Answers
What is Dr. Fishbein fighting for?
Dr. Fishbein wants the NIH and its officials
held accountable for their actions. He wants
the U.S. Congress to investigate the NIH’s
pattern of non-compliance to law and regulation
regarding the ethical conduct of research
and the dissemination of data. He wants
the NIH to reform its procedures to assure
that grantees are capable and qualified
to conduct human research, no matter the
setting.
Why has
Dr. Fishbein chosen this moment to blow
the whistle on misconduct at NIAID?
Dr. Fishbein raised serious questions about
scientific and professional misconduct at
NIAID when he first began his employment
in July, 2003. He brought his concerns to
the attention of his superiors consistent
with established procedures. When his superiors
failed to act, he took his evidence of wrongdoing
to various government regulatory agencies
as well as members of the United States
Congress.
As a federal employee, Dr. Fishbein has
a mandatory duty, as set forth in both law
and regulation to provide evidence of “fraud,
waste and abuse” to “appropriate
authorities.” These authorities include
members of Congress. Dr. Fishbein fulfilled
his mandatory obligation as a public servant
when he disclosed abuses within the NIH
which directly compromised the public health
and safety.
What are Good Clinical Practice
(GCP) standards?
Good Clinical Practice (GCP) is an international
ethical and scientific quality standard
for designing, conducting, recording, and
reporting trials that involve the participation
of human subjects. Compliance with GCP assures
that the rights, safety, and well-being
of trial subjects are protected and that
the clinical trial data are credible.
The GCP is a unified standard of the EU,
Japan, and the United States to facilitate
acceptance of clinical data by the regulatory
authorities of these jurisdictions. GCP
was developed by an expert working group
of the international Conference on Harmonization
(ICH) with the consultation of numerous
regulatory agencies as well as the World
Health Organization.
The GCP Consolidated Guidance was published
in the Federal Register on May 9, 1997,
and is consistent with FDA regulations and
guidelines (Federal Register Vol.62, No.90,
May 9, 1997, pp. 25691-25709).
Does the
FDA recognize Good Clinical Practice (GCP)
standards as defined by the International
Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals
for Human Use (ICH)?
Yes. FDA Officials emphasize that the ICH
guidelines are entirely consistent with
established GCP requirements, and that the
harmonized documents supplement, rather
than replace, existing U.S. regulations
and guidelines. Agency officials concede
that, in a few areas, the ICH GCP guidelines
clarify current U.S. practice and requirements
better than the FDA’s regulations
and guidelines. (p.150, New Drug Development:
A Regulatory Overview, 4th Edition, by Mark
Mathieu, PAREXEL International Corporation,1997).
What is an Investigational New
Drug (IND) application?
“An Investigational New Drug Application
(IND) is a request for authorization from
the Food and Drug Administration (FDA) to
administer an investigational drug or biological
product to humans. Such authorization must
be secured prior to interstate shipment
and administration of any new drug or biological
product that is not the subject of an approved
New Drug Application or Biologics/Product
License Application.” (FDA)
Why is Dr.
Fishbein criticizing the failure of HIV
012 researchers to use Good Clinical Practice
(GCP) standards?
Good Clinical Practice is the standard
that regulatory authorities rely upon to
assure them that data are credible and the
rights of trial subjects are protected.
HIVNET 012 was an IND study. The principal
investigator was legally obligated to conduct
it according to GCP. Severe violations of
GCP in the activities of data collection,
recordkeeping, and quality control, particularly
in the area of safety, adversely impact
the accuracy of the HIVNET 012 clinical
trial data.
Failing to meet an internationally recognized
standard for assuring credibility, the HIVNET
012 investigators compromised the integrity
of their study data, thus rendering the
results invalid.
The objective record demonstrates that
HIVNET 012 is a study so poorly conducted
that its data must be rendered invalid as
a matter of law, policy, and human health.
Its conclusions must be stricken from the
collective experience of nevirapine in MTCT.
The old adage "garbage in, garbage
out" is apt.
Regardless of the results of subsequent
studies and any and all attempts to rectify
the problems of HIVNET 012, this study should
not be considered as a valid contributor
to the current body of knowledge about the
use of single dose nevirapine to prevent
the transmission of the HIV virus from mother
to newborn.
Is Dr. Fishbein questioning the
effectiveness of nevirapine?
Dr. Fishbein is concerned with the poor
quality of the HIVNET 012 clinical trial
data and believes that as a result, no credible
scientific conclusions can be drawn from
this study. Moreover, the failure of the
researchers to follow Good Clinical Practice
(GCP) standards should invalidate any information
collected during the course of the study.
Dr. Fishbein’s testimony before the
Institute of Medicine (IOM) on January 4,
2005 and his 42-page document outlining
the breaches of GCP standards by HIVNET
012 researchers supports these contentions.
Dr. Fishbein also is concerned with the
effort by the National Institute for Allergy
and Infectious Diseases (NIAID) to cover
up the severity of the audit findings and
the intimidation tactics and retribution
it employs to silence dissent on this matter.
Dr. Fishbein takes no stand on any of the
other clinical trials which have utilized
the same single dose nevirapine regimen,
only that he hopes that those trials were
conducted to Good Clinical Practice standards.
What makes Dr. Fishbein's allegations
so significant?
The problem with HIVNET 012 is not one
of statistics. Neither is it a nevirapine
issue, nor even an AIDS issue. The problem
is one of ethics and regulations -- period.
It is a matter of research integrity in
which both the investigators and their DAIDS
sponsors became so heavily invested in the
trial’s outcome that they were unable
to exercise objectivity in their actions.
Even now, with the evidence against them
mounting, the officials involved with HIVNET
012 remain stoic, refusing to acknowledge
even a scintilla of wrongdoing.
The consequences of their failure not only
strike deeply at the heart of NIH and its
commitment to scientific integrity, but
have grave and sometimes fatal implications
for the lives of real patients.
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