Introduction: Asia's Changing Clinical Trials Landscape
Over the last few years, the clinical trial landscape in Asia has undergone dramatic change. For decades, studies were predominantly performed in US and Europe. Now, an increasing number of clinical trials are being performed in Asia. Recent reports indicate that 17% of all studies are currently conducted in Asia, with Seoul the number one clinical trial destination, followed by Beijing, Taipei, Taiwan, Bangalore, India; and Shanghai. (See Table 1 ).
What is the reason behind this shift in location for clinical trials and what opportunities does this present?
There are certain considerations to note when conducting trials in Asia. First, because of different economic conditions from country-to-country, the reimbursement of certain medications is not uniform across the region. For example, Tumor Necrosis Factor (TNF) inhibitors are fully reimbursed in Taiwan. This is not the case in other countries such as Malaysia5. Second, while treatment guidelines in most countries generally adhere to international standards, there may be local nuances. Finally, face to face meetings are important for relationship- building in many Asian countries, such as Japan. These meetings often take the form of consensus-building discussion forums. While it might be a drawn-out process, it is important to establish key business relationships in Japan before actual partnerships are formalized.
The diversity of Asia’s healthcare environment means that a one-size-fits-all strategy to site identification won’t work. To tap into the vast potential of the region and to maximize this potential, one needs numerous mini-strategies, each tailored to the relevant local clinical healthcare ecosystem.
5-Prong Site Strategy in Asia (Figure 1)
Data-driven feasibility analysis is crucial before taking the first step in developing the site strategy. Feasibility in this case refers to a preliminary assessment to determine if a clinical trial can be executed successfully.This could consist of interrogating a company’s internal database (which includes information from previous clinical trials performed) and/or include an outreach to investigators. Key considerations for a robust feasibility include, among others, the protocol’s inclusion and exclusion criteria, regulatory timelines, competition from other trials in the same indication, the marketing strategy of the company, and the clinical site’s access to the targeted patient population. Quantitative data from previous clinical trial performance, such as prevalence data, start up timelines and so onprovides the ability to objectively ascertain the best countries in which to place a trial. When prior data is not available, surrogate data needs to be used, such as using qualitative data from feedback from potential investigators in the country. Review of the data collated, by various experts like physicians, regulatory experts and project managers is needed to provide that critical appraisal of the data and recommendation for actions.
II. Site Identification
There are two components to Site Identification. First, the need to identify a suitable site. In mature clinical trial ecosystems there will likely be long lists of sites available. One such ecosystem exists in South Korea; The Korean Food and Drug Administration (KFDA) now renamed Ministry of Food and Drug Safety (MFDS) was established in 1996 . In less developed countries there will be need for extensive ground work to be done to identify such sites. For example, if we take a look at Cambodia, there are currently only 39 trials listed as ongoing or have been performed in the clinical trials database (clinicaltrials.gov). 77% are for infectious disease indications . There is only one observational trial performed in Cambodia for diabetes. Prevalence for diabetes in Cambodia is 110,000 (2010) , and while not exceedingly high in comparison to other countries like China or India, it does show that Cambodia has the patient population to contribute to a clinical trial in this indication. What it lacks is an oversight of potential sites and investigators to conduct clinical trials which can only come with experience.
The second component of Site Identification is to identify a site that is best-suited for a study to be placed. Matching site to study requires objective use of performance data that capitalizes on technology. Unfortunately this is where countries and sites with lesser experience in running clinical trials can be in a disadvantageous position as their processes are not backed by data. Sponsors and contract research organizations (CROs) tend to be hesitant to take on these sites owing to the absence of past proven track records.
III. Site Development
The clinical trial landscape in Asia is dynamic with different driving forces behind development in the field. In developed countries, the focus tends to be on cutting edge research. Singapore, as an example, has seen activities largely centered on establishment of facilities that can propel advancement in translational studies. The focus is on building the foundation for future generations of healthcare professionals with the establishment of two Academic Research Centers – the National University Health System (NUHS) and the Academic Medicine Education Institute - SingHealth/Duke-NUS Graduate Medical School . This is a huge contrast to actions that might have to be taken to equip a site in a less developed clinical trial environment which can range from site personnel training in Good Clinical Practice to buying equipment and setting up ethic committees.
IV. Key Opinion Leader and Investigator Networks
Ultimately it is the individual researcher that leads the trial. In addition to executing a clinical trial, these individuals can also be a source of information about the fit of a protocol in the Asian environment. Having access to a network affords the ability to quickly connect with the right individual regardless of the need, be it scientific advice or clinical trial delivery. Many networks, consortiums and collaborations already exist in the region. Most have an active interest towards performing clinical research, for example, Asia Cohort Consortium , Cancer Therapeutic Research Group and Asia Pacific Hepatocellular Carcinoma Trials Group .
V. Site Management
High-performing sites need constant coaching and mentoring to stay at the top of their game. Active site management should not be equated with CRA management but rather focused on engaging with the site’s higher management to drive changes for better productivity, delivery and quality. It has been demonstrated that with active management these sites can enroll more than 50% more than normal sites.
As more clinical trials are being performed in Asia, it has become essential to consider deployment of an Asia Site Strategy to ensure optimal results for clinical trial studies.
Asia is a region that is made up of countries in different stages of development in its economy and healthcare system. The diverse clinical trial ecosystem in Asia means different tactics must be employed when it comes to selection of the ideal country and site to conduct a clinical trial. It must be remembered that there are many other operational pieces to factor in when it is time to execute a clinical trial for example, site start up, clinical monitoring resources, project management, central lab services. The five mini strategies are approaches one needs to consider when building site capacity and operational delivery in Asia. Only by considering these mini strategies will we be able to unleash the potential of Asia for clinical trials.
Dr. Karen Wai
Senior Director and Head of Feasibility and Site Identification Asia, Quintiles
Dr. Karen Wai is currently the Senior Director and Head of Feasibility and Site Identification Asia at Quintiles in Singapore.
She leads a team responsible for feasibility, site identification and KOL mapping across Asia Pacific. Karen is a physician by training, acquiring a MB,BCh,BAO degree from Trinity College Dublin, Ireland. She also obtained her Masters in Business Administration from UCD Michael Smurfit Graduate Business School, Ireland.
Prior to joining Quintiles, Karen was working as a physician in both the public and private healthcare sector. Karen has direct management and operational experience in European, African and Asian environments. She has also served as Medical and Scientific Advisor for over 60 different clinical trial protocols in the following indications: oncology, neurology, cardiovascular, anti-infective and rheumatoid arthritis. Using her medical and safety background she is now focused on ensuring efficiency and quality during the initial planning of a clinical trial with regards to sites and investigators.
Dr. Ken J. Lee
Vice President & Head of Site Services Asia, Quintiles
Dr. Ken J. Lee is currently the Vice President and Head of Site Services Asia at Quintiles in Singapore. He leads a team responsible for feasibility, clinical research site identification/training/development and site/investigator relationships. Ken is a physician by training, acquiring a MBBS degree from the University of Melbourne. He worked as a clinician in both Australia and Malaysia before joining industry.
Prior to Quintiles, Ken held positions in sales and marketing, medical affairs and clinical development over a 10+ year career within the pharmaceutical industry with multinational organizations Bayer, UCB, Aventis and Sanofi-Synthelabo. Ken has worked in both local operational and regional/global strategic positions while being based in a number of countries including China, Malaysia, Singapore, Taiwan, Germany and Australia. He has at various times covered Asia Pacific, Japan, Europe, Canada, Russia, Africa and the Middle East.
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