Global Clinical Trials For Alzheimer S Disease

Global Clinical Trials for Alzheimer’s Disease is a handy one-stop reference for researchers and physicians planning and conducting global clinical trials in this area. This book addresses important considerations that may arise during the successful design and execution of these trials, including site selection, local regulatory issues, pharmacogenomics, ethical matters and much more. Given the saturation of traditional clinical trial markets and the worldwide progression of Alzheimer’s disease, there is a need to focus on clinical trials in emerging markets and developing countries. This book provides you with a practical approach to recognizing the opportunities and tackling the challenges that are present during the planning and execution of global clinical trials for Alzheimer’s disease. Written by leading experts with hands-on experience in designing and running global Alzheimer’s disease and other neurodegenerative diseases clinical trials A step-by-step guide that provides critical information on the design, conduct and standardization necessary to effectively execute clinical trials and accelerate drug development in this area Includes practical examples, ethical considerations, lessons learned and other valuable tools to aid the planning and implementation of Alzheimer’s disease global clinical trials in emerging markets and developing countries

China has the largest number of people with dementia and the incidence is projected to increase much faster than in the developed world. There is a great demand for new drugs that can prevent or treat the disease and great potential for conducting Alzheimer’s disease clinical trials. The majority of Alzheimer’s disease trials that have been conducted in China are local trials. In early years, there were deficiencies in trial design and implementation; however, with more attention from the government and concerted efforts among Alzheimer’s disease experts, the standards for conducting Alzheimer’s disease clinical trials have improved. There are currently 159 clinical trial institutions capable of conducting Alzheimer’s disease trials in China, offering good facilities, experienced investigators and easily accessible patient pools. Recently a few global pharmaceutical companies have expanded their Alzheimer’s disease trials into China. It is expected that with increasing exposure to global standards and improved training, China’s capacity and capability to conduct Alzheimer’s disease trials will be strengthened.

Globalization is increasingly common as a means of more rapidly recruiting patients, shortening clinical trials, abbreviating clinical development cycle times, and preparing for marketing in non-US markets. Globalization refers to the inclusion of trial sites in three or more international regions. Globalization is common and most drug development programs include both US and non-US sites. There has been limited evaluation of the transnational performance of clinical trial instrumentation used in drug development programs. The performance across nations, languages and cultures of the ADAS-Cog, Clinical Dementia Rating, Neuropsychiatric Inventory, quality of life measures, pharmacoeconomic measures, and activities of daily living tools has been inadequately researched. The creation of a library of well-tested and shared instruments would be of value in globalized trials. The approach to diagnosis of Alzheimer’s disease may vary across trial sites and create undesirable heterogeneity within clinical trials. Biological factors such as differences in liver metabolism enzymes, diet, education and head size may all create differences in treatment response in different ethnic settings. Sites across the globe may differ in terms of experience, and institutional review boards may also perform variably with regard to informed consent and human safety. These require vigilance by sponsors performing globalized trials. International efforts such as the Alzheimer’s Disease Neuroimaging Initiative provide data that will help reduce the variance and improve clinical trial quality. Improved understanding of the effects of globalization will enhance clinical trials and speed the development of new medications for patients with AD.

A rapid increase in the globalization of clinical trials is being driven by a need for lower cost, greater speed, and higher quality. Increasing costs—approximately 20% per year—account for much of this effort. Trials in developing countries—done with rigorous controls and safeguards—can lower the cost of drugs, distribute modern science and medicine, and enhance the health of patients around the world. Lesser developed countries offer a large pool of willing, treatment-naïve patients. Globalization of clinical trials introduces potential issues: for example, ethical concerns, harmonization, logistical challenges. Researchers must take into account potential ethnic, genetic, and other differences which can make extrapolation from one geographical region to another problematic. Differences between populations and geographies are divided into intrinsic and extrinsic differences. Historically, these differences have not resulted in changes to the risk–benefit ratio of outsourcing clinical trials.

Considering the difficulty of clinical development for Alzheimer’s Disease (AD), understanding each country’s specific situation is an important first step in reducing the operational burden on clinical trials while maintaining the quality of the study. In this chapter, the long history of clinical development for AD in Japan is introduced. There has been a lot of experience in Japan of AD clinical development from the time of developing donepezil to the current global development of AD disease-modifying drugs. However, this experience has not always been a success story and has often been the cause of much frustration, such as the failure of Phase III studies, high regulatory requirements, development and implementation of neuropsychological tests, influence of ethnic factors, etc. However, all of these points provide us with a good source from which we can learn about the challenges of the clinical trials and discuss how to strengthen the quality and efficiency. It’s important to take advantage of this experience for future success in the clinical development of AD, especially in emerging markets.

Turkey straddles the continents of Europe and Asia, and this unique geographical location steers its economy. On the world economic scale, as an exceptional emerging economy, Turkey is the 16th largest economy in the world and the sixth largest economy as compared with the European Union countries, according to gross domestic product. The Turkish pharmaceutical sector is ranked 16th in terms of market value, and it is 36th in terms of the clinical research conducted and the volume of pharmaceutical exports. Investments by foreign companies have increased since 1984 and 19 foreign capital firms have entered the Turkish pharmaceuticals market since 1990. Today, there are approximately 300 entities operating in Turkey. Turkey has a long tradition of providing clinical trial legislation, regulation and guidelines; the country has taken major steps towards harmonizing its legislation with those of the European Union in the field of clinical research. Currently Turkish regulations are completely in line with EC Directives. Clinical trials performed in the field of Alzheimer’s disease in Turkey since 1997, including their rationale, design, summary, and outcomes, are discussed in this chapter.

This chapter provides an overview of the increasingly important role of emerging markets in Alzheimer’s disease trials, particularly Eastern Europe, where there is a robust population of accurately diagnosed subjects for trial participation, and recruitment rates are on a par with those in Western Europe and the USA. Some of the challenges and opportunities involved in global trials are discussed, such as the potential for high recruitment, availability and compliance with biomarker assessments, reimbursement of background medications, and the overall efficiency of the sites’ and countries’ performance.

The incidence of Alzheimer’s disease is increasing worldwide. The need to fortify global resources conducting clinical trials becomes of paramount importance for sponsors to ensure less delay in marketing their products. This chapter provides a concise and practical approach to building capacity and capability in emerging or developing markets. Lessons learned from countries like China and India, where the top 12 pharmaceutical and biotech companies have become deeply entrenched in the last 10 years, serve as important benchmarks which can be referenced as new emerging markets like Vietnam, Indonesia, and the Philippines establish themselves as available and capable areas for clinical trials. Referenced case studies describe actual events from which valuable practical pearls can be adapted in other settings. Sponsors need to recognize that investing early on in developing project teams that can support these trials creates a better landscape for success.