2. GENERAL PRINCIPLES: ICH E8(R1) Guideline

2.1 Protection of Clinical Study Participants

Important principles of ethical conduct of clinical studies and the protection of participants, including special populations, have their origins in the Declaration of Helsinki and should be observed in the conduct of all human clinical investigations. These principles are stated in other ICH guidelines, in particular, ICH E6-Good Clinical Practice.

As further described in the E6 guideline, the investigator and sponsor have responsibilities for the protection of study participants together with the Institutional Review Board/Independent Ethics Committee.

The confidentiality of information that could identify participants should be protected in accordance with the applicable regulatory and legal requirement(s).

Before initiating a clinical study, sufficient information should be available to ensure that the drug is acceptably safe for the planned study in humans. Emerging non-clinical, clinical, and pharmaceutical quality data should be reviewed and evaluated, as they become available, by qualified experts to assess the potential implications for the safety of study participants. Ongoing and future studies should be appropriately adjusted as needed, to take new knowledge into consideration and to protect study participants. Throughout drug development, care should be taken to ensure all study procedures and assessments are necessary from a scientific viewpoint and do not place undue burden on study participants.

2.2 Scientific Approach in Clinical Study Design, Planning, Conduct, Analysis, and
Reporting

The essence of clinical research is to ask important questions and answer them with appropriate studies. The primary objectives of any study should reflect the research questions and be clear and explicitly stated. Clinical studies should be designed, planned, conducted, analysed, and reported according to sound scientific principles to achieve their objectives.

Quality of a clinical study is considered in this document as fitness for purpose. The purpose of a clinical study is to generate reliable information to answer the research questions and support decision making while protecting study participants. The quality of the information generated should therefore be sufficient to support good decision making.
Quality by design in clinical research sets out to ensure that the quality of a study is driven proactively by designing quality into the study protocol and processes. This involves the use of a prospective, multidisciplinary approach to promote the quality of protocol and process design in a manner proportionate to the risks involved, and clear communication of how this will be achieved.

Across the product lifecycle, different types of studies will be conducted with different objectives and designs and may involve different data sources. For purposes of this guideline, development planning is considered to cover the entire product lifecycle (Section 4). The Annex provides a broad categorisation of study type by objective within the different stages of drug development. Studies should be rigorously designed to address the study objectives with careful attention to the design elements, such as the choice of study population and response variables and the use of methods to minimize biases in the findings (Section 5).

The cardinal logic behind serially conducted studies is that the results of prior studies should inform the plan of later studies. Emerging data will frequently prompt a modification of the development strategy. For example, results of a confirmatory study may suggest a need for additional human pharmacology studies.
The availability of multi-regional data as a result of the increased globalisation of drug development programmes, facilitated by the harmonisation of ICH Guidelines, minimises the need to conduct individual studies in different regions. The results of a study are often used in regulatory submissions in multiple regions, and the design should also consider the relevance of the study results for regions other than the one(s) in which the study is conducted. Further guidance is provided by ICH E5 Ethnic Factors, ICH E6, and ICH E17 Multi-Regional Clinical Trials.

Early engagement with regulatory authorities to understand local/regional requirements and expectations is encouraged and will facilitate the ability to design quality into the study.

2.3 Patient Input into Drug Development

Consulting with patients and/or patient organisations during drug development can help to ensure that patients’ perspectives are captured. The views of patients (or of their caregivers/parents) can be valuable throughout all phases of drug development. Involving patients early in the design of a study is likely to increase trust in the study, facilitate recruitment, and promote adherence. Patients also provide their perspective of living with a condition, which may contribute to the determination, for example, of endpoints that are meaningful to patients, selection of the appropriate population and duration of the study, and use of acceptable comparators. This ultimately supports the development of drugs that are better tailored to patients’ needs.

Source: ICH Expert Working Group