Documents used in Clinical Trials

According to Good Clinical Practice (GCP), all information and processes of clinical trials must be recorded and stored so that they can be correctly reported, interpreted and authenticated. Many different types of documents are created, processed and filed in the process of clinical studies.

As per ICH GCP E6 Section 8, essential documents are those which:

(…) individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements.

Other important uses and objectives of essential documents are:

correct management of the trial in question by investigators, sponsors and monitors;
audits;
inspections by regulatory authorities.

There are mainly three stages in which essential documents are generated and handled, namely:

Before the start of the clinical phase of the trial
During the clinical phase of the trial
After the clinical phase of the trial

All documentation needs to be described and it must be defined whether they are stored in the files of either the study site (investigator or institution), the sponsor, or both. See the European Commission’s Detailed Guidance on the Content of a Trial Master File and Archiving for more information on Trial Master Files. In some cases, documents may be combined if all essential parts are still clear and can be easily identified.

Very few clinical trials are conducted only in one country; many are available in a variety of different sites in different places, so the translation and linguistic adaptation for different target cultures and languages becomes more important. However, requirements as to which types of documents need to be translated differ from country to country. Whereas in some states all documents need to be available in the local language, others assume that specialist-facing text will be understood in English, and only texts that are not directly addressing the study staff involved in the trial need to be translated, such as:

Packaging and labeling
Patient diaries
Patient information sheets
Informed consent forms
Patient questionnaires
Patient-reported outcomes

General essential documents in the three different stages are as follows:

Before the start of the clinical phase of the trial

Authorization/approval/notifications by regulatory authorities (if applicable)

Certificate of Analysis of Investigational Products shipped

Composition of Institutional Review Board (IRB) and Independent Ethics Committee (IEC)

Curriculum Vitae and other relevant information/documents regarding the qualification of the investigators involved in the trial

Decoding procedures for blinded trials

Documentation from IRB (only applicable in the US) and/or IEC providing approval/favorable opinion on:

Protocol and its amendments (if applicable)
Case Report Form (CRF) (if applicable)
ICF(s)
Other written information for subjects
Advertisement for subject recruitment (if applicable)
Subject compensation (if applicable)
Any other documents that require approval/a favorable opinion

Financial aspects of the trial

Information given to trial subjects, such as:

Informed Consent Form (ICF). All applicable translations also have to be filed
Other written information
Marketing material for subject recruitment (if applicable)

Insurance statement

Instructions for handling of investigational product and trial-related materials

Investigator’s brochure

Master randomization list

Medical/laboratory/technical procedures and/or tests:

Certification, or
Accreditation, or
Established quality control and/or external quality assessment, or
Other validation (if applicable)

Normal values for medical/laboratory/technical procedures and/or tests included in the protocol

Pre-trial monitoring report

Sample of labels for investigational product containers

Shipping records for investigational products and trial-related materials

Signed agreement between involved parties, such as:

Investigator/institution and sponsor
Investigator/institution and Contract Research Organization (CRO)
Sponsor and CRO
Investigator/institution and authorities.

Signed protocol and amendments (if applicable); sample CRF

Trial initiation monitoring report

During the clinical phase of the trial

Any revisions to:

Protocol/amendments and CRF
Informed consent form
Other written information provided to subjects
Advertisement for subject recruitment

Certificate of analysis for new batches of investigational products

Curriculum Vitae for new investigators

Dated and documented approval/favorable opinion of IRB/IEC of the following:

Protocol amendments
Revisions of:
Informed consent form
Other written information to be provided to the subject
Advertisement for subject recruitment
Any other documents given approval/favorable opinion
Continuing review of trial (if applicable)

Documentation of CRF corrections

Documentation of investigational products and trial-related materials shipment

Interim or annual reports to IRB/IEC and authority or authorities

Investigational products accountability at the site

Investigator’s brochure updates

Monitoring visit reports

Notification by originating investigator to sponsor of serious adverse events and related reports

Notification by sponsor and/or investigator (where applicable) to the regulatory authority or authorities and IRB/IEC of unexpected serious adverse drug reactions as well as other safety information

Notification by sponsor to investigators of safety information

Record of retained body fluids/tissue samples (if applicable)

Regulatory authorities authorizations/approvals/notifications where required for protocol amendments and other documents

Relevant communications other than site visits