Recruitment and

RetentionA Resource Review for Strategic Planning Clinical Trials in CHINA

Ying Lu

Consulting

January, 2012

INTRODUCTION0 One of the biggest hindrances to clinical trials is the lack of patient

participation. Failure of patient recruitment and retention is the

most common cause of delays in market-launch in the US.

Competing for patient resources and failure of investigators to meet

planned patient recruitment goals are also common problems in

clinical trials in China. Despite satisfactory reports of patient

recruitment rates in global trials conducted by major multinational

firms, many local Chinese pharmaceutical trials have difficulty

meeting required timelines due to noncompliance of patients and

investigators, unwillingness of physicians to enroll patients, overly

rigorous inclusion and exclusion criteria, and competing trials.

INTRODUCTION CONT.

0 The majority of the Chinese population seeks out

traditional Chinese Medicine (TCM) and the government

has structured the reforms to favor hospitals with

expertise in TCM. The widespread concurrent use of

TCM with Western pharmaceutical products represents a

challenge with respect to clinical trial design and

interpretation of trial data.

INTRODUCTION CONT.

0 This presentation is to provide resources for planning

and managing clinical trials in China by highlighting

patient populations with major diseases, State Food and

Drug Administration (SFDA) GCP certified clinical trial

sites, and the commonly used Traditional Chinese

Medicine (CTM).

Overview of Chinese Population Growth Rate in Urban and Rural Areas, and by Age Groups

1982 1990 1995 2000 2005 2006 2007 2008 20090

40000

80000

120000

160000

0

20

40

60

80

Urban Rural 0-14 age 15-64 age >65 age

Popu

latio

n (1

0,00

0)

Year

Rat

e (%

)

Ten Leading Course of Death in Urban and Rural Areas

Malignant NeoplasmasCerebrovascular Disease

Heart DiseasesRespiratory System

Injury & PoisoningEndocrine/Nutritional/Metabolic Disorders

Digestive SystemGenitourinary System

Nervous SystemInfectious Diseases

0 50 100 150 200

Rural Urban

Mortality Rate = total deaths ( caused by diseases) at reference period/average population at same period x 100%.

Morbidity Rates of 10 Major Chronic Diseases (%) in Urban & Rural Areas in 2009

Hypertension

DiabetesCerebrovascular diseaseIschaemic heart disease

Intervertebral disc disorderGastroenteritis

Rheumatoid arthritisCOPD

Cholelith & Cholecystitis

Peptic ulcer

0 40 80 120

Rural Urban

Mortality Rate = total deaths ( caused by diseases) at reference period/average population at same period x 100%.

Rates of Urban And Rural Area Outpatient/Office Visits in 2008 (0/00)

Acute Upper Respiratory InfectionHypertension

Heart DiseaseDiabetes

Acute GastritisGenitourinary Diseases

Cerebrovascular DiseasesCOPD

ArthritisCancer

Gallbladder DiseaseInfectious Diseases

PneumoniaCirrhosis

0 10 20 30 40 50

Rural Urban

Rates of Urban and Rural Area Inpatient Hospital Stays in 2008 (0/00)

Heart DiseaseCerebrovascular Diseases

HypertensionCancer

DiabetesGenitourinary Diseases

Gallbladder DiseaseCOPD

Acute Upper Respiratory InfectionPneumonia

Acute GastritisInfectious Diseases

ArthritisCirrhosis

0 2 4 6 8 10

Rural Urban

Two-week Hospital Outpatient Visit Rate by Age in 2008

A

0-4 5-14 15-24 25-34 35-44 45-54 55-64 >650

50

100

150

200

250

300

350Urban Rural

Age (year)

Two-

wee

k ho

spita

l vis

it ra

te b

y ag

e (‰

)

Two-week Hospital Outpatient Visit Rate by Hospital Level & Preference (2008)

Percentage of Drug and Traditional Chinese Medicine Usages

Urban and Rural Household Income and Healthcare Expenditure (Yuan, 2008)

Urban Rural0

4000

8000

12000

16000 Disposable Income, 15,781

Net Income, 4,761

Non-productive Expenditure;

11,243

Non-productive Expenditure;

3,661Healthcare; 786 Healthcare; 246

Yuan

Average Expenses of General Hospital Outpatient Visits and Inpatient Stays (Yuan/per patient, 2008)

Medication Diagnostic & Treatment

Other10

100

1000

10000

Out-patient (per visit) In-patient (per patient)

Patie

nt F

ee (Y

uan)

Current China Clinical Trials Registered in Chinese Clinical Trial Registry

Overview of 10 Year New Chemical Entity (NEC) SFDA Applications

2001-2010 Class I New Chemical Entity SFDA Application

SUMMARY0 Mortality rates of major diseases were relatively higher in

rural than in urban areas. Morbidity rates of cardiovascular disease and diabetes were higher in cities, and morbidity rates of acute upper respiratory infection, pneumonia, acute gastritis, infection, cirrhosis were higher in countries. High two-week hospital visit rate was reported in rural area by all age groups. People in rural area were less likely visit above prefecture-level hospitals. Short distance and high level expertise of physicians were major factors for selecting hospital visits. Current SFDA GCP certified over 400 clinical trial sites are hospitals at above county levels, therefore including patients in rural areas can be a challenge.

SUMMARY CONT.

0 Although incidences of infectious diseases were relative low, anti-microbial agents were top rated drugs used in hospitals. Main applications of Traditional Chinese medicine (TCM) were Cardio/Cerebrovascular diseases, cancer, respiratory diseases, and musculoskeletal disorders. Wide use of TCM and other medications might require extra caution on designing and selecting study subjects. Majority China clinical trials can be found at clicinaltiral.gov (NIH) and Chinese Clinical Trial Registry; these are good resources for identify competing trials for study subjects. Information presented above might provide valuable resources for analyzing threats and opportunities in China clinical trial patient recruitment and retention.

REFERENCES AND USEFUL LINKS

• Health statistics: http://www.stats.gov.cn/tjsj/ndsj/2010/indexeh.htm• pre-clinical study site list:

http://app1.sfda.gov.cn/datasearch/face3/base.jsp?tableId=11&tableName=TABLE11&title=临床前研究单位备案名单&bcId=118714711342967566418335831165

• SFDA GCP certified study site list: http://app1.sfda.gov.cn/datasearch/face3/base.jsp?tableId=19&tableName=TABLE19&title=药物临床试验机构名单&bcId=118714941832181502104731901420

• SFDA new drug clinical trial list: http://app1.sfda.gov.cn/datasearch/face3/base.jsp?tableId=8&tableName=TABLE8&title=%C5%FA%D7%BC%C1%D9%B4%B2%D1%D0%BE%BF%B5%C4%D0%C2%D2%A9&bcId=124356683643430217478147499292