Traditionally, studies have been run with a process of study design, study conduct, study report. Whilst this is more straight-forward it is not flexible and does not allow for modifications or changes that may be desirable during the course of a trial. An adaptive design allows for the flexibility of interim reviews of the data, followed by pre-specified changes to the trial based on the review whilst maintaining the integrity of the trial, interim reviews may also result in outcomes such as a sample size re-estimation These prior planned adaptations are different to ad hoc protocol amendments, as the adaptations are already allowed for in the protocol.
Updates to the trial design may include additional treatment arms, removing treatment arms, randomisation ratios, dosing and visit schedules etc, which in turn, result in the requirement for an updated data collection tool, usually the eCRF. Updating eCRFs during the conduct phase of a clinical trial can be complex and there are many considerations for the data manager:
- Downtime for the sites – ensuring that the site users have minimal disruption
- Updating the structure of a live clinical trial database without affecting the subject data which is already entered.
- Ensuring that the eCRF is easy and logical for site users once updates are made, yet still captures the data required in the protocol.
- Subjects will potentially follow different paths through the trial and so not all forms or programmed checks will be applicable to all subjects, the use of form rules and skip logic will require careful planning.
Adaptations in a trial can result in a lower exposure to an investigational product than initially planned, thus reducing risk to subjects and resulting in more ethical trials. Another key benefit of adaptive trial design can be a reduced cost, and so it is essential that the data management tools used offer the flexibility to be able to update the design during the trial, with minimal disruption to the site users.
Phastar has partnerships with Medidata RAVE and Medrio for EDC data collection. Both allow for development of eCRF amendments in a separate development instance which reduces the downtime of implementing these amendments to a live study. User acceptance testing and validation of the amendments can take place without affecting the live study database availability.
Pharmaceutical companies are accelerating adoption of adaptive clinical trial designs, according to the Tufts Center for Drug Development1, to reduce clinical development timelines and costs while increasing program success rates. These trial designs, which can alter subject sample size or dosing during the course of a trial, require new technology to implement changes in randomization in the trial and to manage the trial’s clinical drug supply chain.
Rave EDC and Rave RTSM supports adaptive trials by providing the ability to manage cohorts, add or drop treatment arms mid-study, and adjust dosing factors and visit schedules, all while protecting the trial’s integrity and ensuring tight integration between the clinical operations and supply chain teams.
From a data management perspective careful planning, tracking and effective communication with all stakeholders are key to ensuring the associated challenges are met head on. Phastar has the experience and tools to be able to create the adaptive designs required in complex protocols. Our clinical data management team includes staff with a wealth of experience in complex database design in a number of different databases – learn more here.
References
- Profiles of New Approaches to Improving the Efficiency and Performance of Pharmaceutical Drug Development, Tufts Center for Drug Development
