WALTHAM, MASS - Cytel Inc. and F. Hoffman-La Roche Ltd., have partnered together to pioneer the application of a unique bias assessment method in health technology assessment. The new research appears in Nature Communications, one of the most highly regarded peer-reviewed scientific journals in the world.
While randomized controlled trials are widely considered the gold standard for generating comparative efficacy data in clinical research, single-armed trials with externally-derived real-world data comparator arms are gaining traction in the era of personalized medicine. While externally-controlled trials are generally considered to generate less scientifically valid results due to potential sources of bias, scientists at Cytel have found ways to systematically quantify bias, based on wide research and experience. These methods should aim to reassure decision makers that the results of such studies are indeed scientifically valid.
The method known as quantitative bias analysis has not been widely applied within pharmacoepidemiological research. There are no clear standards within the clinical research industry for how to achieve success using these methods, but Cytel and Roche are working with health technology assessment agencies such as NICE and academics on a related project called “Quantitative Bias Analysis for the Assessment of Bias in Comparisons between Synthetic Control Arms from External Data and Lung Cancer trials” or QBASEL. QBASEL is a first of its kind partnership to assess how these methods could be integrated into the health technology assessment space.
"While there is significant concern that studies involving single armed trials will yield biased results, few have thought to ask just how biased such a result is," said Ms. Grace Hsu, Associate Director of Advanced Epidemiology at Cytel Inc. Ms. Hsu was a principal investigator on this project and an industry pioneer for quantitative bias analysis. "No one thought to ask, just how much bias is there? What we have shown through the implementation of these techniques is that when you measure the bias, it is sometimes very small, too small to warrant concern that patients will receive subpar therapies."
In all the examples cited above, data from Flatiron Health was used as the RWD source. Flatiron Health is known to offer some of the most comprehensive oncology RWD in the world. Yet, these studies demonstrate that using high quality RWD sources is complemented by the benefits of QBA—neither can entirely replace the other.
"QBA requires strong expertise," says Dr. Sreeram Ramagopalan, the Global Head of Real World Evidence for Market Access at Roche, "It was impressive to see how methodological advances can help decision makers quantify bias present in RWD."
In addition to being published in Nature Communications, initial results from QBASEL will be presented at HTAi.