Unethical research on pregnant women with herpes

PUBLIC CITIZEN PRESS RELEASE


Drug-Company Sponsored Research Trial Needlessly Put Indigent Pregnant
Women and Their Infants at Risk

Placebos Administered to Pregnant Women With Genital Herpes Simplex
Virus Resulted in Unnecessary Cesarean Deliveries

WASHINGTON, D.C. – Dozens of primarily indigent pregnant women
enrolled in a drug-company sponsored research trial were needlessly
put at risk by being treated with a placebo rather than a generic drug
proven to help them, according to a letter authored by Public Citizen
and two medical school professors and obstetricians published in the
December edition of the journal Obstetrics & Gynecology.

The trial, funded by Glaxo-Wellcome (now GlaxoSmithKline), measured
the efficacy of valacyclovir administered to pregnant women with a
history of genital herpes simplex virus (HSV) in reducing outbreaks of
genital HSV lesions at the time of labor. Women with HSV outbreaks
during pregnancy, especially those who experience a first episode, are
more likely to have another outbreak while in labor. When this occurs,
a Cesarean delivery is routinely performed to prevent HSV transmission
to the baby, which can result in sometimes-fatal neonatal HSV
infection.

The clinical trial ran from April 1998 to November 2004 at Parkland
Hospital in Dallas, which serves a predominantly low-income
population. The results were published in the July 2006 edition of
Obstetrics & Gynecology, the official journal of the American College
of Obstetricians and Gynecologists (ACOG).

Valacyclovir is a drug that is converted in the body into acyclovir.
Since 1999, acyclovir has been recommended by ACOG to be considered at
36 weeks of gestation for pregnant women with their first episode of
HSV during that pregnancy to prevent another outbreak at the time of
labor and the need for a Cesarean delivery. The authors of the study
ignored this guideline by including in the trial 62 women who had a
first episode of genital HSV during the pregnancy, most presumably
recruited after the ACOG guidelines were published.

In addition, four of the researchers who wrote the 2006 article
published a review article in 2003 that concluded that acyclovir
significantly reduced Cesarean rates for women with both first and
recurrent episodes of HSV compared to a placebo. Nonetheless, for more
than a year after submitting their findings, the researchers continued
to enroll women with both first and recurrent episodes, half of whom
received placebos.

"At the very same time these researchers were publishing their
conclusion that acyclovir could reduce Cesareans, they weren't
offering this drug to these indigent patients," said Dr. Adam Urato,
an obstetrician at the University of South Florida and one of the
letter's authors. "They were knowingly placing their patients at
higher risk. Did the patients understand that the researchers
themselves had concluded that acyclovir reduced the risk of Cesarean?"

As a result of this conduct by both the drug company and the
researchers, a significant number of the women assigned to receive the
placebo had an HSV outbreak that led to a Cesarean section – an
outbreak that likely could have been prevented if they had been
appropriately treated with acyclovir. The Declaration of Helsinki,
developed by the World Medical Association as a statement of ethical
principles in medical research involving human subjects, states that
any "new method should be tested against those of the best current
prophylactic, diagnostic, and therapeutic methods."

The authors of the letter called upon the University of Texas
Southwestern Medical Center at Dallas, which authorized the study, to
issue a formal apology to the pregnant women enrolled and to perform a
full investigation as to what went wrong to allow such a trial to take
place. They also called for compensation for the women involved in the
trial who were not properly treated and underwent Cesarean sections.

In addition, they urged ACOG and the editors at Obstetrics &
Gynecology to initiate an inquiry as to how this study was handled by
the journal. The Declaration of Helsinki also implores journals that
"reports of experimentation not in accordance with the principles laid
down in this Declaration should not be accepted for publication."

"Indigent pregnant women represent a particularly vulnerable
population," said Dr. Aaron Caughey, an obstetrician at the University
of California, San Francisco, and the lead author of the letter. "That
a research trial could be performed that put pregnant women at risk
when an effective medication was available flies in the face of
responsible medical research."

Public Citizen has a long history of involvement in the debate over
the appropriate use of placebos in clinical trials, particularly in
developing countries. "We have long contended that if researchers and
drug companies could get away with administering placebos under
questionable conditions in developing countries, they would do the
same to poor people in the United States," said Dr. Peter Lurie,
deputy director of Public Citizen's Health Research Group. "Now they
have."