Trials using adaptive design have been an area of continued interest for the clinical trial industry due to the promise of improved efficiency and mitigated risk of failure in the clinical research process. With increased industry pressures to reduce both the cost and time it takes to bring a new drug to market, the prospect of leveraging adaptive trial designs to identify both successes and failures earlier in the trial process and making adjustments to a study design based on analysis of data collected is attractive to many companies, but also introduces challenges that need to be overcome.
Designing a valid statistical approach using either Bayesian or Frequentist methods that removes bias and provides a framework to analyze the results of the trial is certainly a large part of the challenge posed when using an adaptive trial design. Our partners at Cytel (http://www.cytel.com/) have been thought leaders in this area for many years and I would recommend that anyone interested in the statistical challenges take a look at their many blog posts on the topic. For this post I will focus on the ways that an IRT/IWRS can be leveraged to assist with the operational challenges of running an adaptive trial.
Implementation of Complex Randomization
IRT systems are designed and validated to manage the algorithms required for a variety of randomization schemes. Many trials, even non-adaptive designs, would be impossible to conduct without a computerized system managing the randomization. An IRT/IWRS to manage randomization is especially important when the possible treatment arms or randomization ratios may change mid-study and need to be rolled out to all sites globally using a centralized system.
Access to Unblinded Data
When performing ongoing analysis of the trial, the Data Monitoring Committee (DMC) needs access to both the clinical data for the existing subjects along with the unblinded treatment information for the subjects being reviewed. Using an EDC to collect the clinical data and an IRT/IWRS to manage the randomization ensures that both the clinical data and unblinded randomization assignments can be obtained in real-time as subjects enter the trial and data is recorded.
When designing an IRT/IWRS for an adaptive trial it is important to ensure that unblinded treatment assignments are available to appropriate members of the study team or DMC through web-based reports or an integration with the IRT/IWRS provider’s API/Web Service so the data can be accessed quickly when needed. Given the sensitive nature of the data, it is important to make sure the data retrieval method is appropriately secured through a permissions-based access control framework.
Fine-Tuned Control of Design Changes
When an adaption decision is made and needs to be implemented, the IRT/IWRS provides the tools for the appropriate users to implement the changes in a controlled manner through web or mobile-based functionality.
By designing a flexible system with the functionality to control the changes, an IRT/IWRS vendor can ensure that the study team can make the required design changes to the study and have those changes take effect immediately for any newly randomized subjects without having to rely on the vendor’s support and project management team to implement back-end system changes.
The functions used to make the adaptations can also be designed to capture the user’s electronic signature, providing full traceability for when the study design changes were implemented and who signed off on the change being implemented.
Advanced Drug Supply Management
A significant logistical challenge created by certain types of adaptive designs is planning and managing the drug supply, since treatment arms/doses may be dropped mid-study and other treatment arms/doses may enroll more subjects than originally planned.
An IRT/IWRS system with robust drug supply management functionality allows a drug supply manager to tightly control the supply sent to sites and adjust the supply strategies for sites based on the remaining treatment arms and new ratios. An IRT/IWRS system can also enable a Just In Time (JIT) labeling and shipping strategy, further reducing supply waste on adaptive trials.
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Adaptive trial designs are one way companies can improve the efficiency of clinical research and bring new therapies to market faster while improving safety for trial participants -- but they also require additional planning up front. Working closely with your IRT/IWRS provider when setting up the trial can provide reliable and fast access to unblinded data when required, as well as tight control over the implementation of study design changes based on the DMC adaption decisions.