Abstract PL03-05: International clinical research-Barriers and challenges: A vision from independent and publicly funded trials

Clinical research is vital to the development and improvement of methods to prevent, detect, and treat cancer. The majority of clinical trials take place in the developed world through sponsored pharmaceutical company research. The corresponding lack of research in developing countries results in two unmet needs related to cancer treatment in the developing world. First, recommended treatments do not reflect ethnic (genetic), cultural, and resource differences between developed countries and developing countries that are not subject to clinical research. Second, there is little research conducted on those cancers that are primarily found in developing countries. Thus the ability to diagnose and treat these diseases is impaired. This general picture reflects today9s situation globally, then it is critical to promote clinical research in developing countries mainly with training of all levels of research professionals (data managers, research nurses, etc.) in a local context, and training on identifying resources to fund research outside of pharmaceutical company sponsorship. The American Cancer Society highlights the disproportionate amount of cancer clinical research performed in the United States and the rest of the world (roughly two times more). Less than 15% of the clinical trials are conducted in developing countries. In addition, and according to data from the American Society of Clinical Oncology (ASCO) from a survey to the international membership conducted in 2007, 21% of members are not satisfied with ASCO9s involvement in clinical research education. In the same survey, 61% of respondents think that a clinical trial workshop held in their country would be very helpful compared to 29% for a workshop in the United States. At the recent ASCO World Oncology Leaders Forum, leaders of societies around the world agreed that training and research skills are needed to address the lack of research conducted in developing countries. The critical role of publicly funded clinical trials networks in cancer research: The most important objective of a publicly supported cancer clinical trials system is the identification of optimal therapies for cancer patients. This objective differs from the primary objective of pharmaceutical and biotechnology companies, which want first and foremost to get their innovative product evaluated quickly, and, if found to be effective, approved for marketing. How best to integrate active new agents into cancer treatment regimens for a variety of cancer sites, age groups, and clinical scenarios is a secondary objective for companies. In addition, many important cancer trials do not involve experimental agents and thus lack a pharmaceutical sponsor. A recent trial randomized men with early-stage prostate cancer to radical prostatectomy or radiation or watchful waiting. Although this trial question was of great importance in the management of prostate cancer, it did not evaluate a new chemotherapeutic or biologic agent and thus had no pharmaceutical sponsor. Without public funding, such trials will not be done. Another critical objective for publicly funded trials is to identify the most effective treatments, which national health care systems should make available, as well as identify ineffective treatment, which health care systems should not support. In this context, health care coverage should be adapted to different resource levels. Publicly funded trials also will determine whether interventions found to be effective in other countries are also effective in one9s own country. Health care systems vary from country to country. National populations vary by age structure, co-morbidity, and genetic background. Particularly with the newer generation of biologic agents, we need to establish whether treatment effect or toxicity varies by population genetics. Institutional participation in clinical trials improves quality of care for all patients treated at that site. Doctors and nurses who participate in clinical trials are more likely to adopt effective innovations into routine practice, as well as to practice cancer care more rigorously. Another potential benefit from publicly funded trials networks is the addition of translational research components to cancer trials. These additional components may include epidemiology, evaluation of biologic mechanisms, development and validation of prognostic markers, evaluation of novel imaging, evaluation of cost-effectiveness, and evaluation of the intervention in select populations. All these additional components have the potential to add great value to an individual trial. In many cases, companies may not be willing or able to support these critical components. Publicly funded cancer trials networks facilitate the translation of research discoveries from academia into clinical practice. Too often, investigators at publicly funded research institutes and universities are not able to bring new discoveries into clinical evaluation, because they do not have easy access into clinical trials networks and may not be able to stimulate interest from pharmaceutical and biotechnology companies in partnership. Publicly funded cancer networks can expand the opportunities for evaluation of novel interventions from industry. Often, companies may only be able to underwrite evaluation of their novel agents in the most common cancers. By collaborating with a publicly funded network, companies can facilitate the evaluation of their new agent in less common cancers, as well as in age groups which are more difficult to study, such as children and the elderly. Publicly funded cancer networks can encourage the evaluation of novel agents from several different companies in combination. Frequently, companies will see other companies as rivals and not consider combinatorial strategies. A national cancer network can foster collaboration between companies. The presence of a national publicly support clinical trials network attracts interest from the international pharmaceutical companies both in potential collaboration as well as in the potential market for their new agents. Companies are attracted by the existence of a clinical trials network with proven capability and expertise. Conducting clinical trials globally : The world distribution of cancer patients shows that 61% are outside the United States, Europe, and Japan. Latin America has 10% of the world cancer patient population, 30% are in Asia, and 28% are in China. The issue of trials placement has become increasingly complex. The traditional geographical locations such as the United States and Western Europe have been performing good quality trials. Today, costs are rising and accrual is limited to the size of the populations. In this regard, the international patient population is a potential extraordinary source of information and knowledge. It is important to consider that regulatory processes are evolving and that harmonized regulatory requirements should be promoted. Global trials include demographics and epidemiology together with ethnicity issues. Today it is possible to perform trials faster and better at a global scale. On the other hand, at the local level knowledge and technology transfer are important besides the fact that local expertise together with global and local publications will be improved. Additional reasons to conduct clinical trials globally are Improvements in good clinical practices, dossier review, regulatory authorization, quality control systems and established processes. Global efforts promoting independent clinical research should include increase participation in phase I and II studies, explore opportunities for early phase drugs, strength collaboration with academic cancer research centers, increase partnership with other cancer research organizations, continuous educational and training programs. It is mandatory to expand investment in exploratory and proof-of-concept trials, mainly those that are relevant for the different world populations and according to the different resource levels. Improving cancer outcomes through international collaboration in academic cancer treatment trials : The need for international collaboration in cancer clinical trials has grown stronger as we have made progress both in cancer treatment and screening. It is necessary to identify those efforts already underway which facilitate such collaboration, as well as barriers to greater collaboration. It is also important to review the collective experiences of many cooperative groups, governmental organizations, nongovernmental organizations, and academic investigators in their work to build international collaboration in cancer clinical trials across multiple disease sites. More than a decade of work has led to effective global harmonization for many of the elements critical to cancer clinical trials. Many barriers remain, but effective international collaboration in academic cancer treatment trials should become the norm, rather than the exception. Our ability to strengthen international collaborations will result in maximization of our resources and patients, permitting us to change practice by establishing more effective therapeutic strategies. Regulatory, logistical, and financial hurdles, however, often hamper the conduct of joint trials. We must work together as a global community to overcome these barriers so that we may continue to improve cancer treatment for patients around the world. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PL03-05.