Regional Clinical Trial in Indonesia: Challenging yet Promising. Marlinang D Siburian

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1 Regional Clinical Trial in Indonesia: Challenging yet Promising Marlinang D Siburian

2 Disclaimer These Power Point slides are the intellectual property of NCGM under the copyright laws. Used by permission. All rights reserved. NCGM and the NCGM logo are registered trademarks of the National Center for Global Health and Medicine. 2

3 INDONESIA GEOGRAPHY Tokyo Indonesia is the largest island country in the world with 13,446 islands 6 large areas: Sumatera, Java, Bali+NT, Borneo, Sulawesi, Maluku+Papua Climate: tropical with high humidity Rainy season: October-April Dry season: March-September Sumatera Jakarta Borneo Sulawesi Maluku, Papua Java Bali, NT 3

4 INDONESIA POPULATION The 4 th most populous country with 261 million people. Half of the population concentrated in the Java island. 600 different ethnics. The Javanese is the largest ethnics with almost 40% of the total population. Hindu, 1.69% Catholic, 2.91% Buddhist, 0.72% Confucianist, 0.50% Other, 0.13% Sumatera Borneo Sulawesi Maluku, Papua Christian, 6.96% Unstated, 0.38% Muslim, 87.18% Muslim Christian Catholic Hindu Other Java Bali, NT Source: National Statistics

5 Sub-District Govt. District Gov. DOH 556 District hospitals 3,320 Community Health Center (with beds) (Puskesmas) 34 Provincial Gov. POH 99 Referral hospitals MOH 33 National hospitals Decentralized system The primary care facility is the Community Health Center (Puskesmas), available down to the sub district area. INDONESIA HEALTH SYSTEM Total hospitals in Indonesia are 5,734 hospitals. 5

6 Health Expenditure Government, others, 39% 1% OOP, 60% INDONESIA HEALTH PROCUREMENT National Health Insurance (BPJS Kesehatan) initiated in 2014 and aim for Universal coverage by 2019 PROCURE- MENT 6

7 Negative List Seminar with JICA Jakarta (June 2016) and with Japanese companies (Sept 2016): Negative List Revision The New Negative Investment List 2016: Presidential Regulation No 44/2016 7

8 Negative List Seminar with JICA Jakarta (June 2016) and with Japanese companies (Sept 2016): Negative List Revision 459 million USD India 30% 153 million USD Europe 10% 919 million USD China 60% 67% FDI Medical equipment testing facilities 100% FDI Pharmaceuticals raw materials Source of APIs: 95% of Active Pharmaceuticals Ingredients (APIs) are imported Total market value >1.5 Billion USD Source: Quintiles; Pharmaboardroom.com 8

9 Negative List Seminar with JICA Jakarta (June 2016) and with Japanese companies (Sept 2016): Negative List Revision Overseas Production Base is now a possibility. 9

10 Negative List Seminar with JICA Jakarta (June 2016) and with Japanese companies (Sept 2016): Negative List Revision Indonesian Pharmaceutical Market: Total Value >6.5 Billion USD Average Growth 12.5% Increase Demand for Generic Drugs 10

11 Negative List Seminar with JICA Jakarta (June 2016) and with Japanese companies (Sept 2016): Negative List Revision 49% FDI for Medical Equipment/Devices with Permits from MOH Orthope dic Implants 6% Diagnosti c imaging 33% Others 30% Consuma bles 23% Dental products Auxiliary 2% Equipme nt 6% Medical Device Market Share Annual market growth for medical devices is 13%. Diagnostic imaging holds 33% of the total market share. Source: Quintiles; Pharmaboardroom.com 11

12 INFECTIOUS DISEASE CURRENT STATUS (1) Inadequate disease surveillance systems, (2) Geographical barriers million people distributed in more than 17,000 islands; (3) Limited testing facilities - large proportion of people remaining undiagnosed (Mulyono, 2018) NON COMMUNICABLE DISEASES (NCDs) have emerge as major health problems in particular due to the changes in the societies lifestyles. Testing device Point-of-care RDT (Rapid Diagnostic Test) Low cost Easy to use High specificity and sensitivity 12

13 Sumatera Borneo Sulawesi MALARIA API<< 0.85 Java Bali, NT Maluku, Papua 8 million people living in high risk area 1 st line medication: ACTs (Artemisininbased combination therapies) (MOH, 2015) Low prevalence of resistance 1-2% (Lampung, 2016) Source: Malaria Elimination in SEA, 2014 TUBERCULOSIS % Aceh Sumatera Utara Sumatera Barat Riau Jambi Sumatera Selatan Bengkulu Lampung Bangka Belitung Kepulauan Riau DKI Jakarta Jawa Barat Jawa Tengah DI Yogyakarta Jawa Timur Banten Bali Nusa Tenggara Barat Nusa Tenggara Timur Kalimantan Barat Kalimantan Tengah Kalimantan Selatan Kalimantan Timur Sulawesi Utara Sulawesi Tengah Sulawesi Selatan Sulawesi Tenggara Gorontalo Sulawesi Barat Maluku Maluku Utara Papua Barat Papua Sumatera Java Bali, NT Borneo Sulawesi 13 Maluku, Papua 2 nd rank in the world Incidence 399 per 100,000 people MDR TB 12% from former cases HIV-TB 6.2% MDR TB success rate 54% Bedaquiline (Sirturo) phase III study ongoing (WHO, 2015)

14 HIV-AIDS Sumatera Borneo Sulawesi Maluku, Papua Java Bali, NT HIV cases, 13% had antiretroviral % B C HEPATITIS B/C Aceh Sumatera Utara Sumatera Barat Riau Jambi Sumatera Selatan Bengkulu Lampung Bangka Belitung Kepulauan Riau DKI Jakarta Jawa Barat Jawa Tengah DI Yogyakarta Jawa Timur Banten Bali Nusa Tenggara Barat Nusa Tenggara Timur Kalimantan Barat Kalimantan Tengah Kalimantan Selatan Kalimantan Timur Sulawesi Utara Sulawesi Tengah Sulawesi Selatan Sulawesi Tenggara Gorontalo Sulawesi Barat Maluku Maluku Utara Papua Barat Papua Sumatera Java Bali, NT Borneo Sulawesi Maluku, Papua HBV prevalence % HCV prevalence 1% (Mulyono, 2018) 14

15 AMR National data not available E. coli E. faecalis E. faecium Peni cillin Anti-30S Fluoroqui nolones Cephalo sporins Anti-50S (Isolated from chicken poultry, SEA, 2014) 70% resistance to levofloxacin or ciprofloxacin (in Indonesia it is used as 1 st choice to treat both lower and upper UTIs (Urinary tract infections), cheap-broad spectrum-readily available)). Fosfomycin resistance <20% in E. coli & K. pneumoniae Meropenem resistance 21.3% in K. pneumoniae 15

16 Neglected Bacterial Infections Soil-transmitted helminth (STH) 195 million people live in STH-endemic areas Regular and periodic deworming with either Albendazole or mebendazole Defecation and hand-washing practices Leprosy, yaws, leptospirosis, and rickettsia infections. Leprosy - Java (East, Central, and West Java) Yaws - Papua, Southeast Sulawesi, and Nusa Tenggara Timur province Leptospirosis, and rickettsia widespread, no data Schistosomiasis Caused by Schistosoma japonicum In the province of Central Sulawesi Praziquantel MDA (mass drug administration) by 2020 Neglected Tropical Diseases (NTDs) Neglected Viral Infections Dengue 2nd largest number of cases worldwide Approx deaths annually Chikungunya and Japanese encephalitis - no disease burden Lymphatic Filariasis 125 million Indonesians are at risk for acquiring LF Highest prevalence rates in Maluku, Papua in Eastern Indonesia DEC and Albendazole MDA Coverage is only approximately 30% 16

17 CLINICAL TRIALS REGULATIONS Refer to ICH GCP Require IRB, BPOM (National Food and Drug Control Agency), and MOH approvals Trials involving drugs already approved for marketing are NOT REQUIRED to apply for approval (except for claiming new indications) continue to drug registration Inspection is done by regulatory authorities All biological materials are NOT ALLOWED to be sent abroad, except if the assays could not be performed by local labs 17

18 2-3 months for approval Team set up Local IRB Approval BPOM Approval MOH Approval Start CT - CT Protocol - Safety plan - Monitoring plan - Data Management Plan - Training plan - Contracts - MoU - MoA - MTA National IRB Approval from registered IRB Approval from BPOM MTA (if applicable) Team Set Up IRB Approval 2-4 weeks BPOM Approval 20 days Pharmaceuticals, Academic, Hospitals, CRO IRB *) Documents: A. CT docs (must be in Bahasa Indonesia, except for multiregional CT) - CT protocol - IB - Inform Consent - Form I (CT Application Form to BPOM) B. Testing product docs - Testing product information - Certificate of Analysis (CoA) - Certificate of GMP - Summary Batch Protocol (3 batch in sequence) for biological product (incl. Vaccine) - Lot release (for vaccine only) C. Other related docs - PI s certificate of GCP - Contract with CRO (if applicable) - Insurance (If applicable) - Certificate of Laboratory (If applicable) - CV of PI Organizational structure: Sponsor Chief Investigator Trial management team Host institution Trial Steering Committee Data Monitoring Committee Endpoint Adjudication Committee Coordinating center(s) Central laboratory(ies) SAS (Special Access Scheme) application to BPOM CLINICAL TRIALS PROCESS FLOW SAS approval 1 month MOH Approval SAS approval Import product CT Patients recruitment Monitoring: Status report Amendments? Audit/visit vendor Review contract Ongoing supply IP Maintenance of blinding Shelf life change Routine onsite / central monitoring Additional training? Adverse events? End of Trial IB update Data entry Data queries Electronic data transfer 18

19 National Centers: CROs: INA-RESPOND (The Indonesia Research Partnership on Infectious Disease): Persahabatan Hospital, Jakarta; Prof. Dr. Sulianti Saroso Infectious Diseases hospital, Jakarta; Dr. Hasan Sadikin hospital, Bandung; Dr. Kariadi hospital, Semarang; Dr. Soetomo hospital, Surabaya; Sanglah hospital, Bali; Dr. Sardjito hospital, Yogyakarta; Dr. Wahidin Sudirohusodo hospital, Makassar; Gatot Subroto Army hospital, Jakarta; H. Adam Malik hospital, Medan Eijkman Institute, Jakarta Medical Faculties with Academic Hospitals: 72 medical schools, 32 of them have been accredited A or B Until 2014, there were GPs and specialists in Indonesia IRBs: 55 IRBs registered in the National IRB 11 IRBs recognized by the FERCAP (Forum for Ethical Review Committees in Asia and the Western Pacific) 19

20 CLINICAL TRIALS CURRENT STATUS Others 32% Psychiatric 4% Geriatric 1% Pediatric 5% Local company 16% IDs 19% NCDs 39% Local Academic 25% MNC 36% Local Academic + Int. collaborator 23% There are 297 registered CTs in Indonesia. Most CTs were on NCDs and IDs and were done by the Multi National Company (MNC) pharmaceuticals. 20

21 Trial cost << Less strict regulations Wide variety of diseases NCDs, IDs, NTDs Research subjects >> Muslim's market Capable and qualified manpower Economic growth middle income country (GDP growth 5.3%) Economic cooperation between Japan- Indonesia Less standardized IRBs - Accreditation of IRBs Lack of insurance companies - National Health Insurance Geographic disparity - infrastructure constructions, Community Health Center Opportunities Challenges 21

22 ありがとうございます Terima kasih Thank You 22