Introducing the Office of Clinical Trials Management
The Office of Clinical Trials Management (OCTM), directed by Dr. Eric W. Hoffman, is the management force behind the LICR’s Clinical Trials Program (CTP), centrally coordinating the Institute’s clinical trials and the production of study reagents, and managing the logistical, legal and regulatory aspects of the convergence of laboratory and clinical research in the Institute.
The OCTM exists to facilitate the goals of the CTP which are:
- To conduct, in an academic environment, clinical trials to explore and evaluate the potential therapeutic applications of LICR discoveries in early phase clinical trials
- To provide patient-grade clinical reagents and strong laboratory support for clinical trials, without the need to rely on the pharmaceutical industry for production
Briefly, a clinical trial is initiated by an LICR principal investigator (‘PI’) - a Branch scientist or an Affiliate – proposing a Clinical Trial ‘Concept’. The Clinical Investigation Committee (CIC), which is chaired by Dr. Lloyd J. Old (LICR Director, and Director of the Clinical Program) judges the Concept based on its scientific merit, its contribution to the overall program relating to the study agent (‘Drug X’), and logistical considerations including the amount of Drug X available, capacity for monitoring (if the trial is a vaccine trial), personnel available, and likely patient accrual at the site. If the CIC approves the Clinical Trial Concept, the PI prepares and submits a comprehensive Clinical Trial Protocol, which incorporates any CIC recommendations, to the Protocol Review Committee (PRC). The PRC, which is chaired by Dr. Herbert F. Oettgen, considers the ethical, medical, regulatory, safety, scientific, and statistical issues relating to the proposed trial. The protocol is then reviewed by the local ethics and regulatory authorities of the hospital(s) in which the trial will be performed.
If Drug X has not been used in humans before, the OCTM must lodge an Investigational New Drug (IND) application (Table 1), with the appropriate federal authorities or regulatory agencies that deal with safety and legal issues. If Drug X is based on a recombinant DNA product (naked DNA or recombinant virus) a Recombinant DNA Advisory Committee (RAC) submission must also be made (Figure 2). LICR conducts clinical trials and registers study agents in accordance with the standards and regulations set by the International Conference on Harmonisation (ICH) / WHO Good Clinical Practice standards, and the ICH Technical Requirements for Registration of Pharmaceuticals for Human Use, respectively. These standards and regulations are endorsed by the European Union (EU), Japan, and the United States, as well as Australia, Canada, the Nordic countries and the World Health Organisation (WHO).
Table 1. Investigational New Drug Applications held by LICR as of December 1st 2003.
| Agent | Number of INDs |
| Monoclonal Antibodies | 5 |
| Cancer Vaccine Peptides | 2 |
| Cancer Vaccine Proteins | 2 |
| Small Molecules | 1 |
| Viral Vectors / DNA | 2 |
| Total | 12 |
Concurrent with the protocol preparation, review, and approval process, the OCTM coordinates the supply of Drug X, and the availability of monitoring and clinical resources and personnel. Once the patients are enrolled in the trial (see Table 2. for the LICR Clinical Trial Centers), the OCTM is responsible for ensuring that the trial is conducted according to the approved protocol, and events such as adverse reactions to Drug X are reported to the appropriate authorities. The OCTM is also responsible for data management, monitoring, and analyses. The OCTM maintains its own regulatory and monitoring capabilities to Food and Drug Administration (USA) standards. In order to perform preclinical experiments and clinical trials that conform to the highest regulatory standards, the LICR has developed Biological Production Facilities (BPF) for in-house study reagent production using current Good Manufacturing Practice (cGMP). The BPFs will be described in detail in a future NewsLink article.
Therapies currently in clinical trials (see Table 2 for Clinical Trial Centers) are primarily either cancer vaccines (from the Cancer Vaccine Program), or monoclonal antibodies (from the Antibody Targeting Program). As of December 1st 2003, there were 31 active studies and 32 closed studies. Trials of inhibitors of angiogenesis and lymphangiogenesis, and signal transduction enzymes, from the Angiogenesis and Signal Transduction Programs respectively, may begin as early as 2004.
Table 2. The Clinical Trial Centers of the LICR’s CTP. The majority of the trials are conducted at the Brussels, Frankfurt, Lausanne, Melbourne, New York, and Zürich centers.
| Brussels, Belgium LICR Branch for Human Cancer Cell Genetics / Clinique Universitaires Saint-Luc |
Mie, Japan Mie University School of Medicine |
| Frankfurt, Germany Krankenhaus Nordwest |
Nagasaki, Japan Nagasaki University Graduate School of Biomedical Sciences |
| Lausanne, Switzerland LICR Branch for Tumor Immunology / Centre Hospitalier Universitaire Vaudois |
New York, USA Columbia-Presbyterian Medical Center |
| Melbourne, Australia LICR Branch for Tumor Biology / Austin Hospital |
New York, USA Mt. Sinai School of Medicine |
| New York, USA LICR Branch for Human Tumor Immunology / Memorial Sloan-Kettering Cancer Center |
New York, USA New York University School of Medicine |
| Zürich, Switzerland University Hospital Zürich |
New York, USA Weill Medical College of Cornell University |
| Boston, Massachussetts Dana-Farber Cancer Institute |
Nijmegen, Netherlands University Hospital Nijmegen |
| Beijing, China Peking University Health Sciences Center |
Okayama, Japan Okayama University Medical School |
| Buffalo, USA Roswell Park Cancer Institute |
Osaka, Japan Osaka University Graduate School of Medicine |
| Gunma, Japan Gunma University School of Medicine |
Oxford, United Kingdom John Radcliffe Hospital |
| Hamburg, Germany University Hospital Hamburg-Eppendorf |
Rochester, USA Mayo Clinic |
| Homburg, Germany University of Saarland Medical School |
Uppsala, Sweden Uppsala University Hospital |
Figure 1. The staff of the OCTM stands at 12, with independent contractors utilized routinely to supplement the expertise of the OCTM staff in the areas of biostatistics, data monitoring, regulatory affairs, and cGMP regulations.
Dr. Eric W. Hoffman, Pharm. D. Director of the Office of Clinical Trials Management.
Figure 2. An indication of the work required to obtain regulatory approval for just one clinical trial. From left to right, Dr. MaryJane Rafii (Head of Regulatory Affairs), Ms. Eliza Ruiz (Administrative Assistant), and Dr. Linda Pan (Clinical Program Associate) stand behind: A) one copy of the submission to the Recombinant DNA Advisory Committee; B) the final versions of the Clinical Trial Concept and Protocol (this folder doesn’t include all the drafts and re-writings); and C) one of the six copies required to submit an Investigational New Drug Application – all 2500 pages in each copy of the IND must be manually numbered.
