The LICR Clinical Trials Model

LICR, like other academic institutes, has made significant research discoveries that could potentially prove useful in the clinic. However, unlike most other academic institutes, LICR has assumed primary responsibility for evaluating the clinical utility of its research discoveries. To do this, the Institute has developed, internally, the infrastructure required to handle all aspects of the clinical trials process; from obtaining and holding its own regulatory approvals, to the production of regulatory-standard reagents, to sponsoring and conducting its own clinical trials. The LICR model of clinical discovery, described below, reflects the Institute’s belief that the earliest clinical trials must focus primarily on discovery, not product development, if the full potential of a therapy is to be explored. A systematic academic research approach is used to develop rational therapeutic strategies in the only setting that really counts - cancer patients.

The subject of ‘academic’ clinical research is currently of great interest in the international academic community. The USA’s National Institute for Health recently published their ‘NIH Roadmap’ (http://nihroadmap.nih), a strategy to shape the future of the NIH, with one of the three components of the Roadmap being “Re-engineering the Clinical Research Enterprise”. Additionally, the British Medical Association has just announced the institution of a panel to “help revitalise-and reinvent-academic medicine”. The current discussion by the NIH and the BMA shows the foresight of LICR’s approach; our translational model has been fully active since 1996 (with a handful of trials being conducted several years prior to that).

In order to appreciate the LICR model, it’s necessary to review how the vast majority of “non-LICR” early phase clinical trials are sponsored and conducted. Traditionally, the research discovery of a scientist is patented either by a biotechnology or pharmaceutical (biotech/pharma) company, or directly by the scientist's academic institute, in which case a biotech/pharma company is typically then licensed to produce, develop, and use the reagent. The discovery is routinely taken into the clinic by the company, which sponsors early phase clinical trials at a hospital that is amenable to providing medical specialists, resources, and patients for the trial. This sponsorship may be financial and/or may take the form of providing the study reagent, in which case the regulatory approval is held by the company. The vast majority of clinical reagents in early phase clinical trials are provided by industry, meaning that many hospitals and academic institutes are, in essence, performing contract research for biotech/pharma companies.

Additionally, the scientists who made the initial discovery usually have little more than a consultancy role (if that) once the discovery enters the clinical trial process, with the biotech/pharma company deciding on all critical elements of protocol design. The company decides on patient population, dose, frequency of delivery, modality of delivery, methods for monitoring the patient’s response/s to the novel therapy being tested, the criteria for evaluating the therapy’s efficacy, and the cancer against which the discovery should be trialed; all too often marketing-driven, rather than medically-driven, choices. In the vast majority of trials, there is little monitoring, other than broad clinical responses, and there is only one criterion for evaluating the effectiveness of the discovery – did the patient’s tumor shrink? Typically, there is little effort to understand how and why the discovery succeeds or fails to produce tumor regression, or an extension of survival.

There are four crucial differences between the typical clinical trial paradigm outlined above, and the LICR model:

  1. First, LICR philosophy is that early phase clinical trials are the last step of the initial discovery phase, and not the first step of a new drug development phase. Thus the scientists who made the discovery, and have a thorough understanding of the science underlying it, can be intimately involved in the early phase clinical trials. LICR believes that there can be enormous benefit in the scientists who performed the laboratory research participating in the design and implementation of the clinical research, and being part of the clinical trial team. This model provides a two-way flow of research; from the laboratory into the clinic and from the clinic back into the laboratory. This close interaction between the laboratory and the clinic provides the foundation for rational and informed decisions regarding clinical trial design, including dose and delivery methods.
  2. LICR takes an aggressive but inclusive approach with the Institute's intellectual property (IP), believing that protection of our IP is essential for the full and proper development of research discoveries into cancer therapies through the control of the study phase of clinical development. LICR has carefully built an 'IP architecture' around each research program, to ensure that the end results of the targeted research programs offer secure proprietary positions for ultimate corporate licenses. At the same time, we wish to retain our top scientists, and encourage individual entrepreneurship within, and for, the Institute. Academics who want to fulfill clinical aspirations frequently have to go outside their institutions, but LICR has personnel and processes to handle aspects such as IP and regulatory approval, leaving the academics free to continue their research and be involved in the clinical discovery process. Thus the scientific team is involved in decision-making relating to their discovery, and shares in royalties generated by their patented discoveries.
  3. The third difference is that the LICR Clinical Trials Program (coordinated centrally by the Office of Clinical Trials Management), is conducted in multiple, Clinical Trial Centers that are integrated with laboratories, and apply standardized clinical evaluation, and, if a cancer vaccine trial, monitoring techniques. This system of coordinated, parallel trials allows the comparative testing of single variables, thus decreasing the therapy’s time-in-development, and efficiently comparing all development aspects. This is in contrast to the traditional approach, in which trial variables are tested sequentially.
  4. The fourth distinctive feature of the LICR model relates to the issue of clinical trial sponsorship. Most academic institutions conduct industry-sponsored clinical trials. LICR takes responsibility for its own regulatory applications and approvals, processing and producing clinic-grade study agents, and ensuring that trials comply with internationally recognized and approved standards. The primary advantage conferred by LICR sponsoring its own trials is that LICR is able to establish its own priorities, deciding whether and how to test and evaluate a promising discovery.

The outcome of the LICR clinical trials model is that the Institute controls the early clinical evaluation and development of our discoveries. LICR believes that this commitment, from the discovery level in the laboratories, through the licensing level (by the Office of Intellectual Property), clinical development, reagent production, and standardization of delivery and monitoring (by the Office of Clinical Trials Management), to the final licensing and/or sale of developed therapies for marketing etc (by the Office of Technology Licensing), is essential to achieve the Institute’s ultimate objective - translating research discoveries into patient benefit.