SOP_24-Clinical Data Management, Paper or Electronic Format-Procedures

Title Clinical Data Management, Paper or Electronic FormatCode SOP-24Pages 8History of Validated VersionsDateVersion Pages Description of Change dd/mm/yyyyHistory of SOP ImplementationVersion Datedd/mm/yyyydd/mm/yyyy Version Datedd/mm/yyyy Version DateApproval of Site SOPSignature Datedd/mm/yyyyTable of Contents1. Policy2. Objectives3. SiteResponsibilities3.1. Research Centre Director3.2. Sponsor-Investigator or Investigator / Qualified Investigator3.3. Person Responsible for the Site SOPs4. Procedures4.1. Generalities4.2. Confidentiality and Direct Access to Clinical Data4.3. Collection and Capture of Clinical Data4.4.Quality Control and Modifications to Clinical Data4.5.Processing of Clinical Data4.6. Storage of Clinical Data5.References6. AppendixAppendix 1 – Site Specific Instructions1. PolicyWithin the framework of the principles inherent in Good Clinical Practice (GCP) of the International Conference on Harmonisation (ICH) and those adhered to by Health Canada, as well as regulations of the FDA, this standard operating procedure (SOP) describes the management of clinical study data in terms of collection and entry into case report forms (CRFs), wether paper or electronic format.This SOP concerns all institutional personnel working in clinical research and should be adhered to by all personnel working on clinical studies involving human subjects.2. ObjectivesOne of the objectives of this operating procedure is to define the different stages of management of clinical data entered onto the CRFs, whether on paper or electronically.This SOP describes the stages of collection, capture and storage of data, as well as quality control and corrections to clinical data collected during the study.The other objective is to ensure that the collection, follow-up, control and confidentiality of all clinical data entered in a CRF, paper or electronic, conform to the principles of the ICHand the laws and regulations in force (to be completed). In order to achieve this goal, it is imperative that the system used for applicable capture and processing of data is validated, and that the databases in which clinical data are stored accurately represent the subject’s data.3. Site Responsibilities3.1 The Research Centre Director or his delegate is responsible for:3.1.1 Approving or updating site SOPs that will be used in the institution according tointernal institutional validation procedures;3.1.2 Informing members of the Ethics Committee that this site SOP will be implementedwithin the institution;3.1.3 Implementing and managing this site SOP within the institution;3.2 The Sponsor-Investigator or Investigator/Qualified Investigator is responsible for:3.2.1 Ensuring that, during the clinical study, the research team, which will be underhis/her supervision will comply with this site SOP.3.3 Under the supervision of the Research Centre Director or his delegate, the personresponsible for site SOPs should:3.3.1 At the time of implementation of each SOP ensure that clinical study personnel at theinstitution are trained in procedures and comply with this SOP.3.3.2 In the event that an SOP is modified, provide training for institutional clinical studypersonnel regarding the change(s) and ensure their compliance with any changes.4. Procedures4.1 GeneralitiesThe sponsor-investigator, who is responsible for the management of clinical data for the study, should:4.1.1In accordance with the ICH, employ appropriately qualified individuals to supervisethe overall conduct of the study, to handle and verify data, to conduct statisticalanalyses, and to prepare the study reports, ICH 5.5.1;4.1.2In the case where management of clinical data is performed directly by a servicewithin the institution, develop instructions according to the recommendations madeby the Society for Clinical Data Management (SCDM) and The Good Clinical DataManagement Practices;4.1.3Manage authorizations for access to clinical data within the clinical research unit,whether physical or electronic access to the clinical study data;4.1.4 Ensure the protection and security of clinical study data;4.1.5Ensure adherence to applicable regulatory requirements regarding confidentiality ofthe identity of subjects and their data by using unambiguous identification codes thatallows identification of all data reported for each subject, ICH 5.5.5;4.1.6 Precisely enter the data from the CRFs as required by the protocol. This data shouldcorrespond at every point with the data and source documents for all subjectsparticipating in the clinical study;4.1.7Ensure that the electronic system used for clinical data management is valid andcomplies with regulatory requirements, ICH 5.5.3a, FDA and MSSS;4.1.8Retain the original or a certified copy of the certified data backup as well as an audittrail, ICH 5.5.3.F and 5.5.4;4.1.9Ensure that clinical study reports are prepared and provided to regulatoryagency(ies) as required by the applicable regulatory requirement(s), ICH 5.22;4.1.10Ensure that a summary of the study results is provided to the ethics committee, ICH4.13;4.1.11Safeguard the blinding, if any (during data capture and processing), ICH5.5.3g.4.2. Confidentiality and Direct Access to Clinical Data4.2.1 A document identifying persons authorized to access, enter or correct clinical data inthe CRFs, should be retained with the essential study documentation, as describedin ICH-GCP, section 8.3 Essential Documents for the Conduct of a Clinical Trialpoint 8.3.24, and the document of the MSSS, Cadre global de gestion des actifsinformationnels - Volet sécurité, a. 4.1.2, par. 3.. Moreover, the MSSS documentstates that a control mechanism should be set up for tracking entry/exit of personsaccessing the site.4.2.2 This document should be updated according to the roles and responsibilitiesdelegated by the sponsor-investigator or the investigator/qualified investigator, asdescribed in SOP 03.4.3. Collection and Clinical Data Capture4.3.1All clinical study information should be recorded, processed, and stored in a waythat allows its accurate reporting, interpretation and verification, ICH 2.10.4.3.2In order to ensure the integrity and tracking of all clinical data, a procedure forcollecting, capturing, controlling, verifying, correcting and processing data should beestablished while respecting the fact that the study is blinded, if applicable, ICH5.5.3g .4.3.3Two methods can be used for the data capture: single or double data entry, this isdependant on type of CRF used and the location where it is carried out (site, CRO, etc). The method of capture is defined by the investigator or the sponsor-investigator in the protocol or other document.4.3.4 A system for tracking data entry and modification should be available for the periodof document retention according to the regulations in force.Paper CRFs:4.3.5Paper CRFs should be filled out according to SOP 25.Any modification made to theclinical data before capture should be justified and authorized by the investigator or his delegate. The process of modification should correspond to the procedure described in SOP 25. The CRF should be signed and dated by the investigator or his delegate, as described in the delegations/signatures document SOP 03 and in section 8.3 item 8.3.24 in ICH-GCP.4.3.6Data entry onto paper CRFs is carried out according to the method of double dataentry by two people. Comparison of the two entries and correction of errors can be made by a third person.4.3.7If clinical data is captured directly by the research team, only those authorized bythe investigator can then enter the CRF data into the database. This delegation of tasks will be documented, as described in SOP 03.4.3.8In the case where capture of clinical data is made by an external organization(CRO), as defined by the protocol, a copy of the CRF should retained by the investigator.Electronic CRFs:4.3.9Installation of an electronic system should be validated within the infrastructure ofthe clinical research unit, in order to ensure its reliability and precision, as well as its expected performance, ICH 5.5.3a. and FDA Guidance for Industry: Computerized System used in Clinical Trials.4.3.10 Only persons authorized by the sponsor-investigator or the investigator/qualifiedinvestigator and those who have an authenticated identification have access to the electronic data management system. Measures of protection, detection and correction should be in place (electronic signature or secure electronic signature).4.3.11In the case of online data entry, both methods of data entry are applicable.4.3.12 The sponsor-investigator or the investigator/qualified investigator should ensure thatthose using the clinical data processing system are trained in the use of the electronic system and follow the instructions described in Appendix 1 of SOP 02.4.3.13If, as stipulated in the protocol, clinical data are transferred to another system, thetransfer should be validated and secure.4.4 Quality Control and Modifications to Clinical Data4.4.1 In order to ensure the integrity of the data, the sponsor-investigator should establishquality control systems so that studies are conducted in accordance with theprotocol, with GCP and with the regulatory requirements.4.4.2 Quality control should be applied to each stage of data handling to ensure that alldata are reliable and have been processed correctly, ICH 5.1.3.4.4.3 In order to decrease errors during the data capture process (single or double),interactive quality controls can be established, whether it is for paper or electronicCRFs.4.4.4 In order to ensure coherence of the data within the same CRF, other quality controlsshould be applied once data capture is completed.4.4.5 Once the contents of a CRF are confirmed, all modifications made to the data byauthorized persons should be justified and documented.4.4.6 These modifications can be requested and documented on paper or electronicallyusing the Data Clarification Form (DCF), prepared by the research team or by theCRO in charge of data capture at the time the clinical study was initiated. Theseforms should be re-examined and signed by the investigator/qualified investigator orhis delegate. The original document should be retained by the sponsor/sponsor-investigator and a copy should be retained by the investigator/qualified investigator,ICH 8.3.15.4.4.7 A tracking system (paper or electronic) of all data modifications should be retainedfor 25 years in the case of clinical studies using an investigational product oraccording to the regulations in force for clinical studies without investigationproducts. This system should be accessible in the event of an audit and inspection.4.5 Clinical Data ProcessingProcessing of clinical data should be described in the protocol or in the statistical analysis plan.If the sponsor/sponsor-investigator uses electronic data processing systems at the site or at a remote site, he should ensure that the data processing is performed in accordance with study methodology such as blinding, if applicable, ICH 5.5.3 g4.5.1 The sponsor may consider establishing an independent data-monitoring committee(IDMC) to assess the progress of a clinical study, including safety data and thecritical efficacy endpoints at certain intervals, and to recommend to the sponsorwhether to continue, modify, or stop a study, ICH 5.5.2.4.5. The IDMC should have written operating procedures and maintain written records ofthe minutes of all their meetings, ICH 5.5.2.4.5.3 The sponsor-investigator can perform interim statistical analyses, while the study isbeing conducted, if so stipulated in the protocol.4.6 Storage of Clinical Data4.6.1 For any clinical study, the investigator/qualified investigator should ensure that theclinical data (paper or electronic) are protected against the effects of time andagainst all accidental destruction.4.6.2 In the case of a clinical study using a drug or medical device, paper or electronicCRFs, like all other source documents, should be retained for the necessary storageperiod required by Canadian regulations, C.05.012 (4), of 25 years.4.6.3 In the case of a clinical study without a drug or medical device, the period ofretention should comply with the schedule of storage of documents submitted by theinstitution to the provincial authorities. (Loi sur les archives. L.R.Q., chap. A-21.1 art.8, 9 and 35) (Recueil de règles de conservation des documents des établissementsde santé et services sociaux, section 4, dossier X1-0350, dossier de l’usager).4.6.4 The same period of document retention applies to the identification of thedocuments for archiving to, the recording of the information and to the assurancethat the archiving department has been informed that a medical file is related to aclinical study and that this file cannot be purged.5.ReferencesHealth Canada, Guidance for Industry, Good Clinical Practice: Consolidated guideline, ICH Topic E6, 1997.Food and Drug Administration (FDA), Electronic Records; Electronic Signatures Final Rule.21 CFR Part 11, Federal Register Vol. 62, No 54, March 20, 1997.Food and Drug Administration (FDA), Guidance for Industry: Computerized systems used in clinical trials, April 1999,Quebec, Archives Act (R.S.Q., A-21.1 a. 8, 9 and 35).Quebec, An act respecting access to documents held by public bodies and the protection of personal information (R.S.Q., A-2.1).Ministère de la santé et des services sociaux (MSSS), Cadre Global de Gestion des Actifs Informationnels appartenant aux organismes du réseau de la santé et des services sociaux : Volet Sécurité, septembre 2002.SCDM, Good Clinical Data Management Practices, Version 3, September 2003.SOP-02 Organizing a Site for Clinical Research.SOP-03Research Team: Role Definitions, Responsibilities and Task DelegationSOP-25 How to Fill In a Case Report Form and Modify DataSOP-26 Security and Confidentiality of DataAPPENDIX 1 INSTRUCTIONS SPECIFIC TO THE SITE (EXAMPLES)1. Filing System2. Location of Filing System3. Annual Approval or Revision4. Specific Responsibilities of the Institution5. Procedures6. References7. Appendices。