Our Mission is Translation
The mission of the BIH is medical translation. The BIH translates findings from biomedical research into novel approaches for personalised prediction, prevention, diagnostics and therapy. Conversely, it utilizes clinical findings to help researchers in developing novel approaches. The aim is to deliver relevant medical benefits for patients - turning research into health.
What approach does the Berlin Institute of Health take to address the challenges of medical translation? How can the success of translation be measured? The BIH has summarised this in a mission paper as outlined below.
What are the challenges and opportunities of translation?
Currently, the translation of innovative approaches into clinical practice requires much in the way of time and resources, and unfortunately is often not as successful as it could be. Available data shows that the number of approved drugs per billion USD (adjusted for inflation) in research investments has on average halved every nine years since 1950. To change this, various challenges need to be overcome:
Complexity of the Translational Value Chain
A major reason for this decline is the complexity of the steps required along the translational value chain, from innovative idea to real-world clinical application. In addition, a multitude of infrastructures and technologies, as well as professional groups with different skill sets, are required to contribute to the process and work towards a common goal.
Different Communities and Technical Languages
Another challenge lies in the combinations of people involved in these various stages, who often have different priorities, speak different languages and work in different communities. Translation cannot, and should not, be divided into ‘basic scientific knowledge’ and ‘implementation in clinical practice’. On the contrary, translation-oriented teams and facilities must both be anchored in the clinic, and in the laboratory. The necessary ‘mindset’ for translation can only arise within this context.
Limits of Traditional, Organ-oriented Concepts
Another challenge for medical translation is the pathophysiological limits of traditional, organ-oriented, concepts in medicine and research. These promote a deep understanding of individual structures, but do not take sufficient account of the fact that the different functions and structures within an organism are closely linked; physiological and pathological mechanisms overlap, and genetics and the environment affect all organs and systems simultaneously.
At the same time, fundamentally new opportunities are opening up for translational medicine through the digital revolution including new technologies such as: machine learning/artificial intelligence, biomimetic materials, 3D printing, human-on-a-chip, pluripotent stem cells, organoids, genome editing, the dramatically increasing level of detail and speed of molecular analysis (omics: genomics, proteomics, metabolomics), as well as new approaches in diagnostics and therapy development at the cellular level. As an example, Novel Therapies (Advanced Therapy Medicinal Products - ATMP) - a new class of personalized therapeutics at the cellular basis (Living Medicines) - offer new options for more effective translation in the area of academic research.
The BIH is not a typical research institute. Its innovative approach is to utilize a novel concept of clinically-anchored cross-organ systems medicine in a comprehensive translational ecosystem to significantly increase the speed and effectiveness of medical translation. One of the main reasons for the success it enjoys in translational research is the clinical and scientific environment at the Charité and across Berlin, enabling a high degree of interaction due to the proximity of different partners. The MDC (Max Delbrück Center for Molecular Medicine) is central to the development of technologies and new mechanistic approaches.
The translational ecosystem of the BIH
The BIH establishes coordinated structures in one place and thus creates a translational ecosystem. Such an approach enables the various professional groups involved to use their expertise to establish new preventive strategies, develop new diagnostics and effective therapies, and to discover how these options can be effective for patients. The BIH ecosystem bundles a variety of competencies and infrastructures in the vicinity of the Charité clinical facilities, confirming the findings that:
- translational processes are usually not linear, as suggested by the concept of the translational value chain; and
- a variety of skills, infrastructures and support mechanisms are essential for effective translation
As such, this environment allows continuous optimization of ideas and solutions in one iterative ‘bench to bedside’ and ‘bedside to bench’ process. Crucial for the achievement of the BIH mission is the continuous development of the ecosystem as a learning system.
Cross-Organ Systems Medicine
The BIH focuses on cross-cutting issues: for example, digital medicine, and cell-based therapies as innovative drivers and enablers; and not organ-specific approaches such as cardiology and cancer research. The BIH, thus, works across systems medicine, examining processes that arise from the interaction of various organs and systems in the body. The systems medicine translation approach at the BIH is therefore a necessary addition to the disciplinarily oriented approach of the German Centers for Health Research, which uses a decentralized network of expertise at several locations, with each focusing on widespread diseases.
To fulfill its mission, the BIH’s translational ecosystem is based on three components: innovation enablers, translation hubs, and focus areas. These three components provide different support mechanisms for the translational process and the implementation of specific projects with a high level of innovation and translational potential. While the development of the translational environment is a continuous task that affects the entire faculty, highly-relevant questions from the various focus areas can be addressed by experts in the respective translational fields and adapted dynamically to scientific and clinical development.
The basis of the ecosystem is the translation-oriented mindset of all stakeholders involved in the process and the constant support of the faculty in all phases of translation. Developing this is the task of the BIH’s four Innovation Enablers:
The BIH Academy (BIA) continuously promotes doctors and scientists with translational skills and interests, designs specific further-education programs, and identifies group-specific career paths.
The BIH QUEST Center has developed and implemented new approaches to ensure the quality and sustainability of research through all phases of the value chain.
The BIH Translation Booster develops mechanisms and incentives to overcome the hurdles along the chain.
BIH-Innovations promotes the early, and targeted, transfer of innovative ideas into products and clinical solutions at all levels of translation.
The four Innovation Enablers thus create competence, quality, efficiency and promote technology transfer. These four functions are essential in all areas of medical translation. However, as they do not directly address organ-oriented medical questions, they are not usually the focus of translational initiatives. To address this, and add a further dimension to the effectiveness of translation, the BIH has set up the innovation enablers to optimize conditions for the development and maintenance of the translational ‘mindset’ and ‘support’ over the long term.
Each translational institution must select which research and development priorities it wants to focus its activities and resources on. In accordance with the strategic decision for a cross-organ approach, the BIH has selected topics that can make fundamental systems medicine contributions to translation.
The translation hubs represent topics and technologies that will revolutionize medicine across various disciplines in the coming years:
- The translation hub Digital Medicine enables the extensive use of data-based approaches
- Multi-Omics ensures phenotyping at the highest level
- Organoids and Cell Engineering make the targeted modulation of cells and 3D organ cultures usable for innovative, precision-based medical approaches
- The translation hubs support effective translational research through the Clinical Translation hub
The translation hubs link experts* and build up a research community. They develop innovative technologies and methods. They offer excellent scientific services (Core Facilites).
The focus areas bring concrete translational research and development projects into the translational ecosystem. These focus areas are characterized by:
- taking a systems medicine approach
- having a high potential for groundbreaking success in translation
- successful and decisive implementation in the translational ecosystem
Three focus areas have been established at the BIH, each using different elements of the BIH’s translational value chain:
- Regenerative Therapies at the BIH Center for Regenerative Therapies (BCRT)
- Vascular Biomedicine
- Single Cell Approaches for Personalized Medicine
Focus areas are fundamentally dynamic and are continuously adapting to scientific, technological and translational developments.
The integration of both the available expertise necessary for research projects with that not available on site, as well as the piloting of concepts and technologies particularly relevant for translation, is carried out via the dynamic Excellence Fund. High-risk projects with high potential are given the opportunity to show evidence of medical added value through temporary funding and to connect with external funding agencies.
By which criteria does the BIH measure its success?
As the BIH’s translational approach differs significantly from other basic research institutes, it is essential to develop new criteria for evaluating the success of the BIH that go well beyond the usual indicators, such as impact factors or third-party funding. The success of translational research cannot be measured in terms of the number of individual publications and, as a rule, cannot be assigned purely to individuals. Both specific criteria for translational projects and new evaluation principles for researchers working in translational research must therefore be defined.
Specific indicators must focus on the BIH mission, i.e. reflect the relevant medical benefits for patients.
- Introduction of new preventive, diagnostic and therapeutic procedures into the clinic
- Products and launches
- Changes to guidelines, treatment and therapy guidelines
- Returns from sales and licensing
- Social added value (virtual proceeds)
- PROMS (Patient Reported Outcome Measures)
Single steps of translation
These direct indicators only emerge at the end of the successful translation and, therefore, with a considerable delay in the important preparatory steps. However, these contributions are indispensable and can also be measured at short notice. They also need to be assessed and incentivized:
- Proof of principle studies
- Manufacturing permits, etc.
- First in human - studies and clinical studies based on own concepts (IIT)
- Ratio: from number of patents or patent applications to patents being used
- Licensing, spin-offs and corresponding cooperation
Quality and sustainability of translation
Also relevant for the BIH strategy are additional parameters that assess quality and sustainability at all levels of translation, such as:
- Open Access publications
- Open Data/Open Science
- Publication of negative results
- Confirmatory Studies
The BIH is a new type of scientific institution. The involvement in the Charité enables the BIH to strive for new standards on a structural level, that ranges from education – such as the promotion of young researchers into new translational career paths - to quality assurance and structural support in the processes of a research hospital in project selection, recruitment, and entrepreneurial support.