JULY 2023LIFE SCIENCES REVIEW9generated at the early stages of the clinical trials. Applying the concepts of quality of design and systematic critical thinking during the early stages of clinical development and First-In-Human (FIH) studies can deliver the accurate and adequate data-driven information needed to accelerate this decision and gain momentum in the global clinical program as a result. The thinking around FIH study design has moved away from the traditional design targeting winning a fast proof of the drug safety and tolerability as primary objective to more dynamic thinking of the secondary objectives desired to gain additional information beyond the safety and the pharmacokinetics (PK) data to enable better and faster-informed decision in the further steps. Several sub-studies found their way to be implemented as essential parts in the FIH study design to accelerate the clinical program by leveraging the phase 1 unit settings which offer a better-controlled environment that allows collecting and investigating tests that might not be feasible or accessible in later stages of outpatients clinical studies settings. Food-effect studies are easily added to a healthy volunteer group during the conduct of the FIH study to inform the decision about the future usability and market use of the drug in real-world settings. Drug-drug interaction studies during FIH study offers accelerated access to data that can significantly influence the decisions for further studies. The FIH study settings in the phase I unit provide an excellent opportunity to implement continuous ECG recording to obtain QTc critical data that can offer a significant advantage through de-risking the clinical program and open up a potential pathway for regulatory waivers for a separate Thorough QT study with tremendous benefits for the program timelines and resources. Based on the safety and PK data obtained in earlier SAD cohorts, an accelerated dose escalation process can allow MAD cohorts to be initiated before the completion of all SAD cohorts which can shorten the time to get access to the entire unblinded study data without compromising the safety of the participants. Data from patients' cohorts in the FIH studies can add great insight into the pharmacokinetics and pharmacodynamics and speed up the decision for any required dose adjustment or additional safety monitoring assessments. Sensible and well thought out studying of specific biomarkers related to the drug MoA pathway in the patients' groups in the FIH can inform the design, schedule of events and duration of required testing in later phases.Planning for diversity in clinical trials is essential. This planning should typically start in the early phases of clinical development. Although the sample size is naturally small at this stage, diverse data can shed light on any significant outliers such as significant differences in biomarkers response and PK variabilities between sex, race or comorbidities. This can boost the thinking of the study design and the target population in later phases of clinical development. The recent FDA guidance for diversity highlighted the need for adequate planning for diversity at early stages in clinical development. Getting early diverse data can significantly boost clinical development milestones. Careful considerations of this accelerated design and strategies in the FIH study can enable early insight into how the drug can progress in later stages, how the target product profile can be modified as a result of these findings, and what value the new investigational drug can deliver in the competitive market, how the drug differentiates from its class therapeutics, and what impact the drug can have on the patient's life in real-world settings. These elements can certainly increase the value of the new investigational drug at very early stages and shorten the timeline to deliver the drug to patients.
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