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The New Horizons Series: Adaptive Multi-arm Multi-stage Clinical Trials

Cyrus Mehta-1

Innovation in trial designs are offering new routes forward for organizations of any size. They are now also aligned with the overarching goals of improved clinical development, better pre-planning, greater patient safety, less medical waste, and/or increased knowledge.

Cytel is hosting "New Horizons Webinar Series" that will introduce biostatisticians to the latest innovations in statistical trial design. The first webinar in the series on Adaptive Multi-arm Multi-stage Clinical Trials is going to be presented by Cytel's President & Co-Founder, Cyrus Mehta. Click on the button to register.

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Significant advances have been made to enhance the efficiency of clinical trial designs. However, the traditional methods deployed by many companies are fraught with challenges. Patients end up waiting a long time for therapies or receive suboptimal therapies. Millions to billions in revenue is sacrificed by delays to market, competitive shutouts, unfavorable product profiles, and unproven treatments.

Innovative designs enable researchers to mitigate uncertainty by pre-planning ways to adapt as they learn. These adaptive designs are also very helpful in dealing with uncertainty and the variability in the data that is collected during clinical trials.

There are several innovative designs and approaches being used by sponsors today; Multi-arm multi-stage (MAMS) is one such method. Multi-arm multi-stage adaptive trials compare several treatment arms to a common control arm over several stages. The treatment arms might originate within the same organization, or several organizations might each contribute a treatment arm to be tested on a common platform. At any stage treatment arms may be dropped either for overwhelming efficacy or futility. The sample sizes of the remaining arms, the number and spacing of the remaining stages and the alpha spending function may then be adaptively altered while nevertheless preserving strong control of the family wise error rate (FWER). Two methods are available for designing trials that have such a high degree of flexibility.

The stage-wise MAMS approach was historically the first to be developed, and is based on the notion of combining independent p-values. The cumulative MAMS approach is a more recent development that has evolved as a generalization of the group sequential methodology.

In Cytel’s upcoming webinar, Cyrus will introduce each method and discuss how they differ in their approach to FWER control. He will then demonstrate that the cumulative MAMS designs out-perform stage-wise MAMS and recommend that they replace the latter as the method of choice for designing multi-arm multi-stage adaptive designs. The methods will be applied to a multi-arm trial of heart failure in patients with reduced ejection fraction.

Click on the button to register for the on demand webinar.

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