After years of legal maneuvering, Pfizer may soon face its Nigerian guinea pigs in court.
What if a drug company experimenting on critically ill children doesn't get the proper parental consent, 11 of those children die and a whistleblower is fired?
Those are the charges leveled against Pfizer in a legal battle that has dragged on for the past seven years in Manhattan federal court and in Nigeria, where the government is seeking $8.5 billion in restitution and damages--and jail terms for various Pfizer officials, including former chief executive William Steere.
Things may come to a head soon. A federal appeals court is expected to rule on whether the children's parents can go after Pfizer in New York. Meanwhile, to avoid what's shaping up to be an ugly court battle, Pfizer is said to have offered to settle with the Nigerian government for $150 million, plus money to modernize and equip a Nigerian infectious disease hospital.
Pfizer says the children died from the disease, not from the drug trial, won't confirm a possible settlement, and says it's "proud" of its role during the 1996 epidemic, an ugly trifecta of meningitis, cholera and measles. Twelve thousand Nigerians died from meningitis alone, many of them children.
What really happened at a remote sub-Saharan hospital in Kano, Nigeria may never be known. But interviews with Pfizer employees, parents of some of the victims, Food & Drug Administration officials, court filings and other legal documents provide an unsettling look at the pitfalls of doing hurried drug trials in Third World countries.
That's happening more often these days. Under pressure to reduce research costs and win fast-track approvals, drug companies do 43% of their clinical trials abroad, up from 14% ten years ago. The Tufts Center for the Study of Drug Development says that number will rise to 65% within three years.
Roll the tape back to the spring of 1996. Outside the cluster of cinder block structures that make up Kano's Infectious Diseases Hospital, hundreds of sick children are lined up, awaiting treatment from Doctors Without Borders, the nonprofit group, which has set up a tent on hospital grounds.
The doctors are injecting the children with oily chloramphenicol, endorsed by the World Health Organization as the recommended treatment for bacterial meningitis epidemics. The half-century-old drug is rarely used in developed countries because of a sometimes fatal side effect (blood disorders). But it's readily available in Third World countries because it is economical and effective.
Five thousand miles away in a Pfizer research lab in Groton, Conn., infectious disease specialist Scott Hopkins is surfing the Internet when he spots a story on the epidemic--and sees opportunity. Pfizer was waist-deep in an ambitious test of Trovan, an antibiotic showing promise against a wide variety of infections, from bronchitis to pneumonia. It had potential to be Pfizer's answer to Bayer (nyse: BAY - news - people )'s Cipro, then the leader in the $11 billion anti-infection market.
Pfizer had already enrolled thousands of adults in Trovan clinical trials but had not tested it yet on children, which posed a problem. Trovan belongs to a category of powerful antibiotics called quinolones, which have the ability to penetrate tissues to kill bacteria.
But there can be serious side effects, including liver problems and cartilage and tendon abnormalities. In early stage testing quinolones had caused liver and joint damage in young rats and dogs. In order to gain maximum market share, Pfizer would have to develop an oral form of Trovan that proved safe for pediatric use.
Hopkins put together a group of five researchers and within six weeks had chartered a DC-9 to Kano, Nigeria. Normally, it takes nine months to design a late-stage drug trial. Pfizer says the trip could never have been made so quickly if a global pediatric trial hadn't already been in the works.
One physician stayed behind. Pfizer had hired Juan Walterspiel, a pediatric infectious disease specialist at Yale Medical School, in 1994 for Trovan's pediatric clinical development. Pfizer says it doesn't know why Dr. Walterspiel wasn't selected to go to Nigeria. But Dr. Walterspiel, who declined to speak with FORBES, would later write to chief executive Steere that the Nigerian study was "in violation of ethical rules for the conduct of medical experiments in humans."
Once in Nigeria, Dr. Hopkins and his team set up shop near the Doctors Without Borders tent. Over the course of two weeks they picked 200 out of the thousands of children awaiting treatment, between 3 months and 18 years old. Half got a full daily dose of Trovan, orally or by injection, depending on age and/or ability to swallow, for five days. The control group got an injectable dose of Rocephin, a Hoffmann-La Roche drug widely used against meningitis. Those kids got 100mg of Rocephin on the first day but only one-third of that dose each of the next four days.
Why? Pfizer argues that Rocephin injections can be painful. The full dosage takes several seconds to inject. "Kids don't like needles," says a spokesman.
Plus, Pfizer says one of its on-site doctors had helped develop Rocephin at Roche and believed the lower dose "more than enough." But that wasn't proved until seven years later, when a Doctors Without Borders study showed the lower dose to be effective.
A month later five children in the Trovan group and six in the Rocephin group were dead. Pfizer says those results were "remarkable," given that the epidemic killed 10% of those infected.
But parents of the dead children in the Trovan group claim they were never shown--or were read--a consent form and weren't told about Trovan's risks or that a proved treatment from Doctors Without Borders was just steps away.
Parents of the dead children in the Rocephin group argue their children would have lived had Pfizer given them the full dose. Dozens of others allege that the trial left their children paralyzed, deaf, mute or blind.
Pfizer says it had bilingual nurses on-site who obtained oral consent from all the parents. The company also says it has all the patient charts with "yes" and "oral" boxes checked as to whether and how their consent was obtained. But Pfizer declined to show these consent forms to a reporter.
Are all the plaintiffs in fact the parents of the dead and injured children? Pfizer says that not all the names on the complaint match up with initials of patients listed on the medical charts. (Pfizer says it's common to record only initials to protect confidentiality.)
The drug trial ended in May 1996. Dr. Walterspiel's letter to Steere, dated Dec. 18, 1997, was not well received. Among the points he made: "Some of the children were in critical condition and most of them malnourished, which made oral absorption even more unpredictable. At least one died after a single oral dose; such a patient … should never have received an experimental antibiotic orally."
Responding in a Feb. 26, 1998 letter, a Pfizer lawyer refuted everything in Dr. Walterspiel's letter: "The company acted appropriately and with complete regard for all legal, ethical, and humanitarian concerns."
The next day Dr. Walterspiel was fired. Pfizer confirms that, but says it was "completely unrelated" to his complaints. Really? A wrongful termination suit subsequently filed in a
Connecticut federal court was later settled. Neither Pfizer nor Dr. Walterspiel would comment on the settlement.
During a 1997 FDA audit Pfizer produced a letter dated a week before the trial began from a Nigerian hospital granting it ethical clearance. But the letter doesn't really help Pfizer's case: It was backdated.
Pfizer concedes the backdating is "unfortunate" but now argues there's no Nigerian law or regulation requiring ethical committee approval before conducting a clinical trial. "Therefore," Pfizer argues, "there was no need to obtain what the law did not require."
However the lawsuits turn out, no more patients will be exposed to Trovan. Having initially applied to use it for pediatric meningitis, Pfizer withdrew that use from its application after the FDA audit found dozens of discrepancies in Pfizer's records. The company says it intended to renew its application following a global pediatric trial already under way.
But it never had the chance. After approving Trovan for 14 other uses in 1997, the FDA advised Pfizer to pull the drug--two years and more than 2.5 million prescriptions later--citing "safety concerns." The problem: deaths from Trovan-linked liver injuries.