The Nigerian doctor who supervised a 1996 Pfizer Inc. drug experiment on desperately ill children said in an interview that his office created a backdated ethics approval document that the American pharmaceutical company later used to satisfy U.S. regulators and to justify its conduct of the human testing.
Abdulhamid Isa Dutse, the physician who oversaw the test of the antibiotic Trovan on children with meningitis, said the letter may have been written as long as a year after the test was completed when Pfizer officials asked him for proof the test was reviewed by a Nigerian ethics board. Nigerian officials are now examining the roles played by Dutse and others in conducting the American company's drug trial, which was the subject of an investigation by The Washington Post.
Pfizer spokesman Andy McCormick said last week that he was unaware of possible irregularities in the Nigerian ethics approval document. "We are currently investigating it. We are cooperating with the authorities in Nigeria," he said.
The New York-based company gave the letter to the U.S. Food and Drug Administration in 1997 during an audit of records supporting its application to use Trovan for treatment of children during a meningitis epidemic. U.S. regulations require that if a company intends to use foreign medical research to support a drug application, the experiments must be reviewed and formally approved in advance by an ethics committee.
FDA officials last week declined to comment on the Pfizer case, but one official said it is a violation of federal law to knowingly submit false documents to a government regulatory agency.
Typed on the letterhead of the Aminu Kano Teaching Hospital and dated March 28, 1996 -- six days before Pfizer's experiment began -- the letter said the hospital ethics committee had reviewed the plan to test Trovan on 100 children with meningitis and found the protocol to be "adequate." The letter gave permission for the test to proceed.
But Sadiq S. Wali, the hospital's medical director, recently told The Washington Post the document was "a lie." He said the hospital had no ethics committee at the time Pfizer's test was underway and did not organize it -- or create the letterhead stationery bearing his name that was used in the approval letter -- until months later.
"The hospital is quite clear: We had no ethical committee," he said in a telephone interview.
Reached by telephone in Kano last week, Dutse said it was "possible" that the approval letter was drafted up to a year after the trial.
Dutse, who was listed as Pfizer's "principal investigator," said he felt that the letter reflected the informal approval he had obtained from three doctors, who reviewed Pfizer's test plans and told him they saw no ethical problems. No records were prepared at the time, he said.
But one of the doctors Dutse cited, Idris Mohammed, last week disputed Dutse's account. Reached in London, Mohammed said: "There was no ethical committee at the time of the trial, none met, and no approval was properly given for the trial."
In fact, Mohammed said that he challenged the legality of Pfizer's experiment while it was underway and that he demanded unsuccessfully to see documents proving it had been properly authorized.
"You shouldn't try an experiment in an epidemic," said Mohammed, a medical professor who now heads the Nigerian federal immunization program. "You needed to give these patients something that was proven."
Mohammed said that in 1996 he took his concerns to a senior official in the Nigerian government -- then controlled by a military dictator, Gen. Sani Abacha -- but was overruled.
Since the experiment, Pfizer repeatedly has cited the Nigerian committee's approval as proof its experiment was ethical. The testing was carried out on children and infants during a record-breaking meningitis epidemic that killed more than 15,000 Africans.
The Post's Dec. 17 article recounted how Pfizer physicians tested the company's then-unapproved antibiotic in the impoverished northern Nigerian state of Kano. The drug was later associated with liver damage and deaths in the United States and its use was restricted.
Pfizer described the Nigerian test as a humanitarian venture, but medical specialists and international aid workers attacked it as unethical and challenged the company's claim that the children knew they were part of an experiment.
Pfizer officials have said that the Nigerian ethics committee approved giving some Nigerian children an oral formulation of the antibiotic instead of a fast-acting intravenous version used in U.S. meningitis tests.
A Pfizer spokeswoman also said the ethics committee decided there was no need to warn Nigerian parents that young lab animals given Trovan-class antibiotics had suffered joint damage. American parents were told of the lab animal results in a subsequent Trovan trial.
After receiving a copy of the ethics approval letter from The Post, Wali said he confronted Dutse and the doctor "did admit to me he was wrong," although he provided few specifics.
Tim Menakaya, Nigeria's health minister, said he had appointed a federal investigative panel charged with determining whether the trial was conducted legally and, if so, whether the experiment was "morally right."
"I am investigating all of it," Menakaya said.
The probe is headed by Abdulsalami Nasidi, a senior health official who said that he, like Mohammed, considered the experiment to have been unethical in 1996 but failed in attempts to block it.
"It is a very serious problem; procedures were not followed," Nasidi said. "We are going to get to the root of the problem."
Nasidi said that his investigation, whose findings will be forwarded to Nigerian President Olusegun Obasanjo, failed in initial attempts to locate "detailed evidence" that Pfizer's investigators had secured the needed authorization before launching the experiment. Dutse said he spent two days last week addressing a closed session of the panel.
The Post's investigation has generated a flurry of stories in the Nigerian press, which have reported that "widespread condemnation rages." Editorials have called for international investigations, federal lawsuits and criminal prosecutions.
Nigerian newspapers -- always fiery and at times less than entirely factual -- have quoted parents who contend their children had serious disabilities or died after treatment.
"The government has a duty to tell us whether our children were used as guinea pigs and, if so, who committed such criminality and who is liable," said the Vanguard newspaper.