Aceme Nyika Ethics Coordinator AFRICAN MALARIA NETWORK TRUST The Trovan Trial Case Study: After profits or to save lives? Available at: http://www.amanet-trust.org/discuss/viewtopic.php?t=2 Aceme Nyika Ethics Coordinator AFRICAN MALARIA NETWORK TRUST Tanzania Commission for Science and Technology Building P.O. Box 33207, Dar es Salaam, Tanzania Tel: 255 (022) 2700018, Fax: 255 (022) 2700380 E-mail: anyika@amanet-trust.org

Outline of presentation Epidemic outbreak of bacterial meningitis in Kano Treatment of patients and testing of Trovan at Kano government hospital Scientific rationale for testing Trovan in children given by Pfizer The aftermath of the Trovan Trial Different schools of thought Unpacking the ethical issues: interactive discussion

Epidemic outbreak of bacterial meningitis in Kano Bacterial (meningococcal) meningitis epidemic in Tudun Wada, Kano, Nigeria in 1996 Overpopulated, filthy and hot conditions prevailing in Kano were ideal for the spread of the infectious disease. An estimated 15 000 people died and thousands of children were permanently disabled

Treatment of patients and testing of Trovan at Kano government hospital A non-governmental organisation (NGO) called Medecins Sans Frontieres (MSF) provided free emergency treatment at the government Infectious Diseases Hospital in Kano. Pfizer team joined the government and the MSF at the government hospital in Kano. The Pfizer team recruited children to test a drug called Trovan, or Trovafloxacin. At least 200 children were recruited into the trial. The government hospital and the MSF were using chloramphenicol for treatment of children.

Scientific rationale for testing Trovan in children Trovan is a flouroquinolone, and other similar drugs in the same antibiotic class had been successfully tested in children before. Ciprofloxacin, a flouroquinolone, was cited as an example that had been used in infants without any serious side effects.

The aftermath of the Trovan Trial Pfizer has been accused of conducting trial without Approval from relevant regulatory authorities Ethical approval Informed consent It is alleged that Trovan maimed or killed some children recruited into the trial, and that Pfizer left before the epidemic was over Pfizer dismissed the accusations, and claimed that Trovan lowered the mortality rate to 6%, while chloramphenicol lowered the rate to 9.1%. Pfizer responded that it was invited to help fight the epidemic; could not obtain informed consent because of illiteracy; they were given permission by the authorities The case is now in the courts in the USA and Nigeria

Different schools of thought (1) Pfizer researchers took advantage of The absence of a functional ethics committee (institutional one at Kano or national committee). The desperation of the affected poor, illiterate people. The emergency situation that greatly facilitated recruitment of participants at a single site.

Different schools of thought (2) Pfizer went to Kano to assist the Nigerian government during a serious epidemic, and they offered free treatment. Whereas some of the 200 children they treated with Trovan may have experienced some serious side effects that in some cases led to death, some participants in the trial responded well to Trovan and thus benefited. After all, some patients in the government and MSF camp responded poorly to chloramphenicol treatment and died. Thus the deaths would probably have occurred anyway even if Pfizer had not come on board.

Different schools of thought (3) The trial was led by a local Nigerian physician, with some local Nigerian nurses and doctors participating. Thus even if there was no approval and oversight from an ethics committee and/or government, participants were afforded respect and protection by the local Nigerian collaborators. Pfizer merely provided the antibiotic to be tested and other resources. If Pfizer team indeed left Kano before the bacterial meningitis epidemic was significantly contained then they were not in Nigeria on a humanitarian mission in the first place but to conduct a clinical trial.

Questions to guide discussion (1) Is it possible to conduct research ethically during an epidemic? (2) Did Pfizer exploit the poor desperate people with severely ill children? (3) Does illiteracy justify the fact that Pfizer researchers did not obtain proxy consent for the children they enrolled into their trial? (4) Did they help to fight the meningococcal meningitis epidemic at all or they had their own agenda? (5) Are the local health personnel who collaborated with Pfizer researchers to blame for the unethical recruitment of children into the Trovan trial?

Questions to guide discussion (6) Who had invited Pfizer to come to Nigeria in the first place, and for what purpose? (7) The trial took place in Nigeria and the children who were enrolled into the trial were Nigerians, but Pfizer is an American company and the legal battle is being fought in America, with American lawyers representing the Nigerian families. Are there no legal mechanisms of dealing with such issues locally (i.e. in Nigeria or in Africa)?

Who are the players who should be involved in preventing unethical health research from taking place in developing countries?

Some stakeholders and gatekeepers a. Collaborating researchers from the developed countries? b. Local collaborating researchers c. Ethics committees in the developed countries d. Local ethics committees in the countries where the research is taking place e. Institutions where the research is based f. Local drug regulatory authorities g. Ministries of Health h. The participants themselves once they know their human and civil rights Stakeholders have complementary roles to play