Premature Infants Would Go Untreated, Die in Proposed Latin American Drug Trial

Feb. 22, 2001

Premature Infants Would Go Untreated, Die in Proposed
Latin American Drug Trial

FDA May Endorse Unethical Placebo-Controlled Study
of Drug for Respiratory Distress Syndrome

WASHINGTON, D.C. — Hundreds of premature infants with a potentially fatal medical condition would be given placebos — and thus be more likely to die — in a drug company study in Latin America that the Food and Drug Administration (FDA) is considering endorsing, Public Citizen has learned.

In a letter sent today to Health and Human Services (HHS) Secretary Tommy Thompson, Public Citizen called on the FDA to immediately halt plans for the study unless it is redesigned to treat all patients.

“One expects drug companies to be profit-driven and act accordingly,” said Dr. Peter Lurie, deputy director of Public Citizen?s Health Research Group. “But the FDA?s job is to stop this kind of unethical behavior, not encourage or endorse it. The fact that the agency is seriously considering this study is beyond belief.”

In the study, hundreds of infants with Respiratory Distress Syndrome (RDS) would be treated with an experimental synthetic surfactant drug called Surfaxin, while a control group of hundreds of premature infants with the syndrome would be given placebos — instead of one of four FDA-approved surfactant drugs that could save the infants? lives. Many infants given placebos likely would die unnecessarily, a Public Citizen analysis shows. Surfactant is a kind of drug that makes it easier to inflate the lungs of newborns with RDS. A third group of infants would get an already-approved drug.

The study is to be conducted in one or more of the following four countries: Bolivia, Ecuador, Peru and Mexico. The company proposing the study is Discovery Laboratories Inc., which is based in Doylestown, Pa., and which has licensed the drug from Johnson & Johnson. Although approved surfactants are available in some hospitals in these countries, Discovery Laboratories plans to conduct the study in hospitals where surfactant is not available.

The FDA has acknowledged in internal documents that the proposed study would be unethical in the United States, where the new drug would be studied by treating one group of infants with the new drug and a second group with a drug already proven to treat RDS, but no infant would receive a placebo. One surfactant drug has been approved in the U.S. on the basis of studies with this design, and Discovery Laboratories plans to use this design in a European study.

But the FDA has long expressed a preference for studies with placebo controls, even for conditions that are not minor, and companies prefer them because it is easier to prove one?s drug is superior to nothing than to prove that it is as effective as a competitor?s drug that is known to work.

Public Citizen learned about the proposed study through documents obtained from an internal meeting at the FDA at which the proposed study was discussed. The meeting was entitled, “Use of placebo-controls in life threatening diseases: is the developing world the answer?” Because the drug is still under development, some details of the proposed study — such as the name of the drug company — were not included in the FDA documents. However, in a phone call with Public Citizen, Discovery Laboratories? president, Robert J. Capetola, confirmed that his company is the sponsor of the proposed trial.

Surfactant was heralded in a 1993 New England Journal of Medicine article as “without doubt the most thoroughly studied new therapy in neonatal care.” A statistical summary of studies of synthetic surfactant has concluded that the drug reduces neonatal mortality by 34 percent and that “further placebo controlled trials of synthetic surfactant are no longer warranted.”

The use of a placebo in this study violates the Declaration of Helsinki, an international ethics document. A recent revision to the Declaration says that, “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods.” Public Citizen?s letter notes that in light of this language, “the sort of study contemplated here is expressly forbidden” by the Declaration.

Discovery Laboratories claims that it will make the drug available at a reduced cost in those countries where it conducts the study, but it hasn?t defined those costs precisely. Pharmaceutical sales in Latin America represented just 7 percent of international pharmaceutical sales in 1999, compared to 40 percent in North America and 27 percent in Europe.

“The infants who would get placebos are being used by the company for reasons having to do with corporate bottom lines in order to get their drug approved,” said Public Citizen?s Health Research Group director, Sidney M. Wolfe, MD. Public Citizen also is asking the new Office of Human Research Protections in HHS to use its influence to immediately stop the study.

“If this study occurs, it will be a landmark of unethical and exploitative behavior, ” Lurie said. “We have a profit-driven drug company turning to the developing world to conduct studies that could never be done in the United States or even in some parts of the study countries. This company wants to experiment on the poorest of the poor, and that is despicable.”