Public Review is Open for Comment: ICH Draft Revision of Guideline on General Trial Design and Conduct

The draft 2020 ICH(E8)R1 is three times the length of the original and is available for Sponsor comment. The ICH has taken its many years of data and identified principles which, among other things, will facilitate the acceptance of sponsor data worldwide, help ensure subject recruitment by involving subjects in study design and placing an emphasis on quality at every step of a trial.

Patient Input into Study Design

Patient organizations have already weighed in the updated Guideline reflects this critical input. Designing a study which fits the patients’ lifestyle (considering their disease state), will ensure that the drug itself will be better tailored to the population that will actually use the drug, post-approval.  From ICH(E8)(R1) 2.3:

“Involving patients at the early stage of study design is likely to increase trust in the study, facilitate recruitment, and promote adherence, which should continue throughout the duration of the study. Patients also provide their perspective of living with a condition, which contributes to the determination of endpoints that are meaningful to patients, selection of the right population, duration of the study, and use of the right comparators.”

Investigator Input into Study Design

ICH(E8)(R1) offers very early-stage study planning guidance and, not unexpectedly, it has found that reliance on just a few key opinion leaders for study design has to be augmented by opening the study to challenge by other subject matter experts: subjects and the potential investigators. From ICG(E8)(R1) 3.3.3:

“Clinical investigators and potential study subjects have valuable insights into the feasibility of enrolling subjects who meet proposed eligibility criteria, whether scheduled study visits and procedures may be overly burdensome and lead to early dropouts, and the general relevance of study endpoints and study settings to the targeted patient population”

Create a Sponsor Culture that Supports Open Dialogue

Interestingly, the ICH has identified a critical Sponsor success factor as “Establishing a Culture that Supports Open Dialogue” [ICH(E8)R1, 3.3] by rewarding team and individual critical thinking and encouraging open dialogue to go beyond “reliance on tools and checklists”. From the Guideline:

“Choose quality measures and performance indicators that are aligned with a proactive approach 169 to design. For example, an overemphasis on minimising the time to first patient enrolled may result in devoting too little time to identifying and preventing errors that matter through careful design.”

And:

“Study designs should be operationally feasible and avoid unnecessary complexity and unnecessary data collection. Patient consultation early in the study design process contributes to these factors and would be likely to result in fewer protocol amendments.”

Deemphasize Factors Such as First-Patient-In

The Guideline suggest that shifting team focus onto high-level quality goals in the planning stages, as opposed to micro-goals tied to enrolment, will contribute to overall study success:

“Choose quality measures and performance indicators that are aligned with a proactive approach to design. For example, an overemphasis on minimising the time to first patient enrolled may result in devoting too little time to identifying and preventing errors that matter through careful design.”

And:

“Consider whether nonessential activities may be eliminated from the study to simplify conduct, improve study efficiency, and target resources to critical areas.” [ICH(E8)(R1) 3.3.2]

Guidance on Operational Criteria

The Guideline provides Sponsor guidance to help achieve another critical success factor:  proactive, routine communication of changing study priorities and ongoing risks mitigation activities to its study sites, as site understanding of priorities and necessary resource allocation will enhance the correct implementation of a study protocol (ICH E8(R1). One possible solution would be implementation of sub-program management team, with an emphasis on crafting routine communication to update investigators on the changing study priorities (outside of the Protocol) and any operational issues such as drug availably, delays in safety reporting by other study sites and whatever else a sponsor may think a site needs to know to increase its investigators knowledge of the drug.

The draft is currently under public consultation. Stakeholders may submit comments or questions to step2comments@ich.org

Read the draft guideline here: https://bit.ly/2Jyzzjl