Real World Evidence (RWE) can be used to inform decisions throughout the life cycle of a drug, from development through post-approval. Across Asia, many countries have begun incorporating real world evidence, and while some are fast adopters in terms of RWE collection and use, other countries have shown less inclination to implement this approach.
True experiments such as randomised controlled trials (RCT)—the gold standard when it comes to the approval of pharmaceuticals— are often criticised as being unrealistic. The results of these trials do not always generalise well and may not be applicable in the real world. The use of real world data and real world evidence to supplement RCTs may be one solution to this problem. According to the US FDA, real world data is “data collected from sources outside of traditional clinical trials,” and real world evidence is the evidence derived from this data. These real world sources include observational studies, registries, health surveys, and even administrative or insurance claims databases, and they provide a great deal of insight into how a drug may perform when patient adherence is not rigorously supervised. For these reasons many companies are beginning to look at real world evidence to help inform pricing and reimbursement decisions, as well as other critical decisions in drug development. A recent study by the Tufts University Center for the Study of Drug Development in Boston, Massachusetts asked a working group of eight major international biopharma companies to rate their perceived appropriateness of different data sources for reimbursement decisions (Figure 1).
While many companies attempt to discern how real world evidence should be used in drug development, many countries around the world are debating its use in regulatory decision making. In Europe, real world evidence has been used to support drug pricing and reimbursement for years. In 2015 the EMA conducted a pilot program for their Adaptive Pathways approval path which would incorporate RWE into the drug approval process. Still some countries shy away from the use of RWE. Brazil has several public administrative databases that are filled with data, however Brazil has strict laws in place to protect the privacy of its citizens, and these laws restrict the use of these databases. Additionally, there are significant issues with the connectivity of these databases, as well as the quality and completeness of the data they contain.
Similar to the pattern seen around the world, the use of RWE in Asia varies from country to country, and spans the entire spectrum. Some countries work to fully embrace real world evidence, like Japan, which recently began its “Rational Medicine” initiative in an attempt to make the Japanese health care system more patient-centric and evidence-based. Other countries, like India, seem far less interested in the use of real world evidence. Many other countries, like China, fall somewhere in the middle.
As mentioned, one country leading the charge in terms of real world evidence is Japan. Dr. Tatsuya Kondo, Chief Executive of Japan’s Pharmaceuticals and Medical Devices Agency, recently described the new ‘Rational Medicine’ initiative, which has the goals of providing ‘better insight into the risk/benefit balance of drugs, medical devices, and regenerative medical products’ and creating ‘a medical environment where the care provided is strictly evidence based.’ In order to move toward these goals, the PMDA intends to use real world data to increase the sophistication of their safety measures.
In addition to the ‘Rational Medicine’ Initiative, Japan has several registries and databases, including the Medical Information Database Network (MID-NET), which has been in development since 2011. MID-NET collects laboratory and other types of data and can be analysed to assess drug safety and answer a variety of other questions. Analysis of the data is expected to be in full operation in 2018, however some analysis has already begun. MID-NET is expected to be used to contribute to regulatory decision-making.
Another country that appears to be incorporating real world evidence is Taiwan. In 2012, researchers looked at the amount of healthcare data being collected in several Asian countries, as well as the utilisation of the data. Among these countries, Taiwan appeared be one of the most active in terms of collecting and utilising real world data from a variety of sources.
Sources of real world data in Taiwan include: the administrative data collected by the National Health Insurance (NHI), surveillance systems established by the Center for Disease Control to monitor epidemics and outbreaks, the Cancer Registry, the Bureau of Labor Insurance’s ‘labor insurance claim data set,’ and multiple annual health surveys.
Many of the data sets within Taiwan have been linked together by the Office of Statistics within the Department of Health, further improving the usability and comprehensiveness of the data sets. Additionally, many of the data sets are readily accessible to the public for research purposes, and the protocol for accessing other data is well established. RWE in Taiwan is frequently used for decision making in the health sector. It is also used for research, and for health care technology assessments.
Singapore also seems eager to incorporate real world evidence. In 2010 the Health Sciences Authority (HSA), Singapore’s drug regulatory agency, partnered with MIT to explore an Adaptive Licensing pathway similar to the one recently piloted by the EMA. The Adaptive Licensing pathway allows a drug to be granted conditional approval for a limited patient population at first, with the limitations being increased or decreased as safety data is obtained from the real world.
Other countries have found a use for RWE, as well. In the Philippines, companies are required to conduct post-marketing studies on all marketed drugs. Post-marketing studies are observational studies meant to examine the safety, tolerability, and effectiveness of a drug in more diverse populations than the populations seen in RCTs. In Thailand, as the government searches for ways to lower healthcare costs, payers are using RWE to determine which therapies offer the best value, both in cost and outcome. In particular, payers in Thailand are looking at patient, disease, and product registries.
While some countries are rapidly incorporating real world evidence into industry processes, other countries have opted for a slower paced adoption. Among these countries is China, where we can see signs of the market turning toward the use of RWE, but where there remain some significant challenges.
Like Japan and Taiwan, China has many sources of real world evidence. There are registries for infectious diseases, rich hospital-level data, and even the use of wearable devices, another potential source of real world data, is on the rise in China. There are also two government databases with medical insurance information. However, these data bases belong to separate departments within the government and are not linked together. Additionally, hospitals all use their own information systems and do not share data. In some cases medical records and files are not fully digitised, making the data harder to access.
In spite of the incompatibility of the various sources of data, the use of RWE by decision-makers and in health service research is expected to rise. As the Chinese government works towards reducing healthcare expenditure, big companies have begun to move towards ‘evidence-based, scientific-driven sales models.’
While the demand for RWE by the market and regulators is expected to rise in China, researchers have already conducted several studies there. For example, the Shanghai Clinical Center for Endocrine and Metabolic Diseases has completed several studies on non communicable diseases and the risk factors of noncommunicable diseases, the China Cardiometabolic Registries have been used to research treatment outcomes for cardiovascular and metabolic diseases, and researchers have conducted a retrospective study investigating the risk of HIV transmission in serodiscordant couples.
South Korea, like China, is moving toward the use RWE at a more moderate pace. Like China, South Korea has many databases which could be analysed. One of the largest is the National Health Insurance Corporation database, which represents the entire South Korean population. However, this database only collects information on procedures covered by the National Health Insurance system, which means it is incomplete in regards to total procedures conducted. The validity of this database has been questioned, as well, due to inaccurate coding.
Despite this, by 2012, the NHIC database had been used to conduct two studies of disease burden in South Korea. Additionally, in August 2016, the Korean Ministry of Health and Welfare announced that 16 Big Data analysis centres would be established around the country. These centres would provide claims data from the NHIC database to private sectors in order to assist with research.
Although many countries are moving toward the collection and use of real world evidence, in some countries there is little movement in this direction. India is among the countries showing little, though not zero, interest in real world evidence.
One hurdle the use of RWE in India must face is a lack of sources of data. Few people in India have health insurance, so most medical treatments are paid for out of pocket. As a result, there is no insurance claims database, and little incentive to develop other sources of RWE such as registries or other databases. A few medical registries have been developed, such as the National Cancer Registry and the Indian Transplant Registry, but there remain far fewer than are typically seen in many other countries. (Table 1)
Even without these sources of RWE, India has made some strides towards its use. The Indian Health Ministry is developing legislation that would protect the privacy of its citizens while improving the country’s ability to collect and store personal health data. The legislation would also help India move toward the development and use of Electronic Health Records. These Electronic Health Records are part of the Digital India initiative, an application that will receive health data from hospitals around India in real time.
India may currently lack much of the infrastructure necessary to capitalise on RWE, however some large international companies are bringing the needed technology to India. IBM has announced the ‘Watson for Oncology’ platform for Manipal Hospital’s communal training facilities. ‘Watson for Oncology’ will be able to help oncologists offer more personalised healthcare through the analysis of data and recommendation of evidence-based treatment options. In 2015, Fitbit distributed their fitness trackers to 300 towns around India. As more companies bring their technology to India, we may begin to see an acceleration in India’s adoption of RWE.
However how countries view RWE is only one side of the coin. As more and more companies begin using RWE to support pricing and reimbursement, formulate marketing strategies, and even begin incorporating it into product development, it is important to mention how these companies view Asia—as an increasingly important market. Bayer recently announced the completion of the first Pan-Asian real world evidence study examining the use of Rivaroxaban for stroke prevention in patients with atrial fibrillation. The study looked at data from 10 countries and results were consistent with previous smaller studies. With Asia Pacific making up 25 per cent of Bayer’s global pharmaceutical sales in 2015, senior vice president and head of commercial operations Claus Zieler says it is reassuring to have real world evidence showing that their products have the same effects in the real world as they do in controlled clinical trials.
Other companies are turning to Asia precisely because of geographic differences in diseases and drug performance. “We are doing some work … where the pattern of diabetes in Asia is entirely different than in the US and European Union” said global chief of Quintiles’ Real-World and Late Phase Research, Nancy Dreyer.
Large companies are not the only ones conducting more real world research around Asia; increasingly, universities and hospitals are using RWE to answer research questions. In South Korea, RWE studies have been conducted investigating dementia and antipsychotic drug use in the elderly, and misuse of medications among the elderly. In Malaysia, researchers have looked at drug related ER visits, and the effects of paediatric acute otitis media on parental quality of life using real world data. Hong Kong is another location where significant amounts of real world research is conducted.
As a result of this increased real world attention from large companies and universities, Asia has become something of a hub for real world research. While the US remains the world leader in terms of number of real world studies being conducted, one analysis of clinicaltrials.gov indicates that Asia is quickly catching up. According to this 2017 analysis, 321 real world studies have been or are being conducted in the US, 268 in Europe, and 234 in Asia.
The use of real world evidence is on the rise around the world, and this is true throughout Asia as well. Although individual countries are following this trend at their own pace, it is clear that they are all moving toward the incorporation of RWE in some capacity. And while each country sets its own pace in terms of regulations, there are indications that many large corporations and universities are looking to quickly turn Asia into a hub of real world research.
Zachary Peter Smith completed his B.S. at Florida Southern College, and completed his M.A. at Brandeis University. He has worked as a research assistant at a variety of labs including the Etter Lab at the University of Massachusetts, and the Evolutionary Psychology Lab at Harvard University.
Christopher-Paul Milne joined the Tufts Center for the Study of Drug Development (Tufts CSDD) in 1998 as a Senior Research Fellow in order to address legal and regulatory issues. His current research interests include: challenges to the R&D of new drugs; innovation capacity in the developing world; incentive programs for pediatric studies, orphan products, and neglected diseases; assessing the impact of regulatory policy; and, tracking progress of new initiatives to improve safety and efficacy and exploratory development such as Regulatory Science, Translational Medicine and Personalized Medicine. He is currently Associate Director of the Tufts CSDD, Research Assistant Professor at Tufts Medical School, a member of the Editorial Board of the Food & Drug Law Journal, and an Honorary Fellow at the University of Edinburgh.
