2020 Volume 2 Issue 2 Pages 36-41
Translational science comprises studies conducted to apply medical knowledge and innovative technologies developed in basic research in real-world settings for the prevention, diagnoses, and treatment of diseases. Translational medicine is challenging and requires input from individuals with multiple areas of expertise. Thus, programs designed to train young researchers who wish to work in drug development are needed. Here, we report the establishment of an intensive training program, called the Translational Science and Medicine Training Program (TSMTP), which provides training for young researchers in academia and pharmaceutical companies and staff members at industrial, academic, or governmental agencies throughout Japan. TSMTP disseminates information on the latest technology used by the National Center for Advancing Translational Sciences (NCATS) at the US National Institutes of Health (NIH). Through this program, young researchers can receive an overview of drug development from instructors who are experts in each step of the process, allowing them to apply this knowledge for future research.
● Two full days of intensive lectures and group discussion at the TSMTP bootcamp.
● One full day of intensive lectures and consultation at a TSMTP workshop.
Many pharmaceutical companies have recently begun the promotion of open innovation to foster creation of novel drugs [1, 2]. Drug discovery and development is highly challenging and requires the integration of expertise from diverse disciplines . Despite the major achievements made in basic research in Japan, a system of translational science that links these new findings to drug development is still in progress. Indeed, the ability to “translate” and comprehend language used by experts in industry, academia, or government personnel is required to meet this aim. To promote translational science in Japan, it is important to properly train the investigators who will perform this work. Several programs related to drug development have been set up in Japan, but no single program has offered training in a comprehensive set of skills relevant to the process in Japan.
The National Center for Advancing Translational Sciences (NCATS), a part of the US National Institutes of Health (NIH), has created training opportunities for high school, undergraduate and graduate students, and postdoctoral fellows (https://ncats.nih.gov/training-education/training) to help them acquire skills necessary to progress basic biomedical discoveries into clinical applications. One such program, the Translational Science Training Program (TSTP), is an intensive training program where intramural postdoctoral fellows and graduate students can learn how to apply basic scientific knowledge to the creation of a novel therapeutic, device, or diagnostic . The TSTP provides two full days of intense bootcamp training and a one-day preclinical development workshop. At the bootcamp, experts in varying areas teach trainees about specific topics relevant to translational research. The pre-clinical development workshop focuses on the methods and technologies required to perform translational science and covers topics from target validation to Investigational New Drug (IND) submission. After the TSTP program, the NCATS found that 37.8% of participants were still in training positions; however, of the remaining participants, 75.7% held a position in the translational science field, and 24.3% were pursuing scientific careers outside the translational field .
To train young people to understand the basics of translational thinking and to perform drug discovery in the future, we (the authors of this paper) have established a program called the Translational Science and Medicine Training Program (TSMTP) to provide an overview of drug development in Japan. To achieve this, we formed a working group, modeled on the TSTP, to discuss the content of a program that would be suited to the Japanese pharmaceutical industry. This group was composed of translational science experts from the Incubation Center for Advanced Medical Science (ICAMS) at Kyushu University, the Japan Pharmaceutical Manufacturers Association (JPMA), the Japan Agency for Medical Research and Development (AMED), and NIH/NCATS. Our working group met seven times and discussed the TSMTP program content, participants, and instructors. Here, we have reported on the establishment of the TSMTP in Japan and have presented data relevant to its participants.
We held the first TSMTP bootcamp at The University of Tokyo on August 26 and 27, 2017; the second was held at the Nihonbashi Life Sciences Building (in Tokyo) on August 25 and 26, 2018; and the third was held at the same venue on August 31 and September 1, 2019. As planned, like the TSTP, the TSMTP was set up as an intensive training program with two days of bootcamp and a one-day workshop. The workshop was held separately to the bootcamp. Target participants in the bootcamp were young researchers from academia and pharmaceutical companies and staff members at industrial, academic, or governmental agencies throughout Japan. We also permitted individuals to participate as an observer if they were not necessarily young researchers or able to take part in the full program. The course was team-taught by experts in a variety of fields from academia, regulatory authorities, and pharmaceutical companies in Japan (Supplementary Table 1).
The agenda of lectures and discussion for both days is shown in Table 1. The instructor initially explained the program goals, discussed the current state of translational science in Japan, and outlined the drug development process. Next, the instructor emphasized the importance of the target product profile (TPP) and a clinical development plan (CDP). In this module, participants learned the strategies and tactics used in the process of drug development. In the “Intellectual property and patents” module, participants were provided an outline of intellectual property and the importance of patents for drug development, with a focus on requirements in academia. The instructor also explained the importance of contracts in setting up cooperative agreements between academia and industry. At the second bootcamp, a “Project management” module was added to stress the importance of project management in clinical studies and in the analysis of quality and risk management.
TPP, Target product profile; CDP, clinical development plan; GLP, good laboratory practice; GMP, good manufacturing practice; CMC, chemistry, manufacturing and controls; GCP, good clinical practice; PMDA, pharmaceuticals and medical devices agency; COI, conflict of interest.
In drug development, most new molecular targets are identified in basic research laboratories where drugs can be evaluated for their effects on the target molecules. In reality, only a small percentage of drugs identified in this manner are approved and used therapeutically [5,6,7]. In our program, we focused in particular on the translational development of small molecules. In the module “Target identification and validation”, the instructor reviewed the methods of target identification and validation in drug discovery using case studies, and participants were introduced to useful strategies that increased the probability that a drug will proceed through the development process. In the “Assay development” session, the instructor outlined assay methods and strategies used for drug development, from in vitro assay development to the validation of drug effects in vivo. In the “Medicinal chemistry” session, the participants learned about the measures used to increase drug safety by examining case studies from pharmaceutical companies.
After the drug screening period, safety, efficacy, manufacturing, and quality design become important considerations. In the module “Non-clinical studies and good laboratory practice (GLP)”, the instructor presented GLP procedures in Japan, preclinical studies (with a focus on non-clinical studies, such as safety and toxicity tests), and case studies relevant to pre-consultation at the Pharmaceuticals and Medical Devices Agency (PMDA). In the “Good manufacturing practice (GMP) and Chemistry, manufacturing and controls (CMC)” session, the instructor reviewed quality assurance, the outline of CMC procedures, and details relevant to pharmaceutical formulation.
After pre-clinical studies in animal models, investigational drugs are normally evaluated for safety and efficacy in human (clinical) trials. In the module “Investigator’s brochure”, the instructor reviewed the investigator’s brochure and other documents relevant to drug development. The module “Good clinical practice (GCP), clinical trial notification, and clinical development” included information related to the type and processes of clinical trials, GCP, and related laws and regulations. In the module “PMDA-evaluation and review of new drugs”, an invited instructor from the PMDA explained the role of the PMDA and pre-consultation, as well as provided an outline of new drug evaluation. The module “Ethics & conflict of interest (COI) management” provided a discussion of various ethical and legal frameworks related to medical research, as well as ethical guidelines for medical research on humans and COI management. In the module “Marketing and product launch”, students learned marketing strategies and about the current status of medical innovation.
In the final module, small discussion groups were utilized. At the first TSMTP bootcamp, participants formed four groups; each group was given different task based on the program content (see Table 2). After the discussion, participants gave a presentation on the important points learned relevant to the task and discussed these points with instructors. To improve the group discussion, for the second bootcamp, we separated participants into several groups assigned the same task, which involved a non-clinical study related to small molecules used to treat a standard treatment-resistant tumor (Table 2 and Supplementary Table 1). In Japan, research into regenerative medicine, including cell and gene therapy products, has recently progressed from basic scientific investigations to clinical applications [8, 9]. Thus, we created a task related to cell-therapy (regenerative medicine) for standard treatment-resistant tumor at the third TSMTP bootcamp (Table 2 and Supplementary Table 2). At the second and third TSMTP bootcamps, participants discussed the tests necessary for a non-clinical study based on guidelines prepared by PMDA within their groups and, subsequently, with instructors and other participants.
We have now held three TSMTP bootcamps. The first included 12 participants (mostly graduate students) and four observers (Fig. 1A). For the second, we obtained financial support from the AMED and were able to almost double the number of participants (participants, 25; observers, 18) and to include participants from pharmaceutical companies and industrial-academic-governmental agencies (Fig. 1A and 1B). At the second TSMTP bootcamp, the number of graduate students was decreased, but the number of academic researchers was increased (Fig. 1A and 1B). At the third TSMTP, bootcamp enrollment was increased to 53 participants (mostly young researchers from pharmaceutical companies) and 12 observers (Fig. 1C). Thus, the number of participants has increased yearly (Fig. 1). The participant surveys indicated that the modules “TPP & CDP” and “Group discussion” generated the most interest at all three TSMTP bootcamps (Fig. 2).
Pie charts showing the number and attributes of the Translational Science and Medicine Training Program (TSMTP) bootcamps. Attributes and number of participants and observers for the first (A), second (B), and third (C) TSMTP bootcamps.
Survey designed to evaluate the participants’ interest in lectures given at Translational Science and Medicine Training Program (TSMTP) bootcamps. The number of answers indicating interest in particular discussions provided at the first, second, and third TSMTP bootcamps. Multiple answers were allowed.
The first TSMTP workshops, in 2018, were conducted at Kyushu University on January 6 and at The University of Tokyo on January 8. The second took place at Nihonbashi Life Sciences Building in Tokyo on January 29, 2019. The demographics of the workshop participants were similar to those who attended the bootcamps. For the workshop, the instructors included persons involved in translational science at the NIH/NCATS and experts working in Japanese pharmaceutical companies (Supplementary Table 2).
The workshop consisted of a full day of lectures and group discussion and included instructors from NIH/NCATS (Table 3). The working language was English. The staff of Kyushu University first introduced the TSMTP and described the current status of translational science in Japan. In the module “Biologically and pharmacologically relevant assay development and design”, the instructor reviewed the critical points related to assays used in drug discovery and development, as well as biochemical and cell-based assays used for high-throughput screening developed at the NIH/NCATS. In “Concepts in Medicinal Chemistry”, the instructor outlined the compound progression pathway using examples, such as kinase inhibitors. In the module “Overview of NCATS drug discovery and development technologies”, information on high throughput screening systems under development at NCATS was provided. In the module “Case study: pre-clinical drug discovery”, the instructor explained each step of drug discovery and biological evaluation by using a case study. In the module “Small group discussion of a translational science exercise”, participants presented their own research seeds and discussed them with instructors from NIH/NCATS.
We held the TSMTP workshop twice and canceled the third owing to the COVID-19 global pandemic. The first included nine participants (from Fukuoka) and eight participants and seven observers (from Tokyo) (Fig. 3A and 3B). Similar to the TSMTP bootcamp, we received AMED support for the second workshop. For both, individuals from academia were the main participants and participants from both pharmaceutical companies and industry, academia, or government joined as observers (Fig. 3). We also conducted participant surveys (Fig. 4). In the first workshop, participants found “Biologically & pharmacologically relevant assay development & design” most interesting, whereas “Case study: pre-clinical drug discovery” was the most interesting in the second workshop. Overall, participants in both found the lectures important and informative (Fig. 4).
Pie charts showing Translational Science and Medicine Training Program (TSMTP) workshop participant attributes and numbers. The attributes and numbers of participants and observers for the first TSMTP workshop at Kyushu University (A), the first TSMTP workshop at the University of Tokyo (B), and the second TSMTP workshop at the Nihonbashi Life Sciences Building (C).
Survey designed to evaluate participant interest in lectures at Translational Science and Medicine Training Program (TSMTP) workshops. The number of answers indicating interest in particular discussions provided at the first and second TSMTP workshops; multiple answers were allowed.
We established and conducted the TSMTP in cooperation with the JPMA, AMED, and NIH/NCATS. Through this program, young researchers received an overview of drug development that should advance their knowledge and benefit their future research. Our goal is to allow TSMTP participants to become more active researchers in translational science in Japan and, in future, to promote translational science worldwide. To assess the effects of this program, we will survey the career status of past participants of this program in the near future.
Kyushu University has been selected as a Translational and Clinical Research Core Center (TCRCC) and has conducted several innovative programs. We will soon ask for authorization to introduce this project starting in 2022 (https://www.kantei.go.jp/jp/singi/kenkouiryou/tyousakai/dai21/siryou4-1.pdf). We also expect that educational programs, such as TSMTP, will be held at newly authorized TCRCCs in the near future (https://www.mext.go.jp/b_menu/shingi/chousa/shinkou/054/gaiyou/1421360.htm).
This work was supported by the AMED [grant numbers: JP18lm0203009, JP19lm0203009]. The authors acknowledge the leadership, guidance, and support of Dr. Eishi Baba (Director of Center for Clinical and Translational Research (CCTR)) and Dr. Yoichi Nakanishi (previous Director of CCTR). Special thanks are owed to co-organizers of the TSMTP: Dr. Toshiyuki Isoe (Hospital Clinical Research and Medical Innovation Center Hokkaido University), Dr. Sumimasa Nagai (Hospital Translational Research Center The University of Tokyo), and Dr. Takahiro Inoue (Department of Medical Innovation Osaka University), and mentoring supporters: Dr. Anton Simeonov, Dr. Matthew Hall, Dr. Nathan Coussens, and Dr. Samarjit Patnaik (NIH/NCATS). We would also like to thank Dr. Ayako Yumine (Kyushu University), the staff of JPMA who were instrumental in launching this program, the instructors of the TSMTP (Supplementary Table 1), the administrative staff of ICAMS Kyushu University, and E. Lamar for his critical reading of the paper.