The sponsor should implement a system to manage quality throughout all stages of the trial process.
Sponsors should focus on trial activities essential to ensuring human subject protection and the reliability of trial results. Quality management includes the design of efficient clinical trial protocols and tools and procedures for data collection and processing, as well as the collection of information that is essential to decision making.
The methods used to assure and control the quality of the trial should be proportionate to the risks inherent in the trial and the importance of the information collected. The sponsor should ensure that all aspects of the trial are operationally feasible and should avoid unnecessary complexity, procedures, and data collection. Protocols, case report forms, and other operational documents should be clear, concise, and consistent.
The quality management system should use a risk-based approach as described below.
5.0.1 Critical Process and Data Identification
During protocol development, the sponsor should identify those processes and data that are critical to ensure human subject protection and the reliability of trial results.
5.0.2 Risk Identification
The sponsor should identify risks to critical trial processes and data. Risks should be considered at both the system level (e.g., standard operating procedures, computerized systems, personnel) and clinical trial level (e.g., trial design, data collection, informed consent process).
5.0.3 Risk Evaluation
The sponsor should evaluate the identified risks, against existing risk controls by considering:
(a) The likelihood of errors occurring. (b) The extent to which such errors would be detectable. c) The impact of such errors on human subject protection and reliability of trial results.
5.0.4 Risk Control
The sponsor should decide which risks to reduce and/or which risks to accept. The approach used to reduce risk to an acceptable level should be proportionate to the significance of the risk. Risk reduction activities may be incorporated in protocol design and implementation, monitoring plans, agreements between parties defining roles and responsibilities, systematic safeguards to ensure adherence to standard operating procedures, and training in processes and procedures.
Predefined quality tolerance limits should be established, taking into consideration the medical and statistical characteristics of the variables as well as the statistical design of the trial, to identify systematic issues that can impact subject safety or reliability of trial results. Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.
5.0.5 Risk Communication
The sponsor should document quality management activities. The sponsor should communicate quality management activities to those who are involved in or affected by such activities, to facilitate risk review and continual improvement during clinical trial execution.
5.0.6 Risk Review
The sponsor should periodically review risk control measures to ascertain whether the implemented quality management activities remain effective and relevant, taking into account emerging knowledge and experience.
5.0.7 Risk Reporting
The sponsor should describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report (ICH E3, Section 9.6 Data Quality Assurance).
5.1.1 The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s).
5.1.2 The sponsor is responsible for securing agreement from all involved parties to ensure direct access (see 1.21) to all trial related sites, source data/documents , and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities.
5.1.3 Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly.
5.1.4 Agreements, made by the sponsor with the investigator/institution and any other parties involved with the clinical trial, should be in writing, as part of the protocol or in a separate agreement.