By Ann Neuer
March 15, 2010 | Companies that actively embrace adaptive methods will be tomorrow’s leaders in the biopharmaceutical industry, says Michael Rosenberg, president and CEO of Health Decisions, and author of the recently released book, The Agile Approach to Adaptive Research. According to Rosenberg, “The impact of adaptive clinical trials is going to be so profound that it’s going to change the dominant players. This happens in every industry when there is fundamental change.”
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| Michael Rosenberg |
Yet despite this prophetic call, Rosenberg says that implementation of adaptive clinical trials (ACT) is very much in its infancy, and he estimates the percentage of sponsors using this technique as down in the low single digits. “Mostly, we’re seeing companies starting with sample size re-estimation (SSRE), which refers to changing the size of the study population based on treatment effect, placebo response and other factors. It’s one of the easiest ways to stick your toe into the adaptive pool,” he comments.Once stakeholders become comfortable with SSRE, the goal should be to expand the effort by implementing a series of agile design steps that make for a continuously updated flow of information. Rosenberg’s book explores many of these steps, such as combining multiple phases in clinical trials, and implementing adaptive randomization. Each step is intended to bring measurable efficiencies and improved decision-making to an industry that spends in excess of $50 billion annually in R&D, while the output—the number of new drug and biologics approvals—is anemic, in the range of two dozen per year by the Food and Drug Administration (FDA).
The Agile Approach also describes the critical importance of adaptive operational changes linked to monitoring, enrollment issues, data quality, site closeout, and database lock. Regarding monitoring in particular, Rosenberg says, “Monitoring accounts for one-third of study budgets, and is a tremendous source of inefficiency. Basically, they look to see that data from the source is accurately transcribed into the database.”
A vast improvement and significant cost savings would come from re-defining the monitor’s role from a boxchecker to someone in charge of managing the sites, with a focus on what’s critical to a study’s success, namely reaching enrollment targets in a timely manner and generating clean data. In an adaptive trial, this could be accomplished by dispensing with rigid adherence to monitoring intervals established at the beginning of the study, and moving toward the use of better electronic tools such as the SmartPen (see, Health Decisions Celebrates 20 Years of Adaptive Clinical Research). The SmartPen Advanced Electronic Data Capture (EDC) system enables continuous tracking, which helps monitors identify sites in need of help. This approach not only results in dramatically less travel for monitors and all of the costs associated with it, but also fewer queries and faster database lock.
Health Decisions, Rosenberg’s company, is using some of these adaptive techniques to yield impressive outcomes such as completing a study for metastatic breast cancer nine months ahead of schedule, and saving $32 million of a $110 million Alzheimer’s study by shortening the five year timeline to 3.5 years.
In an industry notorious for adopting efficiency-yielding technologies in a slow, incremental fashion, Rosenberg says this approach is no longer sustainable or affordable. Instead, stakeholders need to completely change their processes to realize outcomes. “It’s not about adopting a specific technology to improve part of a decades-old style of clinical development. Only decisive action will bring about improvements needed to increase safety for subjects, lower development costs, shorten timelines, and realize the promise of personalized medicine. Our industry can do a lot better in terms of productivity. That’s why I wrote the book,” Rosenberg comments.