Clinical Development in China: Current Status and Future Trends

2008-8-15

Soaring drug development costs ¨C coupled with slim prospects for obtaining blockbuster
products ¨C have driven pharmaceutical companies to look for cost-reduction strategies in
nearly every area of their business. One of the leading initiatives for cost reduction is the
mobilization of more clinical trials to Asia and Latin America.
In the current environment, China has become an increasingly attractive place to host
global standard clinical studies. Not only does China provide the vast number of patients
suitable for a variety of therapeutic areas pursued by global pharmaceutical companies
and medium- and small-scale biotechnology firms, but it also provides the fastest
growing pharmaceutical market worldwide. This scenario allows ample commercial
return as a result of successful registration using Chinese clinical study results.
Benefits of Conducting Research in China
Opening Chinese study sites likely is the best insurance policy for the timely completion
of ongoing or planned clinical studies for almost all drug development programs. tIndeed,
timeline delays have been a major issue for many drug development programs. Statistics
have demonstrated that more than 70 percent of trials drag beyond the expected
completion deadline. ¡°Last patient enrolled¡± becomes an ever-demanding milestone for
many clinical study teams to reach.
Incorporating China into a company¡¯s global development program often allows the
project team to boost patient enrollment mid-way into the study, enabling the enrollment
curve to ramp up quickly and achieve recruitment goals in advance of the expected
timeline. This time savings frees up additional resources for both the clinical team and
the development team. In addition, an advanced development timeline usually leads to
faster registration, which translates into a highly significant commercial advantage. For
example, a blockbuster product entering the market one day earlier than planned can
result in hundreds of thousands of dollars in additional sales worldwide.
Acceptance of Chinese clinical study data has been demonstrated by both verbal
communications and actions taken by the Food and Drug Administration (FDA), the
European Medicines Agency (EMEA) and Japanese regulatory agencies. There have
been seven audits performed in trial sites in seven different cities throughout China by the
FDA since 1999 which yielded no major citations. The FDA also has granted label
changes based on a large outcome study solely performed in China.
The EMEA repeatedly has accepted Phase II and Phase III studies with Chinese patients
as a significant component of the studies. Moreover, the Japan regulatory agency, Kikko,
recently has acknowledged a willingness to accept data generated from clinical studies in
China.
Finding Right Chinese Partner Is Key
Naturally, driven by increasing market demand and supported by a positive regulatory
landscape, moving clinical studies to China already is occurring. To date, most of the
Western-standard clinical studies are conducted by contract research organizations
(CROs) and Chinese subsidiaries of global biotech or pharmaceutical companies. One
important aspect of making these studies successful is identifying the right partner(s) in
China. For a typical clinical trial, sponsors usually work through a Chinese CRO or an
internal clinical operational group in China.
In either case, it is important for a pharmaceutical or biotechnology company to establish
a well-thought out communication plan. This plan not only must support communication
within the operational team, but also has to adequately manage communications with
investigators and the clinical research associates (CRAs). For companies that do not have
a division in China, choosing the right CRO to implement projects is the most important
decision.
In terms of evaluating different CROs in China, sponsors often are impressed by low
price quotations and sometimes overly positive promises, which can be both misleading
and inaccurate. To avoid common CRO selection pitfalls, sponsors should interview key
personnel on the project team, e.g., the project manager, and the lead CRA, data manager,
etc.
Questions focusing on the trial¡¯s details usually can identify potential weaknesses early in
the interview process. In addition, the communication and working style of these key
team members are very important. CRO staff should be able to communicate effectively,
using English, in oral and written forms. They should also value and practice basic
teamwork tenets, i.e., honesty, openness, the ability to work independently and
responsibility for their deliverables.
One unique aspect of conducting clinical studies in China is that CRAs spend more hours
at the investigator sites as compared to time spent for studies performed in the United
States or the European Union. Because the clinical research experience levels are
different among the Chinese investigators, it is critical that CRAs set appropriate levels of
monitoring for each site. Prior to study initiation, CRAs need to properly gauge the level
of experience at each particular site and work with the investigator and site coordinator to
address all details required by protocol during initiation and subsequent study visits.
The additional hours spent per study site rarely results in higher cost of clinical studies,
because the number of sites required in China is much lower than those that would have
been needed for the United States. This decrease in sites in China is attributed to the
number of patients enrolled per site ¨C typically 10 to 20 times higher than those in the
United States. China has a highly concentrated hospital system in metropolitan areas and
Chinese hospitals are usually large, with up to 1,500 to 3,000 beds per hospital. Due to a
lower number of sites and a high patient enrollment rate, it is highly feasible for each
CRA to focus on two-to-three key sites in the same city for a particular study. This allows
more consistency in monitoring and controlling study implementation processes.
Clinical Trial Offerings in China To Increase
As China hosts more and more global standard clinical studies, it is not hard to imagine
that the scope of supporting services also will expand. For example, global central
laboratories have begun to put their footprints in China by opening subsidiaries in cities
like Beijing and Shanghai. Related pharmacogenomic as well as biomarker analytical
capabilities also are being established in China. Leading CROs in China already have
expanded into this area and are expediting blood sample analysis by conducting assays
locally during and after clinical studies.
In the near future, the central lab business will grow tremendously as a result of both an
increasing number of trials and a lack of alternatives. It is a well known fact that the
Chinese government purposely restricts shipping blood samples outside of China due to
concerns over leaked genetic information. This makes it necessary to analyze blood
samples for Chinese subject locally.
Challenges To Consider
In the midst of a booming clinical studies surge in China, there are a few challenges that
need to be overcome to improve the overall environment for clinical study there. One of
the biggest challenges is the investigational new drug (IND) review timeline. Currently, it
takes at least eight to 10 months to open an IND in China. China¡¯s State Food and Drug
Administration (SFDA) is rolling out a ¡°green channel¡± concept, which could accelerate
the review timeline to six-to-eight months. Review priorities will be given to compounds
or biologicals that are novel, first-in-class and address significant, unmet medical needs
in China through their commercialization.
In light of the long regulatory approval time, to fully benefit from the excellent patient
enrollment results in China it is critically important to have a well-planned global
development program that includes China early in the process. If China is only an
afterthought or a last resort due to a delayed trial, the long IND review timeline is likely
to undermine the clear benefit of high Chinese trial enrollment rates to the global
development program.
Many study sites in Beijing and Shanghai host at least four ongoing clinical studies. The
majority of the Chinese divisions of global pharma companies also are located in these
two cities. As a result of this concentration, hospitals in these areas were the first to be
accessed by the Chinese divisions of the top 10 players in the industry.
Although experienced investigators may be occupied with several therapeutic areas
(especially in oncology, cardiovascular and diabetes, etc.) in the top hospitals in first-tier
cities, companies must recognize that there are numerous SFDA-certified hospitals in the
second-tier cities that are willing to cooperate with sponsors to conduct early- or latephase
clinical trials. These investigators have already passed good clinical practice
training and have been audited by the SFDA; they are very cooperative, eager to learn
and willing to follow procedures. With the proper training and monitoring, these sites can
and will deliver the same quality of clinical trial conduct as the top sites in Beijing or
Shanghai provide.
In summary, China has proven to be capable of delivering high-quality clinical studies
with moderate cost, and increasingly supportive and associated services for clinical
development also are being established in China. As such, these factors are driving most
of the top 20 pharmaceutical and biotech companies worldwide to incorporate China into
their routine drug development programs.
However, there are new challenges to face as more clinical studies make their way into
China. Improving IND review timelines and clinical study expertise at more clinical trial
sites, especially those in secondary cities, are two of the most important priorities to
ensure China¡¯s continued success and allow it to be the preferred country for clinical
research.
Dr. Joanne Jiang, Ph.D., MBA, is the co-founder of Fountain Medical Development, a
contract research organization (CRO) offering a full range of ICH GCP-compliant
clinical research services in China for multinational clients. In the pharmaceutical
industry for 12 years, Dr. Jiang started her career in preclinical pharmacology area at
Bayer pharmaceutical and Eli Lilly, working as research scientist, lab head and project
leader, and furthered her expertise in drug development and project management as a
global project manager. She has worked for Aventis and Daiichi Sankyo, managing drug
development and life cycle management projects, encompassing preclinical to Phase IV
activities, with a particular focus on clinical trial planning and management, and the
integration of marketing plans and regulatory strategy to enable optimal trial design.
joanne.jiang@fountain-med.com

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