The Food and Drug Administration (FDA) established the Bioresearch Monitoring (BIMO) program of inspections and audits to monitor the conduct and reporting of clinical trials to ensure that data from these clinical trials meet the highest standards of quality and integrity and conform to FDA’s regulations.
Computerized systems used in clinical trials refer to the creation, modification, maintenance, archiving, retrieving or transmitting clinical data intended for submission to the Food and Drug Administration (FDA).
Audit Trail: a secure, computer-generated, time-stamped electronic record that allows reconstructions of the data course of events relating to the creation, modification, and deletion of an electronic record.
Certified Copy: it is a copy of the original information that has been verified, as an exact copy having all of the same attributes and information as the original. It must have a dated signature.
Computerized System: it is the computer hardware, software, and associated documents (i.e manuals) that create, modify, maintain, archive, retrieve, or transmit in digital form information related to the conduct of a clinical trial.
Electronic Case Report Form (e-CRF): designed to record information required by the clinical trial protocol to be reported to the sponsor on each trial subject.
Electronic Patient Diary: an electronic record into which a subject participating in a clinical trial directly entrees observations or directly responds to an evaluation checklist or questionnaire
Electronic Record: a combination of text, graphics, data, audio, pictorial, or any other information representation in digital form that is created, modified, maintained, archived, retrieved or distributed by a computer system.
Electronic Signature: a computer data compilation of any symbol or series of symbols, executed, adopted, or authorized by an individual to be legally binding equivalent of the individual’s handwritten signature.
Software Validation: verification and validation is the process of checking that a software system meets specifications and that it fulfills its intended purpose. For these guidelines, the design level validation is that portion of the software validation that takes place in parts of the software life cycle before the software is delivered to the end-user.
Source Documents: original documents and records including, but not limited to, 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.
Security measures should be in place to prevent unauthorized access to the data and to the computerized system.
1-Identify at which steps a computerized system will be used to create, modify, maintain, archive, retrieve, or transmit data.
2-Documentation should identify what software and, if known, what hardware is to be used in computerized systems that create, modify, maintain, archive, retrieve, or transmit data. This document should be retained as part of the study records.
3-Source documents should be retained to enable reconstruction and evaluation of the trial.
4-When original observations are entered directly into a computerized system, the electronic record is the source document.
5-The design of a computerized system should ensure that all applicable regulatory requirements for recordkeeping and record retention in clinical trials are met with the same degree of confidence as is provided with paper systems.
6-Clinical investigators should retain either the original or a certified copy of all source documents sent to a sponsor or contract research organization, including query resolution correspondence.
7-Any change to a record required to be maintained should not obscure the original information. The record should clearly indicate that a change was made and clearly provide a means to locate and read the prior information.
8-Change to the data are stored on electronic media will always require an audit trail, in accordance with 21 CRF 11,.10(e). It should include who made the changes, when, and why they were made.
9-The FDA may inspect all records that are intended to support submissions to the Agency, regardless of how they were created or maintained.
10-Data should be retrievable in such a fashion that all information regarding each individual subject in a study is attributable to that subject.
11-Computerized systems should be designed so that all requirements assigned to these systems in a study protocol are satisfied and to preclude errors in data creation, modification, maintenance, archiving, retrieval or transmission.
As we read in this blog about guidance for the industry around computerized systems revolts around data quality and data integrity. The users or people using the data from these systems should have confidence that the data are no less reliable than data in paper form.
In the next blog, we will cover audits and inspections, data entry into this computerized system, security and electronic signatures as a way of certifying the data.
CFR 11 and ICH