Adaptive design in clinical trials Advantages of outsourcing

The pharmaceutical industry faces growing pressure to reduce cost and accelerate timelines for new therapeutics while navigating regulatory changes, increasing competition and the continuing effects of a global pandemic. To accelerate therapeutic development and to de-risk studies, adaptive clinical trials are being used more frequently. This type of design allows researchers to anticipate and modify trial elements during conduct, while preserving scientific and statistical integrity. The advantages of adaptive designs, include:

• -Potentially reduced timelines for the development
• -Reduced risk of trial failure since the trial can adaptive to the trial reality instead of being anchored in the assumptions
• -Resources can be allocated to the most promising therapeutics in the portfolio

Benefits of adaptive design

Learning from data collected during the trial, adaptive trial design offers sponsors flexibility as the trial is progressing using pre-defined rules and designated checkpoints within the trial timeline. There are a variety of trial design elements that can be adapted, including:

• -Total sample size (e.g. increasing the sample size due to higher than expected variability)
• -Treatment regimens (e.g. increasing a dose level, or dropping an ineffective treatment)
• -Randomization ratios (e.g. allocating more subjects to a better performing arm)
• -Completing the trial early with evidence of efficacy or futility
• -Choice of primary and secondary endpoints
• -Study population characteristics (inclusion/exclusion criteria)
• -Analysis methods
• -Combinations of the above

As noted by the U.S. Food and Drug Administration in recent draft guidance, adaptive design can “provide a greater chance to detect the true effect of a product, often with a smaller sample size or in a shorter timeframe.” This alone is a significant advantage as fewer patients may be needed, which helps speed up recruitment timelines and reduce costs for sponsors. But, more importantly, the ability to adapt a trial can yield fewer patients exposed to unnecessary risk of an ineffective or potentially less safe/unsafe investigational treatment, and can expand a trial that would have otherwise been underpowered to better meet patient needs.

Study teams may also be able to better understand dosing responses to help pinpoint a safe and effective dose for use. Additionally, through interim reviews of data, study teams may also be able to understand patient populations most likely to benefit from a treatment.
Despite the potential benefits to considering adaptive designs, adoption has been fairly slow until the last few years. Interest is steadfastly growing among sponsors, but there are several key considerations sponsors and study teams have to factor in as well.

Unlike traditional fixed trial design, adaptive designs require more time in the upfront to ensure the appropriate pre-defined rules around data checkpoints and planned adaptations are set while maintaining trial validity and integrity. These rules are rigorously examined via statistical analysis, requiring thorough expertise.

Outsourcing advantages

The foundation to planning adaptive trials requires detailed statistically based simulations to better understand all advantages and potential risks to various trial adaptations of interest and the related pre-set rules around them. For sponsors, in-house teams may not always have biostatisticians with adequate expertise to ensure appropriate adaptive trial design. Also, hiring consultants to fill this gap may entail very high hourly rates that may further inhibit consideration of adaptive trial design.

Considering a Functional Service Provider (FSP) model may allow sponsors to quickly onboard expert staff to oversee and/or perform core clinical research tasks, who may otherwise be hard to find or too costly to hire on a consultant basis. In working with a FSP who has extensive background in various types of adaptive trial design and related statistical analysis, the interim data check points will be effectively set up to evaluate data insights quicker and potentially make pre-determined changes to ultimately optimize trial efficiency and ensure a successful trial completion sooner. Use of artificial intelligence/machine learning technologies to extract meaningful data insights requires experience leveraging the tools effectively.

Additionally, given FSP experts have years of experience in working in this capacity, they can integrate quickly into clinical research teams and adjust in using the sponsor’s established processes to keep the research timelines on track. FSP staff add experience beyond that otherwise available on the sponsor team, including that in adaptive design and other complex trial analysis, to enhance trial processes. In some cases, this may mean also incorporating the FSP-owned tech-enabled solutions to optimize trial design and execution.

To be viable in the long term, FSPs must be able to deliver additional expertise, efficiency, and speed to trials, all helping sponsors reduce costs overall. The persistent growth of this model over the last couple years is evidence of its success.

Please contact GlobalFSPGTM@iqvia.com directly to learn more about FSP capabilities specific to adaptive trial design, please visit www.iqvia.com/fsp