E 8 General Considerations for Clinical Trials

1 Official address Domenico Scarlattilaan 6 1083 HS Amsterdam The Netherlands An agency of the European Union Address for visits and deliveries Refer to Send us a question Go to +31 (0)88 781 6000 European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. 14 October 2021 EMA/CHMP/ICH/544570/1998 Committee for Human Medicinal Products ICH guideline E8 (R1) on General Considerations for Clinical studies Step 5 Transmission to CHMP 25 April 2019 Adoption by CHMP 25 April 2019 Release for public consultation 10 May 2019 Deadline for comments 30 September 2019 Final adoption by CHMP 14 October 2021 Date for coming into effect 14 April 2022 ICH guideline E8 (R1) on General Considerations for Clinical studies EMA/CHMP/ICH/544570/1998 Page 2/25 E8(R1)

2 Document History E8 Code History Date E8 Approval by the Steering Committee under Step 4 and recommendation for adoption by ICH regulatory bodies. 17 July 1997 Revision of E8 Code History Date E8(R1) Adoption by the Regulatory Members of the ICH Assembly under Step 4. 6 October 2021 ICH guideline E8 (R1) on General Considerations for Clinical studies EMA/CHMP/ICH/544570/1998 Page 3/25 ICH guideline E8 (R1) on General Considerations for Clinical studies Table of contents 1. Objectives of this document.

3 5 2. General principles .. 5 Protection of Clinical study participants .. 5 Scientific approach in Clinical study design, planning, conduct, analysis, and reporting .. 6 Patient input into drug development .. 7 3. Designing quality into Clinical studies .. 7 Quality by design of Clinical 7 Critical to quality factors .. 8 Approach to identifying the critical to quality factors .. 8 Establishing a culture that supports open dialogue .. 9 Focusing on activities essential to the study.

4 9 Engaging stakeholders in study design .. 9 Reviewing critical to quality factors .. 9 Critical to quality factors in operational 10 4. Drug development planning .. 10 Quality of investigational medicinal product .. 10 Non- Clinical studies .. 11 Clinical studies .. 11 human pharmacology .. 12 Exploratory and confirmatory safety and efficacy studies .. 12 Special populations .. 13 Post-approval studies .. 14 Additional development .. 14 5. Design elements and data sources for Clinical studies.

5 14 Study population .. 15 Treatment description .. 16 Choice of control group .. 16 Response variables .. 17 Methods to reduce bias .. 17 Statistical analysis .. 18 Study data .. 19 6. Conduct, safety monitoring, and reporting .. 20 Study conduct .. 20 Protocol adherence .. 20 Training .. 20 Data management .. 20 Access to interim data .. 20 Participant safety during study conduct .. 20 Safety monitoring .. 21 ICH guideline E8 (R1) on General Considerations for Clinical studies EMA/CHMP/ICH/544570/1998 Page 4/25 Withdrawal criteria.

6 21 Data monitoring committee .. 21 Study reporting .. 21 7. Considerations in identifying critical to quality factors .. 22 Annex: types of Clinical studies .. 24 ICH guideline E8 (R1) on General Considerations for Clinical studies EMA/CHMP/ICH/544570/1998 Page 5/25 1. Objectives of this document Clinical studies of medicinal products are conducted to provide information that can ultimately improve access to safe and effective products with meaningful impact on patients, while protecting those participating in the studies.

7 This document provides guidance on the Clinical development lifecycle, including designing quality into Clinical studies, considering the broad range of Clinical study designs and data sources used. The ICH document " General Considerations for Clinical Studies" is intended to: 1. Describe internationally accepted principles and practices in the design and conduct of Clinical studies that will ensure the protection of study participants and facilitate acceptance of data and results by regulatory authorities 2.

8 Provide guidance on the consideration of quality in the design and conduct of Clinical studies across the product lifecycle, including the identification, during study planning, of factors that are critical to the quality of the study, and the management of risks to those factors during study conduct 3. Provide an overview of the types of Clinical studies performed during the product lifecycle, and describe study design elements that support the identification of quality factors critical to ensuring the protection of study participants, the integrity of the data, the reliability of results, and the ability of the studies to meet their objectives 4.

9 Provide a guide to the ICH efficacy documents to facilitate user's access General principles are described in Section 2 of this document, followed by a discussion of designing quality into Clinical studies in Section 3. A broad overview of drug development planning and the information provided by different types of studies needed to progress development through the lifecycle of the product is given in Section 4. In Section 5, important elements of Clinical study design are described that reflect the variety of designs used in drug development as well as the range of data sources available.

10 Section 6 addresses study conduct, ensuring the safety of study participants, and study reporting. Some Considerations for identifying factors that are critical to the quality of a study are provided in Section 7. The ICH Efficacy guidelines are an integrated set of guidance covering the planning, design, conduct, safety, analysis, and reporting of Clinical studies. ICH E8 provides an overall introduction to Clinical development, designing quality into Clinical studies and focusing on those factors critical to the quality of the studies.