Michael Rosenberg of Health Decisions discusses the new role of adaptive research in the biotech industry
Adaptive research, the ability to alter clinical studies in progress based on analysis of partial results, is among the most important developments in the biopharmaceutical industry for several decades. For smaller and emerging biopharmaceutical companies, adaptive techniques present an unusual, perhaps unique, opportunity to improve development efficiencies and gain competitive advantage over much larger companies.
Adaptive techniques are the latest and perhaps most significant stage in a transition from big pharma’s long domination of drug discovery and development, to a new and more competitive era in which big pharma is just another player. Advances in technology have lowered barriers to entry, transforming drug development from a capital-intensive, smokestack industry into a technology-leveraged, knowledge-based enterprise. Smaller companies are now on an equal footing with industry giants. Indeed, in many cases, quicker decision-making processes have enabled small companies to lead the way in adopting innovative ideas and methods.
Innovations in drug discovery include combinatorial chemistry, molecular design, RNAi, production of biologics in vivo by recombinant DNA, high-throughput screening, and the use of DNA microarrays. Such innovations have enabled small, ambitious competitors to enter drug discovery, and have yielded vast numbers of candidate drugs and treatments. The leading role played by smaller companies in many of these advances would have been unthinkable just a decade ago.
While innovations in discovery have expanded the number of potential drug candidates, clinical trials remain a chokepoint. They also contribute substantially to development costs estimated at more than US$800 million per drug (1). Even such astronomical spending levels have brought surprisingly few new drugs to market. The US pharma industry’s annual R&D spending reached an all-time high of $40 billion in 2006 but resulted in the approval of only 18 truly new drugs, the lowest number in recent years (2).
THE ADAPTIVE APPROACH
The fundamental difference between adaptive capabilities and more traditional development is reliance on a ‘refine as you go’ rather than a ‘black box’ approach. An adaptive design permits adjustments along the way based on experience. This common sense approach stands in stark contrast to the familiar routine of waiting until all the data are available before analysing it and determining success – an approach best summed up as ‘making a guess and keeping your fingers crossed’. Because adaptive requires continuous refinement along the way, these techniques translate to shorter timelines and lower costs. Indeed, continuous adaptive adjustments guarantee success at meeting informational goals at minimum cost in time and money.
Figure 1 illustrates how adaptive approaches continuously acquire knowledge by examining both data and the operational aspects of a study while it is being conducted. In contrast to the usual knowledge gap between the time at which data or study performance metrics (which are most often not available at all, except in the crudest sense, during a study) are available, clean, and in an understandable form, adaptive designs and processes focus on immediately transforming a stream of raw data into meaningful information that can quickly be transformed to knowledge. This capability demands more effective data collection and management than is commonly used.
Adaptive research refers to a broad range of capabilities, all of which relate to what has occurred most recently in a clinical trial. The intellectual groundwork was first laid in 1763 by Thomas Bayes, who gave formal mathematical expression to what many would consider the essence of common sense: continuously updating or revising beliefs in the light of the latest evidence.
