2. Definition of the Source Document
A source document is a document in which data collected for a
clinical trial is first recorded. These data are usually later entered
in the Case Report Form.
• The ICH-GCP Guidelines define source documents
as Original documents, Data, and Records (e.g., hospital
records, clinical and office charts, laboratory notes,
memoranda, subjects' diaries or evaluation checklists,
pharmacy dispensing records, recorded data from automated
instruments, copies or transcriptions certified after verification
as being accurate copies, microfiches, photographic
negatives, microfilm or magnetic media, x-rays, subject files,
and records kept at the pharmacy, at the laboratories and at
medico-technical departments involved in the clinical trial).
(ICH E6 Guidance, 1.52)
• The FDA does not define the term "source document."
2
3. There are Source Documents of 2 types:
• Electronic
• Paper
Electronic record means any combination of text, graphics, data,
audio, pictorial, or other information representation in digital form
that is created, modified, maintained, archived, retrieved, or
distributed by a computer system.
• 21 CFR Part 11, Electronic Records; Electronic signatures (1997)
• Guidance for Industry: Part 11, Electronic Records; Electronic Signatures
− Scope and Application (2003)
• Guidance for Industry: Computerized Systems Used in Clinical
Investigations (2007)
• Guidance for Industry: Electronic Source Data in Clinical Investigations
(2013)
3
Types of the Source Documents
4. In regards to Electronic Source Documents:
1) Requirements to the computer system (validation)
2) Requirements to electronic records (audit trail)
3) Requirements to electronic signatures
4) Requirements to users and technical support
4
Types of the Source Documents
5. 5
Types of the Source Documents
Paper Source Documents can be:
• Handwritten data on the pre-printed
forms which have been prepared in
advance
• Handwritten records
In both cases the source documents
are only the records, either
handwritten or printed out, with the
original handwritten Investigator’s
signature.
6. While choosing the appropriate type of source documentation
for a clinical trial, the following aspects should be taken into
consideration:
• Design and organization of the Trial:
Inpatient, outpatient or combined?
Is a clinical site within one clinical department or
several departments (hospitals)?
Who coordinates the trial
(a chair of the Medical University / Academy or a
hospital)?
• Specifics of clinical research documents retention
(archiving) at a Medical Institution.
6
Types of the Source Documents
7. The most common type of Source Documentation (SD) is:
official medical documentation, which is used in Medical Institutions
on regular basis:
Medical History
Outpatient Medical Chart
Various Logs / Hospital Charts
(Functional Diagnostics Log – form № 047/о)
The templates of official medical documentation required in Ukraine
can be found in the following documents:
• Ministry of Healthcare Order # 110 dated 14 Feb 2012
• Ministry of Healthcare Order # 435 dated 29 May 2013
7
Types of the Source Documents
9. General GCP requirements to the Source Documents Verification
(SDV):
• The purpose of trial monitoring is to verify that the reported
trial data are accurate, complete, and verifiable from source
documents. (ICH E6, 5.18.1b)
• If allowed by the investigational plan (protocol), data may be
entered directly onto the case report forms. The case report
form would then be considered a source document. If this
case report form is then transmitted to the sponsor, it is
necessary for the study site to retain a copy to ensure that the
principal investigator can provide access to the source
documents to a monitor, auditor, or regulatory agency.
(ICH E6, 6.4.9).
9
GCP requirements to the Source
Documents Verification
10. 10
Challenge Aspects of Source Documents
Verification
The main challenges during SDV are:
• Informed Consent process
• SAE and AE reporting
• Inappropriate ways of
corrections and loss of audit trail
• Not properly certified copies
of original records
• Inclusion/exclusion criteria listed
but not really confirmed
11. • Before having signed the Informed Consent Form (ICF), the patient can
undergo only routine medical procedures which are applicable in a
certain medical institution for such category of patients.
• The subject must personally sign, date and time the latest version of the
EC approved informed consent form before any trial-related procedures
start.
• The subject must be given sufficient time to read the ICF and be given
the opportunity to ask questions (the Informed Consent process must be
fully described in SD).
• The PI or his/her designee must sign, date and time the informed
consent form on the same day as the subject.
• An original sample of the signed, dated and timed ICF (and addendum if
applicable) must be given to the subject. The second original must be
filed in the ISF.
Informed Consent Form
12. Situation №1
A male, DOB 27Feb1972, was brought to the hospital admission department
by the ambulance at 10:30. The preliminary diagnosis is Acute
Cerebrovascular Event, dextral hemiparesis, coma. Loss of consciousness at
09:50 on the way to the office. The ambulance was called for by the
passersby.
11:00 – the diagnosis is Ischemic Stroke at the left middle cerebral artery
circulation area. Dextral hemiparesis. Coma I.
Recommended: thrombolytic therapy.
The patient is considered for the participation in the clinical trail of tissue-type
plasminogen activator. Thrombolysis should be performed within 3 hours after
symptoms onset.
Can this patient be included into the clinical trial?
12
Informed Consent Form
13. Answers №1
a) If it was possible to contact promptly a legal representative or a relative,
he/she can provide an Informed Consent. As soon as the patient comes
to consciousness, Informed Consent of the patient should be obtained.
b) In case it was impossible to contact a legal representative or a relative,
the patient cannot participate in the clinical trial.
In emergency situations, when prior consent of the subject is not possible,
the consent of the subject's legally acceptable representative, if present,
should be requested. When prior consent of the subject is not possible, and
the subject’s legally acceptable representative is not available, enrolment of
the subject should require measures described in the protocol and/or
elsewhere, with documented approval/favorable opinion by the IRB/IEC, to
protect the rights, safety and well-being of the subject and to ensure
compliance with applicable regulatory requirements. The subject or the
subject's legally acceptable representative should be informed about the trial
as soon as possible and consent to continue and other consent as
appropriate (see 4.8.10) should be requested. (ICH E6, 4.8.15)
13
Informed Consent Form
14. 14
Informed Consent Form
Situation №2
A patient, who has been suggested participating in the clinical trial,
cannot read due to cataract.
Could you please describe the Informed Consent obtaining
procedure in this case?
15. 15
Informed Consent Form
Answers №2
• The patient should provide a medical recording proving his/her diagnosis. The
Informed Consent obtaining procedure is performed involving an impartial witness.
After having read out loud the Informed Consent Form and explaining its essence to
the patient, and after having obtained the oral informed consent of the patient to
participate in the clinical trial, and, if possible, after the patient has signed and dated
the ICF, the impartial witness should sign and date the ICF. In this way the impartial
witness certifies that ICF information was correctly provided and explained to the
patient, and that the patient provided his/her voluntary consent to participate in the
clinical trial.
If a subject is unable to read or if a legally acceptable representative is unable to read,
an impartial witness should be present during the entire informed consent discussion.
After the written informed consent form and any other written information to be provided
to subjects, is read and explained to the subject or the subject’s legally acceptable
representative, and after the subject or the subject’s legally acceptable representative
has orally consented to the subject’s participation in the trial and, if capable of doing so,
has signed and personally dated the informed consent form, the witness should sign and
personally date the consent form. By signing the consent form, the witness attests that
the information in the consent form and any other written information was accurately
explained to, and apparently understood by, the subject or the subject's legally
acceptable representative, and that informed consent was freely given by the subject or
the subject’s legally acceptable representative. (ICH E6, 4.8.9)
16. 16
Informed Consent Form
Situation №3
The patient with the diagnosis of schizophrenia, qualified as disabled, is
considered for the participation in the clinical trial.
How the Informed Consent procedure should be conducted in this
case?
Who should sign the Informed Consent Form?
17. 17
Informed Consent Form
Answers №3
• The Informed Consent Form should be signed and dated by the
subject’s legally acceptable representative, and, if possible, by the
patient himself/herself. The investigator who conducted the Informed
Consent procedure should also sign and date the ICF. The patient
should be informed about the trial to the extent compatible with the
subject’s understanding.
When a clinical trial (therapeutic or non-therapeutic) includes subjects who
can only be enrolled in the trial with the consent of the subject’s legally
acceptable representative (e.g., minors, or patients with severe dementia),
the subject should be informed about the trial to the extent compatible with
the subject’s understanding and, if capable, the subject should sign and
personally date the written informed consent. (ICH E6, 4.8.12)
18. 1. E6 Good Clinical Practice: Consolidated Guideline
4. Investigator
4.8 Informed Consent of Trial Subjects
2. 21 CFR Part 50: Protection of Human Subjects
(Informed Consent)
18
Informed Consent Form
