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Asia: Preferred Destination for Clinical Trials

 

Asia is the fastest-growing medicines market globally, with China currently the world’s second-largest market after the US, with medicines spending of $137 billion in 2018, up $40 billion from a decade earlier.

Due to cost pressures, global biopharma companies are increasingly outsourcing both manufacturing and R&D activities.

In Asia-Pacific as a whole, expenditure on CRO services is growing twice as fast as the global average, and forecast to reach almost $16 billion by 2024.

Challenges

Conducting clinical trials in the traditional locations of North America and Western Europe is becoming more challenging. This is driving a much greater focus on Asia as a destination for clinical trials:

  • 70% of trials are affected by enrolment issues.
  • Challenges in meeting complex and changing regulatory requirements.
  • Increasing costs in areas such as staff and admin, clinical procedures and site monitoring.

The Benefit of running clinical trials in Asia

Asia is an increasingly important location for clinical trials driven by its large and growing urban population, improving infrastructure, and efforts by governments to promote clinical research.

  • Growing base of Key Opinion Leaders and experts
  • Large participant populations
  • Cost efficiencies
  • Improving regulatory efficiencies
  • Increasing IP protection
  • Diverse ethnicities
  • Equivalent quality standards

Despite the vast opportunities, Asia presents several challenges for clinical trial management. Varying cultural, language, and regulatory requirements in each country can make for a complex operating environment.

Biopharma companies are engaging regional CROs with in-country offices and experience to manage these issues.

This report summarises some of the key trends and developments in Asia’s CRO landscape and examines the main drivers behind the strong growth in demand for CRO services. Information for this report has been obtained from a review of published literature, as well as interviews with sponsors and investigators undertaking clinical trials in Asia.

Introduction

Overview and key findings:

  • The fastest growth in CRO services will be in Asia-Pacific, which is forecast to see growth of almost 15% annually and will account for 20% of the global CRO market by 2022.
  • The estimated number of clinical trial sites opened by biotech companies in Asia-Pacific has been increasing by over 40% each year on average compared to 11% in the rest of the world, with growth as high as 79% in China, between 2016 and 2018.
  • For Oncology and Immuno-Oncology studies, trials involving sites in Asia resulted in a higher recruitment rate and reduced recruitment periods when compared to trials in the US.

The global biopharmaceutical sector continues its record growth, largely fuelled by demand for new innovative medical products, aging populations, and strong growth in demand from emerging nations.

In 2018, global spending on medicines approached $1.3 trillion, and is expected to grow 5% per annum to reach $1.6 trillion by 2022. Global data, however, masks significant regional variations, with the fastest growth set to occur in the “pharmerging” markets, particularly in Asia. China is now the world’s second largest medicines market, with spending of $137 billion in 2018, up from $40 billion a decade earlier. Although growth in medicines spending in China has slowed in recent years, it is still forecast to increase by around 6% per annum, well ahead of markets in North America and Europe1. Significant growth is also expected in markets such as India, Thailand, the Philippines and Vietnam, indicating the increasing importance of Asian markets in the global biopharmaceutical sector.

In addition, biopharmaceutical companies are also looking at operational efficiencies, driven by pressure from payers on product prices. A key cost-cutting strategy is more outsourcing in areas such as manufacturing and clinical research using contract manufacturing organizations (CMOs) and contract research organizations (CROs).

Globally, expenditure on CRO services was estimated at $49.7 billion in 2019 and is forecast to reach $71.7 billion by 2024 at a CAGR of 8% between 2019 and 2024. Some biopharma companies have even adopted a fully ‘virtual’ model of drug development, outsourcing to CROs all services from early discovery to commercial application of a drug. While many biopharma companies continue to engage CROs to provide support for discrete projects, there has been a trend in recent years towards establishing long-term relationships with CROs through partnerships. Global R&D expenditure by the biopharma industry was estimated at $167 billion in 20182, but only 26% of this expenditure is currently devoted to CROs, indicating significant opportunity for growth for CRO services. Mirroring the increased importance of Asia in the medicines market, the fastest growth in CRO services will be in Asia-Pacific, which is forecast to see growth of almost 15% annually and will account for 20% of the global CRO market by 2022, up from 15% in 20173.

Asia, with 59% of the global population, is an increasingly attractive location for clinical trials, driven by its large population of over 2.3 billion living in urban areas in 2019, improving infrastructure and a greater focus by governments on supporting medical research. In addition, there is a significant investment in new specialized clinical trial centers with state-of-the-art equipment and advanced technology to cater to the growing demands of patients and R&D. Fast-growing Asian economies have leapfrogged the traditional path of enhancing legacy IT systems and are at the forefront of innovation with rapid adoption of data management systems and electronic medical records.

Over the period 2016 to 2018, for example, the estimated number of clinical trial sites opened by biotech companies in Asia-Pacific increased by over 40% each year on average compared to 11% in the rest of the world, with the Chinese market having more than tripled during that period (+79% each year on average)4.

At the same time, Asia also presents challenges for clinical trial management. Differing cultures, languages and regulatory requirements in each country can make for a complex operating environment. Increasingly however, biopharma companies are engaging a regional CRO with in-country offices and experience to manage these issues.

This report summarizes some of the key trends and developments in the CRO landscape in Asia, describing the main drivers behind the strong growth in demand for CRO services. Data for this report has come from a review of published literature, as well as interviews with sponsors and investigators undertaking clinical trials in Asia.

The Global Clinical Trials Environment

Globally, medicine sales are estimated to have reached $1.27 trillion in 2018 and will grow to $1.6 trillion by 2022 at a CAGR of 5.4% between 2015 and 2022. Although R&D intensity (R&D expenditure as a percentage of sales) will fall slightly during this period, total biopharmaceutical R&D expenditure is forecast to reach $181 billion by 20225. With R&D expenditure at 13% of sales in 2018, the biopharma industry has one of the highest levels of R&D intensity of any global industry. Amongst leading biopharma companies, R&D intensity can be even higher, averaging 20% of prescription medicine sales at the top 20 global biopharma companies in 2016, and forecast to still exceed 17% in 20226.

A number of factors are contributing to the continued growth in medicines sales and associated R&D expenditure, including ageing populations, increased burdens of chronic diseases, innovation and technological advances, healthcare reforms, emerging nation populations, and an increasing focus on Orphan drug development:

Ageing populations: The proportion of older persons is rising steadily, with the number of people aged 60 years and over projected to double from 11% of the world population in 2009 to 22% in 2050. Ageing populations will have a profound impact on the demand for healthcare services, pharmaceutical products and medical devices with a significant increase in the number of people suffering from chronic diseases and disabilities.

Chronic diseases: Chronic diseases such as heart disease, stroke, cancer, chronic respiratory diseases and diabetes are the leading cause of mortality in the world, representing 63% of all deaths. It is projected that chronic diseases will account for seven out of the top ten causes of death in the world in 2030. The number of new cancer cases around the world is projected to increase from 12.7 million in 2008 to 21 million in 20307. Oncology drugs dominate the development pipeline, accounting for 34% of drugs in development in 2018, up from 27% in 20108. As well as cancer, other chronic conditions that account for a significant part of the development pipeline include diabetes, arthritis and Alzheimer’s.

Innovation and technological advances: Technological advances in gene and cell therapies, as well as advanced diagnostics are transforming the healthcare technology industry. Strong R&D focus and innovation around smarter, faster and more targeted tools will continue to drive this sector.

Healthcare reforms: Advanced and emerging economies are undertaking healthcare reforms to improve access to quality healthcare and outcomes, the performance and efficiency of the health system and control spending.

Orphan drug development: There are an estimated 7,000 rare diseases affecting between 6% and 8% of the worldwide population. About 350-400 million people worldwide have a rare disease9, with 25-30 million affected people in the USA10, while over 45 million people may be suffering from a rare condition in Asia, with 20 million people in China alone11. Biological patents worth $67 billion are due to expire by 2020 so with many blockbuster drugs losing protection, big pharma companies have gravitated towards specialty drugs and Orphan drugs. In fact, most of the drugs approved by the FDA and EMA in 2018 were Orphan medicines.

Clinical Trial Challenges in Europe and North America

Adding to the appeal of Asia-Pacific, sponsors in Europe and North America are facing increased challenges around participant recruitment and retention, lengthy timeframes and relatively high costs. These factors combine to delay drug development which can now take up to 12 years and $2 billion.

Participant Recruitment and Retention: The main reason for trials missing timelines is a failure to recruit participants. Sanofi estimates that at least 70% of trials are impacted by enrollment issues.12 A key challenge for recruitment is the relatively advanced healthcare systems which means participants are less likely to join trials to access novel treatments. The sheer number of clinical trials on at any one time means clinical trial competition is also a major cause of recruitment challenge.

Many studies also have exclusions based on the participant not having received prior treatments, having an advanced stage of disease, or not being newly diagnosed. A study of 114 trials in the UK indicated that only 31% met enrollment goals13. One study identified that 25% of cancer trials failed to enroll a sufficient number of patients, and 18% of trials closed with less than half of the target number of participants after 3 or more years14.

Lengthy Timeframes: Challenges meeting complex and changing regulatory requirements can affect timelines. For instance, in the United States, sponsors must not only follow federal regulations but also adhere to state and local policies in multi-site trials. The same challenges apply to European Union member country policies.

Relatively High Cost: Clinical trials account for up to a third of drug development costs. The major cost drivers include staff and admin (20%), clinical procedures (20%), site monitoring (14%) and site retention (12%)15.

Consequently, biopharmaceutical companies are increasingly looking for options that support participant enrolment and reduce trial timeframes and costs. Conducting clinical trials in Asia is an increasingly viable way to address these challenges.

The Advantages of Asia as a Trial Destination

Asia has become a key location for clinical trials, driven by its large patient population, scale of medical facilities, government support for clinical trials, strategic importance of Asian economies as end consumer markets, lower trial costs, and high-quality standards.

Large potential participant populations: Asia offers access to large numbers of treatment-naïve participants in urban populations who are willing to participate in trials. The clinical trial density is still significantly lower in Asia than in developed markets such as the US, offering significant opportunities for growth with relatively few patients so far exposed to trials.

Asia is already home to 54% of the world’s urban population, totalling over 2 billion people16. However, with per capita healthcare spending generally significantly lower in Asia than in developed markets, and much lower rates of medicine reimbursement by governments, Asian populations are more likely to be interested in gaining access to innovative new therapies through clinical trials.

Some Asian hospitals offer massive scale for clinical trials, for example the Chang Gung Memorial Hospital in Taiwan, the world’s largest hospital, with 10,000 beds and serving 8.2 million outpatients a year, and West China Medical Centre of Sichuan University with 4,300 beds and attending to approximately 3.5 million people a year. It employs 6,100 permanent staff including over 550 associate professors and professors17.

Greater efficiency of clinical trials: Asia is often a more efficient region in which to conduct clinical trials, as evidenced by a comparison of recruitment rates and durations for clinical trials in oncology initiated in 2018 and 2019. Overall, trials involving sites in Asia-Pacific resulted in a higher median recruitment rate and reduced recruitment periods when compared to trials in the US, as well as the worldwide median.

Greater efficiency for complex trials in Immuno-oncology: Most Asian countries lack systematic reimbursement of IO standard of care which means clinical trials are often the only channel that patients can access these treatments. This ultimately stimulates recruitment rates and encourages patient adherence to research therapies.

Over 600 sites across Asia-Pacific have been involved in the clinical development of now approved IO drugs, and hundreds more are experienced in managing clinical trials with immunotherapies for both monotherapy and combination therapies. Immuno-oncology drug clinical studies conducted in Asia-Pacific showed a rate of recruitment up to +60% and +15% faster than in the US for mono and combo therapies respectively18.

Cost efficiencies: Low operational costs positions Asia as a highly attractive destination for clinical trials when compared with the US and Western Europe. Data provided by Medidata Grants Manager indicates that doctor visits, medical treatment and procedures tend to cost less in Asian countries. In addition, rapid start-up and recruitment phases reduce the risk and costs of needing to open new sites or extending studies to meet timelines.

Diverse ethnicity: With populations of Asian ethnicity (especially Chinese and Indian) growing significantly in Western countries, clinical trials in Asia are increasingly attractive because regulatory agencies require researchers to recruit subject samples reflective of their communities at large.

Growing importance of Asia as a medicines market: As the Asia region wealth increases, it is becoming increasingly significant as a medicines market. While Asia accounted for around 45% of global middle-class consumption in 2015, by 2030 it is forecast to reach 60%, with the vast majority— almost 90 percent—of the next billion entrants into the global middle-class coming from Asia: 380 million Indians, 350 million Chinese, and 210 million other Asians.19

Key opinion leaders’ expertise: Asia has knowledgeable key opinion leaders (KOLs) and experts across many therapeutic areas. Many KOLs are global experts in their field, and their inclusion in trials is extremely beneficial. Many Asian KOLs have been part of the World Health Organization’s Technical Advisory Board and published papers in reputable medical journals. The number of citable medical journal articles that came from Asia-Pacific grew by +10% between 2015 and 2018, while numbers from the rest of the world remained flat over the same period (+1%). Locations such as China, Thailand or Malaysia/Singapore demonstrated growth in citable medical documents of +15%, +23% and +13% during that period. In 2018, 28% of worldwide medical citable documents came from Asia-Pacific compared with 19% in 2005.20

Disease patterns similar to the West: Asian countries show similar or higher incidence rates of major diseases to Western nations, providing a comparable environment to conduct clinical trials. While most disease patterns in Asia increasingly mirror those of Western countries, certain conditions show significant spikes in prevalence. For example, The Asia-Pacific region contributes to three quarters of chronic HBV patients worldwide. Specifically, the Western Pacific region comprising of countries including China, Japan, South Korea, Philippines and Vietnam account for 50% of the worlds chronic HBV population.21

The high incidence and prevalence of certain diseases in Asian countries make the region extremely attractive for conducting clinical trials, given the shortage of patients in the US and Europe for these diseases.

Regulatory efficiencies: In Asia, approvals including Institutional Review Board (IRB), regulatory, import licensing and contract negotiations can often be undertaken simultaneously. Asian countries have varying requirements for local language translation, import or export licensing, and data on local patients. However, significant changes have occurred in recent years to further facilitate clinical trials in the region. The most significant changes have occurred in China where regulatory timelines have decreased by 16 months since 2016.

Asia-Pacific countries are also becoming more diligent in developing regulatory regimes that protect intellectual property (IP) rights, a factor previously regarded as a challenge in many Asian markets. The International Property Rights Index report, 2018 (a barometer of the state of property rights in all locations of the world) indicated that several Asia-Pacific locations (New Zealand, Australia, Singapore, Hong Kong and Japan) are in the top 20% of locations globally, and several more (South Korea, Taiwan and Malaysia) are in the second quintile. China and India have moved to the third quintile, ahead of a number of European countries.22

Governments in Asia-Pacific have been implementing measures to improve the regulatory environment for clinical trials in their countries. This has resulted in major advances in markets such as Greater China, South Korea, and Singapore.

In Taiwan, for example, in 2017 the Taiwan Food & Drug Administration (TFDA) introduced specific enhancement measures for clinical trials protocol review, including establishing cell therapy/gene therapy clinical trials fast-track review mechanisms, streamlining first in human trials review process, Hong Kong offers a fast approval timeframe within 3-6 months and has established the Clinical Research Ethics Committee of the Hong Kong Doctors’ Union. The Committee is empowered to issue IRB approval for research conducted in private practice. Once IRB approval is obtained, principal investigators can apply for a clinical trials certificate from the Department of Health.23 Singapore has introduced an Exemption and Expedited review process for studies that involve minimal or less than minimal risks and will be reviewed by the SingHealth Centralized Institutional Review Board (CIRB) within 30 days.24 In South Korea, the new Comprehensive Five-year Plan will involve a significant increase in expert staff to support rapid approval processes.

In China, The Chinese NMPA (previously Chinese FDA) proposes fast-track reviews for breakthrough technologies and clinical priority areas. The NMPA issued a series of regulatory reforms to address concerns around the promotion of R&D activity in China, especially from foreign companies. The main goals of the new reforms were mostly focused on improving the drug review process, shortening the Investigational New Drug (IND) and New Drug Application (NDA) review timeline and encouraging new drug innovation.

Experienced investigators: The global pool of investigators is shifting from the US to other countries, with non-US investigators now approaching parity in numbers with their US counterparts.25 Across Asia-Pacific there are a growing number of experienced investigators. In 2019, there are over 43,000 active principal investigators across Asia-Pacific markets, which is comparable to North America.

Equivalent quality standards: Asian countries are rapidly becoming more competitive by building appropriate site experience, technological expertise, infrastructure, and scale to manage large clinical trials. Asia-Pacific clinical trials are demonstrating compliance levels equivalent to Europe and North America, as indicated by analysis of the outcomes of US FDA inspections by region.26

The Need for Specialized Support in Asian Clinical Trials

While Asia has become a key location for clinical research, the region also presents challenges that drive the need for specialized CRO support in clinical trials.

Regulatory complexities: Regulatory regimes are heterogeneous across the region, however significant change is underway in the regulatory frameworks that govern clinical trials in each country. The IRB approval, regulatory, import licensing and contract negotiation processes can be undertaken simultaneously in some countries, while in others they are sequential. There are also varying requirements for local language translation, import or export licensing, and data on local patients. Material Transfer Agreements (MTAs) may also be needed for export of biological samples.

Language and cultural differences: North America, Australia, New Zealand and Western Europe, have a high level of English fluency, but this is not the case in Asia where a wide variety of languages are spoken. This drives a requirement to translate material into local languages, increasing the complexity of conducting a trial. Social status and the importance of “face” are also important cultural issues in Asian societies, for example, it is usual for senior staff members to communicate non-compliance to principal investigators, and junior employees to submit improvement ideas via process-based templates in order to avoid uncomfortable hierarchical conflict between junior and senior staff. There can also be issues in the collection of an informed consent from participants, with one study in India indicating that community leaders can play a role in influencing the decision of local residents to consent for clinical trials.27

The factors mentioned above drive a need to partner with a CRO that fully understands the clinical trials environment in Asia, allowing the sponsor to benefit from the advantages the region offers as a clinical trials location. Some of the factors that should be considered in choosing an appropriate CRO partner are listed below.

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