AIDS Research Chief Rewrote Safety Report

Tue Dec 14, 6:58 PM ET

 Health - AP

By JOHN SOLOMON, Associated Press Writer

WASHINGTON - The government's chief of AIDS (news - web sites) research
rewrote a safety report on a U.S.-funded drug study to change its
conclusions and delete negative information. Later, he ordered the
research resumed over the objections of his staff, documents show.

Dr. Edmund Tramont, chief of the National Institutes of Health (news - web
sites)'s AIDS Division, took responsibility for both decisions. He cited
his four decades of medical experience and argued that Africans in the
midst of an AIDS crisis deserved some leniency in meeting U.S. safety
standards, according to interviews and documents obtained by The
Associated Press.

Tramont's staff, including his top deputy, had urged more scrutiny of the
Uganda research site to ensure it overcame record-keeping problems,
violations of federal patient safety safeguards and other issues that
forced a 15-month halt to the research into using nevirapine to prevent
African babies from getting AIDS from their mothers.

AP reported Monday that NIH knew about the problems in early 2002 but did
not tell the White House before President Bush (news - web sites) launched
a plan that summer to spread nevirapine throughout Africa. Now, officials
have new concerns the drug may cause long-term resistance in the hundreds
of thousands of African patients who received it, foreclosing future
treatment options.

"I am not convinced that the site is indeed prepared to become active,"
Dr. Jonathan Fishbein, an expert NIH hired to improve the agency's
research practices, wrote Tramont in July 2003.

Fishbein contended he should be given time to review Uganda's capabilities
and safety monitoring before letting the site reopen, or NIH would risk
being "toothless" in its new efforts to clean up sloppy research
practices. He added that professional safety monitors hired by NIH had
reservations about the site.

Tramont dismissed the safety monitors' concerns, saying he didn't believe
they fully understood AIDS.

"I am convinced that this site is ready to resume given the limitations of
doing research in any resource-poor, underdeveloped country," Tramont
wrote July 8, 2003, in response to Fishbein.

"I want this restriction lifted ASAP because this site is now the best in
Africa run by black Africans and everyone has worked so hard to get it
right as evidence by the fact that their lab is now certified," he wrote.

NIH officials acknowledge Tramont rewrote the report and overruled his
staff on the reopening, but said he did so because he was more experienced
and had an "honest difference of opinion" with his safety experts. They
noted he had no financial interest in nevirapine and that the troubled
study began well before he joined NIH in 2001.

Those who raised objections "were part of a large team of which Dr.
Tramont was the head, and it is important that the people involved in that
team should express their opinion and there should be discussion," said
Dr. H. Clifford Lane, the NIH's No. 2 infectious disease specialist and
one of Tramont's bosses. NIH designated Lane to speak to AP on Tramont's
behalf.

"But at the end of the day the final responsibility lies with the head of
the team and it is his job to put that together the way he sees it," Lane
said.

Lane said an internal NIH review concluded Tramont had not engaged in
scientific misconduct. Separately, the National Academy of Sciences (news
- web sites) continues to investigate whether the Uganda research was
valid.

NIH believes it helped save hundreds of thousands of African babies by
allowing nevirapine to be used in single doses to block the AIDS virus,
Lane said. But he acknowledged the research was imperfect, and NIH now
believes nevirapine should no longer be a first choice for newborn
protection — if other options exist — because of the newly discovered
problems about resistance.

Tramont wrote in 2003 e-mails that he reopened the clinics because he
didn't want NIH "perceived as bureaucratic but rather thoughtful and
reasonable" and that it was important to encourage Africans' fight against
AIDS "especially when the president is about to visit them."

Bush visited the continent a few days after Tramont ordered the clinics
reopened.

Tramont's actions, however, drew a blunt reply from his top deputy.

 

"I think we are cutting off our noses to spite our face here," AIDS
Division Deputy Director Jonathan Kagan wrote. "...We should not be
motivated by political gains and it's dangerous for you, of all people, to
be diminishing the value of our monitors."

Tramont prevailed and the research resumed. A few days later, Tramont sent
a note to his staff ordering the end of an 18-month-long debate inside NIH
over whether the science from the Uganda trials was valid and safe. That
debate began in early 2002 when two audits divulged widespread problems
with the research.

The Uganda trial "has been reviewed, re-monitored, debated and
scrutinized. To do any more would be beyond reason. It is time to put it
behind us and move on," Tramont wrote in a July 13, 2003 e-mail
instructing his staff that future issues about the drug be handled
directly by his office.

Five months earlier, Tramont surprised one of his own medical officers who
had written a report summarizing safety concerns uncovered during a second
review of the Uganda trial.

Dr. Betsy Smith's report, finished in January 2003, said the Uganda trial
suffered from "incomplete or inadequate safety reporting" and that records
on patients were "of poor quality and below expected standards of clinical
research."

She strongly urged NIH not to make sweeping conclusions about nevirapine
based on the Uganda research. "Safety conclusions from this trial should
be very conservative," she wrote.

Behind the scenes, Tramont asked to see Smith's report before it was
submitted to medical authorities, including the Food and Drug
Administration (news - web sites). "I need to see the primary data — too
much riding on this report," Tramont wrote Jan. 23, 2003.

A few weeks later, the safety report was published and sent to FDA (news -
web sites) without Smith's concerns and with a new conclusion.

The study "has demonstrated the safety of single dose nevirapine for the
prevention of maternal to child transmission," Tramont's version
concluded. "Although discrepancies were found in the database and some
unreported AEs (adverse reactions) were discovered ... these were not
clinically important in determining the safety profile."

In disbelief, Tramont's staff began inquiring how Smith's report got
changed. An answer came back from the top.

"I wrote it," Tramont responded.

___

On the Net:

Documents gathered by AP for this story are available at:
http://wid.ap.org/documents/nevirapine2.html

National Institutes of Health: http://www.nih.gov

AIDS Research Chief Rewrote Safety Report

Tue Dec 14, 6:58 PM ET

 Health - AP

By JOHN SOLOMON, Associated Press Writer

WASHINGTON - The government's chief of AIDS (news - web sites) research
rewrote a safety report on a U.S.-funded drug study to change its
conclusions and delete negative information. Later, he ordered the
research resumed over the objections of his staff, documents show.

Dr. Edmund Tramont, chief of the National Institutes of Health (news - web
sites)'s AIDS Division, took responsibility for both decisions. He cited
his four decades of medical experience and argued that Africans in the
midst of an AIDS crisis deserved some leniency in meeting U.S. safety
standards, according to interviews and documents obtained by The
Associated Press.

Tramont's staff, including his top deputy, had urged more scrutiny of the
Uganda research site to ensure it overcame record-keeping problems,
violations of federal patient safety safeguards and other issues that
forced a 15-month halt to the research into using nevirapine to prevent
African babies from getting AIDS from their mothers.

AP reported Monday that NIH knew about the problems in early 2002 but did
not tell the White House before President Bush (news - web sites) launched
a plan that summer to spread nevirapine throughout Africa. Now, officials
have new concerns the drug may cause long-term resistance in the hundreds
of thousands of African patients who received it, foreclosing future
treatment options.

"I am not convinced that the site is indeed prepared to become active,"
Dr. Jonathan Fishbein, an expert NIH hired to improve the agency's
research practices, wrote Tramont in July 2003.

Fishbein contended he should be given time to review Uganda's capabilities
and safety monitoring before letting the site reopen, or NIH would risk
being "toothless" in its new efforts to clean up sloppy research
practices. He added that professional safety monitors hired by NIH had
reservations about the site.

Tramont dismissed the safety monitors' concerns, saying he didn't believe
they fully understood AIDS.

"I am convinced that this site is ready to resume given the limitations of
doing research in any resource-poor, underdeveloped country," Tramont
wrote July 8, 2003, in response to Fishbein.

"I want this restriction lifted ASAP because this site is now the best in
Africa run by black Africans and everyone has worked so hard to get it
right as evidence by the fact that their lab is now certified," he wrote.

NIH officials acknowledge Tramont rewrote the report and overruled his
staff on the reopening, but said he did so because he was more experienced
and had an "honest difference of opinion" with his safety experts. They
noted he had no financial interest in nevirapine and that the troubled
study began well before he joined NIH in 2001.

Those who raised objections "were part of a large team of which Dr.
Tramont was the head, and it is important that the people involved in that
team should express their opinion and there should be discussion," said
Dr. H. Clifford Lane, the NIH's No. 2 infectious disease specialist and
one of Tramont's bosses. NIH designated Lane to speak to AP on Tramont's
behalf.

"But at the end of the day the final responsibility lies with the head of
the team and it is his job to put that together the way he sees it," Lane
said.

Lane said an internal NIH review concluded Tramont had not engaged in
scientific misconduct. Separately, the National Academy of Sciences (news
- web sites) continues to investigate whether the Uganda research was
valid.

NIH believes it helped save hundreds of thousands of African babies by
allowing nevirapine to be used in single doses to block the AIDS virus,
Lane said. But he acknowledged the research was imperfect, and NIH now
believes nevirapine should no longer be a first choice for newborn
protection — if other options exist — because of the newly discovered
problems about resistance.

Tramont wrote in 2003 e-mails that he reopened the clinics because he
didn't want NIH "perceived as bureaucratic but rather thoughtful and
reasonable" and that it was important to encourage Africans' fight against
AIDS "especially when the president is about to visit them."

Bush visited the continent a few days after Tramont ordered the clinics
reopened.

Tramont's actions, however, drew a blunt reply from his top deputy.

 

"I think we are cutting off our noses to spite our face here," AIDS
Division Deputy Director Jonathan Kagan wrote. "...We should not be
motivated by political gains and it's dangerous for you, of all people, to
be diminishing the value of our monitors."

Tramont prevailed and the research resumed. A few days later, Tramont sent
a note to his staff ordering the end of an 18-month-long debate inside NIH
over whether the science from the Uganda trials was valid and safe. That
debate began in early 2002 when two audits divulged widespread problems
with the research.

The Uganda trial "has been reviewed, re-monitored, debated and
scrutinized. To do any more would be beyond reason. It is time to put it
behind us and move on," Tramont wrote in a July 13, 2003 e-mail
instructing his staff that future issues about the drug be handled
directly by his office.

Five months earlier, Tramont surprised one of his own medical officers who
had written a report summarizing safety concerns uncovered during a second
review of the Uganda trial.

Dr. Betsy Smith's report, finished in January 2003, said the Uganda trial
suffered from "incomplete or inadequate safety reporting" and that records
on patients were "of poor quality and below expected standards of clinical
research."

She strongly urged NIH not to make sweeping conclusions about nevirapine
based on the Uganda research. "Safety conclusions from this trial should
be very conservative," she wrote.

Behind the scenes, Tramont asked to see Smith's report before it was
submitted to medical authorities, including the Food and Drug
Administration (news - web sites). "I need to see the primary data — too
much riding on this report," Tramont wrote Jan. 23, 2003.

A few weeks later, the safety report was published and sent to FDA (news -
web sites) without Smith's concerns and with a new conclusion.

The study "has demonstrated the safety of single dose nevirapine for the
prevention of maternal to child transmission," Tramont's version
concluded. "Although discrepancies were found in the database and some
unreported AEs (adverse reactions) were discovered ... these were not
clinically important in determining the safety profile."

In disbelief, Tramont's staff began inquiring how Smith's report got
changed. An answer came back from the top.

"I wrote it," Tramont responded.

___

On the Net:

Documents gathered by AP for this story are available at:
http://wid.ap.org/documents/nevirapine2.html

National Institutes of Health: http://www.nih.gov