Clinical trials in Madagascar :

past and today

Voahangy RasolofoUnité des Mycobactéries

Institut Pasteur de Madagascar

"Ethical Issues in Clinical Trials" European Commission Project “TBETHICS”

Institut Pasteur, Paris, October 29th-30th, 2003

since the creation of the Institut Pasteur de Madagascar at the end of the 19th century…

Evolution of the value senses and issues when considering clinical trials,

… to now

At the end of the 19th century,

1896 : Madagascar, French colony / Gal Galliéni urgent problem of smallpox and rabies

in the general interest,1898 : "Institut vaccinogène et antirabique de Tananarive" 

Director : André Thiroux

1899 : "Institut Pasteur de Tananarive" 

1900 : Delivery of smallpox vaccine…

… and rabies vaccine

Plague’s epidemic since 1921

1922 : Georges Girard,physician, scientific and humanist

1927 : "Institut Pasteur de Madagascar"

1946 : therapeutic regimen for plague WHO

1931 : Vaccine EV against plague (G. Girard and J. Robic)Efficacy in laboratory animalsHuman experimentation  they inoculated themselves

1932 : Authorization / General Governor of the colonyVaccination campaign

Tuberculosis

1924 : BCG strain from Calmette

1926 : production of the BCG vaccinefirst vaccination of infants with BCG vaccine

1949 : treatment of pulmonary TB with streptomycin (18 patients)

1993 : production of BCG vaccinebrought to an end

New orientation of the IPM,

1961 : Agreement between IPM andMalagasy Republic

Public Health / coll. Ministry Health

1975 : IPM, in the International Networkof the Pasteur Institutes

From the independence of Madagascar,

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)

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

Internal Regulations of the NEC

-role and mission

-attributions

-functioning : compositionorganisationdeliberationmeeting (at least 1/year)legal

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

Institution / Projects

Ministry of Health

National Ethical Committee

Advice

Authorization

NEC operational since February, 2001

5 projects examined in 2001 :

-1 on schistosomiasis / Institut Pasteur de Madagascar

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 holdIPM :malaria, tuberculosis…

1- tuberculosis (VACSIS / UE) : problem of the introduction of the HIV test in the protocol

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“

Country Z / Project

Ministry of Health

National Ethical Committee

Advice

IPM as a collaborator

unfavourable

Country Z / Projects

Ministry of Health

National Ethical Committee

Advice

Authorization

IPM as a collaborator

unfavourable

In developing countries,

Political interests > ethics ?

But which solution to face this problem :

Conclusion,

Ethical issues in clinical trials in developing countries :

Human rights,consentcultural issuesetc.