Clinical Trials and Tribulations: Need for a Paradigm Shift in Drug Development
The overall burden of drug development has increased exponentially over the last decade or so.
The overall burden of drug development has increased exponentially over the last decade or so. Consequentially, the global health care economics is being strained both in developed and in developing nations around the world. With pharmacoeconomics and “Pay for Performance” gaining universal acceptance, coupled with the fact that clinical trials are becoming intellectually and laboriously intensive, sponsors and CROs are earnestly and constantly exploring ways and means to reduce costs without compromising on quality, so that patients ultimately reap the benefit. Perhaps, it is time for us to redefine the existing clinical trial approaches including trial management pathways involved in drug development.
A study conducted by Tufts’s CSSD in 2010,1 the first of its kind on the quantitative assessment of the impact of protocol design on the clinical trial performance, revealed that the median number of procedures per clinical trial increased by 49% between 2000-03 and 2004-07, while the total execution burden grew by 54%. Additionally, growth in complexity and execution burden grew at the slowest rate for protocols in Phase III, as companies, looking to contain costs, gathered more data in early phases of clinical research.
Relatedly, the annual PBS (Australian Pharmaceutical Benefits Scheme) expenditure2 on anticancer drugs rose from $65 million in 1999-2000 to $466 million in 2011-2012. This is an average increase of 19% per annum. The average price paid by the PBS per anticancer drug prescription, adjusted for inflation, increased 133% from $337 to $786.
Evidently, the reasons are multifactorial, but there is widespread recognition and acknowledgement that pharmaceutical industry could perhaps use some “disruptive philosophy” to address this challenge. Therefore, the need of the hour more likely appears to be an “Integrated Drug Development Model.”
A true “Integrated Drug Development Model” is one where all the stakeholders, from early phase to late phase have a role to play right from the start to finish, so there is a seamless transition of intellectual capacity as the asset moves through the different phases of development. Furthermore, maintaining the continuum throughout the developmental lifecycle of an asset is critical. This is different from the tried and tested traditional approach, which is more like an “Isolated Drug Development Model” where every phase of drug development acts and functions independent of each other with no continuity.
In order to achieve this, an objective review of the existing structure of study teams, methodologies, systems, and processes is warranted so we can ask ourselves some very difficult, yet, honest questions and try to find ways to conduct clinical trials more efficiently with sole aim of bringing drugs of value to the market on time.
Study Teams: It would be gainful for the late phase teams to have clinical representation from the early phase teams and vice versa. Knowledge gained from designing early phase studies should be complementary when designing late phase studies so that the data for the application is robust. This not only enables effective and timely knowledge transfer, but also offers an opportunity to gain insights as the asset moves forward.
Methodologies: More widespread use of predictive modeling and application of adaptive trials early on in the development pathway could reduce the time and cost that is being invested. It is critical for the “go" and “no go” decisions on the targets made as early as possible so as to re-focus resources on more promising and viable assets.
Systems: Developing and implementing systems with minimal manual intervention (automated) and one that can be maintained throughout the entire life cycle of the program as the asset moves from early phase to late phase will not only reduce the cost immensely but also improve the quality of the data.
Processes: It is imperative that processes should be fool proof yet not restrictive, so if needed, they are interchangeable between the different phases of drug development. Flexible processes in place that can be applied across will have a profound advantage on resources.
Advent of innovative technology and application of a smarter drug development approach can only help us accomplish this common goal of reducing drug development costs.
References:
1. http://csdd.tufts.edu/files/uploads/mayjuneimpactrpt10summary.pdf
