In April 2012, speaking from Japan, a very symbolic location, the UK Minister for Universities and Science David Willetts announced the opening of a £180 million Biomedical Catalyst scheme to provide grant funding for innovative small and medium sized enterprises (SMEs) and academics to develop solutions to healthcare challenges. Prime Minister Cameron, and before him Blair , had emphasised that “Invention is one of the things we do really well in the UK”. Without a doubt, the emphasis is for translational research to be at the heart of science policy in the UK and to ensure that scientific innovation gets translated into applied uses in business.
The NIHR, through the Biomedical Research Centres (BRCs) and Units (BRUs), the Comprehensive Local Research Networks (CLRN), the NIHR Office for Clinical Research Infrastructure (NOCRI), and the Technology Strategy Board (TSB), to name only a few, have all been established to facilitate the process of translating bioscience breakthroughs into patient benefit by providing clinical infrastructures and personnel, funding, access to patients and to businesses.
However, numerous obstacles remain and this paper will outline three of the most important barriers to effective translational breakthroughs. These have been identified based on my 17-year experience working in the UK, from the bench to the clinic and beyond, in areas as various as basic sciences trying to understand the mechanism of cancer progression to the conduct of international phase III HIV prevention trials.
Translational medicine aims to bridge the gap between basic science and its application to human diseases, from bench to bedside, and beyond. It is a long and complex process too often inappropriately conceptualised as a stepped progression in which one stage of product development leads to another. In fact, it is much more appropriate and accurate to consider translational medicine as a whole, as a system designed and managed for the purpose of bringing medical innovation to the public.
The process is fraught with pitfalls and drawbacks and the risk for failures are numerous and high at every stage. The following three areas represent what I believe are the most important barriers to effective translation.
Intellectual Property (IP)
This is an area often overlooked at the early stage of research and development. However, existing IP can restrict access to products and technologies on which some innovations are built. Combining different IP is often difficult. Owners of background IP see a potential danger in mixing IP from different products and technology, in terms of ownership as much as because they fear potential damages from unexpected outcomes of the research.
At a later stage of development, unsettled or unexplored IP issues can threaten the development and roll-out of scientific innovation. Working with the industry and trying to understand and agree IP management and exploitation requires highly qualified professionals who are not always available in an academic environment where the translational process starts.
Art search and the patenting process are long, time-consuming, and costly. They require a non-negligible effort and contribution from researchers to provide background information about their products which they don’t necessarily have. Nowadays, several grant schemes have stressed this aspect of product development (such as the MRC DPFS/DCS scheme), but they have also created further difficulty by tying funding to their own IP terms. Gates and EU grants require favourable pre-agreed terms for access in developing countries whilst projects are still at an early stage. This is unwarranted as commercial success is unpredictable in the early days of development but creates barrier to access.
There is a giant step between making and testing a product arising from a bioscientific breakthrough in a research lab or in pre-clinical settings, and then manufacturing and trialling the same product for the purpose of using it in humans. Rules and guidance for product manufacturing (cGMP) and the conduct of trials (ICH-GCP), decided at EU level and implemented nationally, are complex and constraining. Regulations in the US and elsewhere are also different.
Overall, such regulations create different levels of requirements which limit and complicate opportunities for product manufacture and development. Further, regulations often fail to distinguish between products for use in early stage human studies and products for late phase III trials leading to increased cost and delay in manufacture and development.
The constraining frameworks created by these regulations have been recognized. In 2011 the EU conducted a Public consultation on a concept paper on the revision of the ‘Clinical Trials Directive’ (2001/20/EC) to assess its functioning. Much work needs to be done in order to simplify and streamline regulations and construct them so that they address the specific risk associated with new discoveries.
Management and coordination
Translational Medicine Management is about filling the gaps, joining the parts and building bridges between numerous infrastructures, people, interests and concerns. Skilled and efficient management from start to finish, from idea to end user is critical and pivotal in overcoming the many obstacles that thwart translational medicine.
The knowledge required is vast in scope (from basic science to trial regulations and public health policy) and necessitates skills in administration, finances, business and IP, as well as a sound knowledge of institutional practice. Several organisations have been set up to provide some support to researchers and clinicians wanting to engage in the process, but the breadth of the task ahead remains daunting.
Innovators have to juggle many other tasks in parallel and are not necessarily trained to manage a seamless transition from the bench to the bedside. Universities rarely provide the skilled managers and operational support required and inventors are left to deal with a high level of complexity on their own, not always knowing where to start and where to go for advice and support/assistance. It would be useful to create a roadmap from breakthrough to patient as there is one for the conduct of clinical trials .
Navigating the rapids, in what David Willetts called a “valley of death” towards commercial successes that will benefit patients remains a slow, expensive, and failure-prone endeavour . There is help at hand but the multiplicity of frameworks and stakeholders creates barriers to the translation of innovation into practical applications.
With the current emphasis on conducting research that benefits patients and contributes to the UK economy, the cost remains an issue at all stages but projects that are worth developing are able to raise and attract funding when they receive appropriate institutional and business support. Funding, now often milestones-based, decreases the risk for the funder to invest in a product for which development remains uncertain.
There is a need for building and understanding the big picture that would help identify roadblocks and leverage points to fasten and simplify the translation research process in line with government aspiration.