Pediatr Drugs 2009; 11 (1): 67-68 1174-5878/09/0001-0067/$49.95/0

CONFERENCE PAPER

© 2009 Adis Data Information BV. All rights reserved.

Clinical Investigation in Pediatrics Challenges and Opportunities in Toronto, Canada Shinya Ito Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Abstract

We discuss the challenges and opportunities we face at The Hospital for Sick Children in Toronto, ON, Canada in conducting clinical investigation in children. Three areas are discussed: (i) the program structure of the Research Institute; (ii) the Toronto Centre for Phenogenomics as a common platform for preclinical studies across the university campus; and (iii) evolving clinical research infrastructure. Because preclinical and clinical investigation are becoming increasingly resource-intensive, we are witnessing a trend toward functional amalgamation of research teams, centralization of major experimental facilities, and the expansion of research infrastructure at local and national levels. Although these trends are common to clinical research in all age groups, pediatric investigation is further challenged by its relative paucity of research-related human resources, and patient numbers at local and even national levels. To promote drug research in children, these organizational changes in the research framework need to be seen on a much broader international level.

As supplementary information for the overall theme of the Toronto satellite symposium, this summary is a concise account of the three key presentations on pediatric clinical investigation at The Hospital for Sick Children in Toronto, ON, Canada: Physiology and Experimental Medicine Program: Translational Research at SickKids (Dr Palma Ottaviani; see also Ottaviani[1] in this issue of Pediatric Drugs), Toronto Centre for Phenogenomics: Innovations in Preclinical Studies (Dr Colin McKerlie), and Clinical Reearch Infrastructure: Setting the Stage for Studies in Children (Ms Julie Gibson). Clinical investigation in pediatrics at The Hospital for Sick Children is integrated into the academic and clinical missions of the institution. Affiliated with the University of Toronto, the hospital has multiple academic departments on its campus, and it is a main site of the university’s Department of Paediatrics.[2] All research activities are overseen by the Research Institute of the hospital,[3] which provides important infrastructure for investigators and their research programs. An overall trend of research operations in Toronto can be summarized as the disappearance of boundaries of research programs and individual institutions affiliated to the university. For the next several years, this trend is likely to become much clearer in clinical investigation including pediatric drug studies. Like it or not, this is the direction we are heading into, which is driven at

least partly by the increasing complexity of current drug study design and conduct, and the sheer sizes of these studies in both subject numbers and costs.[4] Facing these challenges, our research operations have been evolving, albeit slowly, as described in this article. Physiology and Experimental Medicine Program Studies involving children, including drug-related studies, are conducted mainly by researchers who belong to the Physiology and Experimental Medicine program of the Research Institute.[3] This program is the largest of the six major programs in the Research Institute, and has more than 60 principal investigators. All Research Institute programs are structured in the same way, with a program head who administers the key functions of the program, such as evaluation of investigator performance and seminar organization. Because of its program mandate, the clinical research unit with patient beds is operated by the Physiology and Experimental Medicine program. The program details are described in the paper by Ottaviani[1] in this issue of Pediatric Drugs and also on the website of The Hospital for Sick Children in Toronto.[3] The clear trend within our research institute is more formal collaboration and ‘cross-fertilization’ among individual research teams.

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Toronto Centre for Phenogenomics Although animal experiments are not directly related to pediatric drug studies, the role of preclinical studies using animal models is an important step toward innovative drug development. In particular, some safety aspects such as long-term effects of intrauterine and postnatal drug exposure may be analysed in depth using animal models. In Toronto, all mouse facilities in the research institutes of the university teaching hospitals have been amalgamated into a stateof-the-art mouse center, called the Toronto Center for Phenogenomics (TCP).[5] This center holds 36 000 mouse cages with innovative research facilities in areas including genetics, genomics, physiology, pharmacology and imaging. Dr Colin McKerlie, who is also a member of the Physiology and Experimental Medicine program of the Research Institute at The Hospital for Sick Children in Toronto, directs the TCP. The TCP illustrates an inevitable trend toward centralization of local facilities, which is necessary for the acquisition and efficient utilization of expensive research equipment and expertise. Clinical Research Infrastructure Clinical investigation requires a specific research infrastructure in addition to various fundamental functions such as grant/award administration, training program administration for students and fellows, and computation and biostatistics services. These clinical study-specific needs include a Research Ethics Board (REB), clinical research office, and clinical investigation unit. In Toronto, the system for investigator support and research administration has been under constant evolutionary pressure, as is likely the case in other institutions worldwide. As of 2008, there are two review panels that are under the single REB of the institution, which handles about 30 new protocols every month, excluding chart review studies. Overall, there are about 2000 active human-subject protocols. Partly due to the large number of the protocols and necessity for more detailed science review, we have implemented a formal scientific review process which precedes the REB’s protocol review. These scientific reviews are performed by a committee within the clinical division relevant to the particular protocol. The committee usually comprises two to three members with faculty appointment who discuss scientific merit and provide constructive criticism. The clinical research office supports budget planning of the protocol, development of standard operating procedures, monitoring of studies, and communication with regulatory agencies. In addition, public relations activity for knowledge translation is © 2009 Adis Data Information BV. All rights reserved.

becoming increasingly important after studies are completed. Although these functions are much needed and appreciated, service demand tends to exceed what the institution can offer. Concluding Remarks To maximize our capacity for and quality of pediatric clinical investigation, our efforts have been intensified over the last several years. As described in this article, we have been lucky enough to witness significant improvement in various aspects of pediatric clinical investigation infrastructure in Toronto. However, challenges continue to emerge. Knowledge generation from clinical research and its translation into clinical practice require substantial financial and human resources, which are only partially available (or not available at all). Facing this challenge, research infrastructure, including that for clinical studies, began to be consolidated at many levels into more efficient systems across the entire university campus. Studies themselves are becoming projects of multidisciplinary and multicenter teams. At present, infrastructure consolidation is mainly observed at local and national levels, and less frequently at international levels. However, because of a relative lack of human resources and of research subject numbers, pediatric clinical investigation and drug studies often require large-scale collaboration compared with adult studies. Clinical investigation in children and its supporting structures may need a meta-system with cohesive networks of international research teams. Acknowledgments No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.

References 1. Ottaviani PT. Physiology and experimental medicine: translational research at SickKids. Pediatric Drugs 2009; 11 (1): 71-3 2. Department of Pediatrics, University of Toronto [online]. Available from URL: http://www.paeds.utoronto.ca/site5.aspx [Accessed 2008Nov 14] 3. SickKids. Research institute programs [online]. Available from URL: http:// www.sickkids.ca/researchprograms/ [Accessed 2008 Nov 14] 4. Malakoff D. Clinical trials and tribulations: spiraling costs threaten gridlock. Science 2008; 322: 210-3 5. The Toronto Centre for Phenogenomics. Research and support programs [online]. Available from URL: http://www.phenogenomics.ca/ [Accessed 2008 Nov 14]

Correspondence: Prof. Shinya Ito, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Canada. E-mail: [email protected] Pediatr Drugs 2009; 11 (1)