1. Clinical trials in Madagascar : past and today Voahangy Rasolofo Unité des Mycobactéries Institut Pasteur de Madagascar "Ethical Issues in Clinical Trials" European Commission Project “TBETHICS” Institut Pasteur, Paris, October 29 th -30 th, 2003

2. since the creation of the Institut Pasteur de Madagascar at the end of the 19 th century… Evolution of the value senses and issues when considering clinical trials, … to now

3. At the end of the 19 th century, 1896 :Madagascar, French colony / G al Galliéni urgent problem of smallpox and rabies in the general interest, 1898 :"Institut vaccinogène et antirabique de Tananarive" Director : André Thiroux

4. 1899 : "Institut Pasteur de Tananarive" 1900 : Delivery of smallpox vaccine…

5. … and rabies vaccine

6. Plague’s epidemic since 1921 1922 : Georges Girard, physician, scientific and humanist 1927 :"Institut Pasteur de Madagascar"

7. 1946 : therapeutic regimen for plague WHO 1931 : Vaccine EV against plague (G. Girard and J. Robic) Efficacy in laboratory animals Human experimentation  they inoculated themselves 1932 :Authorization / General Governor of the colony Vaccination campaign

8. Tuberculosis 1924 : BCG strain from Calmette 1926 :production of the BCG vaccine first vaccination of infants with BCG vaccine 1949 : treatment of pulmonary TB with streptomycin (18 patients) 1993 : production of BCG vaccine brought to an end

9. New orientation of the IPM, 1961 : Agreement between IPM and Malagasy Republic Public Health / coll. Ministry Health 1975 : IPM, in the International Network of the Pasteur Institutes From the independence of Madagascar,

10. In the 1990s, In absence of any Ethical Committee, the Minister of Health issued with authorization for studies : - treatment of chromomycosis - malaria / chloroquine - treatment of scalp pediculosis with different pediculicides / "Comité Consultatif Français de Protection des Personnes dans la Recherche Médical" (Madagascar in the protocol) - TB:ethambutol vs streptomycin (2EHRZ/HT vs 2SHRZ/HT)

11. At the end of 1990s, - Several projects concerning therapeutic trial in human beings were submitted to the Ministry of Health - Art. 17 and 19 of the Malagasy Constitution, recognize that each subject has a right to health, etc. By decree n°5855/99-SAN of June 17, 1999, modified by the decree n°4583/2000-SAN of May 08, 2000, Creation of the National Ethical Committee for Biomedical Researches

12. Internal Regulations of the NEC -role and mission -attributions -functioning : composition organisation deliberation meeting (at least 1/year) legal

13. Appointment of the members by the Minister of Health - Ministry Scientific Research - Ministry Law - Ministry of Health - Enseignement supérieur - Faculty of Medicine - Hospitals - Research institutes : IPM, CNARP, IMRA - “Comité National de Défense des Droits de l’Homme” - Dentists’ Association - Malagasy Medical Association - Chemists’ Association - Midwife - Catholic - Protestant

14. Institution / Projects Ministry of Health National Ethical Committee Advice Authorization

15. NEC operational since February, 2001 5 projects examined in 2001 : -1 on schistosomiasis / Institut Pasteur de Madagascar

16. Since 2002, New President, New Government... and actually, restructuring of the NEC, - workshop for the members of the NEC - updating the functioning rules - guidelines for the NEC members As a consequence, all projects are on hold IPM :malaria, tuberculosis… 1- tuberculosis (VACSIS / UE) : problem of the introduction of the HIV test in the protocol

17. and... 2- A serious problem that should be examined by the NEC  Country Z - disease X absent, but worrying it could be introduced -production of drug B, but no animal model proving its efficacy  Madagascar - disease X present - treatment (WHO) with drug A / good efficacy - Drug B not available “Safety and efficacy of the drug B versus A for the treatment of the human disease X: to verify in Malagasy patients that drug B efficacy is not inferior to drug A“

18. Country Z / Project Ministry of Health National Ethical Committee Advice IPM as a collaborator unfavourable

19. Country Z / Projects Ministry of Health National Ethical Committee Advice Authorization IPM as a collaborator unfavourable

20. In developing countries, Political interests > ethics ? But which solution to face this problem : Conclusion, Ethical issues in clinical trials in developing countries : Human rights, consent cultural issues etc.