Drug Testing in Nigeria Operational

Drug Testing in Nigeria

Operational Analysis

Strategic Analysis

In the article analyzed, Drug testing in Nigeria, the researchers, Debora Spar and Adam Day, describe the situation of a clinical test of an experimental drug, Trovan, conducted in a Third World country under suspect conditions, with shoddy supervision and for questionable reasons. Though the Trovan trial was perhaps exceptional, it is also considered an example of what can happen when pharmaceutical corporations conduct research on humans in poor countries with bad supervision.

A nervous system infection, Meningitis can kill a child in a matter of hours if left untreated. It killed more than 12,000 children in six months in and around Kano, a mostly Muslim city. Pfizer, a pharmaceutical giant drug company saw this scenario as an opportunity to do clinical research on 200 live humans, while possibly helping sick people. Half of the 200 children received Trovan and the other half received a "proven meningitis treatment," ceftriaxone, though they administered a dose lower than recommended. Pfizer has maintained its records demonstrate that not one of the deaths could be linked to Trovan or to substandard treatment, and that the clinical study shows there is a better survival rate for patients on Trovan than for patients who receive the standard drug. Survivors sometimes sustain brain damage or other complications from the disease, even if they are "cured" (AP, p. 1).

Nigeria alleges Pfizer did not obtain the required approval for tests, nor did it get proper consents from patients. Pfizer countered by saying the alleged victims were affected by meningitis and not the drug, and that Trovan saved many lives (Oboh, p. 1).

There was a compelling reason to look at Trovan because it was an oral formulation, it was known to have shown efficacy in meningitis and was a five-day treatment so it was perfect for an epidemic setting," Edozien told Reuters (Oboh, p. 1).

In the United States, blockbuster drugs are like gold. The financial analysts said Pfizer would make $1 billion per year if Trovan won approval by the FDA for use against several ailments. Pfizer wanted to test its use against meningitis, and in Africa there was an epidemic of it. Meningitis is rare in the United States, so researchers came to Kano to test it against the dying (Stephens, p. 1). But a hostile reception was faced by Pfizer in Kano, which has a history of rejection of Western medicine. The state government actually banned vaccines against polio in 2003 for nine months, saying the immunization campaign was a U.S.-led plot and the vaccine caused HIV and infertility. This caused a resurgence of the polio disease in Africa.

Background

In January of 1996, a bacterial meningitis epidemic swept across Nigeria. The deadly infection of brain and spinal cord began killing hundreds of children and adults in a land already besieged by cholera and measles epidemics. Some lay on the bare ground writhing with convulsions, doctors recalled. By February, 120 new patients were arriving daily at Kano's stinking, poorly equipped hospital for infectious diseases. Other aid organizations rushed in supplies of approved drugs to hospitals in Nigeria, but U.S.-based Pfizer quickly found a trial drug and chartered a plane to bring its own labs and doctors to the suffering. There, Pfizer gave ill children doses of its experimental drug, Trovan, without parental consent. They went so far, according to the lawsuit filed in New York in 2001, as to under-dose one group of children as a control group. As a result 11 children died, 5 on Trovan and 6 in the control group; many others continued to live but with physical disabilities and brain damage (AP, p. 1). The statistics of this study are quite interesting in that they show equal results for Trovan as for the control group, though there are those who are bemoaning the overall lack of correct supervision, which may shed doubt on the value of the research statistics.

In the court case open against Pfizer, Ngozi Edozien, managing director of the U.S. pharmaceutical company in West Africa, says it was answering an international call for help during a meningitis epidemic among children in Nigeria. The northern state of Kano has joined Nigeria in suing Pfizer for $8.5 billion (Oboh, p. 1).

In 2005, a judge threw out the case, when it was first brought to courts in the United States. He said it should instead be heard in Nigeria. But in October, 2007, Pfizer will be defending itself in two courts, civil and criminal, against charges brought by the Kano state government, while the federal government has brought civil and criminal charges as well (Oboh, p. 1).

Trovan was a drug which had been clinically tested on some 5,000 people before being used in Nigeria. It was licensed for use on adults by the U.S. Food and Drug Administration beginning a few months after it was the subject of this trial, and was a Pfizer's top-selling drug briefly. But the authorities have put severe restrictions on its use since it has been found "to cause serious liver injuries in some patients" (Oboh, p. 1).

Mustapha Maisekili is the father of two victims in the Kano trial. His two young daughters were suffering from the flu-like symptoms typical of meningitis. But they were talking and walking when he took them in to the Infectious Diseases Hospital. They died a couple of weeks later. It appears most of the victims have lost any hope of getting justice on this issue. "If we are compensated through the court judgment we shall be relieved somehow. Most of us are living hand-to-mouth." (Oboh, p. 1)

Another little Nigerian girl's death has made the news in the United States; she is only known as No. 6587-0069. Ten years old and weighing only 41 pounds, she contracted meningitis and found herself in a medical camp where Pfizer doctors had come to give the ill meningitis children antidotes for free. Doctors Without Borders had erected a treatment center, trying to save lives behind a gate besieged by sick people. Next to them, researchers for Pfizer Inc. had set up a second center and, according to some of the doctors who work for Doctors Without Borders, to be using Nigeria's meningitis epidemic to experiment on children with a drug that was not yet approved in the United States.

At testing site No. 6587, the doctors drew spinal fluid from the little girl, wrote down her symptoms and logged her in as patient No. 0069. They administered 56 milligrams of Trovan. A day later her strength was disappearing and one of her eyes froze in place, the Pfizer records show. She died on the third day. Pfizer records were clear. Action taken: "Dose continued unchanged." Outcome: "Death" (Stephens, p. 2).

Another one of the major issues examined was an ethical one, in that though she may have been beyond all hope, no one will know if the girl might not have lived had she been taken off the experimental drug and had been given a proven remedy. The circumstances suggest a big problem involving the ethics of a large corporation (Stephens).

In Africa, Eastern Europe, Latin America and Asia, a booming, poorly regulated testing system dominated by private interests often betrays patients and consumers alike. Experiments occur too often that involve risky drugs, dispensed with little oversight, and poorly educated, impoverished patients who are sometimes tested without their knowledge that they are human guinea pigs. A hollow promise of quality medical care sometimes proves fatal (Stephens, p. 1).

In this environment, drug makers cross national borders easily with little governmental red tape. The U.S. Food and Drug Administration has limited authority and not enough resources to police experiments overseas, so U.S. drug giants pay foreign doctors to test human subjects in countries in Eastern Europe and the Third World, using these human subjects to produce new drugs which are new sources of income. But in a way it is the fault of the lobbyists for disease victims and Congress that they are under pressure to develop new medicines quickly. Patients in wealthy countries will purchase new drugs provided by these foreign trials in poor countries that utilize huge pools of human guinea pigs (Stephens, p. 1).

No matter where one lives, the FDA requires patients in such tests to consent fully to experiments if results are used to win approval for marketing in the U.S. While many tests in many of the Third World countries are conducted conscientiously and expedite the making of life-saving drugs, investigations have found that in other instances the rules are bent or ignored. Industry guidelines have no regulations for conducting meningitis experiments for an antibiotic in a short-staffed, squalid medical camp amid a terrible epidemic, while lacking the most basic of diagnostic equipment.

Alexander Ershov's cancer had metastasized into his lymph nodes, and this had two immediate effects: His voice turned into a throaty whisper, and this brought his worsening condition to the attention of Dr. Peter Karlov. It so happened that Russian doctor Karlov was trying to find patients for another clinical trial for an experimental drug, and Ershov fit the requirements to enter the study. "They told me the treatment was safe," says Ershov. "I trust my doctor completely." Like 90% of Karlov's other clinical-trial patients, he immediately signed the consent form (Lustgarten, p. 1). Russia is one of those countries that suffers from high costs and low standards of medicine as well as lack of doctors.

Outsourcing of medical trials is on the rise. As many as 40% of all drug testing is going to "emerging markets" and this number is rising. Vioxx and Zocor, created by Merck, tested in Russia as well as a few other developing nations, and many of Pfizer's drugs that earned them billions of dollars (AP, p. 1).

These experiments "raise questions about corporate ethics and profits on a frontier of globalization where drug companies wield enormous influence, and where doctors paid by U.S.-based corporations sometimes perform experiments on ill-informed patients in authoritarian societies" (Stephens, p. 1). A Nigerian physician who was present during the Kano experiment felt it was "a bad thing," but because Pfizer's test appeared to be backed by the U.S. And his own government, he did not object. "I could not protest," said Amir Imam Yola. "The system you have in America and the system we have here, there is a wide gap. Freedom of speech is still not here" (Stephens).At that time a military junta ran Nigeria's government, with a record of corruption and of being one of the world's worst human rights violators.

Analysis

While 11 of the 200 stricken children enrolled in Pfizer's experiment died, others suffered an inability to walk or talk, deafness, blindness, lameness, seizures, and disorientation, which are meningitis-related symptoms, Pfizer records show (Stephens, p. 1). This analysis will look at the operational, strategic and ethical ramifications of these results.

Pfizer said it wanted to study the effectiveness and safety of the antibiotic while providing a breakthrough treatment for this suffering Third World country. It validated its practices, given the horrendous conditions found, by showing how many children's health improved while maintaining a fatality rate of 6%, comparing favorably to bacterial meningitis victims treated by hospitals in the U.S. A company spokeswoman said the Trovan experiment was approved by the Nigerian ethics board to be "sound from medical, scientific, regulatory and ethical standpoints" (Stephens, p. 1). However, it was later revealed that there was no Nigerian ethics board. In addition, the samples were not tested correctly, resulting in study results so tainted that the results wee not accepted (Spar, p. 3).

As far as operational analysis, it took Pfizer researchers just over six weeks to prepare the study, instead of a year or so, as is common in the U.S. And here meningitis patients usually receive intravenous medicines, while the researchers gave the Nigerian subjects oral Trovan, which had never been tested (Stephens, p. 1).

During the trial, the ten doctors, including physicians practicing medicine in developing countries, meningitis specialists and pediatricians, were interviewed about Patient 0069's death and were troubled by her case. They focused on whether doctors "left the child on the drug too long while her health declined." Normally, if a human subject is not responding to an experimental drug, they are given already proven medication and are removed from the test. In addition, guidelines urge researchers to conduct a second spinal a day or so following commencement of treatment to see if the medication is having the desired affect. Pfizer researchers said they did not perform a second spinal tap on Patient 0069 and left her on the drug until she died. Pfizer chose to make such spinal exams optional in Nigeria. A Nigerian physician still working in Kano said "The patient died because [the doctor] refused to help." (Stephens, p. 2).

Pfizer spokeswoman said Patient 0069 could have died with treatment by any antibiotic and their researchers did not suspect Trovan was not working (Stephens, p. 1). A Nigerian doctor hired by Pfizer to run the experiment, Abdulhamid Isa Dutse, said physicians should change medication of any patient who is not improving on the current one. "To be very, very honest, in retrospect, maybe we should have done something about that," he said of the girl. Dutse has since been removed from his post, (Stephens, p. 1).

Patients did not understand they were part of an experiment, said the doctors who had been involved in the experiment. "The patients did not know if it was research or not," agreed a Nigerian laboratory technician who took part. "They just knew they were sick." Pfizer disputes that, and said local nurses explained to families who participated, but did not have them sign consent forms (Stephens, p. 1).

In the United States Pfizer got approval to sell Trovan to adults, but bringing it to market turned out badly. It was never approved for use by children in the U.S. Or in Nigeria. Regulators found dozens of discrepancies in Kano experimental results. They advised doctors that use in adults might cause liver damage and death. European regulators forbid sales altogether (Stephens, p. 1).

As far as strategic critiquing, Pfizer's Nigerian clinic opened and closed in a relative short time: Three weeks after they arrived in a chartered plane, the team flew out again. The doctors involved returned once more to examine their patients but did not follow up for long-term recovery. "If I had the power," said a doctor who watched the experiment across the compound, Dr. Lodi of Doctors Without Borders, "I would take away their medical licenses." (Stephens, p. 1)

For Pfizer, the timing was oddly fortuitous. The New York-based, then-$11 billion-a-year corporation was pushing to submit Trovan for FDA approval. A bacteria fighter, Trovan had shown promise against a broad range of infections - sinusitis, bronchitis, gonorrhea and pneumonia. Thousands of patients had enrolled in international drug studies in the company's biggest testing program ever. Wall Street analysts predicted that Trovan could be one of the most financially successful new drugs of its kind in years. There were worries, however, about possible side effects in children. Trovan belonged to the quinolone class of antibiotics, and quinolones had caused joint damage in experiments on young rabbits and puppies (Stephens, p. 2).

We had to move quickly," explained Pfizer's Betsy Raymond. "You would not be able to find those numbers of children with spinal meningitis in the U.S." (Stephens, p. 2)

Hopkins who then headed Trovan development, pushed for the experiment in Africa, saying its success would make all their drugs look good (Stephens). So Pfizer authorized the venture to win FDA approval for Trovan use in meningitis epidemics. Hopkins says that the designation proved the experiment philanthropic rather than a cheap, unethical way to get drugs approved for use on American children (Stephens, p. 1).

But of course Pfizer was hoping to gain from this venture. Even though the drug was not approved by the FDA, had never been used with an oral administration, and the experiment was conducted under the worst conditions by unethical supervisors, under unsanitary and haphazard conditions, with faulty record-keeping, Pfizer still hoped to gain a useful drug which would be in demand. A specialist, Creighton University pediatrics department Chairman Stephen Chartrand, said use of an oral drug under those circumstances would be "unconscionable." (Stephens, p. 1)

Though most of the trials in Third World countries and Russia are conducted without troubling issues, there are enough instances of breakdowns in the scientific process and ethical abuse to create a concern. Other charges concerning other trials which have endangered unwitting patients or which were followed through lacking proper ethical review have occurred over the years. (Lustgarten, p. 1)

Some of the materials we needed to establish that Pfizer was fraudulent only came out after we filed the suit," said Irukera of the trial now going on in Nigeria. An earlier suit only levied a lesser charge of "fraudulent representation." (AP, p. 1)

We stand by our previous statements on this issue," Pfizer said. "The Trovan study was approved in advance by the federal government of Nigeria, it was conducted in an ethical and appropriate manner, and it helped save lives. To our knowledge there is no additional information in the case. Any purported new facts more than 11 years after the study was conducted are simply rehashed allegations dressed up differently, and equally without merit." (AP, p. 1) This statement only underlines the unethical basis upon which Pfizer stands, as the fact that its "approval" by the Nigerian board of ethics was found to be fabricated.

While the authorities in the state and city of Kano blame the Pfizer controversy for creating suspicion of government public health policies, Islamic leaders in the mainly Muslim city of Kano have pointed at the Pfizer controversy as sure evidence of an overall U.S.-led conspiracy. (AP, p. 1).