Good Clinical Practice: A Question & Answer Reference Guide - May 2011 - (Page 223)

Section 6: Source Data/Documentation 6.1 Q. What constitutes valid source documentation in a clinical trial? A. Source documents in a clinical trial are the records on which clinical observations are first recorded. They are legally valid raw data that support a study’s findings. At an investigational site, source documentation is often the medical record, but it can also be a computer printout of lab values, a patient diary, or a physician’s notes on a 3x5 card—or even a napkin. A cardinal rule in good clinical practice (GCP) compliance is that case report forms and the source documents/ medical record must match, data point to data point. A patient’s medical record should support the data on the case report form, which should, in turn, support the data listings and statistical results provided to regulatory agencies. “FDA’s acceptance of data from clinical trials for decision-making purposes depends on FDA’s ability to verify the quality and integrity of the data during FDA on-site inspections and audits,” the agency states in its May 2007 industry guidance entitled, “Computerized Systems Used in Clinical Investigations.” Source documentation is the beginning of a clean, verifiable audit trail. FDA officials point out that the ICH’s GCP guideline was the first to define the terms “source data” and “source documents” for clinical trials. Subsequent FDA guidances have adopted the ICH GCP definitions: Source data: “All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies)” (1.51). Source data would include medical history information, medical examination results, all lab results, demographic data (DOB, gender, weight), patient ID number, study number, drug dispensing information, informed consent, IRB approval, visit dates, concomitant medicines, and intercurrent illnesses.” Source documents: “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 and complete, 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)” (1.52). The guideline adds that the purpose of source documents is “to document the existence of the subject and substantiate the integrity of trial data collected [and] to include original documents related to the trial, to medical treatment, and history of [the] subject.” In regulatory terms, source documents, along with case report forms, comprise what FDA regulations refer to as “case histories.” According to 21 CFR 312.62(b), “an investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms, any medical records, for example, progress notes of the physician, the individual’s hospital chart(s), and nurses’ notes.” Source documents, then, can include hospital records and medical charts, clinical and office charts, laboratory reports, patient diaries, pharmacy dispensing records, data recorded from automated instruments, diagnostic reports (x-rays and EKGs), and surgical reports. Photocopies of completed case report forms are not valid source documents. 6.2 Q. How often are documentation and records-related issues cited as deficiencies in FDA GCP inspections? A. Consistently each year, records-related issues (i.e., inadequate/inaccurate records) represent the second-most commonly cited deficiency in CDER’s GCP compliance inspections of clinical trial investigators and sites (i.e., after failure to adhere to the clinical protocol). In FY2010, 32% of the clinical investigators/sites inspected by CDER were cited for records-related issues (compared to 28% in FY2009, 23% in FY2008, 28% in FY2007, 23% in FY2006 and 36% in FY2005). While 29% of U.S.-based sites inspected in FY2010 were cited for recordsrelated problems (compared to 27% in FY2009, 24% in FY2008 and 27% in FY2007), 37% of foreign-based 223

Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2011

Good Clinical Practice: A Question & Answer Reference Guide - May 2011
Table of Contents
Introduction
Section 1: GCP Regulations, Standards and Guidelines for Clinical Research
Section 2: Investigators/Sites
Section 3: Form FDA-1572/Statement of the Investigator
Section 4: Study Sponsors and Clinical Trial Monitoring
Section 5: Informed Consent
Section 6: Source Data/Documentation
Section 7: Clinical Trial Protocols/Protocol Changes/Protocol Violations
Section 8: Institutional Review Boards
Section 9: Drug/Study Safety and Safety Reporting
Section 10: FDA Inspections, Quality Assurance Activities, and Study Auditing
Section 11: Computerized Systems, e-Clinical Trials, and Electronic Records Rules
Section 12: Patient Recruitment
Section 13: Conflicts of Interest/Financial Disclosure
Section 14: The HIPAA Privacy Rule and FDA-Regulated Clinical Trials
Section 15: Drug Accountability, Administration, and Labeling
Section 16: Fraud, Negligence, and Regulatory Non-Compliance
Section 17: Subject Diaries
Section 18: GCP and Clinical Research Standards in the European Union and An Interview with Fergus Sweeney, Ph.D., EMA Head of Sector, Compliance and Inspection
Section 19: Clinical Trial and GCP Standards in Selected Leading Countries/Regions: Latin America, China, Russia, and India
Section 20: GCP Compliance Statistics and Trends
21 CFR Part 11 — Electronic Records; Electronic Signatures
21 CFR Part 50 — Protection of Human Subjects
21 CFR Part 54 — Financial Disclosure by Clinical Investigators
21 CFR Part 56 — Institutional Review Boards
21 CFR Part 312 — Investigational New Drug Application
ICH Consolidated Guideline on Good Clinical Practice (E6)
ICH Guideline on Clinical Safety Data Management (E2A)
European Union Clinical Trials Directive
European Union Good Clinical Practice Directive

Good Clinical Practice: A Question & Answer Reference Guide - May 2011