Institutional and sociopolitical factors in supporting clinical translation: the case of biomedical implant research in Hannover, Germany

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 multidimensional and complex meaning lacks a clear and distinct understanding in the literature [2, 3]. Despite these multidisciplinary efforts, there is no single or binding definition of what clinical translation 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 successful launch of a medical product could also be meant (Figure 1).

Figure 1:

Idealized way from “bench-to-bedside”: The transfer of academic research ideas/prototypes to patient care is not always a straight route.

On one side, clinical translation of medical products would be a successful market entry that can be used clinically 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 “translational blocks.” Block one means the transfer of new 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.

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.

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 marketable solutions, a detailed understanding of translational processes (Figure 2) is crucial so that research and knowledge do not get “lost in translation” [3]. Improvements in bridging the gap (“valley of death”) between scientific discovery and health service delivery are relevant for both funding agencies and industrial partners [5]. The valley of death describes the period when an innovative medical product has been developed but its marketability 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 innovations can reach respective patients. While talking about the translational process of medical products such as implants, it is necessary to distinguish between the marketing 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 consortium BIOFABRICATION located in Hannover, Germany, as a case to achieve insights into clinical translation processes. The collaboration BIOFABRICATION is embedded into a well-equipped academic research side of the Hannover Medical School (MHH), Leibniz University Hannover (LUH) and the Hannover University 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 Development (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. 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 development, as well as business development and licensing. Depending on how many of these main capacities translational centers have implemented, these institutions can be categorized into three levels: Level 1 lists the requirements 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 completes 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 Hannover basically all requirements for a highly efficient translational research center (level 1) are fulfilled (Figure 3). Also, some aspects of level 2 are accomplished. Interestingly, 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 specialized 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 management and business development.

Figure 3:

Schematic comparison of required infrastructures for different levels of translational research centers and the translational situation 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.

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 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 efficient 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 authorities. Supporting the communication between all parties concerned will be an important consideration [11, 12].

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].

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 communication with the stakeholders.

As first steps, a training programme to provide knowledge about translational aspects and to offer a platform for communication between stakeholders was developed. Moreover, standardized processes for an adequate documentation of research data were implemented. The efficiency of the provided framework conditions on translational success will be evaluated by a more detailed investigation of the translational background knowledge of the stakeholders as well as the communication between 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 biomedical academic research outside NIFE.