Nurturing the Clinical Research Leaders of Tomorrow

GOOD REGULATORY SCIENCE IN ASIA/PACIFIC: PART 2 365 Nurturing the Clinical Research Leaders of Tomorrow Feng-Pin Chuang, MD Tri-Service General Hospital, National Defense Medical Center, Wing-Kai Chan, MD Departments of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; National Center of Excellence for Clinical Trials and Research Center, Taiwan Min-Hui Chen, MD, MS Division of Clinical Sciences, Yen-Huei Chang, MD, MS Chih-Shung Wong, MD Tri-Service General Hospital, National Defense Medical Center, Herng-Der Chern, MD, PhD Executive Director, Center for Drug Evaluation, Well-designed and performed pivotal trials are critical in providing the efficacy and safety of a new drug for regulatory approval. The success of clinical drug development relies on the ability of clinical trial leaders to design and conduct international clinical studies. Physicians can do good clinical practice quality trials by following the protocols accurately but may not be able to design a complicated trial or lead an international clinical trial team. Clinical trial leaders are rarely born but have to be trained and learn through clinical research experience. Academic centers and drug industries have identified this need and proactively designed programs to nurture the clinical trial leaders of tomorrow via multidisciplinary programs. Using Taiwan as an example, the government has set up a Center of Excellence for Clinical Trials and Research (CECTR) in four medical centers. These national CECTRs complete a nationwide clinical trial network; strengthen clinical trial and clinical research infrastructure; set up national clinical trial and translational research centers; provide education and training for clinical researchers, doctors, nurses, and pharmacists; and improve quality, capacity, capability, and results of clinical trials. They are among the best in the world. Major pharmaceutical companies sponsored 200 international clinical trials for New Drug Applications in Taiwan in 2007. Our clinical investigators showed their clinical trial leadership by chairing many international clinical trials in Asia and worldwide. A Clinical Trial Academy for the training of clinical research leaders in Asia-Pacific is held regularly at the National CECTR at National Taiwan University Hospital. In collaboration with distinguished speakers from the industry, academia, and the local regulatory agency, promising young physicians from Asia-Pacific are trained in practical small-group workshops. Topics selected included how to perform international investigator meetings, how to write principal investigator (PI)-initiated clinical trial protocols, the concept of new drug development from the perspective of industry, experience in the institutional review board review of investigational new drug protocols, and so on. These investments in human resources have been well reflected in the number of clinical trials performed in Taiwan. Other than Australia, Taiwan has the highest number of PI-initiated clinical trials in Asia. We believe a good clinical research environment can attract young physicians to develop careers in clinical research and become clinical trial leaders of tomorrow. Key Words Clinical trial leader; Clinical researcher; Clinical trial; Clinical research; Academic medicine; Taiwan Correspondence Address Herng-Der Chern, MD, PhD, 1F, No. 15-1, Sec.1, Hangjou S. Road, Taipei 100, Taiwan (email: hdchern@cde.org.tw). INTRODUCTION Clinical research, defined as any investigation involving human subjects, intends to discover or verify the clinical, pharmacological, and other pharmacodynamic effects of investigational new products; to identify any adverse reactions to investigational products; and to study absorption, distribution, metabolism, and excretion of investigational products with the objectives of ascertaining the safety and efficacy of the product. Clinical research consists of a wide spectrum of research activities such as clinical trials, translational research, epidemiological research, health service research, and outcomes research. Clinical research is critical in translating the results of basic science into applicable health care products and services (1). Clinical trials must follow the guidance of good clinical practice (GCP), which is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. GCP compliance provides assurance that the rights, safety, and well-being of trial subjects are protected, consistent with the Declaration of Helsinki, and that the clinical trial data are credible (2). Testing of new medical treatments has become global. Beyond North America and Europe, Asia is involved in more sponsored trials Drug Information Journal, Vol. 43, pp. 365 369, 2009 0092-8615/2009 Printed in the USA. All rights reserved. Copyright 2009 Drug Information Association, Inc. Submitted for Publication: January 20, 2009 Accepted: February 15, 2009

366 GOOD REGULATORY SCIENCE IN ASIA/PACIFIC: PART 2 Chuang et al. (18.1% of all protocols globally) than any other emerging region (3). Contributing 5.9% of global clinical trial sites, Asia is second to Eastern Europe (8.9%) in emerging regions. India, Korea, and Taiwan stand out as the most active locations of multinational industry-sponsored trials in Asia. According to the data from the USbased trial register (www.clinicaltrials.gov) on January 31, 2008, the number of clinical trials in Taiwan (573) is second to Australia (665) in the Asia-Pacific region. The globalization of sponsored clinical trials has provided opportunity for Taiwan to attract international companies to the region and development of local life science industries. Over the last four years, the number of multinational clinical trials sponsored by the industry increases 10 22% every year. More investigators will be needed due to the increasing number of clinical trials in Taiwan. Well-designed and performed pivotal trials are critical in proving the efficacy and safety of a new drug for regulatory approval. The success of clinical drug development relies on the ability of clinical trial leaders to design and conduct international clinical studies. Physicians may do good GCP quality trials by following the protocols accurately but may not be able to design a complicated trial or lead an international clinical trial team. Clinical trial leaders are rarely born but have to be trained and learn through clinical research experience. Academic centers and drug industries have also identified this need and proactively designed programs via a multidisciplinary approach. Given the limited patient pool and pharmaceutical market, Taiwan has aimed high to nurture the clinical trial leaders of tomorrow in a strategic approach. LIMITATIONS FOR YOUNG PHYSICIANS TO BE CLINICAL RESEARCHERS In Taiwan, clinical researchers encounter problems similar to those of researchers in many other regions of the world, such as rising health care costs, slow results, inadequate funding, mounting regulatory burdens, fragmented infrastructure, and a shortage of qualified clinical investigators and willing study participants (1,4 12). Specific obstacles for young physicians to become clinical researchers in Taiwan include: 1. Lack of clinical research training programs 2. Heavy clinical service load, financial pressure, and lack of funding 3. Lengthy clinical subspecialty training and additional clinical research training 4. Uncertain prospects for promotion and lack of role models LACK OF CLINICAL RESEARCH TRAINING PROGRAMS Until a few years ago, Taiwan lacked clinical trial research training courses for medical students, resident doctors, fellows, or attending doctors. There was even less understanding of the multidisciplinary principles for new drug clinical development in terms of regulations, ethics committees, the market, legalities, intellectual property, and so on. CLINICAL SERVICE, FINANCIAL PRESSURE, AND FUNDING The clinical service load of young physicians is heavy for them to generate clinical revenues for their institutions and earn their salaries. In many medical centers, financial support for clinical researchers is limited. The extra years required for clinical research training after specialist training may result in reduced salaries, adverse financial pressure, and family objections for the research trainees. Many young clinical researchers lack experience in grant writing and hence have decreased success in obtaining financial funding or sponsorships. Only doctors who can secure independent funding early in their careers are able to become successful clinical investigators. Physicians without independent funding may have to rely on the availability of hospital funding. Unfortunately, in this era of managed care when hospital profits are very limited, faculty members without independent clinical research funding must increase their clinical service load to maintain their income and have no time left for any research efforts. Even though conducting company-sponsored trials may generate some financial return for the

Nurturing Research Leaders of Tomorrow GOOD REGULATORY SCIENCE IN ASIA/PACIFIC: PART 2 367 physicians, this is not very attractive to the brightest young physicians unless they can have some intellectual contribution and academic reward via publication. LENGTHY CLINICAL SUBSPECIALTY TRAINING AND ADDITIONAL CLINICAL RESEARCH TRAINING Most physician-scientists have to complete the clinical training for a medical subspecialty before they can begin their research training. In Taiwan, the length of subspecialty training is increasing from four to six years. Many physicians do not want to spend additional years of training to develop a clinical research career with no additional incentives but extra work. ACADEMIC PROMOTION AND CLINICAL RESEARCH Basic science studies are more useful for promotion than clinical research in Taiwan. It is much easier and quicker to publish articles in basic science research compared to clinical trials and clinical research in general. Moreover, the funding success rate for clinical trial proposals is much lower than for basic science proposals. Medical schools in Taiwan do not value clinical research in the faculty promotion process. Young clinical researchers have no recognition or promotion opportunities in their career paths. However, clinical research is critical in the advancement of medicine and standard of translating the results of health care. If properly designed and conducted, the results can be published in many prestigious journals and have profound impacts on public health. We need to attract young physicians to become good clinical researchers and nurture the next generation of clinical trial leaders. HOW CAN WE NURTURE THE CLINICAL TRIAL LEADERS OF TOMORROW? The government of Taiwan has taken steps to encourage and support clinical research by streamlining the environment for clinical research, strengthening the infrastructure of clinical research, and providing funding for education and training in clinical research, such as fellowships in general clinical research centers (GCRCs) since 1999. The Taiwan-Biomed Technology Island Project was initiated in 2005, including the establishment of four Centers of Excellence for Clinical Trials and Research (CECTR) and the Clinical Researcher Award Program, to improve clinical research in Taiwan. GENERAL CLINICAL RESEARCH CENTERS In order to strengthen the infrastructure of clinical research, the Department of Health (DOH) of Taiwan has been subsidizing 20 regional teaching hospitals and medical centers to establish GCRCs since 1999. The purposes are to integrate hospital and laboratory resources, develop training programs, set up research management units, and improve the quality of clinical research. The GCRCs also provide a forum for education and career development in clinical research for health care professionals. Therefore, GCRCs serve as an important model for young clinical researchers in learning about clinical research. TAIWAN-BIOMED TECHNOLOGY ISLAND PROJECT In 2005, the DOH launched the Taiwan-Biomed Technology Island Project, which provides five years of funding of NT $15 billion (US $500 million) for programs in National Health Information Infrastructure, Taiwan Biobank, and the National Clinical Trial and Research Project, including four CECTRs in four regional medical centers, and the Clinical Researcher Award Program. NATIONAL CENTERS OF EXCELLENCE IN CLINICAL TRIALS AND RESEARCH The government of Taiwan sponsors four national CECTRs. With the existing GCRCs, these national CECTRs complete a nationwide clinical trial network; strengthen clinical trial and clinical research infrastructure; set up national clinical trial and translational research centers; provide education and training for clinical researchers, doctors, nurses, and pharmacists; and Drug Information Journal

368 GOOD REGULATORY SCIENCE IN ASIA/PACIFIC: PART 2 Chuang et al. improve quality, capacity, capability, and results of clinical trials. They are among the best in the world. Major pharmaceutical companies sponsored 200 international clinical trials for new drug approvals in Taiwan in 2007. Our clinical investigators showed their clinical trial leadership by chairing many international clinical trials in Asia and worldwide. CLINICAL RESEARCHERS AWARD PROGRAM In order to train clinical researchers, the DOH of Taiwan has been awarding scholarships to physicians, nurses, pharmacists, and clinical statisticians under the Taiwan-Biomed Technology Island Project Clinical Researcher Award Program since 2005. Two types of research scholarship are available for physicians. Physicians awarded the full-time scholarship will have to spend more than 80% of their normal work hours in clinical research while those awarded parttime scholarships need to spend more than 30%. The Clinical Researcher Award Program also provides physicians interested in regulatory science with scholarships for three months to one year of training in the Center for Drug Evaluation (CDE), Taiwan. Trainees attend daily regulatory activities and have hands-on experience in reviewing investigational new drug protocols under the supervision of senior clinical reviewers. In 2007, five attending doctors each had three-month full-time training in CDE. The third category of scholarship is awarded to experienced clinical researchers to receive three months to one year of training in distinguished institutions worldwide, which will help them to become instructors in clinical research and well connected with international best practice. In the past three years, about 200 clinical researchers in 18 medical institutions have been awarded scholarships through this Clinical Researcher Award Program. CLINICAL TRIAL ACADEMY TO TRAIN CLINICAL TRIAL LEADERS Additional programs for nurturing clinical trial leaders are being provided to researchers to improve their capability in areas of protocol design, conduct, and education. A virtual Clinical Trial Academy for the training of clinical research leaders in Asia-Pacific is held regularly at the National CECTR at National Taiwan University Hospital. In collaboration with distinguished speakers from the industry, academia, and the local regulatory agency, promising young physicians from Asia-Pacific are trained in practical small-group workshops with case studies and role-playing. Topics selected included how to perform international investigator meetings, how to write PI-initiated clinical trial protocols, the concept of new drug development from the perspective of industry, experience in the institutional review board review of investigational new drug protocols, and so on. These trainees are viewed as members of this virtual Clinical Trial Academy. They will have a learning passport that guides their future learning in a systemic approach. These investments in human resources have been well reflected in the number clinical trials performed in Taiwan. Other than Australia, Taiwan has had the highest number of principal investigator (PI)-initiated clinical trials in Asia (13). For these trials, the protocols were designed locally by PI, sponsored by research grants, and intended for publication in the most prestigious journals. Hence, the number of PI-initiated clinical trials can be regarded as a good indicator for clinical trial leaders in that country. CONCLUSION Clinical researchers face great challenges in selecting a career track as physicians in clinical research because of (a) lack of clinical research training programs; (b) heavy clinical service load, financial pressure, and lack of funding; (c) lengthy clinical subspecialty training and additional clinical research training; and (d) uncertain prospects for promotion compared to non clinical researchers. The strategic investment by the Taiwan government to nurture the next generation of clinical trial leaders has shown promising results in the number of PIinitiated or company-sponsored clinical trials, with the trend of simultaneous global develop-

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