Bringing together academia’s innovation and pharma’s resources12 January 2018
Tight budgets mean that combining the forces of academia’s innovation with pharma’s resources is happening with increasing frequency. Dr Christopher Milne, associate professor of medicine and director of research at the Tufts Center for the Study of Drug Development, tells Bradford Keen about the popularity of these outsourcing relationships, and why the traditional view of academia and pharma standing in opposition no longer rings true.
There is a well-worn worry in academia: publish or perish. A rather emotive phrase, its logic is simple; if academics do not publish breakthrough research and insights, their careers will soon be over. Those working in the pharma industry, meanwhile, constantly need to guarantee profits and product development in order to earn promotions.
Historically, prevailing opinion has considered these goals in opposition. However, as Dr Christopher Milne, director of research at the Center for the Study of Drug Development at Tufts University (Tufts CSDD), argues, this has been tempered in recent years.
“Research for research’s sake is becoming less attractive as a scientific philosophy – namely, the dilemma of basic versus applied research – in academia and industry,” he says.
Of greater concern, according to Milne, is how medical research is often guided by the dictates of political lobbies and advocacy groups. This can lead to a disparity in therapeutic areas in which advances are taking place, such as cancer, versus those in which innovation seems to be more stagnant, such as cardiovascular disease or musculoskeletal disorders. Consequently, important public health issues can be overlooked and medical needs left unmet.
While these powerful controlling forces persist, circumstances have rendered collaboration between academia and pharma more frequent and increasingly favourable.
A study conducted by Tufts CSDD a few years ago examined more than 3,000 grants involving 450 industry sponsors and 22 medical schools in the US. The findings suggested that these partnerships, while traditionally from different research cultures, have been able to foster the synergy that leads to the development of new medicines and devices.
Indeed, this collaboration has been brought about by evolving demands. Big pharma has been dismantling its early stage R&D capacity for years due, in part, to the US Government’s declining investment in basic biomedical research.
The National Institutes of Health (NIH) budget stagnated at the beginning of the millennium leading to decreased funding for medical research institutions from federal agencies as well as state governments.
Academic medical centres (AMCs) received 69% of their R&D funding from federal, state and local governments in 2009, according to the National Science Foundation. Two years later, NIH funding had dropped to the point where only 18% of all grant applications were approved.
Decreased funding is an issue for AMCs, while diminished profits plague pharma companies. An article published on the Institute for Research in Immunology and Cancer’s website counts the average amount of time for a drug to be developed being between ten and 15 years, with half as many spent trying to identify a target before this can even begin.
After all that, approximately one in 5,000 compounds tested in the pre-clinical phase will become an approved drug, while 90% of compounds entering clinical trials will not be approved.
Consider the cost, time and failure rates of pharma’s in-house R&D as well as the ‘low-hanging fruit’ having already been picked – Milne says scientific challenges that real medical breakthroughs present are increasingly complex – and it’s no surprise pharma has had to look for new ways to innovate.
“For small and medium-sized enterprises (SMEs), the challenges are similar, but there is the added impetus of trying to get through the ‘valley of death’ that often occurs at the juncture from late discovery to early clinical,” Milne argues.
Developing relationships is made a little easier in these cases, however, as there is a degree of familiarity between those at many SMEs and their counterparts in academia – the former having often launched their organisations as spin-offs from academic research programmes.
And collaboration is not just happening in the US; the Association of the British Pharmaceutical Industry (ABPI) launched a tool in June 2017 to help build research relationships between pharma and UK academics. The Library of Initiatives for Novel Collaborations (LINC) is a research database for helping to identify and connect collaboration opportunities. Those looking for partnerships can do so by searching the database for pre-clinical and clinical initiatives, funding, compounds, investigator-initiated studies, equipment and resources, facilitators and challenges.
Just as the prevalence of industry-academia relationships has increased over the years, so too have the different types of structures underpinning these partnerships.
Choosing the right fit, Milne says, depends on the nature of collaboration and the language of the contract. “The former is usually more concerned with the bricks and mortar details,” he notes, “and the latter with the less tangibles resources such as who will do what, intellectual property rights, funding mechanisms, and starting and ending the collaboration.”
A number of relationship models have been widely used in the past, but they are losing popularity. The unrestricted grants model is an example. This is when a pharma company provides an AMC with unrestricted research support so that the academic partner can operate independently, requesting funds when needed.
Companies have also chosen to establish a relationship with a single principal investigator to research a specific problem. In this case, the company grants access to its resources and provides direction on its research goals.
Some pharma companies choose to partner with a specific university in a relationship that includes multiple principal investigators working together on a research topic or area. This requires a master agreement to facilitate how information is exchanged and resources are used to maintain a long-term collaborative relationship.
Also waning is the fee-for-service model, in which a company defines a problem and solution, and contracts universities for these particular projects.
New styles of partnership are being established to challenge older modes of working together. The competition model, for instance, involves a pharma company soliciting ideas and compounds from academic scientists, granting them access to evaluation means, and selecting the most promising leads for further development.
Companies also opt to hire experts from a consortium of universities to collaborate on specific problems or they might donate a large sum to an existing academic institution addressing a problem they wish to solve. These models, while pursued in some case, have yet to become prominent.
Those that have grown in popularity include corporate Mini-Lab or Biocluster in which company researchers combine the use of university labs and facilities, as well as the expertise of academic scientists with their drug development capabilities and resources.
Academic Drug Discovery Centres (ADDCs) are also becoming a more familiar model. This sees independent centres that share teaching affiliations with universities seeking external collaborations for development with companies or contract research organisations in multi-disciplinary and inter-organisational partnerships.
Risk-sharing models refer to universities sharing part of the financial risk in exchange for companies taking on more control of the research project. They pool resources and assets, and divide proceeds from commercialisation.
An even newer emerging model includes open innovation, which refers to semi-autonomous entities, governed by both partners, pursuing medical needs that do not compete with a company’s existing core. AMCs receive milestone payments, and companies can in-license for a price or cut a partner loose.
Benefits of collaboration
Whatever the means of collaboration, benefits are likely to be reaped by industry and academic partners alike. Pharma wins by getting “broader access to patients, key opinion leaders, state-of-the-art healthcare facilities, breakthrough research, as well as participation in ‘open science’ and publication opportunities,” Milne says.
He argues that the benefits to academia include more consistent access to project and equipment funding, new technology, investigational products and pathways, external support for residents and fellows, on-the-job training, continuing education programme support, as well as commercialisation opportunities for academics who don’t want to go down the start-up route.
In a modern knowledge economy in which data abounds, Milne says, “University-industry collaborations provide better access to the raw materials such as the investment and intellectual capital that are necessary to create compelling data to achieve the quantum of proof for a specific project.”
For instance, in the Tufts CSDD study of more than 3,000 AMC-industry grants between 2008 and 2010, the amount averaged at $100,000. The implication, Milne says, is that money doesn’t go to ‘moonshots’, but rather studies that target specific problems or research questions.
A useful way to think about these collaborations is in terms of procurement, where “risk-sharing and resource-sparing” are definitive considerations. “Problems that typically arise with patient and investigator recruitment, and procurement of bio-samples are something the university brings to the table, as well as access to comparator drugs,” Milne says. “Whereas the industry partner usually provides the study drug and funding.” Facilities, equipment, staff and experts tend to be provided by both parties.
Challenges can arise no matter what type of agreement or model is chosen. These are the same as “disputes and disruptive events that plague any business relationship,” Milne says.
There may be disagreements on how to proceed at critical junctures in the project, for example. Industry, for instance, may decide to shelve technology because of the strategic priorities of the company, or lack of sufficient cash flow. Perhaps industry might have problems with the quid pro quo of externalising not only some of the work, but also some of the control.
On the other hand, academic researchers may not be able to handle compromising their focus from whatever draws their intellectual curiosity. This would likely lead to a lack of responsiveness to the pressures of a corporate lab.
It also depends on the type of partnership agreed to. Collaboration with multiple players from the private and public sectors can lead to ‘consortium exhaustion’ in which research-active companies and big-name universities overextend themselves. Additionally, problems sometimes arise when partners do not adhere to the agreement, or when goals and leadership are not properly defined at the beginning stages.
Partnerships will need to navigate the potential hurdles and juggle the competing desires of ‘publish or perish’ with ‘products, profits and promotion’. However, the prevailing scientific philosophy, as well as the logistical and economic circumstances warranting collaboration, will ensure these relationships continue to thrive.