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As long as their trials are well-designed and based on prior data, safeguard participants, and meet all current federal standards, drug developers have wide latitude in clinical trial design. Though clinical trials still largely follow traditional designs, some notable advances made over the last two decades are having a positive impact on drug development.
Traditional Trial Design
Well-controlled randomized clinical trials are the gold standard in trial design. Traditional trials assign patients randomly to two or more study groups (or arms), each receiving either an investigative therapy or an approved medicine (and in some cases, a placebo) to establish which is more effective in treating a particular disease. A traditional design rigidly follows a specific study protocol without regard for any new data or insight during the trial period.
Adaptive Trial Design
The concept of adaptive trial design can be traced back to the 1970s, but the approach has gained more attention following the FDA’s Critical Path Initiative of 2004. An adaptive trial allows pre-planned modifications based on the analysis of accrued trial data before the trial is complete. Modifications can include dosage, sample size, study or reference drug, patient selection criteria, and combination therapies.
Trial modifications may also include changes to how patients are allocated to different arms, which patients are sampled at what timepoints, when a “losing” arm can be dropped, and when a study can be terminated. Changes can also be made to the hypothesis, the primary endpoint, statistical methods, and patient population. One final change that can be used in an adaptive trial is what’s referred to as the “seamless” Phase II/III trial, which allows drug developers to add patients to the most promising trial arms and move right from Phase II to Phase III testing.
The aim of an adaptive trial is to more quickly identify which drugs and doses are effective in a given patient group. Because adaptive trials are more flexible than traditional designs, they can be fast and efficient in making critical decisions. This, in turn, leads to trials with more precisely targeted patient subgroups, resulting in easier enrollment and fewer patients treated with ineffective doses.
Adaptive trials are considered to be among the most significant shifts in clinical trial design across most therapeutic areas. Due to the complexity of different tumor types and patient responses to therapy, oncology trials in particular have benefited tremendously from adaptive design. The wealth of information coming out of genetic research is shifting the way we think about and treat cancer. As researchers move toward categorizing cancers by their genetic mutations rather than their organ tissue types, new trial designs have emerged.
The Role of Technology
Although adaptive trial designs represent a significant advance in clinical drug development, they also present a series of operational and conceptual challenges, allowing greater flexibility overall. Having smaller patient groups puts more demand on analyzing and applying data than ever before. Quick and reliable electronic data capture is therefore essential for successful execution of an adaptive trial, which relies on having the relevant data available for critical decision making.
The emergence of adaptive design trials has also motivated advances in new technologies. eClinical systems must now support the increasingly complex mid-study changes outlined in adaptive design protocols. This new requirement is spurring technical innovation within the eClinical arena that offers “controlled flexibility” for clinical trial teams. Team members have the flexibility to modify aspects of the trial within the context of the adaptive protocol design without losing the necessary access controls that ensure data integrity.
eClinical technologies must support traditional collection and management practices while also facilitating adaptive design activities throughout the lifecycle of the clinical trial. XClinical provides a range of integrated modules in one platform, enabling the seamless flow of data, regardless of the complexity and design of the trial.
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