CSMUH Clinical Trial CentersCSMUH Clinical Trial CentersExperiences on The Experiences on The

Implementation of Clinical TrialsImplementation of Clinical Trials

James Cheng-Chung Wei, MD, Ph.D.James Cheng-Chung Wei, MD, Ph.D.

          Chief, Division of Allergy, Immunology and Rheumatology Chief, Division of Allergy, Immunology and Rheumatology      Director, Chinese Medicine Clinical Trial Center      Director, Chinese Medicine Clinical Trial Center 

     Chung Shan Medical University Hospital     Chung Shan Medical University Hospital

Taichung, Taiwan. Taichung, Taiwan. 

OutlinesOutlines

1.1. Global clinical trials trendsGlobal clinical trials trends

2.2. CSMUH experiencesCSMUH experiences

3.3. Suggestions to sites, sponsors & health Suggestions to sites, sponsors & health authoritiesauthorities

Map of All Studies in Map of All Studies in ClinicalTrials.govClinicalTrials.gov

All Studies in ClinicalTrials.govAll Studies in ClinicalTrials.govAsia Pacific areaAsia Pacific area

1.1. Taiwan   1537Taiwan   15372.2. Korea  1455Korea  1455

3.3. China   1372 China   1372 4.4. Japan   1305 Japan   1305

5.5. India   1115 India   1115 6.6. Thailand   602 Thailand   602

7.7. Singapore   588Singapore   5888.8. Hong Kong   462Hong Kong   4629.9. Philippines   339Philippines   339

10.10. Malaysia   279Malaysia   279

Australia   2373 Australia   2373

New Zealand   553New Zealand   553

How did sites/countries selectedHow did sites/countries selected

Country Attractiveness Index for Clinical TrialsCountry Attractiveness Index for Clinical Trials

Source of subjects for interventional Source of subjects for interventional clinical trialsclinical trials, Nov 15, 2013 , Nov 15, 2013 Kmr GroupKmr Group

Taiwan Strength in Clinical TrialsTaiwan Strength in Clinical Trials

Population size 2.3 million Population size 2.3 million Patients pooling, coverage of national Patients pooling, coverage of national

insuranceinsurance PI reputationPI reputation CRO/Site Team GCP quality CRO/Site Team GCP quality Study site cost Study site cost Regulatory framework efficiencyRegulatory framework efficiency IRB review time and qualityIRB review time and quality

OutlinesOutlines

1.1. Global clinical trials trendsGlobal clinical trials trends

2.2. CSMUH experiencesCSMUH experiences

3.3. Suggestions to sites, sponsors & health Suggestions to sites, sponsors & health authoritiesauthorities

Chung Shan Medical Chung Shan Medical University HospitalUniversity Hospital

Chinese Medicine Clinical Trial Center

Chung Shan Medical University HospitalChung Shan Medical University Hospital

• One of 4 medical centers in mid-TaiwanOne of 4 medical centers in mid-Taiwan• 1500 beds, 4 districts1500 beds, 4 districts• Certify by Certify by ISO27001, FERCAPISO27001, FERCAP• Inspected by TFDA, FDA, Japan PMDAInspected by TFDA, FDA, Japan PMDA• Contract template with Contract template with Norvatis, GSK, Norvatis, GSK,

SanofiSanofi

Chung Shan Medical University HospitalChung Shan Medical University Hospital GCRC (General Clinical Research Center)GCRC (General Clinical Research Center)

SMO (site-management organization) SMO (site-management organization) model granted by the DOH, Taiwanmodel granted by the DOH, Taiwan

SMO (site-management organization)SMO (site-management organization)

GCRC (General Clinical Research Center)GCRC (General Clinical Research Center) CMCTC Chinese Medicine Clinical Trial CenterCMCTC Chinese Medicine Clinical Trial Center

SMO (site-management organization)SMO (site-management organization)

GCRC (General Clinical Research Center)GCRC (General Clinical Research Center) CMCTC Chinese Medicine Clinical Trial CenterCMCTC Chinese Medicine Clinical Trial Center

AdministrativeAdministrative 2 assistants2 assistantsAdministrativeAdministrative 2 assistants2 assistants

Clinical affairsClinical affairs 1 CRA/HN1 CRA/HN 9 CRC9 CRC

Clinical affairsClinical affairs 1 CRA/HN1 CRA/HN 9 CRC9 CRC

DataData management management1 Statistic PhD1 Statistic PhD2 Statistic MS2 Statistic MS

DataData management management1 Statistic PhD1 Statistic PhD2 Statistic MS2 Statistic MS

3 MD 3 MD 1 Pharmacist1 Pharmacist3 MD 3 MD 1 Pharmacist1 Pharmacist

CSMUH Chinese Medicine Clinical Trial CenterCSMUH Chinese Medicine Clinical Trial Center

04

Clinical Trials in CSMUH

Clinical trials in CSMUH

Clinical trials in CSMUH

Dr. Wei Global Trials ExperiencesDr. Wei Global Trials Experiences

About 60 trials in the past 5 years, 27 trials ongoing.About 60 trials in the past 5 years, 27 trials ongoing.**World top one enroller in **World top one enroller in

-Norvatis RHAK study: IL-17 MoAb in ankylosing spondylitis.-Norvatis RHAK study: IL-17 MoAb in ankylosing spondylitis.

-Pfizer: Etanercept in non-radiographic axial spondyloarthritis.-Pfizer: Etanercept in non-radiographic axial spondyloarthritis.

**Taiwan top one enroller in **Taiwan top one enroller in

-BMS IM101-174: Abatacept in rheumatoid arthritis-BMS IM101-174: Abatacept in rheumatoid arthritis

-UCB RA-0083: Anti-IL6 in rheumatoid arthritis-UCB RA-0083: Anti-IL6 in rheumatoid arthritis

-MSD MK0663-108: Etoricoxib in ankylosing spondylitis-MSD MK0663-108: Etoricoxib in ankylosing spondylitis

-Twi: IL-1 receptor antagonist in gouty arthritis-Twi: IL-1 receptor antagonist in gouty arthritis

-TSH: TuNex (Etanercept biosimilar) in rheumatoid arthritis-TSH: TuNex (Etanercept biosimilar) in rheumatoid arthritis

FDA inspectionFDA inspection CSMUH, Oct 18-20, 2010.CSMUH, Oct 18-20, 2010.

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2020

21

CONFIDENTIAL July 2009

BLISS Phase 3 GeographyBLISS Phase 3 Geography

USUS

Puerto RicoPuerto Rico

CanadaCanada

MexicoMexico

Costa RicaCosta Rica

ArgentinaArgentina

BrazilBrazil

ChileChile

ColombiaColombia

PeruPeru

AustriaAustria

BelgiumBelgium

Czech RepublicCzech Republic

FranceFrance

GermanyGermany

IsraelIsrael

ItalyItaly

The NetherlandsThe Netherlands

PolandPoland

Romania/Romania/RomaniaRomania

RussiaRussia

SlovakiaSlovakia

SpainSpain

SwedenSweden

UKUK

AustraliaAustralia

Hong KongHong Kong

IndiaIndia

KoreaKorea

The PhilippinesThe Philippines

TaiwanTaiwan

1,693 patients from 223 centers in 31 countries1,693 patients from 223 centers in 31 countries

22

CONFIDENTIAL July 2009

Enrollment - BLISS-52

867 patients from 90 centers in 13 countries867 patients from 90 centers in 13 countries

Dr Wei Academia CreditsDr Wei Academia Credits

Steering committee and paper authorshipSteering committee and paper authorship• Etanercept in axial spondyloarthritisEtanercept in axial spondyloarthritis• Tofacitinib in ankylosing spondylitisTofacitinib in ankylosing spondylitis• ASAS classification criteria for SpondyloarthritisASAS classification criteria for Spondyloarthritis• Treating spondyloarthritis, including ankylosing Treating spondyloarthritis, including ankylosing

spondylitis and psoriatic arthritis, to target: spondylitis and psoriatic arthritis, to target: recommendations of an international task force.recommendations of an international task force.

International Advisory BoardInternational Advisory Board• Pfizer, EtanerceptPfizer, Etanercept• Abbvie, AdalimumabAbbvie, Adalimumab• UCB, Certolizumab PegolUCB, Certolizumab Pegol

My Investigator-Initiated StudiesMy Investigator-Initiated Studies1.1. Immunogenicity, Immunogenicity, adalimumab adalimumab levels and clinical response in ankylosing levels and clinical response in ankylosing

spondylitis patients during 24 weeks of follow-up. Annals Rheum Dis 2013spondylitis patients during 24 weeks of follow-up. Annals Rheum Dis 2013

2.2. Tramadol/acetaminophen combination (Ultracet) Tramadol/acetaminophen combination (Ultracet) as add-on therapy in the as add-on therapy in the treatment of patients with ankylosing spondylitis. Clin Rheumatol 2013treatment of patients with ankylosing spondylitis. Clin Rheumatol 2013

3.3. Efficacy and Safety of Efficacy and Safety of Herbal Medicine Yun-Cai Tea Herbal Medicine Yun-Cai Tea in the Treatment of in the Treatment of Hyperlipidemia: A Double-Blind Placebo-controlled Clinical Trial. Chinese Hyperlipidemia: A Double-Blind Placebo-controlled Clinical Trial. Chinese Journal of Integrative Medicine 2013Journal of Integrative Medicine 2013

4.4. A randomized, double-blind, placebo-controlled study to evaluate the A randomized, double-blind, placebo-controlled study to evaluate the efficacy and tolerability ofefficacy and tolerability of Danshen (Salvia miltiorrhiza) Danshen (Salvia miltiorrhiza) as add-on anti-as add-on anti-hypertensive therapy in Taiwanese patients with uncontrolled hypertension. hypertensive therapy in Taiwanese patients with uncontrolled hypertension. Phytotherapy Research 2012 Phytotherapy Research 2012

5.5. Vitamin B6 Vitamin B6 supplementation improves pro-inflammatory responses in supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis. Eur J Clin Nutr. 2010 patients with rheumatoid arthritis. Eur J Clin Nutr. 2010

6.6. Efficacy and immunomodulation of Efficacy and immunomodulation of Sterols/Sterolins Sterols/Sterolins in patients with in patients with allergic rhinitis: A randomized double blind placebo-controlled clinical trial. allergic rhinitis: A randomized double blind placebo-controlled clinical trial. Formosan Journal of Rheumatology 2009Formosan Journal of Rheumatology 2009

Consortium for Globalization of Consortium for Globalization of Chinese Medicine, CGCM Chinese Medicine, CGCM

OutlinesOutlines

1.1. Global clinical trials trendsGlobal clinical trials trends

2.2. CSMUH experiencesCSMUH experiences

3.3. Suggestions to sites, sponsors & health Suggestions to sites, sponsors & health authoritiesauthorities

Suggestions to SitesSuggestions to Sites IRB process IRB process

• CIRB/JIRB fast trackCIRB/JIRB fast track Contract processContract process

• Sponsor-Site template, DOH templateSponsor-Site template, DOH template Access to HIS, eg. Data mining, AlertAccess to HIS, eg. Data mining, Alert EMR EMR

• tracking system and CRA/CRC authenticationtracking system and CRA/CRC authentication More support to clinical trials More support to clinical trials

• Space, manpower, study fee usageSpace, manpower, study fee usage

Suggestions to SponsorsSuggestions to Sponsors

Bring more studies to Taiwan Bring more studies to Taiwan More budgetMore budget

• PI fee/ SC fee/ Lab testsPI fee/ SC fee/ Lab tests• Ask additional fee, eg. Feasibility survey fee, Ask additional fee, eg. Feasibility survey fee,

Overhead fee, start-up fee, SAE reporting feeOverhead fee, start-up fee, SAE reporting fee Recruitment network and advertisingRecruitment network and advertising Support on PI-initiated studiesSupport on PI-initiated studies

Suggestions to DOHSuggestions to DOH

DOH/CDE processDOH/CDE process IRB evaluationIRB evaluation Template of clinical trials contractTemplate of clinical trials contract Researcher network or consortiumResearcher network or consortium Bridging rules to ChinaBridging rules to China TCM licenses need clinical trialsTCM licenses need clinical trials All doctors can prescribe TCM All doctors can prescribe TCM Health foods Health foods alsoalso need clinical trials need clinical trials

ConclusionsConclusions

1.1. Taiwan has strengths in clinical trials Taiwan has strengths in clinical trials quality and patients poolingquality and patients pooling

2.2. Clinical trials business is arisingClinical trials business is arising

3.3. Need to improve IRB/Contract processNeed to improve IRB/Contract process

4.4. Bridging regulations to China and Asia Bridging regulations to China and Asia countriescountries

5.5. TCM and health foods also need clinical TCM and health foods also need clinical trials to prove efficacy and safetytrials to prove efficacy and safety

Chung Shan Medical University Hospital Chinese Medicine Clinical Trial Center

Chung Shan Medical University HospitalChung Shan Medical University Hospital

Clinical Trial Center Clinical Trial Center

James Cheng-Chung Wei, M.D., Ph.D.

Taichung, Taiwan

wei3228@gmail.com, +886 975 128095