clinical Trials Data Bank, is to come
from the published literature, should be linked by including the unique
MEDLINE identifier for citations of publications.

You can use the *link* section provided to allow pointers to Web pages
directly relevant to the protocol. If you link to other Web pages from
your entries, you should ensure that the links do not misbrand your
products, for example, by promoting the products before the product or
an indication is approved. (See 21 U.S.C. 321(n), 331(a)(b)(c)(d),
352(a)(n)
[*http://www.fda.gov/opacom/laws/fdcact/fdcact1.htm*](http://www.fda.gov/opacom/laws/fdcact/fdcact1.htm).)
When inputting links to other web pages, the database will instruct you
that the links should be directly relevant to the protocol, and that you
should not link to sites whose primary goal is to advertise or sell
commercial products or services.

## J. Should I continue submitting information to the ACTIS and PDQ databases?

No. All information for AIDS and cancer protocols that meet the
requirements of section 113 of the Modernization Act must now be
submitted to [*ClinicalTrials.gov*](http://ClinicalTrials.gov/) through
the PRS. Data from the current AIDS Clinical Trials Information System
(ACTIS) and Physician\'s Data Query (PDQ) databases are included in
*ClinicalTrials.gov*. Information from the Rare Diseases and National
Institute of Aging Databases is also included in *ClinicalTrials.gov*.

#  {#section-1 .TOC-1}

## K. Are there exemptions for submitting clinical trials information?

Information about an investigation will not be included in the data bank
if you provide a detailed certification to the Secretary of Health and
Human Services that disclosure of such information would substantially
interfere with timely enrollment of subjects in the clinical trial and
the Secretary does not disagree. If there is disagreement, the Secretary
will provide a detailed written determination that such disclosure would
not substantially interfere with such enrollment (42 U.S.C. 282(j)(4)).

FDA has not identified specific instances when disclosure of information
would substantially interfere with enrollment of subjects in a clinical
investigation. We solicited comments on this topic for the purpose of
including a listing of acceptable reasons for certification in the final
guidance. We received no comments. Therefore, if you identify a specific
instance when disclosure of information would interfere with enrollment
of subjects in a clinical investigation,

FDA will consider your request on a case-by-case-basis.

All requests for exemption should be forwarded to Director, Office of
Special Health Issues, Office of Communications and Constituent
Relations, Office of the Commissioner, HF-12, 5600 Fishers Lane
Rockville, MD 20857, or by email at
[*113trials@oc.fda.gov*](mailto:113trials@oc.fda.gov), or by fax at
301-443-4555.

## L. Is Institutional Review Board preapproval of the protocol listing required? 

No. Section 113 of the Modernization Act does not require prior IRB
approval when submitting this information to the Clinical Trials Data
Bank. Current FDA guidance recommends that IRB review of listings need
not occur when, as here, the system format limits the information
provided to basic information, such as title, purpose of the study,
protocol

summary, basic eligibility criteria, study site locations, and how to
contact the site for further information. [^14]

## M. Will FDA monitor compliance?

A copy of the protocol listing in
[*ClinicalTrials.gov*](http://ClinicalTrials.gov/) will be sent to the
FDA. FDA\'s Office of Special Health Issues initiated a pilot
educational program in 2002 that included a component to evaluate
compliance. The primary objective of the pilot program is to educate
sponsors about the existence of the guidance document and the
availability of the online PRS data entry tool. The secondary objective
of the pilot program is to evaluate the success of the educational
initiative. The pilot program will measure the number of protocols
(voluntary and required) made available through the *ClinicalTrials.gov*
database. Data from the completed project will help senior FDA officials
assess the need for further efforts to facilitate or perhaps compel
participation in *ClinicalTrials.gov.*

## N. What information about protocol exceptions, single-patient use, and expanded access protocols must I include?

There are situations in which there may be patients with the disease or
condition for which the drug is being developed who are not adequately
treated by existing therapy, who do not meet the eligibility criteria
for enrollment, or who are otherwise unable to participate in a
controlled clinical study. In such a situation, you may wish to provide
the drug to a patient through a protocol exception/exemption, single
patient IND, or expanded access protocol.

The BPCA amended Section 113 of the Modernization Act to require that
you submit, in addition to the information already included in the
Clinical Trials Data Bank, a description of whether and through what
procedure you will respond to requests for protocol exception, with
appropriate safeguards, for single-patient and expanded access use of
the investigational drug, particularly in children.

The PRS includes a mechanism for providing information about protocol
exceptions, single-patient INDs, and expanded access protocols. In order
to comply with the BPCA amendment to section 113 of the Modernization
Act, we suggest that you address the following two questions and provide
a brief description as described below. This information is required for
each new protocol that is listed in the data bank; we encourage you also
to provide this information for protocols currently open to enrollment.

-   Is this investigational drug available for use in adults through a
    protocol exception, single-patient IND, or expanded access protocol?

##### Yes No

-   Is this investigational drug available for use in children through a
    protocol exception, single-patient IND, or expanded access protocol?

##### Yes No

-   Brief description of the procedure for responding to requests for
    expanded access, including contact number and/or email address.

[^1]: This guidance has been prepared by the Implementation Team for
    section 113 of the Food and Drug Administration Modernization Act of
    1997, including individuals from the Office of the Commissioner, the
    Center for Drug Evaluation and Research (CDER), the Center for
    Biologics Evaluation and Research (CBER), and the Center for Devices
    and Radiological Health (CDRH), at the Food and Drug Administration.

    **Paperwork Reduction Act Public Burden Statement:** According to
    the Paperwork Reduction Act of 1995, a collection of information
    should display a valid OMB control number. The valid OMB control
    number for this information collection is 0910-0459 (expires
    03/31/2004). The time to complete this information collection is
    estimated to average 284 hours per response, including the time to
    review instructions, search existing data resources, gather the data
    needed, and complete and review the information collection.

[^2]: See [http://clinicaltrials.gov](http://clinicaltrials.gov/)

[^3]: See <http://www.fda.gov/OHRMS/DOCKETS/98fr/001033gl.pdf>

[^4]: See 66 FR 35798 and
    <http://www.fda.gov/OHRMS/DOCKETS/98fr/001033gd.pdf>

[^5]: See 67 FR 12022 and
    <http://www.fda.gov/OHRMS/DOCKETS/98fr/00d-1033_gdl0003.pdf>

[^6]: See 42 U.S.C. 282(j)(3)(A) at
    http://www.fda.gov/opacom/laws/pharmkids/contents.html.

[^7]: Section 113 says \"not later than 21 days after the approval of
    the protocol.\" Because the Agency does not approve protocols, we
    have interpreted this to mean within 21 days after the trial is open
    for enrollment.

[^8]: See *[http://prsinfo.clinicaltrials.gov]{.underline}*.

[^9]: CDER guidances are available at
    http://www.fda.gov/cder/guidance/index.htm.

[^10]: That a drug is intended to treat a serious or life-threatening
    disease or condition, however, does not mean that it fills an unmet
    medical need and qualifies for fast track designation under section
    506 of the Food Drug and CosmeticAct (21 U.S.C. 356).

[^11]: Listing a trial in the Clinical Trials Data Bank is not a
    guarantee that the trial design is considered adequate to support
    approval of a drug, nor does it reflect any judgment on the conduct,
    analysis, or outcome of the study.

[^12]: \"Group C protocols\" refers to investigational drugs designated
    by FDA for the treatment of specific cancers. These drugs have
    reproducible efficacy in one or more specific tumor types. Such a
    drug has altered or is likely to alter the pattern of treatment of
    disease and can be safely administered by properly trained
    physicians without specialized supportive care facilities. *See*
    [National Cancer Institute Handbook for Investigators]{.underline},
    Appendix XV, \"Policy for Group C Drug Distribution,\"
    http://ctep.info.nih.gov/HandbookText/Appendix_XV.htm#Proc_Mgmt_GrpC_Prot.

[^13]: There are a number of mechanisms FDA has used to provide access
    to promising investigational therapies. In addition to treatment
    INDs and treatment protocols, which are described in FDA
    regulations, expanded access mechanisms fall under a variety of
    terms, such as single patient INDs, emergency INDs, protocol
    exemptions, special exceptions, open label extensions, and parallel
    track. FDAMA has codified certain FDA regulations and practices
    regarding expanded patient access to experimental drugs. FDA is
    reviewing current regulations and practices to assure coordination
    with FDAMA.

[^14]: The 1998 update of *Information Sheets: Guidance for
    Institutional Review Boards and Clinical Investigators* provides
    guidance on IRB review and approval of listings of clinical trials
    on the Internet. See
    <http://www.fda.gov/oc/ohrt/irbs/toc4.html#recruiting>.