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Regulatory Focus™ > News Articles > 2022 > 1 > FDA offers examples of innovative study designs accepted into CID pilot

FDA offers examples of innovative study designs accepted into CID pilot

Posted 20 January 2022 | By Joanne S. Eglovitch 

FDA offers examples of innovative study designs accepted into CID pilot

The US Food and Drug Administration (FDA) recently highlighted three case studies showing how sponsors can incorporate innovative study designs in their clinical trials using the agency’s Complex Innovative Trial Designs (CID) pilot meeting program.
 
The aim of presenting the case studies is to help sponsors understand factors that should be considered when proposing a CID. The pilot program was launched in 2018 to accelerate the development of therapies for unmet medical needs. (RELATED: FDA launches pilot program in support of complex trial designs for drugs and biologics, Regulatory Focus 29 August 2018).
 
The CID pilot is intended to “advance the use of complex adaptive, Bayesian, and other novel clinical trial designs,” FDA said in an announcement. The case studies each describe the innovative design aspects of three of the submissions accepted to the program. In an update on the program published in October 2021, FDA had accepted five meeting requests for participation in the pilot.
 
A final guidance was published in December 2020. (RELATED:  FDA finalizes guidance on complex innovative trial design, Regulatory Focus 16 December 2020)
 
FDA provided summaries of three case studies. One was a drug used to treat chronic pain, the other was for a lupus treatment and the third a treatment for a diffuse B-cell lymphoma (DLBCL). Each of these trials used some type of simulation, and all applied Bayesian methods in their analysis.
 
The lupus study incorporated a randomized, double-blind, phase 2 design in patients with systemic lupus erythematosus (SLE), a rare disease with a high unmet need. Patients were assigned to one of four treatment groups: three doses of the product or a placebo. The study pooled data from different dose levels in comparing the treatment to the placebo and used Bayesian methods to estimate response rates across treatment groups.
 
The agency said that, “Compared to more conventional study designs, it appears that this CID will tend to allocate more patients to most effective doses and will increase the power of comparisons of the most effective doses to placebo.” Also, the final analysis results must be carefully reviewed to “to ensure that the correct conclusions are drawn and that correct decisions are made after properly accounting for the study’s complex and innovative elements.”
 
The DLBCL study used a randomized open-label multicenter trial design to evaluate an investigational treatment. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was overall survival (OS). The analysis population for OS will be “augmented by patients from an external control arm so that approximately half of the patients in the resulting control group are comprised of patients from the external control.”
 
The benefit of using the design, said FDA, is that, “If the model assumptions are met, borrowing patients’ data from an external control arm reduces the number of patients necessary to randomize to the control arm of the proposed trial to achieve a specified power.”
 
The chronic pain study incorporated a master protocol design to study multiple interventions for chronic pain. The sponsor proposed a multicenter randomized double-blind placebo-controlled design. A Bayesian model was used to evaluate pain relief, the primary endpoint.
 
FDA said that, “While the proposed CID master protocol design is considered proof-of-concept, FDA accepted the CID into the pilot due to the valuable learning opportunity – a pillar of the CID program – especially given concerns about the impact of borrowed data on the accuracy and precision of treatment effect estimates.”
 
FDA Acting Commissioner Janet Woodcock has long been a proponent of master protocols, citing their ability to evaluate multiple agents effectively once they’re up and running. (RELATED: DIA: Woodcock, other top officials tout benefits of master protocols, want momentum to continue post-COVID, Regulatory Focus 2 July 2021.
 
Disclosure agreements between FDA and sponsors allowed the case studies to be presented.
 
While the program is set to expire in September 2022, the agency explained in the final guidance that sponsors may present and discuss CID proposals through existing pathways for interactions.
 
FDA CID case studies

 

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