Good Clinical Practice: A Question & Answer Reference Guide - May 2012 - (Page 523)

Section 17: Subject Diaries 17.1 Q. How does the FDA’s December 2009 industry guidance entitled, “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims” impact the acceptance of the use of subject diaries in the collection of patient-reported outcomes (PRO) during clinical trials? A. Although the FDA mentions subject diaries sparingly in the 2009 guidance (e.g., with respect to electronic PRO instruments) and does not advocate the use of any specific PRO tools, the document certainly establishes the agency’s willingness to consider the utility of PROs “to measure the effect of a medical intervention on one or more concepts (i.e., the thing being measured, such as a symptom or group of symptoms, effects on a particular function or group of functions, or a group of symptoms or functions shown to measure the severity of a health condition).” While acknowledging the increasing use of PRO instruments in assessing drug effects, the FDA in the past has said that, “as with other labeling claims, the determination of whether the PRO instrument supports an effectiveness endpoint includes an assessment of the ability of the PRO instrument to measure the claimed treatment benefit and is specific to the intended population and to the characteristics of the condition or disease treated. Endpoints measured by PRO instruments are most often used in support of claims that refer to a patient’s symptoms or ability to function.” In the December 2009 guidance, the agency adds that, “generally, findings measured by a well-defined and reliable PRO instrument in appropriately designed investigations can be used to support a claim in medical product labeling if the claim is consistent with the instrument’s documented measurement capability. The amount and kind of evidence that should be provided to the FDA is the same as for any other labeling claim based on other data. Use of a PRO instrument is advised when measuring a concept best known by the patient or best measured from the patient perspective. A PRO instrument, like physician-based instruments, should be shown to measure the concept it is intended to measure, and the FDA will review the evidence that a particular PRO instrument measures the concept claimed. The concepts measured by PRO instruments that are most often used in support of labeling claims refer to a patient’s symptoms, signs, or an aspect of functioning directly related to disease status. PRO measures often represent the effect of disease (e.g., heart failure or asthma) on health and functioning from the patient perspective.” 17.2 Q. What implications does the FDA’s December 2009 PRO guidance have regarding a principal investigator’s retention of source documentation at his or her site when electronic patient diaries are used? A. This has been a controversial issue, particularly with FDA compliance officials. While long-standing FDA regulations require that source documents for clinical study data be maintained by the clinical investigator at the investigational site and that the sites allow the FDA to inspect, review, and copy records at any time (including while the study is in progress), many early e-diary implementations involved either an immediate original recording in the sponsor’s database (if entry by the study subject is web-based or into an interactive voice response system) or short-term capture on some type of device (such as a PDA), with upload to the sponsor’s database. Alternatively, the software vendor may have hosted the database. In its December 2009 guidance entitled, “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims,” however, the FDA makes clear that ePRO systems “may pose a problem” if a sponsor or CRO, rather than a clinical investigator, has “direct control” over the source data. “The investigator’s responsibility to control, access, and maintain source documentation can be satisfied easily when paper PRO instruments are used, because the subject usually returns the diary to the investigator who either retains the original or a certified copy as part of the case history,” the agency’s guidance states. “The use of electronic PRO instruments, however, may pose a problem if direct control over source data is maintained by the sponsor or the contract research organization and not by the clinical investigator. We consider the investigator to have met his or her responsibility when the investigator retains the ability to control and provide access to the records that serve as the electronic source documentation for the purpose of an FDA inspection. The clinical trial 523

Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2012

Good Clinical Practice: A Question & Answer Reference Guide - May 2012
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, Ukraine, 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 2012