How Clinical Research Promoted by Health
Industries Can Contribute to Improve The
Quality of Care?
The Experience in China
Jiyao Wang, MD, MSc, AGAF
Zhong Shan Hospital, Fudan University
Center of EBM, Fudan University
Bench To Bedside : Interdependence
Bench To Bedside
The 3T’s
The Innovation Interface
•Basic/clinical science
•Technology focus
•Public health
•Policy/ Culture
Dougherty, D. et al. JAMA 2008;299:2319-2321
Category of Clinical Research
For product development
Discovery
Launched by
pharmaceutical
company
Preclinical
Toxicology
Phase I
Phase II
Phase III
Time(years)
Phase IV
Launched by
investigators
Regulatory Filing
Efficacy & safety
in selected population
Effectiveness & safety
in real clinical practice
Long term
Clinical outcome
What, Exactly, is IMCT ?
• Include a larger number of participants
• Different geographic locations
• The possibility of inclusion of a wider range of
population groups with different
– genetic
– environmental
– and ethnic or cultural backgrounds
Current Status of IMCT
• Globalization of clinical trials is a reality
• Clinical trials across multiple regions of the
world have become common practice
• China is an increasingly important source of
patients to test new drugs
– As of April 28, 2015, there were 18,9109 clinical
trials globally
– Up to 6040 in mainland China
Source: www.clinicaltrial.gov
Search date: 2015-4-28
Current status of clinical trials
Source: www.clinicaltrial.gov
Search date: 2015-4-28
18,9109
Current status of IMCT in China
Source: www.clinicaltrial.gov
Search date: 2015-4-28
Registry on
clinicaltrial.gov
Mainland
Hong Kong
Taiwan
6040
1059
3917
Open studies of IMCT
527
46
201
What we are doing
Type
Phase I
Phase II
Phase III
Phase IV
IMCT
Ongoing multi-center clinical
trials in our hospital
3
8
24
13
25
Sponsor: Large pharmaceutical companies in Europe and
America
IMCT , Areas of Impact
Simultaneous Global Development
Clinical
Practice
Research
Regulatory
Ethical
Impact of Clinical Research Promoted by
Health Industries
•
•
•
•
Key opinion leaders
Principle investigators
Doctors
Hospital teams
Key opinion leader
•
•
•
•
Organize professional activities
Write and promote guidelines
Practice new evidence in the specialty
Become the primary investigators for the
clinical trials
• Impact on the quality of care of medical
practice
– The standard of care
– Healthcare system
Benefits of participation for the key opinion
leader in the country for his/her expertise
development in his/her speciality
• More access to acquire resources
– More patients
– More facilities, both from hospitals and
pharmacies
• Newer information to be caught
• More experience in the design, management
and evaluation for the whole protocol
Benefits of participation : principle
investigators
• Be familiar with GCPs
• Know the responsibilities as the “PI”
• Establish excellent communication with external
sites
• Establish excellent communication with
international colleagues
• Build an international research reputation
• As a local PI, I have participated a lot of clinical
trials (phase II and III) lunched by pharmaceutical
companies (such as Searl company, Astrazeneca,
Novartis, GlaxoSmithKline, Bristol-Myers Squibb,
Roch, etc) since 1992.
• I am familiar with GCP, established SOPs and
became member of local ethics committee.
• I have been invited to participate the international
multicenter clinical trials organized by famous
experts in the world.
• I have organized multicenter clinical trial within
China in order to get more evidence for improving
quality of health care.
1Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The
Netherlands; 2Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China; 3Gastroenterology
and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 4Gastroenterology and
Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 5Cerrahpasa Medical
Faculty, Istanbul, Turkey; 6National Institute of Infectious Disease, Bucharest, Romania; 7University of
Ankara, Medical School, Ankara, Turkey; 8Department of Gastroenterology and Hepatology, Academic
Medical Center, Amsterdam, The Netherlands; 9Department of Gastroenterology, Fundeni Cinical Institute,
Bucharest, Romania; 10Division of Infectious Diseases and Hepatology, Wroclaw Medical University,
Wroclaw, Poland; 11Department of Internal Medicine, Fundeni Cinical Institute, Bucharest, Romania;
12Department of Gastroenterology, Yuksek Ihsitas Hospital, Ankara, Turkey; 13Department of Infectious
Diseases, Silesian Medical University, Katowice, Poland; 14Department of Public Health, Erasmus MC
University Medical Center, Rotterdam, The Netherlands; and 15Toronto Center for Liver Disease, Toronto
Western and General Hospital, University Health Network, Toronto, Ontario, Canada.
•
(AASLD 2014 presentation and published in Hepatology 2015;61:15121522)
Genetic study of peginterferon treatment in chronic hepatitis B
To identify genetic polymorphisms associated with response to interferon therapy in chronic
Hepatitis B patients
Benefits of participation: Doctors (1)
Need to conduct clinical trial according to Good
Clinical Practice(GCP) Standards
•GCP is a standard for the design, conduct, monitoring, analyses,
and reporting of clinical trials
•The practice of GCP were standard in all Member Sites, before
2002, only a minority of hospital in China had previously were
familiar with the obligations of the different parties of GCP
•IMCT introduced GCP principles to ensure that trials are
conducted in accordance with high standards of ethics and
science
Benefits of participation: Doctors (2)
Drive the Quality care of patients
•IMCT helps doctors ensure continuous quality
improvement of diseases treatment by aligning
clinical care with evidence-based guidelines
•More access to acquire resources
– More patients
– More facilities, both from hospitals and pharmacies
•Newer information to be caught
•More experience in the design, management and
evaluation for the whole protocol
Benefits of participation: the
hospital team
• Access to the most up-to-date research and scientific
publications
• Professional education opportunities, such as workshops
and webinars
• Clinical tools and resources
• Patient education resources
• A competitive advantage in the healthcare marketplace
• National and local recognition for hospital team program
achievement
• Quality improvement, broaden knowledge of short- and
long-term benefits and risks
• Established ethical committee in Hospital level
IMCT Areas of Impact：Research
Improve China clinical trial design and
research level(1)
• Investigator training
• Plan in the protocol : SOPs and Manuals,
including Global Clinical SOPs, data handling SOPs,
operational SOPs
• Adaptive/flexible designs setting
Improve China clinical trial design and research
level(2)
• Quality Assurance
• eCRF
• Electronic Data Capture (for use in clinical trials)
• Data management and data quality
• power estimation / sample size
• Methods for subgroup analysis; Randomization issues /
stratification
• How to describe/present data
The quality of clinical research changed:
2003-2015
•Somewhat Structured
•SOPs not available
•Less Experienced
•Well organized and Structured
•SOPs and Processes in place
•Experienced team
IMCT Areas of Impact：Ethical
•
•
•
•
Informed Consent
Local Ethics Committees, IRB’s
Integrity of research conduct
Data collection/privacy
Pros and Cons for patients in
terms of participation of IMCT
• Pros
• Cons
– Patients will be benefited
– Information not balanced,
from free new effective
misunderstood
medications already on the – Under-treatment if control arm is
market in Europe and
not well designed, like placebo
America
– Safety concern for the very new
– Patients will be benefited
treatments
from tailored follow-up ,
– Impact on activities of daily living?
and will decrease cost
– Some are worried about privacy,
– More convenient for a
asynchronous communication can
clinic (saving time, good
be more efficient.
doctors and nurses)
– Cost saving
IMCT Areas of Impact: Regulatory
On 12/1/2002, ‘Drug Registration
Regulation’ was issued by CFDA, the
first regulation for approval of an
international multi-center trial, then ,
international multi-center clinical trial
showed an increasing trend in China.
On 30/1/2015 , China Food and Drug
Administration(CFDA) issued
‘International multi-center clinical trial
Guideline’ as a framework for good
management in trials of medicines in
China
Encountered problems of IMCT
in China today
Compared with developed countries,
there is a gap
• Less IMCT: For example, Cancer Patients, enrolled in
one of a clinical trial
– >90% , USA
– About 9% , China
• Among the ongoing IMCL in mainland China, the
majority IMCL are industry-sponsored trial ( IST),
while investigator-initiated clinical trial ( IIT) were
viewed as of higher academic value
Types of Ongoing IMCT
• Therapeutic : >90%
•
•
•
•
•
Prevention
Early detection/diagnostic
Disease Management
Correlative
Population-based studies:
• Epidemiological
• Observational
• Quality-of-life
Rare disease research, diagnosis or
treatment compared to marketed drugs
and other new uses
Areas not covered
Need MORE Investigator-initiated clinical trial
A report including combined data from approx. 1140
studies shows that industry-sponsored clinical trials
are significantly more likely to reach conclusions in
favor of the industry vs non-industry studies- possibly
publication bias or selection of an inappropriate
comparator to the drug being evaluated
J. E. Bekelman, Y. Li and C. P. Gross J. Am. Med. Assoc. 289, 454–465; 2003
We has done much to promote national
multi-center clinical trials
•
•
•
•
•
•
Investigator Initiated Trials (IITs)
Investigator Initiated Studies (IISs)
Investigator Sponsored Trials (ISTs)
Investigator Initiated Research (IIR)
Non Registration trials (NRTs)
Non Sponsored Trials
Investigator-initiated China regional multicenter clinical trial in China
What are Today’s Challenges?
• Each participating site needs to be visited
numerous times, making this a large, and
time-consuming administrative activity, not
only for the monitor, but also for the
physicians involved. Monitoring is associated
with high costs
• With Limited funds:
– How to protect the enthusiasm and commitment
of the physicians and attract them to involve.
– Time-consuming, in some cases even to the
extent that they declared not to participate in
these kind of studies again in the future.
How to improve
• A well designed protocol
– Background to evaluate the feasibility of the new
treatment and control arm, based on the best clinical
practice guideline
– Ethical committee fully consider the safety for all the
participants
– Mostly understanding and fully consent to attend by
the participants and their family
– Reimbursement should be prepared and easily got
accessed
• Independent supports from large pharmaceutical
companies
Quality Assurement
• Team building including investigators, nurses,
CRC(clinical research coordinator), CRA(clinical
research associate),statistician
• Timely audit for the projects, both inside
hospital and outside hospital
• supplements including office, network, and
storage space
• Central study pharmacy inside hospital is
promoting
Conflict of Interest (COI)
• COI issues are real
– Focus on financial only
– Tone: non – collaborative
– Unintended consequences – effecting collaborative efforts
• Debate needs broader view: goal - improve public health
• Alternative position
– Include all types of conflicts
– Improve public health is a primary interest
– Checks and balances in place
– Collaboration/ cooperation/ learning /teaching
Future : Integration/Collaboration
• Clinical trial is a good clinical practice
• Only the medical team with good practice can start a
good clinical trial
• Increasing realization that institutions can’t go it alone
• Collaborative efforts in complex systems, Sharing the
rewards
• Focus on unmet medical need/public health value
The bridge between bench and bed
Knowledge gap
unknown
Knowing-doing gap
Known
Clinical Research
Action
Improve quality of care
Thank you!
Trials are short; real-clinical
practice has no time limit