Source Documents in Clinical Trials_part1

Source Documents

By Valentyna Korniyenko

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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."

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There are Source Documents of 2 types:

• Electronic

• PaperElectronic 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)

Types of the Source Documents

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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


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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.

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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.


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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


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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).

GCP requirements to the Source Documents Verification

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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

• 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

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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?


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Answers №1a) 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)


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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?

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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)

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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?

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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)

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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)


Thank you!

Source Documents in Clinical Trials_part1

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