BioNanoMat 2016; 17(1-2): 89–92
aFranziska Duda and Esther Lipokatic-Takacs: These authors contributed equally to this study.
*Corresponding authors: Franziska Duda and Esther Lipokatic-Takacs, Department of Otolaryngology, Hannover Medical School, Feodor-Lynen-Str. 27, 30625 Hannover, Germany, Phone: +495115327303, E-mail: Duda.Franziska@mh-hannover.de (F. Duda); Lipokatic-Takacs.Esther@mh-hannover.de (E. Lipokatic-Takacs) Anneke Loos: Biocompatibility Laboratory BioMedimplant, Hannover Medical School, Hannover, Germany
Nico Lüdtke: Faculty I, Institute for Social Sciences, University of Oldenburg, Oldenburg, Germany
Mathias Wilhelmi and Axel Haverich: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany
Andreas Kampmann: Clinic for Cranio-Maxillo-Facial Surgery, Hannover Medical School, Hannover, Germany
Henning Voigt and Thomas Lenarz: Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Cornelius Schubert: Artur Woll-Haus, University of Siegen, Siegen, Germany
Manfred Elff: NIFE, Hannover, Germany
Letter
Franziska Duda
a,*, Esther Lipokatic-Takacs
a,*, Anneke Loos, Nico Lüdtke, Mathias Wilhelmi,
Andreas Kampmann, Henning Voigt, Cornelius Schubert, Manfred Elff, Thomas Lenarz
and Axel Haverich
Institutional and sociopolitical factors in
supporting clinical translation: the case of
biomedical implant research in Hannover,
Germany
DOI 10.1515/bnm-2015-0023
Received December 21, 2015; accepted March 15, 2016; previously published online April 9, 2016
Abstract: Clinical translation denotes a focused and rapid
process of transferring scientific knowledge into clinical practice and patient care. As a new model of innovation it has gained importance in the biomedical research in recent years. To identify the current state of clinical trans-lation within the routines of hospital based research, we examine structures of the interdisciplinary research con-sortium BIOFABRICATION in Hannover (Germany) with regard to translational strategies. Moreover, we illustrate general requirements and infrastructural conditions, which are essential to establish a top-level translation center. Consequently, a translational training programme,
standardized processes for documentation as well as a platform to support the communication between trans-lational stakeholders were introduced. As an outlook the framework conditions will be evaluated on translational efficiency. The acquired knowledge will be a first step to develop a guideline for an optimized clinical translation of life science research results. It can be finally used as a role model for the planning and optimization of other translational centers.
Keywords: biomedical research; implants; knowledge
transfer; marketing approval; translational medicine.
Clinical translation – how to define
and how to optimize
In the last 10 years the term “clinical translation” has been commonly used in medical research [1]. Its multidimen-sional and complex meaning lacks a clear and distinct understanding in the literature [2, 3]. Despite these mul-tidisciplinary efforts, there is no single or binding defini-tion of what clinical transladefini-tion exactly means.
Basically the definition of translation in medical research context implies a more rapid transfer of scientific research findings into medical practice, whereby the suc-cessful launch of a medical product could also be meant (Figure 1).
On one side, clinical translation of medical products would be a successful market entry that can be used clini-cally or commercially. So a definition could be framed in terms of reimbursement of a medical product within the healthcare system.
Other researchers differentiate between two “trans-lational blocks.” Block one means the transfer of new
90 Duda et al.: Institutional and sociopolitical factors in supporting clinical translation Academic research idea Research in cooperation with industry Industrial development, prototype
Pilot production Clinical trial
Marketing approval (CE-marking) Health economics study Reimbursement of healthcare system Series production, market launch
Figure 1: Idealized way from “bench-to-bedside”: The transfer of academic research ideas/prototypes to patient care is not always a straight route. Development prototype Series production, market launch Establishment in fees catalogues (Reimbursement) Health economics study Marketing approval Clinical study Production of small series Developement Prototype II
Large animal study Small animal study In vitro tests
Figure 2: The long way of a medical product into market.
The reasons for forward (green arrows) and backwards (red arrows) movements have to be examined to optimize the process.
processes (Figure 2) is crucial so that research and knowl-edge do not get “lost in translation” [3]. Improvements in bridging the gap (“valley of death”) between scien-tific discovery and health service delivery are relevant for both funding agencies and industrial partners [5]. The valley of death describes the period when an inno-vative medical product has been developed but its mar-ketability or its practicality has not been proved for full commercialization [6, 7].
But first of all, translation is essential to ensure that potentially significant health improvements and innova-tions can reach respective patients. While talking about the translational process of medical products such as implants, it is necessary to distinguish between the mar-keting authorization of a product and the reimbursement within the health care system.
Case study: biomedical implant
research in Hannover, Germany
Our aim is to analyze current translational strategies for Germany using the interdisciplinary research consor-tium BIOFABRICATION located in Hannover, Germany, as a case to achieve insights into clinical translation pro-cesses. The collaboration BIOFABRICATION is embedded into a well-equipped academic research side of the Han-nover Medical School (MHH), Leibniz University Hanno-ver (LUH) and the HannoHanno-ver UniHanno-versity of Music, Drama and Media (HMTMH). BIOFABRICATION is closely related works hand in hand with to the Lower Saxony Centre for Biomedical Engineering, Implant Research and Develop-ment (NIFE). The founders of NIFE are the LUH, the MHH and the University of Veterinary Medicine Hannover (TiHo). All these universities are located in Hannover and have different histories. Since working groups from various biomedical disciplines come together in a new research building for interdisciplinary work on new medical products, the NIFE is supposed to facilitate and generate better strategies for clinical translation. findings gained in the laboratory into the development of
new methods, therapies or devices and their first testing in humans. Whereas block two describes the translation of results from clinical studies into clinical practice [4].
In this paper, we define clinical translation as the transfer of ideas and findings from clinical practice into interdisciplinary research and back to clinical practice, including the reimbursement of a medical product within the healthcare system (Figure 2). Thus, clinical translation should be a vital component of practice-based biomedical research and health care improvement.
Currently the pace of basic biomedical discoveries is accelerating but the step from “bench-to-bedside” is not keeping up with this trend in the same way. Translational research points to the increasing difficulties in managing the divergent academic, economic and clinical interests in complex medical innovation processes.
Since basic research often fails to develop into market-able solutions, a detailed understanding of translational
Duda et al.: Institutional and sociopolitical factors in supporting clinical translation 91
The BIOFABRICATION projects which follow different translational strategies focus on the development of innovative personalized implants in different medical fields, as otolaryngology, cardiothoracic and vascular surgery as well as dental prosthetics.
Understanding and improving the translational process of various medical products into clinical practice and sustainability in health care is an important challenge for the next years which we want to face.
Required infrastructures for
translational centers
Top-levels
The successful transfer of research data into clinical patient care requires special infrastructural conditions. According to Grunseth et al. [8], research centers with translational orientation should focus on three main capacities: preclinical development, clinical develop-ment, as well as business development and licensing. Depending on how many of these main capacities trans-lational centers have implemented, these institutions can be categorized into three levels: Level 1 lists the require-ments for an institution to be called a “translational research organization.” Level 2 should be the goal for all
organizations that do translational research. Level 3 com-pletes all what is required according to Grunseth et al. [8] to be rated a “superb institution” in terms of translational research. If the model is applied to the situation in Hanno-ver basically all requirements for a highly efficient trans-lational research center (level 1) are fulfilled (Figure 3). Also, some aspects of level 2 are accomplished. Interest-ingly, the situation in Hannover is apparently comparable to the United States: For Hannover and the institutions which have been reviewed in the US by Grunseth and colleagues [8] there is a lack of personnel which is spe-cialized in project management. For the future there is an option for Hannover to reach level 3 if further investments are made to support the existing large animal facilities, to facilitate the formation of multiply good manufacturing practice (GMP) sites and to establish a group of dedicated people specialized in regulatory affairs, project manage-ment and business developmanage-ment.
The stakeholders
An obvious barrier which slows down translational success is a current lack of financial risk management within academic research. Innovative ways of financial risk management and bridge funding to overcome the valley of death have to be identified [9]. For optimizing the transformation of useful ideas into products not only the facility but also a plurality of stakeholders has to be
Business-development personnel to support GMP facilities Large ani-mal/primate facilities Multiple GMP facilities GAP-funding
Level 3 “Superb institution”
Level 2 “Goal for all organizations doing translational research”
Level 1 “Requirements for a translational research organization” Project management personnel on site
Small molecule lead-optimization capabilities on site
GMP fa cility Small animal fa cility Clinical capabilitie s Regulator y af fa irs
personnel on site Phar
macologica
l
kinetic and dynamic
ex
per
tise
IP and contract personnel Quality assuranc
e
personnel
Figure 3: Schematic comparison of required infrastructures for different levels of translational research centers and the translational situa-tion in Hannover (modified from Grunseth et al. [8]).
Green color indicates that structures of required personnel are present and well established. Yellow color indicates structures or personnel who are present but the situation needs improvement. Red color indicates facilities and personnel which are missing.
92 Duda et al.: Institutional and sociopolitical factors in supporting clinical translation
considered. Investigating clinical translation not from a medical but from a sociological point of view, there are three different levels of stakeholders (Table 1). For an effi-cient development of research ideas into medical products they need to act in a concerted way. Clinical scientists and researchers should cooperate with health care providers, patent agents, industrial partners and regulatory authori-ties. Supporting the communication between all parties concerned will be an important consideration [11, 12].
Due to its interdisciplinary network of universities, extramural research centers and industry, Hannover offers a solid platform for excellent clinical translation in implant research. The main reason for this may be due to the excellent infrastructural conditions in Hannover (Figure 3). However, there are still options to improve com-munication with the stakeholders.
As first steps, a training programme to provide knowl-edge about translational aspects and to offer a platform for communication between stakeholders was devel-oped. Moreover, standardized processes for an adequate documentation of research data were implemented. The efficiency of the provided framework conditions on trans-lational success will be evaluated by a more detailed investigation of the translational background knowledge of the stakeholders as well as the communication between Table 1: Overview of different stakeholders in the translational process.
Level Participants Teams
Macro EU/State/Country/Region/Patient representatives/Health insurance/Med. Providers/Lobby
Meso (Self-) Government/Federations/ (Med.) Associations/Academ. Research Institutes and – Associations/Industry/ Hospitals
Micro Health Professionals/Scientific Professionals/Scientific and technical staff/Other employees/Patients Modified according to Offermann [10].
science, clinic and industry. The results should be used to further improve knowledge and communication and to give additional assistance via translational consulting and training and also provide guidelines for individual research groups. Such written guidelines could be applied to other translational centers, supporting the process of developing and marketing of medical devices out of bio-medical academic research outside NIFE.
Acknowledgments: This work was funded by the
Volkswa-gen Foundation and the State of Lower Saxony.
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