Adaptive Clinical Trials Can Bring You “Beyond the Shadow of a Drought”

R&D production in the pharmaceutical industry has fallen more than 70% over the last 15 years, according to a recently published report, “Beyond the Shadow of a Drought: The need for a new mindset in pharma R&D,” by a group of analysts at the Oliver Wyman consulting firm.  According to this insightful analysis, the underlying causes have not seemed too alarming because pharmaceutical companies still continue to have net incomes of 20% to 30%, and the industry has sustained a 6% annual growth even during the current global economic turmoil.

In the face of increasing demands for better, safer and cheaper drugs, however, decreased R&D productivity is creating a fundamental problem for the industry. The authors call for a more radical mindset and for the implementation of changes that correspond to recent developments in science, technology, and society over all.

To show that the change is inevitable, the authors analyzed the period between 1996 and 2010. During that time, 450 new therapeutic drugs were approved by the FDA and placed on the market. The earlier part of this period – from 1996 to 2004 – was characterized by the robust approval of new drugs and the high return on capital, hence the name “Era of Abundance.” This era ended in September 2004 when Merck voluntarily withdrew its major money-maker, Vioxx, from the market. The FDA responded to this situation by imposing stricter regulations. Consequently, the rate of drug approvals has decreased by 40% since 2004. The world economic crisis also contributed to weaker sales and low return on capital. Hence, the years from 2004 to 2010 earned the label “Era of Scarcity.”

After shedding light on multiple intrinsic problems arising from the earlier mindset of pharmaceutical companies, the authors speculate about how the industry should change to create more products, while spending less. They suggest four primary shifts: raising the bar on innovation; considering the payers’ problems; treating drugs as rare; and playing to win (e.g. creating a better balance between competition and collaboration among companies). Finally, the authors discuss in detail how the industry should implement these changes.

Aptiv Solutions has already addressed many of these suggestions in its efforts toward replacing conventional clinical trials with adaptive trials.  Adaptive clinical trials rely on the timely collection of data in defined interim analysis steps providing the opportunity for the trial to adapt to emerging data. For example, following an interim analysis, a decision may be made to re-estimate the size of the trial, stop the overall trial for futility, drop ineffective treatments, or change the randomization allocation in favor of more effective treatments in defined sub-populations of patients. Importantly, these are not ad-hoc changes but are design changes that are pre-specified and planned in advance, which is essential from a regulatory perspective. There are also ethical advantages with fewer patients on unsafe or ineffective doses.

While adaptive design concepts have been available for some time – only recently has implementation (especially for complex design trials) been achievable. This breakthrough has been possible because of the development of integrated technologies specifically designed to support the execution of adaptive trials. Adaptive implementation technology is also opening up the potential for wider use of innovative adaptive designs which will dramatically increase the efficiency of the whole clinical development process.

Thus with an adaptive approach the risk for patients significantly decreases,  the likelihood of meeting FDA regulatory standards and the yield of conclusive data increase,  and, in turn, pharmaceutical firms should realize greater returns on their investment.

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adapted and republished from Aptiv Solutions Blog

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