WAYNE, Pa.—Bracket, a leading clinical trial technology and specialty services provider, has randomized its first patient using Precision Block Design (PBD) technology integrated in its clinical interactive response technology (IRT) platform, including its mobile application. As the first randomization and trial supply management (RTSM) provider to develop and utilize the novel PBD method, Bracket says it is minimizing selection bias, reducing predictability of treatments and improving patient randomization by balancing known and unknown prognostic factors across comparative groups.
“The statistics group at Bracket is committed to generating the highest-quality randomization lists, and the development of Precision Block Design is a true testament to their dedication,” said Jeff Kinell, CEO at Bracket. “This technology ensures block patterns are uniform, and we look forward to maintaining the integrity of controlled clinical studies through this innovative solution to patient randomization.”
As described on the website of clinical technology company Eclipse, IRT technology uses the internet and a web browser to display prompts on a computer. IRT differs from interactive voice response systems, or IVRS, an older type of system which uses telephones to interface with the technology and that was popular when sites weren’t yet using internet-connected computers.
“IRT has the advantage of speed and accuracy, despite occasional web browser compatibility issues and translation limitations,” according to Eclipse. “Prompts are displayed on-screen so the user dictates the pace rather than a recorded voice announcing and repeating information. It’s also more accurate in regards to data entry, as users can see what they are selecting on-screen rather than pushing buttons on the telephone keypad to make selections. IRT does not require any specialized hardware or telecommunications vendors, and anyone with an internet connection can access the system.”
DDNews spoke with Jim Primerano, senior vice president and general manager of eClinical at Bracket, who says, “The fundamental strategy behind Bracket’s Precision Block Design technology is to reduce imbalances in proportion to predictability and ensure an appropriate randomization mix that supports a sponsor’s endpoint analysis. The technology meets the industry’s stringent guidelines for how various clinical trial designs must generate a randomization schema.”
“By leveraging an intelligent Monte Carlo simulation, the technology can determine which blocks will generate the greatest degree of imbalance, and then measure the predictability impact,” he continues. “To help mitigate any imbalances and ensure equal representation across all permutations, PBD guarantees a uniform distribution of block patterns within each stratum, helping sponsors achieve the intended treatment group ratio with greater precision. Ultimately, PBD technology increases the likelihood of success in an endpoint analysis by reducing the risk of imbalance by block design.”
Randomization is a core component in the design and implementation of RTSM in clinical trials, and Bracket developed PBD for sponsors who want or need to utilize block pattern distribution in their randomization lists when using Bracket RTSM. Randomization designs including those with a high number of strata or low number of slots lend themselves best to the utilization of this method.
“Randomization designs with a high number of strata are at a greater risk for imbalance,” Primerano explains. “The more stratification factors a design has results in more permutations that the patients need to be aligned with, often leading to small subsets of patients within strata and a greater chance of imbalance. In this case, the statistical analysis provided by PBD technology is greatly beneficial to ensuring equal representation. PBD technology can be successful in any clinical trial design as the randomization methodology is customized to meet the unique needs of any protocol at the onset of the trial.”
To ensure equal representation across all permutations, PBD helps ensure a uniform distribution of block patterns within each stratum. As a result, PBD does not require acceptance tests nor does it add additional time or costs to the creation of the randomization list. These benefits make PBD a win-win solution, according to Bracket, as it reduces problems with selection bias and predictability while maintaining time and cost efficiencies.
“At Bracket, we’ve created new programming standards, crafted training, updated standard system requirements and modified our SOPs. Maintaining the maximum level of integrity in our randomization technology is our highest priority,” commented Dr. Scott Hamilton, principal biostatistician at Bracket.
“PBD technology is a process used within the IRT system and therefore will not change the core technology or implementation of randomization methodologies, but instead will allow for more effective randomization schemas to be implemented within IRT systems themselves,” says Primerano. “Recently, there has been an embrace of this type of methodology in clinical trials, and in the right circumstance, this solution can be the most effective choice for implementing randomization schema.”
“It will not be long before other IRT providers follow suit and begin offering a similar methodology. We do not have plans to share or license the technology at this time,” Primerano continues. “However, we encourage other IRT providers to develop similar methodologies to benefit clinical development as a whole, and in that event, we will proudly serve as a resource offering domain expertise and thought leadership.”
To date, PBD has been successfully utilized by Bracket in four separate clinical trials.
“Clients will not need to update their systems to access PBD technology. At Bracket, the randomization methodology is uploaded automatically into the IRT system at the onset of the trial,” Primerano notes. “Rather, some sponsors may need to review their standard operating procedures for randomization list generation to determine how they are allowed to generate the lists. In this case, the easiest mechanism is to outsource their randomization process to an IRT service provider such as Bracket, during the protocol design planning process to ensure optimization across the methodology, technology, list generation and endpoint analysis.”