Date: dd/mm/yyyy / Manage Study Documents / WI-G-3-12-01
Property of CRC
May not be used, divulged, published or otherwise disclosed without the consent of
The Director, Clinical Research Centre
WORK INSTRUCTION FOR MANAGEMENT OF STUDY DOCUMENTS
Introduction:
This work instruction provides details on management of study documents for industry sponsored research (ISR) and investigator initiated research (IIR). It covers:
(i) Creation of files.
(ii) Entering documents or information in study files.
(iii) Maintenance of files.
1. Study Master File
1.1 A Study Master File (SMF) is created when a study is planned or conceptualized.
1.2 The format and numbering / labelling of the SMF follow the prevailing filing system in the Institution.
1.3 If deemed necessary, the SMF may be divided into folders to separate communications from essential documents, as well as to separate the essential documents. The numbering / labelling of the folders should be linked to the SMF.
1.4 Essential documents that are placed in the SMF include documents created before clinical phase of study, during the clinical phase and after completion or termination of study1.
1.5 Some essential documents before clinical phase of study are:
1.5.1 Investigator’s Brochure.
1.5.2 Signed protocol and amendments, if any, and sample case report form.
1.5.3 Patient information sheet and informed consent form.
1.5.4 Advertisement for subject recruitment (if applicable).
1.5.5 Insurance policy (if applicable).
1.5.6 Clinical Trial Agreement or any agreement between investigator and funding agency or other parties relevant to the study.
1.5.7 Dated, documented favourable opinion of Ethics Committee for study documents as well as composition of the Ethics Committee.
1.5.8 Dated, documented favourable opinion of regulatory authorities.
1.5.9 Curriculum vitae and/or other relevant documents evidencing qualifications of investigator(s) and/or supporting trial staff to which investigator tasks are delegated.
1.5.10 Normal value(s)/range(s) for medical/laboratory/technical procedure(s) and/or test(s) included in the protocol.
1.5.11 Documents to support competence of study site to perform required medical/laboratory/technical procedures/tests, and support reliability of results.
1.5.12 Instructions for handling of investigational medicinal product(s) and trial related materials.
1.5.13 Distribution records for investigational medicinal product(s) and trial related materials.
1.5.14 Certificate(s) of analysis of investigational product(s).
1.5.15 Decoding procedures for blinded trials.
1.5.16 Trial Initiation Monitoring Report.
1.6 Some essential documents during clinical phase of study are:
1.6.1 Investigator’s brochure updates.
1.6.2 Any revision to study documents including protocol/amendment(s), case report form, patient information sheet, informed consent form, etc.
1.6.3 Dated, documented favourable opinion of the Ethics Committee of the revisions in item 1.6.2 above.
1.6.4 Regulatory authority(ies) authorisations/approvals / notifications where required for revision of study documents.
1.6.5 Delegation log of investigator tasks and curriculum vitae for new investigator(s) and/or supporting trial staff to which investigator tasks are delegated.
1.6.6 Updates to normal value(s)/range(s) for medical/ laboratory/ technical procedure(s)/test(s) included in the protocol.
1.6.7 Updates of certification or accreditation or established quality control and/or external quality assessment or other validation of medical/laboratory/technical procedures/tests.
1.6.8 Documentation of distribution of investigational medicinal product(s) and trial related materials.
1.6.9 Relevant communications other than site visits to document any agreements or significant discussions regarding trial administration, protocol violations, trial conduct, adverse event (AE) reporting, letters, meeting notes, notes of telephone calls.
1.6.10 Signed informed consent forms.
1.6.11 Source documents. Where source documents are filed separately by other agencies, such as medical records of subjects, then a reference should be made in the SMF as to the location of those source documents.
1.6.12 Signed, dated and completed case report forms.
1.6.13 Documentation of case report form corrections.
1.6.14 Notification by originating investigator to sponsor of serious adverse events and related reports.
1.6.15 Notification by sponsor and/or investigator, where applicable, to regulatory authority(ies) and Ethics Committees of suspected unexpected serious adverse reactions and of other safety information.
1.6.16 Notification by sponsor to investigators of safety information.
1.6.17 Interim or annual reports to Ethics Committees and authority(ies).
1.6.18 Subject screening log.
1.6.19 Subject identification code list.
1.6.20 Subject enrolment log.
1.6.21 Investigational medicinal product accountability at the site.
1.6.22 Signature sheet.
1.6.23 Record of retained body fluids/ tissue samples (if any).
1.7 Some essential documents after completion or termination of study are:
1.7.1 Investigational medicinal product(s) accountability at site.
1.7.2 Documentation of investigational product destruction.
1.7.3 Completed subject identification code list.
1.7.4 Audit certificate (if available).
1.7.5 Final report by investigator to Ethics Committees where required, and where applicable, to the regulatory authority(ies).
1.7.6 Clinical study report.
2. Media to be Used1
2.1 Essential documents are prepared in appropriate media such that those documents remain complete and legible throughout the required period of retention and can be made available to the competent authorities upon request. Any alteration to records shall be traceable.
2.2 When records are stored on electronic, magnetic, optical, or other non-indelible media, suitable controls should be implemented to ensure that these records cannot be altered without appropriate authorisation and the creation of an audit trail.
2.3 When original records are transferred to other media, the system of transfer should be validated to ensure that information will not be lost or altered. Such transfers should be certified for accuracy and completeness by someone with appropriate authority as part of the quality assurance system.
2.4 For media that require processing in order to render records into a readable format, the availability of appropriate equipment should be ensured so that this processing can be done.
3. Quality of Essential Documents
3.1 Apply ALCOA to assure data quality:
3.1.1 Attribute: record the author of every entry or revision.
3.1.2 Legible: every entry or revision can be read.
3.1.3 Contemporaneous: collect current study data according to planned time frame.
3.1.4 Original: keep original study documents. If carbon copy was kept, ensure it can be traced back to original copy.
3.1.5 Accurate: data are correctly recorded and no conflicting data recorded elsewhere especially for multicentre trial.
4. Storage of Source Documents and Essential Documents
4.1 The sponsor-investigator or qualified investigator should:
4.1.1 Ensure that the records department is aware that medical file is related to a clinical study, that it cannot be destroyed (or deleted if it is an electronic record) and that it should be stored according to protocol and/or SOP-R-G-4-02.
4.1.2 Archive source documents and essential documents according to protocol and/or SOP-R-G-4-02.
5. Confidentiality and Access to Study Master File (SMF)
5.1 Access to study documents must be controlled and given only to study team, auditor, Institutional Review Board (IRB) members and other parties authorised by law.
5.2 Any person with direct access to the source data should be compliant with the Declaration of Helsinki, International Conference of Harmonisation (ICH), Malaysian guidelines for Good Clinical Practises (GCP), and applicable regulatory requirements, for the maintenance of confidentiality of the identity of subjects.
5.3 A signature sheet identifying those who have access and those who can enter or correct source data should be kept in the investigator’s file as an essential study document.
6. References
6.1 Recommendation On The Content Of The Trial Master File And Archiving (European Commission, 2006)
(http://ec.europa.eu/health/files/eudralex/vol-10/v10_chap5_en.pdf)