Documentation &

Practice and with all applicable regulatory

requirements."

Record-Keeping Essential documents may be audited or

inspected by quality assurance monitors or by
Contents >> 1 of 1 regulatory authorities to confirm the validity of
the study and the integrity of the data
• Part 1: Introduction collected.
• Part 2: Documentation Requirements in
GCP guidelines list the essential documents
GCP and Federal Regulations
(ICH GCP E6 Section 8) that, at a minimum,
• Part 3: Examples of Other Sponsor- must be maintained for every clinical study.
Required Documents These documents are to be maintained by the
site and the sponsor, and are classified
• Part 4: Documenting the Use of
according to the stage of a study at which they
Investigational Drugs
are normally created. These documents may
• Part 5: Summary of Key Points be maintained in multiple locations, depending
on whether they are stored with regulatory files
Part 1: Introduction >> 1 of 1 or as participant documents. The sponsor and
the investigator/institution should maintain a
Proper documentation is critical to the success
record of the location(s) of their respective
of a clinical study. Every aspect of the study
essential documents, including source
must be documented in order to obtain useful
documents. Additional documents may be
data and demonstrate compliance with Good
developed and maintained by the sponsor or
Clinical Practice (GCP) guidelines and with all
the sponsor(s) representatives.
applicable regulations.

This module provides an overview of GCP Before a Study Begins

documentation requirements, requirements in
federal regulations, and sponsor required The following essential documents must be
documentation. created and kept on file at study sites before a
study begins:
Part 2: Documentation Requirements in
• Signed protocol and amendments, if
GCP and Federal Regulations >> 1 of 3 any.
• IRB-approved Informed Consent Form
Documentation Requirements in Good Clinical
Practice Guidelines
and any other written information that
will be given to prospective study
participants to enable them to make an
Essential documents for the conduct of a
informed decision about enrolling in the
clinical study are defined in ICH GCP 8.1 as
trial.
follows:
• Sample case report forms, either
electronic or paper.
"… those documents that individually and
• Participant recruitment advertisements,
collectively permit evaluation of the conduct of
if any.
a trial and the quality of the data produced.
• Documentation that the Institutional
These documents serve to demonstrate the
Review Board (IRB) is set up in
compliance of the investigator, sponsor, and
accordance with GCP and that all
monitor with the standards of Good Clinical
necessary IRB approvals have been
obtained.
 Decoding procedures for blinded trials
•
to document how, in case of an While a Study is in Progress
emergency, identity of blinded
investigational product can be revealed
without breaking the blind for the The following are essential documents that
remaining subjects' treatment, if should be added to the file while a study is in
applicable. progress:
• Documentation of study personnel's
qualifications (e.g., curriculum vitae, • Amendments to the Protocol and
professional licenses). changes to the case report forms
• Documentation of financial agreements (CRFs), recruitment materials, Informed
and any other arrangements between Consent Form, and Investigator's
the parties involved in conducting the Brochure.
study (e.g., investigator(s), institution(s), • Documentation of approval of
sponsor, contract research amendments by the Institutional Review
organization). Board (IRB) and regulatory authorities (if
• Insurance statement, where required, to required).
document that compensation to • Copies of all reports, including interim
subject(s) for trial-related injury will be and annual reports, sent to the IRB and
available. other regulatory authorities.
• If the study involves the use of • Informed consent forms signed by study
an investigational drug, instructions for participants.
handling, dispensing, and tracking the • Signed, dated, and completed CRFs and
investigational product, as well as documentation of any CRF corrections
shipping records, and a sample of the with the signature sheet.
label to be attached to the • Documentation of investigational
investigational product container. products and trial-related materials
• Investigator's Brochure, when shipment.
applicable. • Relevant communications, such as
• Evidence of notification, approval, or letters and meeting notes, that
authorization of the protocol and its document agreements or discussions
supporting documentation by regulatory about issues including protocol
authorities (if required) violations, adverse events, the conduct
• Evidence of approval or certification of and administration of the study, and all
facilities that are performing medical or safety information notifications and
laboratory tests required by the study communications.
protocol. • Relevant communications other than
• Normal value(s)/ range(s) for medical, site visits, such as letters and meeting
laboratory, and/or technical procedures notes.
and tests included in the protocol. • Reports of interim visits by quality
• Reports of site initiation visits and assurance monitors.
qualification visits by quality assurance • Curriculum vitae for new investigators
monitors. and sub-investigators.
• Source documents.
• Participant screening log, enrollment
log, and identification code list.
• Documentation that investigational
drugs, if used in the study, have been
handled and accounted for as required
in the protocol.
 • Records of location and identification of years after the study is discontinued and
retained tissue samples, if any. the FDA is notified.
• Staff signature log, documenting
• Records of all NIH–sponsored studies
signatures and initials of all persons
must be maintained for at least 3 years
authorized to make entries and/or
after the study ends per NIH policy and
corrections to CRFs.
for a longer time if required by
• Updates to CVs, license etc.
regulations or local institutional policies.
After a Study is Completed This requirement applies to all research
projects, including studies of
or Terminated investigational drugs, behavioral studies,
and survey–based studies.

The following are essential documents that Click to Collapse

should be added to the file after a study is
CTN
completed or terminated:

• Documentation that investigational

drugs, if used, were handled, accounted Records of all CTN–sponsored studies must
for, and returned or destroyed as be maintained for at least 3 years after the
required in the protocol. study ends per NIH policy and for a longer time
• List of all participants enrolled in the if required by regulations or local institutional
study at the site (completed subject policies. This requirement applies to all
identification code list). research projects, including studies of
• Reports of closeout visits by quality investigational drugs, behavioral studies, and
assurance monitors. survey–based studies.
• Final reports to Institutional Review
Boards and regulatory authorities. Of note, most facilities where CTN research is
• Clinical study report, which documents conducted are covered entities that must
the study’s results, if applicable. comply with the HIPAA Privacy Rule. Covered
Part 2: Documentation Requirements in entities are required to account for disclosures
(must retain documentation) 6 years from the
GCP and Federal Regulations >> 3 of 3
date of creation on which the accounting is
Documentation Requirements in Federal requested. (Reference the Clinical Research
Regulations and the HIPAA Privacy Rule.)

21 CFR 312.62 requires investigators to: Part 3: Examples of Other Sponsor-

• Maintain adequate records of the Required Documents >> 1 of 1
disposition of investigational drugs.
• Maintain adequate case histories for all
participants in studies that involve the
use of investigational products.
• Retain records for 2 years after the date
a marketing application is approved for
the drug for the indication for which is it In addition to the essential documents included
has been investigated by the U.S. Food in the GCP guideline, the sponsor may require
and Drug Administration (FDA) or for 2 other documentation. The following lists
examples of other documentation that may specific to the behavioral intervention that is
apply to clinical trials. being studied.

Certificate of Confidentiality

A Certificate of Confidentiality provides an

additional level of protection for the privacy of
participants in alcohol and drug use research
studies. (For more detailed information on
Certificates of Confidentiality, go to Source Documents
the Confidentiality and Privacy module.)
Source documents are original documents,
Quality Assurance Documents data, or records that are created during a
clinical study, that relates to the medical
Quality assurance documents may include the treatment and the history of the participant,
following: and from which study data are obtained.
Source documents are one type of essential
• Research site Initiation Activation Form, document that is required by GCP guidelines.
which indicates that a site is ready to
start study enrollment. The purpose of source documents (GCP
8.3.13) is to:
• Site visit logs, to record visits to the
research site by quality assurance • Document the existence of study
monitors and other personnel. participants.
Training Documents • Substantiate the integrity of the study
data collected.
A training plan and verification of compliance
with the training plan, including: Any document in which information, an
observation, or data generated relevant to a
• A training documentation form for each study is recorded for the first time is a source
staff person document. Thus, a scrap of paper, a Post–It ®
note, or an electronic mail message may be a
• Documentation of required source document if it is the original form on
assessments training per the study which information relevant to a study is
training plan. recorded.
• Documentation of study–specific
training. Examples of Source Documents

• Pertinent certifications for clinical staff The following are examples of source
implementing a study intervention. documents:
Behavioral Therapy Documents
• Adverse event and concomitant
Many CTN studies involve behavioral medication logs
interventions. Behavioral studies may require • Reports of diagnostic test results
essential documents different from, or in
addition to, those required by GCP guidelines. • Signed and dated Informed
These documents may include therapy Consent Forms
manuals and materials, audio and videotapes • Participant diaries
of treatment sessions, and other documents
• Appointment calendars
 • Progress notes • Research notes record information
related to the participant's involvement
• Paper case report forms (CRFs) on
in the research phases (e.g., follow-up
which data are entered directly onto the
assessment visits) of the clinical study.
CRF, rather than extracted from another
source document. Click here for a list of information that should
be documented in both clinical and research
progress notes.

Click here for a summary of Good Medical

Record practices that should always be
observed when writing progress notes.

Progress Notes Case Report Forms

These source materials must be readily GCP defines a Case Report Form (CRF) as
available and retrievable for quality assurance follows:
monitoring and for auditing, for example, by the
study sponsor (NIDA) or for inspection by the “A printed, optical, or electronic document
U.S. Food and Drug Administration (FDA). designed to record all of the protocol–required
information to be reported to the sponsor on
The purpose of progress notes is to document each trial subject” (ICH GCP 1.11)
participants’ involvement in the study and the
study–related care they receive. Both research Thus, a CRF may be a printed document that a
and clinical staff may complete progress study team member completes in the clinic or
notes. an electronic document that is sent directly
from a laboratory to the data management
Progress notes are source documents; and center.
may not be recorded in the study database or
sent to the sponsor. Often, progress notes are The purpose of CRFs is to gather study data in
used on–site to monitor the progress of the a standardized format so that the data can be
study. Another important purpose of progress entered into a computerized database and
notes is to substantiate the data recorded in analyzed. The CRFs record all of the
the case report forms (CRFs). information needed to complete the data
analyses used to assess the outcomes of the
Progress notes should be concise but should study.
provide enough information that the
participant’s study–related activities, and the A CRF is a source document only when study
order in which events occurred, can be easily data are entered directly onto the CRF, rather
understood. than extracted from another source document
(e.g., progress notes).
Progress notes are of two types, both
considered to be essential study documents: CTN–Specific Essential Documents

• Clinical notes record information related CTN investigators are required to maintain a
to the experimental treatment that the Certificate of Confidentiality, QA, Training,
participant received during the clinical Behavioral Therapy, Source, Progress Note, and
phases of the study. CRF documents for CTN studies. Additionally,
contact information should be maintained for
the following CTN study personnel:
 • Key personnel at the Lead Node. Documentation of the "Amount of Drug Received"

• Key personnel at the Participating Node.

Documentation of the "amount of drug
• Key personnel at the NIDA Center for the received" must account for:
Clinical Trials Network (CCTN).
• The total number of capsules, tablets,
• The NIDA Study Medical Officer and
etc. in every dosage (e.g., 5 mg, 10 mg).
other parties who must be contacted
when expedited reporting of an adverse • Multiple lot numbers.
event is necessary.
• The type of packaging in which the
Part 4: Documenting the Use of medication is delivered (e.g., bulk
supply, individual kits).
Investigational Drugs >> 1 of 1
Documentation of the "Amount of Drug Used"

Documentation of the "amount of drug used"

21 CFR 312.62 requires investigators to
must account for:
maintain adequate records of the disposition
of investigational drugs, including dates,
• The amount of medication that each
quantities, and use by participants. The
study participant is individually exposed
investigator must also maintain records of
to.
receipt.
• The total amount of medication
The following equation may help in consumed by all study participants.
understanding the process of accountability for
• The amount of medication that is
drug disposition:
returned by participants (i.e. unused).
• The amount of medication that is
wasted (e.g., lost, dropped down the
kitchen sink).
Verification of the "Amount of Drug on Hand"

Inventory must be taken at regular intervals to

verify the "amount of drug on hand." Any
discrepancies must be documented.

To ensure proper accountability, a carefully

designed plan (or standard operating
procedure) must be in place at the beginning of
the study to document the disposition of the
Although this equation may look simple, in investigational product at each site. This plan
practice accounting accurately for the must be adhered to throughout the study and,
disposition of an investigational drug can be if necessary, modified to ensure 100%
quite complicated. The investigator must accountability. The investigator’s records of
account for every unit of the investigational drug disposition must agree with the data
product (e.g., tablet, capsule, inhaler). submitted to the sponsor.

Let’s take a closer look at what is involved in

accounting for every unit of an investigational
product.
Summary of Key Points >> 1 of 1 complete the data analyses used to
assess the outcomes of the study is
recorded in the CRFs.

• Every aspect of a clinical study must be

documented in order to obtain useful
data and demonstrate compliance with
Good Clinical Practice (GCP) standards
and with all applicable regulations.
• GCP guidelines specify the essential
documents that must be maintained for
every clinical study. These documents
are classified according to whether they
are normally created before a study
begins, while a study is in progress, or
after a study is completed or
terminated.
• Federal regulations require investigators
to retain records for 2 years after
approval of the investigational drug by
the U.S. Food and Drug Administration
(FDA) or for 2 years after the study is
discontinued and FDA is notified.
• Sponsors may require specific
documentation in addition to the list of
essential documents specified by GCP.
• Source documents are original
documents created during a clinical
study, from which study data are
obtained. The purpose of source
documents is to document the
existence of study participants and
substantiate the integrity of the study
data collected.
• Progress notes document participants’
involvement in the study and the study–
related care they receive. Progress notes
are used to monitor the progress of the
study and substantiate the data
recorded in the case report forms
(CRFs).
• The purpose of CRFs is to gather study
data in a standardized format so that
the data can be entered into a
computerized database and analyzed.
All of the information needed to