Novel trial designs are reshaping clinical development by improving efficiency, reducing redundancies, and accelerating timelines toward a new era of precision medicine.
As clinical trial design has continued to evolve, the number of novel designs used has risen, such as basket, umbrella, and platform trials. Traditional studies often take years to complete and require significant financial investment. With these new novel designs, clinical operations teams can increase efficiency, reduce redundancies, and improve development timelines.
A review published in Signal Transduction and Targeted Therapy titled, “New clinical trial design in precision medicine: discovery, development and direction,” outlined the discovery and development of basket, umbrella, and platform trials from the perspective of precision medicine.1
“In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities,” the review authors wrote. “Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited.”
The idea of a Phase II basket trial was proposed in 2014 by the American Association for Cancer Research. This design tests a single targeted therapy across different tumor types that share the same molecular alteration. It originated from discoveries such as HER2 overexpression and ALK fusions, which drive proliferation across multiple cancers.
Meanwhile, umbrella trials were developed to evaluate several targeted therapies within a single disease population.
The biomarker-integrated approaches of targeted therapy for lung cancer elimination (BATTLE) trial (NCT00409968, NCT00411671, NCT00411632, NCT00410059, and NCT00410189), an early umbrella model, was initiated in 2006. It assigned non-small cell lung cancer patients to therapy arms based on biomarkers such as EGFR, KRAS, VEGF, and CCND1.
Finally, platform trials are designed on the premise of living master protocols. While basket and umbrella trials both have their advantages, platform trial designs allow for the addition of interventions that show promise and/or subtraction of those lacking clinical evidence.
An example of this model is the STAMPEDE trial (NCT00268476) in prostate cancer, which spanned from 2005 to 2023 and enrolled nearly 12,000 patients. Despite only having six arms when it was initiated, nearly 11 interventions had been investigated when the trial ended.
While these trial designs have helped advance many therapies, the authors looked ahead to “precision medicine 2.0.” They proposed Precision Pro, Dynamic Precision, and Intelligent Precision as guiding principles for biomarker-driven clinical trial design in this next era.
Individualized therapeutic demands are calling for innovation beyond these transformative designs. New biomarker-guided trial design should focus on the entire patient journey, rather than just the primary idea of matching targets, drugs, and diseases.
“The precise thinking model of biological mechanism-driven therapy will be the first principle in future clinical trial design. According to fully integrating theoretical innovation and intelligent technology to address the practical therapeutic demands of individual patients, the ability to control and manage disease precisely will be highly improved,” the authors concluded. “The knowledge system construction based on new clinical trial design will assist researchers in grasping the decision occlusion and making a significant contribution to the rapid development of precision medicine era 2.0.”
Duan XP, Qin BD, Jiao XD, Liu K, Wang Z, Zang YS. New clinical trial design in precision medicine: discovery, development and direction. Signal Transduct Target Ther. 2024 Mar 4;9(1):57. doi: 10.1038/s41392-024-01760-0. PMID: 38438349; PMCID: PMC10912713.
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