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Standard Operating Procedure (SOP) on Study Records Collection and Maintenance for Clinical Trials

 Title: Study Records Collection and Maintenance

Introduction and Purpose:

The purpose of this SOP is to define the procedures for collecting and maintaining study records in the conduct of clinical research at the clinical site and relevant covered entities. In accordance with FDA regulations and Good Clinical Practice (GCP) guidelines, it is essential to maintain original records of clinical findings, observations, and activities for the reconstruction and evaluation of clinical research studies.

Subject-specific records, contained within study participant charts, serve as source documentation of research records. These records encompass various documents such as signed informed consent forms, medical histories, medication logs, treatment records, protocol assessment results, and records of adverse events. Additionally, general study records, including versions of the study protocol and informed consent form, Institutional Review Board (IRB) approvals, investigator's brochures, training records, delegation of authority logs, and monitoring reports, are preserved in the regulatory binder. While not all documents apply uniformly to every study, the fundamental principles outlined in this procedure remain consistent across all clinical research types.

Definitions and Acronyms:

  • Clinical Research: Encompasses all research involving human participants. It excludes secondary studies using existing biological specimens or publicly available data without identifiers.
  • Clinical Trial: Refers to clinical research studies involving human participants assigned to an intervention designed to assess its impact on health-related biomedical or behavioral outcomes.
  • Source Data: All information in original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the study.
  • Source Documents: Original documents, data, and records (e.g., hospital records, clinical charts, laboratory reports, subjects’ diaries, pharmacy dispensing records, radiologic scans and imaging records, etc.) on which source data are recorded.
  • CRF: Case Report Form
  • CRO: Contract Research Organization
  • EHR: Electronic Health Record
  • FDA: United States Food and Drug Administration
  • GCP: Good Clinical Practice
  • ICH: International Council on Harmonization
  • IRB: Institutional Review Board
  • PHI: Protected Health Information
  • PI: Principal Investigator
  • SAE: Serious Adverse Event
  • SOP: Standard Operating Procedure

Procedure:

Standards and Responsibilities:

  • The documentation of source data is crucial for reconstructing, evaluating, and validating clinical research findings, observations, and activities.
  • The Principal Investigator (PI) bears ultimate responsibility for collecting and maintaining research records to ensure their accuracy, completeness, and accessibility throughout the study. However, the PI may delegate specific study record tasks to sub-investigators or coordinating staff, as outlined in the delegation of authority log or other delegation processes.

Clinical research data on source documentation should adhere to the following principles:

  • Attributable: The data's origin or source must be identified and recorded, including an audit trail for electronic and automated records, along with signatures/initials and dates for record entries. Additionally, source documents should include study, subject, and visit identifiers as needed.
  • Legible: Data and records should be clearly readable and interpretable.
  • Contemporaneous: Data must be recorded at the time of the event or observation.
  • Original: Data should represent the initial entry or recording.
  • Accurate: Data should reflect the true observation or results, with errors corrected appropriately.
  • Complete: Study records should encompass all information and data related to the study and subject's health (e.g., adverse events) throughout their participation.
  • The study protocol specifies the required screening (including medical history) and baseline assessments, study procedures, interventions, and follow-up assessments. Source documentation should be created and compiled (as originals or copies) in the study participant chart to demonstrate compliance with each eligibility criterion, protocol requirement, and to provide evidence for validating each case report form entry.
  • Source data may be directly entered into the Case Report Form (CRF) when stipulated in the study protocol or other study documents.
  • Electronic Health Record (EHR) systems, used by the clinical site and relevant covered entities, incorporate electronic signatures and audit trail functions. However, these systems are not validated or documented as compliant with 21 CFR Part 11, as the FDA does not intend to assess the compliance of electronic health records with Part 11.

Source Entry and Corrections:

  • Observations recorded as source data must be signed/initialized and dated by the PI or the study team member making the source entry.
  • Electronic records (e.g., EHR) are signed electronically. Printed copies of EHR source documents included in the study participant chart should feature the electronic signature and date stamp on the printed copy.
  • The practice of transcribing source data from the EHR to a "study visit form" or "source worksheet" before CRF entry should be minimized to reduce transcription errors.
  • When creating source data, blue or black ink should be used; pencil should not be used, original entries should not be overwritten, and correction fluid or markers should not be used to obliterate the original entry. Backdating entries is also discouraged.
  • All source documents should include clear identifiers associating the document with the trial (e.g., study title, study number), study participant (e.g., subject number, initials), and study visit (e.g., date, visit number, cycle).
  • In case an error is identified on a source document, it should be corrected correctly. Handwritten source data corrections involve drawing a single line through the incorrect information, adding the correction beside the original entry, and completing the entry with initials, date, and, if necessary, a reason for the change. The original entry must not be obscured.
  • Electronic source documents created and maintained using automated systems, including the EHR, should have an audit trail documenting any corrections made to the source.

Study Participant Charts:

  • Study participant charts should be consistently organized for all subjects.
  • Charts should be structured with documents arranged in reverse chronological order, with the latest documents on top. A uniform template for chart organization should be followed for all study participants enrolled in a specific study. A separate chart may be maintained to compile detailed records for screen failures (subjects who do not enroll).
  • For a comprehensive list of documents to include in study participant charts, refer to UUSOP-06 Supplement A.
  • Study participant charts must be regularly updated after each study visit or on a defined schedule (e.g., monthly) until the subject's study participation concludes.
  • In certain studies, both paper source documents and electronic source data captured directly in the electronic data capture system or stored electronically (e.g., EHR) may coexist. In such cases, providing an outline of where to find each source document helps avoid confusion during inspections. This outline should specify which data is directly entered into the CRF and therefore does not have a corresponding source document.

Regulatory Binder (Trial Master File):

  • Essential documents and general study records should be collected and maintained in the Regulatory Binder or Trial Master File, in either paper or electronic format.
  • Consistent organization templates for regulatory binders should be adhered to.
  • Certain essential documents, such as the Delegation of Authority log and Screening log, may receive updates with new entries throughout the study's conduct. In cases where new documents contain updated information (e.g., protocol amendment, renewed medical license, changes in financial disclosure), both the original and updated documents should be retained in the regulatory binder.
  • If essential documents are maintained electronically or in a central location, a note-to-file should be placed in the regulatory binder to indicate the location of these records.
  • Maintenance and Storage of Study Records:

  • Study participant charts and regulatory binders should be kept current and up-to-date throughout the clinical research.
  • All research records containing Protected Health Information (PHI) must be stored in an area with restricted access during working hours and in a locked room or cabinet when not in use or outside working hours.
  • Records created or maintained in the EHR are considered source documents. Copies of these records from the EHR included in the study participant charts are not regarded as source documents and do not require certification as such.

Monitoring and Auditing of Study Records:

  • All subject and regulatory records, including electronic records, should be available for review by sponsor representatives, the compliance office, IRB auditors, departmental monitors/auditors, regulatory inspectors, and other authorized individuals.
  • When utilizing an electronic data capture system for direct source entry or storing regulatory records electronically, consideration should be given to whether the system or program allows for external review by the listed entities.
  • At the clinical site, sponsor representatives and regulatory inspectors are permitted to review source documents in the EHR only under supervised log-in and in the presence of a study coordinator or authorized study team member. External visitors will not receive individual log-in credentials, and they will not have unrestricted access to the EHR.
  • Direct review of source documents in the EHR will be limited to study participants, and the duration will be reasonable (e.g., 1-2 hours per day).
  • Entire medical records should not be copied or transferred from the clinical site. A limited number of copies from the EHR may be made for external reviewers; however, personal information that could identify study subjects will be redacted from provided copies.

Archiving Study Records:

  • Following the completion of a clinical study, the study records may be examined and subject to review by internal departmental monitors/auditors, sponsors, or FDA inspectors.
  • After maintaining the study records on-site for a defined period, clinical research records may be moved to long-term archiving, such as clinical site Archives and Records Management, or another secure archive system.

Materials Required:

  • Study source documents and general study records.
  • Access to the EHR system.

References:

  • 21 CFR Part 312.62: Investigator Recordkeeping and Record Retention.
  • 21 CFR Part 812.140: Records and Reports.
  • 21 CFR Part 11: Electronic Records, Electronic Signatures.
  • ICH Guidance for Industry E6(R2): Good Clinical Practice.
  • FDA Guidance for Industry – Electronic Source Data in Clinical Investigations.

Document Approval:

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