NEJM: Foreign Drug Trials Could Hurt U.S. Patients

The increasing use of foreign drug trials may hurt U.S. patients because of genetic and environmental differences in overseas study subjects, a new study in the New England Journal of Medicine suggests. "Are trial results accurate and valid, and can they be extrapolated to other settings?" asks a team from Duke University. "A major concern is the ethical oversight of research involving human subjects in developing countries. Wide disparities in education, economic and social standing, and health care systems may jeopardize the rights of research participants."

While some conditions -- such as meningitis -- are easier to find abroad than in the U.S., critics argue that the use of patients in other countries allows drug companies to make mistakes on populations that don't speak English, are far away from a prying American media, and are too poor and uneducated to sue. In The NY Times:

"More places outside the United States are participating in research -- is that a bad thing?" said Dr. Ezekiel J. Emanuel, the chairman of bioethics at the Clinical Center of the National Institutes of Health in Bethesda, Md. ... Dr. Emanuel cited a clinical trial of the Merck drug Gardasil, a vaccine against the human papilloma virus, that was conducted in Costa Rica, where there is a high incidence of the disease. "This is the kind of case where it is a good thing."

The study doesn't put much of a human face on foreign drug trials. So BNET has gathered some recent coverage of foreign drug trials that does discuss the fate of individuals within them. It isn't pretty:

• From LiveMint: The office of the drugs controller general of India, or DCGI, issued warning letters ...[after it] investigated suspended patient trials of an advanced pneumococcal vaccine at Bangalore's St John's Hospital's National Academy of Health Sciences. Mint had first reported on 15 November that DCGI suspended the clinical trial after the death of an infant, who should not have been included in the trial at all as per the so-called exclusion criteria of the protocol. Background here.
• From the St. Pete Times: Two hours after opening, the pediatric waiting room at All India Institute of Medical Sciences is like the anteroom to hell. Families, anxious, restless, sweaty in the soupy air, cram into plastic chairs, crouch in corners, crowd doorways, clog up aisles. Cries jangle off the ceiling. Feces litter the floor.It recently was revealed that 49 children have died during clinical trials at the institute. Though the hospital blamed the deaths on underlying illnesses, the news triggered unease about a drug-testing phenomenon, propelled by mountains of money, that has swept India with little publicity.
• From the St. Pete Times: Dr. Vinod K. Paul, the hospital's head of pediatrics, dismissed claims that patient care had been slighted ...

  A study that tried over-the-counter mouthwash to prevent sepsis in seriously ill children on ventilators accounted for 22 deaths; 21 deaths occurred in a World Health Organization-sponsored study of the potential benefit of low-cost zinc tablets for children with severe sepsis.

  "Zinc tablets never kill,'' said Paul, pulling a bottle of the pills from a desk drawer and popping one in his mouth. "They keep me happy."

• From the St. Pete Times: [An Indian man brought his father to a Mumbai hospital seeking treatment for brain cancer.] Earnest, intense, worn with worry, the 30-year-old son said the new treatment involved brain surgery followed by chemotherapy and radiation. Though his father now lay weak in a hospital bed, the doctor promised his life would be prolonged."They said without it, he would have maximum three months to survive,'' the son said.But the consent forms Iqbal signed on his father's behalf were in English, a language he neither speaks nor reads. "If they had been in Bengali, I could have followed them," he said through an interpreter, almost apologetically.Sitting in the garden at the monk's ashram at sunset, Iqbal pulled the consent forms from a tattered shopping bag. They indicate that the trial had nothing to do with chemo or radiation. It simply tracked the infection rate in patients whose heads were not shaved before brain surgery.
• From The Call for Ethical Clinical Trials in Developing Countries: Pharmaceutical company AstraZeneca ... conducted clinical trials in India that are not accepted by ethical review committees in Western Europe. The company gave placebo treatment to patients with schizophrenia.
• From BNET: Fourteen children have now died during a pneumonia vaccine trial run by GlaxoSmithKline in Argentina, according to the U.K.'s Daily Mail. Argentine authorities are investigating. GSK says the deaths are not linked to the tests.
• From BNET: In 1996, during a meningitis outbreak in Nigeria, Pfizer tested a drug, Trovan, on children there. About 11 kids died. The Washington Post: "Trovan was never approved for use by American children. The Food and Drug Administration approved it for adults in 1998 but later severely restricted its use after reports of liver failure. The European Union banned the drug in 1999.") Back story here.
• From BNET: [Pfizer is expanding its Chinese operations far faster than the FDA can possibly inspect them.] ... CEO Jeff Kindler told investors in his Q3 conference call that he expects Pfizer "to be in 137 cities" in China by the end of the year. His comment came as he touted Pfizer's new, more nimble research operations:

  In China for example, we told you in March that we had set a goal of moving into a 126 cities by the end of this year. We achieved that goal seven months ahead of schedule, and we are now expecting to be in 137 cities in China by the end of the year. Now China has 160 cities with population above one million people. That makes each of them roughly the size of Dallas or even bigger. That should give you some sense of the opportunities that we have.

  Just to keep tabs on Pfizer alone, FDA officials in China would have to visit one Pfizer facility every 2.7 days. Could they do it? No. Here's a description of the FDA's China capabilities:

  U.S. staffing in Beijing, Shanghai and Guangzhou will total between nine and 12 people, U.S. officials say -- all U.S. imports -- from China and elsewhere -- will require testing and certification by independent laboratories.

• From the Wall Street Journal: Last year, two elderly patients died after Polish investigators enrolled them in a study of a bird-flu vaccine being developed by Novartis AG even though they should have been excluded based on age.

  In the Novartis case, the drugmaker looked into conduct of its study after noticing "irregularities" in data from Polish investigators. After finding evidence that clinicians had recruited participants from an elderly home and a homeless shelter, the drugmaker notified the European Medicines Agency and thea Polish Police, Joerg Reinhardt, head of its vaccines and diagnostics division, tells the paper.

• From BusinessWeek: After struggling for years to get its product approved in the U.S., VTI may be on the verge of a breakthrough ... In America, the company had trouble finding enough people to participate in its clinical trials. But that's not a problem in China, where authorities estimate there could be 130 million hepatitis B patients and carriers--a number larger than the combined populations of Britain and France. Many are poor farmers and workers desperate for medical attention. "You just don't have this [pool] in the U.S.," says Terry E. Winters, a Welsh-born biochemist who is VTI's chairman.
• From the FT: China has overtaken India as one of the fastest-growing locations for drug trials, in a fresh sign of the importance of the world's most populous country to the pharmaceutical industry.

  An analysis by the Financial Times of data on www.clinicaltrials.gov, one of the most comprehensive websites where researchers register their studies, shows that China has 274 clinical trials under way, compared with 260 in India.

• From Time: Asia has become the next frontier for pharmaceutical firms desperate to find their next blockbuster drug while keeping research costs low. In 2006, big drug companies doubled R&D investment in China and India over the previous year, to $2.2 billion. Nearly all of that went into China, thanks to generous government support and strong infrastructure. Beijing wants to attract more than 2% of the world's R&D budget, or about $10 billion, by 2010.

  Foreign drugmakers are happy to oblige. Both U.K.-based AstraZeneca and Swiss outfit Novartis have announced plans to spend $100 million on new R&D labs in Shanghai. In June, the U.S.'s Eli Lilly pledged to spend $300 million within the next five years. Britain's GlaxoSmithKline started 17 drug trials in 2006 and plans to double that number this year.

• Interested in foreign drug trials? This database is where to start. The link takes you to an example of a current drug trial in Africa on the prevention of mother-to-child HIV transmission. This database is searchable by location so users can track where drug trials are occuring.