In any work or process documents that are needed before initiation, Between or generally the end of the process just like in a clinical trial those “Documents which permit evaluation of the conduct of a trial and the quality of the data produced. It is given in the 8th section of the ICH-GCP.

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Essential Documents For The Conduct
of A Clinical Trial (ICH-GCP)
Rajeev Sahai
B.Sc, M.Pharm (Pharmacology)

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INTRODUCTION
 Essential documents are those documents which individually and collectively permit
evaluation of the conduct of a study and the quality of the data produced.
 In any work or process documents that are needed before initiation, Between or generally end
of the process just like in a clinical trial those “Documents which permit evaluation of the
conduct of a trial and the quality of the data produced. It is given in 8th section of the ICH-
GCP.
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IMPORTANCE OF THE ESSENTIAL DOCUMENTS FOR THE
CONDUCT OF A CLINICAL TRIAL
 Essential documents are important for:
 Evaluation of the conduct of a trial and the quality of data produced
 Successful management of the trial by the investigator, sponsor and monitor
 Validation by regulatory authority(ies) and sponsor’s audits
 Depending on the stage of the trial, essential documents
are grouped in three sections according to the stage of the
trial:
 Before the start of clinical trial – It contains 20 documents.
 During the conduct of the trial- It contains 25 documents that are necessary during
the trial/study.
 After the completion or termination of the trial – It contains 8 documents.

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TRIAL MASTER FILE (TMF)
 Guideline E6 (2) states that trial master file should be established at the
beginning of the trial, both at the investigator/institution site and at the
sponsor office.
 A final close – out of a trial only be done when the monitor has
reviewed both the investigator/institution and sponsor files and confirm
that all necessary documents are in the appropriate files.
 The file maintained at the site is often called, “THE SITE MASTER
FILE”
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
Before the Trial:
The following documents should be generated and compiled in
file before the trial.
INVESTIGATOR’S BROCHURE:- To document that relevant and current scientific
information about the investigational product has been provided to the investigator.
SIGNED PROTOCOL OR RESEARCH PROPOSAL:
The protocol demonstrates the guidelines for conducting the trial. It illustrates what will be
made in the study by explaining each essential part of it and how it is carried out. It also
describes the eligibility of the participants, the length of the study, the medications and the
related tests.
PATIENT INFORMATION SHEET (BLANK): The written information of the research to
the patient.
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Cont…
PATIENT CONSENT FORM (BLANK):
A process by which a subject voluntarily confirms his or her willingness to participate in a
particular trial, after having been informed of all aspects of the trial that are relevant to the
subject's decision to participate. Informed consent is documented by means of a written,
signed and dated informed consent form.
ETHICS APPROVAL DOCUMENTATIONS: Ethics approval is needed for any
research that involves human participants, their tissue and /or data to ensure the dignity,
right , safety and well-being of all participants are the primary consideration of the
research project. some of documents that needs to be approval from ethics committee
before initiating trial are follows- current Protocol, ICD, Translated ICD of vulnerable
language, translation certificate, back translation certificate, Insurance, CRF,
advertisement (if any).
CVs OF ALL TEAM INVOLVED: Each individual involved in conducting a trial
should be qualified by education, training, and experience to perform his or her respective
task(s) (as per GCP principle).
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Cont…
SIGNATURE AND DELEGATION LOG:
Information entered in all sections of the log should be legible and correct. The Principal
Investigator and site staff who have been delegated duties/tasks should use the same
signature and initials, as provided on the site signature and delegation of responsibility log,
when signing and initialing patient records and any study related documents.
CLINICAL TRIAL AGREEMENT:
A clinical trials agreement should describe and acknowledge responsibilities, terms of
collaboration, requirements for payment and reimbursement, publication and intellectual
property term and insurance, subject injury coverage, guidelines for dispute resolution,
grounds for termination of contract, and possibility of amending contract terms in the future.
NORMAL VALUES FOR MEDICAL/LABORATORY PROCEDURES AND TESTS
According to the Food and Drug Administration (FDA), normal lab test values are a set of
upper and lower limits generally given as a range since normal values vary from person to
person.
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Cont…
INSTRUCTIONS AND DOCUMENTATION FOR HANDLING / TRANSPORTING
OF ANY TRIAL MEDICATION AND RELATED MATERIALS:
The investigational product(s) should be packaged to prevent contamination and
unacceptable deterioration during transport and storage.
STANDARD OPERATING PROCEDURES (SOPs):
A standard operating procedure (SOP) is a set of step-by-step instructions compiled by an
organization to help workers carry out complex routine operations. SOPs aim to achieve
efficiency, quality output and uniformity of performance, while reducing miscommunication
and failure to comply with industry regulations.
MASTER RANDOMIZATION LIST:
Documents that describes the method for randomization of trial population.
The randomization schedule of a clinical trial documents the random allocation of treatments
(IPs) to subjects. Different trial designs will require different procedures for
generating randomization schedules.
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Cont…
CASE RECORD / REPORT FORM (CRF)
 CRF is a paper or electronic document designed to record all the information for an
individual study subject required by the study protocol.
All CRF’s should include the following data:
 Study title and number;
 Investigator’s name
 study subject/patient ID (Number and Initials)
 Inclusion / exclusion criteria;
 Demographic data;
 Detailed description of dosage regimens of investigation drug;
 Concomitant treatment;
 Adverse events (side effects and intercurrent disease)
 Conclusion on subject’s health
 Investigator’s signature and date
 Lab reports details (If applicable)
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
During the Trial:
In addition to having on file the above documents, the following should be added to the
files during the trial as evidence that all new relevant information is documented as it
becomes available
ANY PROTOCOL AMENDMENTS:
If any amendments in the protocol it should be notify to the Ethics committee and get approval.
ANY UPDATES IN “IB”:
To document that investigator is informed in a timely manner of relevant information as it
becomes available
DATED, DOCUMENTED APPROVAL/FAVORABLE OPONION OF IRB/IEC OF
THE FOLLOWING:
To documents that the amendment(s) and/or revision(s) have been subject to IRB/IEC
reviewed and were given approval/favorable opinion. To identify the version number and date
of the documents.
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
 Protocol amendment
 Revision of:
 Informed consent form
 Any other written information to be provided to the subject
 Advertisement for subject recruitment (If used)
 Any other documents given approval / favorable opinion
 Continuing review of trial (When required)
NOTIFICATION OF SERIOUS ADVERSE EVENTS / ADVERSE EVENTS:
Notification by sponsor and/or investigator, where applicable, to regulatory authorities and
IRB(s)/IEC(s) of serious adverse events/ adverse events.
SUBJECT IDENTIFICATION AND ENROLMENT LOG: Confidential for researcher
only (each patient’s address, date of birth, hospital number)
To document that investigator/institution keeps a confidential list of names of all subjects
allocated to trial numbers on enrolling in the trial. Allows investigator/institution to reveal
identity of any subject. Subject identification log complied only site master file.
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Cont…
INSTRUCTIONS FOR HANDLING OF INVESTIGATIONAL PRODUCT(S) AND
TRIAL-RELATED MATERIALS (if not included in protocol or Investigator’s
Brochure)
To document instructions needed to ensure proper storage, packaging, dispensing and
disposition of investigational products and trial-related materials
SIGNATURE SHEET:
To document signatures and initials of all persons authorized to make entries and/or
corrections on CRFs
INTERIM OR ANNUAL REPORTS TO IRB/IEC AND AUTHORITY(IES):
Interim or annual reports provided to IRB/IEC in accordance with 4.10 and to authority(ies)
in accordance with 5.17.3
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
After completion of the Trial:
After completion or termination of the trial, all of the documents
identified in Sections 8.2 and 8.3 should be in the TMF together
with the following.
INVESTIGATIONAL PRODUCT(S) ACCOUNTABILITY AT SITE:
To document that the investigational product(s) have been used according to the protocol. To
documents the final accounting of investigational product(s) received at the site, dispensed to
subjects, returned by the subjects, and returned to sponsor.
DOCUMENTATION OF INVESTIGATIONAL PRODUCT DESTRUCTION:
To document destruction of unused investigational products by sponsor or at site as per
regulatory guidelines.
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
COMPLETED SUBJECT IDENTIFICATION CODE LIST:
To permit identification of all subjects enrolled in the trial in case follow-up is required. List
should be kept in a confidential manner and for agreed upon time.
AUDIT CERTIFICATE (if available):
To document that audit was performed at the site. It is located only site file.
FINAL TRIAL CLOSE-OUT MONITORING REPORT:
To document that all activities required for trial close-out are completed, and copies of
essential documents are held in the appropriate files.
TREATMENT ALLOCATION AND DECODING DOCUMENTATION:
In case of an emergency, identity of blinded investigational product can be revealed without
breaking the blind for the remaining subjects’ treatment.
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ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS
FINAL REPORT BY INVESTIGATOR TO IRB/IEC WHERE REQUIRED, AND
WHERE APPLICABLE, TO THE REGULATORY AUTHORITY(IES):
CLINICAL STUDY REPORT:
The clinical and statistical description, presentations, and analyses are fully integrated into a
single report.
AND FINALLY:
 If it is not written down, it did not happen !!
 If it is not documented, it does not exist !!
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Thank You