Globalizing Clinical Research
Government-funded scientists' willingness to sacrifice a few African lives in search of a cheap, effective way to save many more backfired nastily when South African parliamentarian Peter Mokaba recently charged South Africa's new AIDS-treatment programs with foisting dangerous and unnecessary Western drugs upon an unsuspecting African public. According to the New York Times, recent revelations of improper conduct in an NIH-funded HIV-transmission trial in Uganda intensified South Africans' receptivity to Mokaba's dangerous accusations. "You set yourself up for these kinds of problems if you don't conduct your study properly," says Lurie. "The researchers have to take responsibility for this."
By all accounts, the quest for rapid results sent Pfizer scientists jetting to Nigeria in late March 1996. Pfizer scientists had been industriously collecting data on its experimental broad-spectrum antibiotic Trovan when one of the worst epidemics of meningococcal meningitis broke out in Nigeria. The scourge presented a golden opportunity to test their hot new drug, which they suspected could effectively treat meningitis in oral form, bypassing the painful injections their competitors' drugs required. "We had to move quickly," a Pfizer spokesperson told the Washington Post. In Nigeria, where the contagion infected more than 100,000, the company could test Trovan on hundreds of patients in a matter of weeks.
The Nigerian government was happy to cooperate, arranging for the company's accommodation and silencing criticism from local physicians, according to court documents. The FDA granted permission to export the experimental medicine the very same day it was requested, Pfizer says. And a Nigerian hospital ethics committee sanctioned the study design, as required by Helsinki, the company claims. Not so, confessed two Nigerian doctors to the Post in January 2001. "There was no ethical committee at the time of the trial, none met, and no approval was properly given for the trial," said one. The "approval" document was cobbled together long after the experiment concluded and was then backdated, the other doctor said. And Pfizer's study design was dangerously risky, critics say. One of Pfizer's own scientists, Dr. Juan Walterspiel, warned management that the study methods were "improper and unsafe" before and after the study was conducted, acts of integrity that led to his swift dismissal.
The company, in a heady mix of haste and arrogance, planned to give 100 deathly ill Nigerian children experimental Trovan either orally or by injection, and compare their outcomes to 100 others given shots of competitor Roche's FDA-approved Rocephin. But an oral form of Trovan, though convenient, was too risky to test on dangerously sick poor kids, Walterspiel complained. "Some of the children were in critical condition and most of them malnourished, which made oral absorption even more unpredictable," Walterspiel wrote to Pfizer officials in a December 18, 1997, letter. According to Nigerian families' class-action suit against the company, Pfizer then forced sick children into its study, failing to inform them either of the experimental nature of the drug they'd be subjected to or the availability of WHO-approved meningitis treatment from a nearby Doctors Without Borders team. Not a single Helsinki-required informed-consent form was signed, the company admits. No witnesses signed statements attesting to the "verbal consent" Pfizer claims to have obtained either, the company admits on its website. "These people had no idea they were part of any clinical trial," says Elaine Kusel, an attorney representing the Nigerian families suing Pfizer.
It wasn't the first Third World trial involving lack of consent. One analysis of South African patients who had participated in a study of HIV transmission found that almost 90 percent felt forced into the trial. Thirteen percent of researchers interviewed by NBAC said they weren't sure if their study participants were aware that they were in a research project. "Informed consent is a joke," a clinical investigator who worked in developing countries commented to NBAC. Pfizer scientists took other liberties as well. When some children resisted the painful Rocephin shots, Pfizer scientists slashed the dose to one-third the FDA-approved levels. This unapproved, reckless deviation from the study protocol endangered lives, Kusel charges. Pfizer disputes the claim.
The extent of the damage from Trovan and the low dose of Rocephin remains unclear. Pfizer claims it lost just 6 percent of its patients in both the Trovan and Rocephin groups, proving that oral and injected Trovan worked as well as Rocephin. But the company didn't adequately track the long-term recovery of its patients, Kusel says. Initial fatality rates may have been relatively low, but with only one follow-up visit (the FDA recommended two in 1998), nobody knows how many children ended up deaf, brain-damaged or dead--whether from meningitis, experimental Trovan or a low dose of Rocephin, she says.
Pfizer defends the study by stressing that the FDA itself found little seriously amiss when it reviewed the data in 1997, a fact maybe more suggestive of the FDA's selective oblivion than Pfizer's propriety. While the agency did decline to consider Pfizer's application, noting "discrepancies," it didn't object to the lack of signed consent forms or note problems with the ethics-approval letter, the company says. The agency's approval of Trovan for no less than fourteen adult indications netted Pfizer more than $160 million until reports of liver damage led the FDA to pull the plug in 1999.