India: Johns Hopkins' cancer drug trial under fire
NEW DELHI, Jul 30 (Reuters Health) - A physician in Trivandrum, a
city in southern India, is questioning the safety of an experimental drug trial
conducted in part by a researcher from Johns Hopkins University in Baltimore,
Maryland.
At the heart of the complaint, Dr. V. N. Bhattathiri, associate professor
and the head of the clinical radiobiology division at the Regional Cancer
Centre (RCC) in the state of Kerala, alleges that clinical trials of an
experimental anti-cancer drug, called M4N, have not followed standard
procedures of approval for use in humans, and that cancer patients injected
with the drug may have suffered harm.
"At least 25 patients with tumors have been injected with M4N...since
1999, and I thought something was wrong when I read a few biopsy reports that
said drug injected area(s) show (signs of) carcinoma," Bhattathiri told
Reuters Health.
"These patients are poor people, and they or their relatives simply
sign papers that say they are prepared to accept any treatment that will make
their condition better," Bhattathiri added.
In recent weeks, Johns Hopkins Medical School has been under investigation
in the US due to the June death of a 24-year-old American woman who had
enrolled in a separate Hopkins asthma trial as a healthy volunteer. Because of
the incident, the federal government's Office for Human Research Protections
temporarily halted almost all the university's federally funded medical studies
involving human subjects. After the short suspension, the university was
granted permission to resume the studies on July 23.
As for the study conducted in India, all such trials are routed through the
Drugs Controller of India. While the Drugs Controller has kept silent on this
issue, Bhattathiri said he has reason to believe that the application for
permission to conduct the trials was forwarded only in February of 2001. The
trials actually took place in 1999 and 2000, according to Bhattathiri.
A. K. Antony, chief minister in Kerala, has gone on record saying that the
matter will be seriously investigated, especially since the reputation of a
premier institute is at stake.
In India, Dr. M. Krishnan Nair, director of the RCC, joins Dr. Ru Chih
Huang, professor of biology at Johns Hopkins University's Krieger School of
Arts and Sciences, as co-principal investigator of the project.
Johns Hopkins University released a statement on Monday saying that they
became aware of the allegations regarding a study conducted in 1999-2000 when
they appeared in news reports in the India media on July 16th.
"Among these, reportedly, were allegations regarding whether proper
informed consent had been secured from patients, whether surgery or other
conventional treatment had been delayed because of the administration of the
experimental drug, and whether the drug had been properly screened for toxicity
before it was administered," according to the statement.
The university notes that a preliminary inquiry revealed that "the
study in question had not been authorized by any department of the (Johns
Hopkins) University, and confirmed that it had not been reviewed or approved by
any of the university's institutional review boards concerned with the
protection of human subjects."
"It was determined that because of the level of involvement of the
Johns Hopkins researcher in this [clinical drug] trial that it should have been
submitted to the institutional review board at Johns Hopkins," said Dennis
O'Shea, a spokesperson for Johns Hopkins University, in an interview with
Reuters Health.
An institutional review board (IRB) is a panel of experts that examines and
advises researchers about prospective drug trials that use human subjects and
either approves or denies the protocol, explained O'Shea.
Currently, Johns Hopkins has asked the researcher to "cease all
activities related to the study" and "has now appointed a panel of
experts who will conduct a formal investigation to more fully develop the
facts."
O'Shea would neither confirm nor deny Huang as the principal investigator
working on the anti-cancer drug trial. However, a Johns Hopkins Web site lists
a pending proposal under Huang's name dated May 2001, for use of a derivative
of a chemical called NDGA in a single blind, placebo-controlled study. The goal
of the trial is to examine the effect of M4N on advanced oral malignancies.
M4N is a derivative of NDGA, an active principal of "chaparral
tea," which is made from leaves of the creosote bush (Larrea tridentata),
a common American desert plant. Although chaparral tea has been used over the
years as an herbal remedy for cancer, it is also well known for the toxic
impact it can have on the liver.
O'Shea told Reuters Health that Johns Hopkins does not have enough
information about the incident to either confirm or deny the allegations,
specifically whether or not the study has been ongoing since 1999 as is alleged
by Bhattathiri.
The university said that in March 2001, they became aware of a trial
conducted in India in 1999-2000, and that their faculty member "reported
that the trial had been approved by the appropriate reviewing authorities in
India, and that proper informed consent had been obtained from patients
enrolled in the study."
The university told the faculty member that a planned follow-up study needed
to be submitted to the university's IRB, and while the "protocol has been
submitted and has been under review," it has not yet been approved.
The extent to which Huang and Nair followed guidelines established at the
RCC to protect patients' rights remain unclear. However, a statement released
late Monday evening in New Delhi by the government's Ministry of Health and
Welfare states that researchers at the RCC were granted permission on February
2, 2001 to import M4N from Johns Hopkins.
The study is evaluating the efficacy of M4N "in advanced oral and
cervical malignancies," according to the statement, which goes on to say,
"the permission was granted on the basis of preclinical and other relevant
data."
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