Translational Medicine Translational Research: Bridging Science and Medicine

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By Shawn Lawrence

Translational research has emerged as a key area of clinical R&D in Canadian hospitals and universities, where a focus on integrating drug discovery and development has become a priority.

Typically the term translational research refers to the “translation” of basic research into real therapies for real patients and emphasizes a link between the laboratory and the patient’s bedside. In more defined terms, it is about taking basic research and discoveries made at the bench directly to the clinic.

Lawson Health Research Institute (LHRI) located in London, ON, is one such institute recognized for its “bench to bedside” approach. Specializing in the fields of biotechnology, imaging and medical devices, LHRI operates as the integrated research arm for the London Health Sciences Centre (LHSC) and St. Joseph’s Health Care London and is one of the largest hospital-based research facilities in Canada.

In all, the institute has 11 primary research programs: Advanced Surgical Technologies, Aging, Rehabilitation & Geriatric Care, Centre for Critical Illness Research, Children’s Health Research Institute, Circulation, Health Outcomes & Health Services Research, Imaging, London Regional Cancer Program, Metabolism & Diabetes, Neurosciences, Transplantation, Immunity & Regenerative Medicine and five core support units.

At LHRI, the discovery process starts with the basic science research conducted at the hospitals and the institute and moves along quickly because of its readily available access to patients that are interested and willing to participate in investigational trials at its member hospitals. The difference between traditional and the translational research being done at the institute is a subtle one but an important one, explains LHRI chief scientific officer and former scientific director of the institute David Hill.

“We still start with discovery, but rather than simply saying we’ll put that knowledge on the library shelf in manuscripts and wait for some pharmaceutical or biotech scientist to read it, we actually try and take it forward through the institute and develop it in-house to the point where we’re starting to do clinical studies,” said Hill.

The goal, states Hill, is to try and cut down on the 10-12 year timeline that it takes traditional researchers to get a product or technology developed and available to health agencies wherever possible. Yet in order to realize the full benefits of translational research, the institute and its researchers have to target its goals wisely.

“That’s why our approach is to focus our objectives towards having a real impact on the standard of heath care, real life goals, certainly for the patients in our hospitals but also in terms of helping to keep people out of our hospitals,” said Hill.

According to Hill, there are two main drivers for all the translational research that occurs at Lawson; first the basic and clinical researchers themselves and secondly the industry partners, licensees and/or research sponsors (biotech, pharmaceutical and medical device companies).

Whether its the development of drugs, which LHRI does through its spin-off companies in partnership with the private sector, or medical devices, which involves a less complicated process, LHRI tries to take its research right through to the level of clinical evidence in the hopes of presenting it and getting approval from the ministry or handing it over to the private sector.

This is where LHRI manager, Technology Development & Commercialization Lawson Business Development, Todd Copeland, and the institute’s business development arm enter into the equation.

Charged with creating an environment in which researchers can do the best possible research, the primary goals of LHRI’s business development approach is to terminate unsuccessful technologies earlier in its development, improve confidence in human drug and technology targets and enhance cost-effective decision-making.

“Our group exists to assist individual researchers and research groups in the identification, protection, development and commercialization of their discoveries,” explained Copeland. “We’re in the business of idea generation and nurturing those ideas to the point of developing research around them and adding value to the point where potential licensees or partners can recognize it.”

Copeland believes that because of the nature of translational research and having the ability to do basic and clinical based research in the same environment, the commercialization process at LHRI is more focused.

“In a traditional research environment many early staged discoveries fail to go anywhere because there’s no clear way push it to a point where an industry partner might be interested or can associate with the discovery. That’s part of our role, to position these technologies developed through translational research and the researchers behind them towards a better position to build relationships with industry,” said Copeland. As such the evidence LHRI’s researchers gather is further along to a point where industry partners are able to relate.

The institute also works proactively with its researchers to understand what they’re doing from a research standpoint. This involves informal meetings and discussions where the research is looked at from the context of potential intellectual property generation and commercialization opportunities. Through the process each discovery at LHRI is fully evaluated from an in intellectual property and market opportunity perspective prior to deciding whether the institute will invest in the patenting, development or commercialization process and if a decision is made to invest, the institute’s efforts shift towards further validating and prototyping of the discovery to position new technologies with industry partners or receptors.

“We feel the process helps both the researcher and the institute understand that there may be potential regulatory considerations in relation to the technology and likewise on the marketing side it gives LHRI a better understanding of what potential receptors may be out there. Generally it gives us a better understanding of the potential size of market for the discovery. They’re almost two separate evaluations but in the end you have to pull them together,” he said.

Through it all, the idea of helping the researcher and the hope of developing a technology or drug that is applicable to patients is the priority of the institute.

Rarely is profit the focus but it is welcome. According to Copeland, essentially anything that comes out of commercialization is solely used to reinvest back in to support further research.

To date Lawson business development has 30 active technology development, license or option agreements in place and has supported the establishment of nine affiliated start-up and spin-off companies.

As beneficial as translational research has been to LHRI, there are still limitations to its effectiveness. Among them states Hill is its fragmented infrastructure, as well as the lack of funding allotted towards it, and most importantly the number of regulatory burdens present because of its bench to bedside approach. At the top of this list of barriers like most biotech is the lack of funding.

For Lawson, the majority of funding concerns occur during the stages of driving discoveries to market. Most translational research is supported by grants as is the case for Lawson, where the process of working with researchers to drive their discoveries to market is supported with funding coming from the submission of proposals to programs such as the CIHR Proof of Principle (POP), NSER Idea-2-Innovation (i2i), Ontario Research and Development Commercialization Funds (ORCDF) and through other sources such as the Ontario Centres of Excellence. This is either accomplished by Lawson on its own or in collaboration with potential industry partners or licensees that keep LHRI on track, directing the institute to meet certain technological goals. But Hill believes there is still a point at which the private sector needs to come in and partner no matter the initiative.

“Generally it’s very difficult for hospital-based institutes to come up with enough internal investment money to really move things along quickly,” said Hill. “In this regard Lawson has been very lucky but there comes a point where there needs to be investment, to develop a technology to prove that its effective and should be put into widespread public use whether it’s a drug or device.”

Copeland agrees, and this is part of the reason Lawson has pushed hard to collaborate with industry partners. A by-product of these collaboration efforts has seen technology-revenues at Lawson average $2.0 million per year over the last three years. In all, the institute maintains agreements for more than 1,800 basic and clinical studies amounting to more than $60 million in external research funding each year, with over 25% of these 1,800 studies being performed on behalf of industry sponsors including Phase I to IV clinical trials required in support of product regulatory approvals. Without these industry sponsors, much of the research being accomplished would not be possible.

Similarly, Hill believes that the health industry itself also has a large financial incentive to invest in translational research conducted by translational medicine groups such as Lawson and in a sense they should be more participative in dictating its direction.

“A whole cycle of identification of need, of commissioning of research and then of translation of that research back into care needs to be present on the part of health policy makers,” said Hill. “Ideally the research questions would be formulated out of the health care sector by health policy makers. The researcher’s job therefore is to provide the solution.”

“I think governments have acknowledged this need somewhat and so have health policy makers,” said Hill.

An example Hill gives relates to the government of Ontario’s decision a few years ago to target cancer and its push for the development of novel cancer drugs.

“There were very few new cancer drugs actually coming into clinical evaluation at the time even though there were plenty of basic science discoveries suggesting that there were novel drugs that could be developed. So they specifically targeted money towards improving the flow of potential new drugs therefore taking a more active role in regulating it and managing it.”

The example was a successful one according to Hill because it shows how a seamless linkage between the discovery, the translation, the investment and then ultimately a link to health policy formulators is supposed to work and thus how to take the discovery into everyday healthcare.

But the responsibility to make the process work doesn’t fall on government and policy makers alone he argues. “Scientists and health institutes also have to take more responsibility in their research with the idea of its bedside applications too, to identify where there is a need, to find a solution to that need and to take it as far as they can towards the evidence base that would drive health policy,” he said.

This is a lesson that Hill said the institute has learned first hand in developing technology. “There have been cases where we’ve made all the right research advances and there was no health policy in place to allow for the implementation of our research into care. We learned from this example, that applying research purely to make advancement is only half the equation. You also need to work with health policy makers to make sure that it is timely to translate your discovery into health policy because if you don’t have the two together, essentially you’re doing research that sits on a shelf and thus wasting resources,” said Hill.

And for Hill that’s what translational research is all about, taking responsibility for the research and not just in creating knowledge but rather creating it for a purpose and passing that knowledge through to an endpoint.