^{Figure 2. Overview and examples of the different types of clinical trial designs}

The type of trial design to adopt is dependent on factors such as the phase of drug development that they are used, the outcome as well as recruitment effects. Umbrella trials for instance, investigate the safety and efficacy of several Investigational Medical Products (IMPs) in a single population, and can be used at any stage of development, while basket trials investigate the safety and efficacy of an IMP or a combination of IMPs across a variety of populations, and are typically used early in drug development.

ICTDs are able to address the drawbacks of conventional clinical trial designs through the following ways, as detailed in Figure 3:

^{Figure 3. Selected features of ICTDs and how they address the pain points of clinical trials}

Adaptive clinical trials in particular, are of increasing interest as changes to treatment arms often allocate subjects to superior treatment regimens. This in turn minimizes the number of participants exposed to ineffective or toxic doses, thereby increasing the likelihood of achieving the study objective in eventuality¹⁸.

The way forward for innovative clinical trial designs: Three things to pay attention to

1. The growing demand to digitize clinical trials

Companies face growing pressure to reduce development costs and increase participation in clinical trials. Digital technology can be used as a tool to improve participant recruitment and retention, as well as to facilitate data collection and analysis in the ways as illustrated below¹⁹:

^{Figure 4. Benefits of digitizing clinical trials}

Incorporating digital technologies into ICTDs will be especially helpful in optimizing recruitment targets for rare disease trials with smaller patient population. Furthermore, digital technologies in the form of devices and advanced analytics software can help improve the accuracy of data collection and facilitate data analysis, thereby assisting in the generation of robust clinical data in the most cost- and time-effective way possible. Coupling both digital and innovative approaches may therefore help in resolving some of the pain points that come with small-sized CGTP trials.

2. Differences in the level of guidance between countries

As innovative clinical trial designs are increasingly used, coming up with guidance to provide Health Authorities’ stances are important. To date, the FDA and European Medicines Agency (EMA) have released work plan guidance (FDA: Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products: Guidance for Industry and Innovation in Clinical Trial design | EMA: ACT EU multi-annual workplan 2022-2026) on the subject matter.

^{Figure 5. Regulatory support (in terms of pre-consultation meetings) provided by regulatory agencies in selected countries.}

The lack of reference could create difficulties for sponsors seeking to conduct innovative clinical trials for eventual approval. Having a one-to-one consultation session to seek alignment with authorities on their expectations when filing for regulatory approval is therefore imperative.

3. Relative novelty and risk of ICTDs

As of to date, little is known about the use of ICTDs for cell and gene therapy products – in the case of adaptive trials, there is a lack of clarity on when they are applicable, what they can or cannot accomplish, what their practical implications are and how their results should be interpreted or reported⁵. Studies leveraging real world data to provide information on a wider patient population may contain inherent biases in their data sources that could limit their value for establishing causality between drug exposure and outcomes²⁰.

Despite the potential benefits that ICTDs may bring for CGTPs, developers must still exercise due diligence in reviewing the suitability of this mode of trial design for their IMPs. To optimize their chances of succeeding in market access, industry stakeholders are recommended to strive to understand and apply the recommendations of regulatory agencies, as well as to partner with providers who have clinical trial experience for a better understanding of the ICTD landscape.

CGTPS offer hope for the treatment of serious diseases with unmet medical need – expertise is required to navigate the regulatory space to ensure regulatory compliance and access into each market. To find out more about cell-based and gene therapy products across the JAPAC region, please click here.

References:

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