Conflict of Interest: Cloud Over AIDS Research?

In December 1989 the U. S. Department of Health and Human
Services (HHS) rejected proposed guidelines intended to control
conflict of interest in research supported by the U. S. National
Institutes of Health (NIH). These guidelines would have greatly
restricted Federally-supported biomedical researchers from having
consulting arrangements with, or owning stock in, companies
affected by their research. Many scientists strongly objected to
the proposed restrictions, on the grounds that they would not
allow the best scientists to work for both industry and
government, and also because, they believed, the paperwork would
be unduly burdensome.

Others are concerned that the present system means that
anything is legal, as there are no rules or standards governing
conflict of interest by academic biomedical researchers supported
by public money. For example, nobody would allow Federal
employees to have undisclosed consulting contracts with companies
affected by their official decisions. But in biomedical research,
the real funding decisions (and often regulatory decisions) are
increasingly made by outside experts (not Federal employees), in
peer-review or other advisory committees. These non-employees can
legally have consulting arrangements with anyone; they might or
might not disqualify themselves in cases of conflict. So just
changing how the decision-makers are paid, from Federal salaries
to Federal contracts or grants, summarily discards the entire
structure of conflict-of-interest regulation which has developed
over decades, potentially threatening the integrity of the public
decision-making process.

In recent months there has been public suspicion of
conflict-of-interest abuses, but few cited examples. The lack of
confidence may result because the public has no way to know how
serious a problem exists. This article outlines some of the
prevalent fears and issues, not only in the financial
arrangements normally considered "conflict of interest," but also
in other cases in which the public pays for research but is ill
served by decisions which place private over public interests.
This article will include these broader issues, suggest questions
to raise, and show why conflict of interest may be a critical
obstacle to AIDS treatment development.

Does Conflict of Interest Impede New Drugs?

In testimony against the NIH conflict-of-interest
guidelines, it was revealed that almost all the principal
investigators in the ACTG (AIDS Clinical Trials Group) system
have industrial consulting arrangements -- usually not disclosed to
the public. Could these private arrangements result in bias
against competing drugs when decisions are made on how to spend
public money? The current issue of Boston Magazine, June 1990,
has a long article on the background of Peptide T, and on the
widespread suspicions that this potential treatment may have been
dismissed unfairly because of fears that it could be a competitor
to CD4 ("Peptide T and the Research Establishment," by Seth
Rolbein).

Others are suspicious about exactly what pharmaceutical
companies are buying through these consulting arrangements. Many
view the ACTG system as unproductive, with little useful
information to show for hundreds of millions of dollars and
several years of time invested. Pharmaceutical companies have
often been frustrated and unhappy in working with the ACTG. Why
then are they paying money to almost all of its principal
investigators? Are they buying scientific productivity -- or
influence over the flow of hundreds of millions of dollars of
public money for AIDS clinical research?

Perhaps the worst suspicions concern the lack of promising
new treatments in clinical trials. Dozens, probably hundreds of
promising chemicals have emerged from laboratories, but then
almost all of them are abandoned; they do not move on to human
trials. The worst drug logjam occurs early in development, at the
stage of finishing preclinical work (such as the manufacturing
quality assurance and the animal toxicity testing required by the
FDA), in order to obtain the "IND" (Investigational New Drug)
approval which is required before human testing can begin. The
public does not notice this early drugjam, because the potential
drugs in question are not yet real treatment options for people;
also, information about preclinical development is proprietary
and usually secret -- even the existence of a Federally-granted IND
is not public information. Only years later does the public
realize that the pipeline is largely empty, and few or no new
treatments are becoming available.

Could conflict of interest be the major cause of this
central problem? The possible scenario -- not proven, only a
suspicion at this time -- is that products early in development do
not have the commercial momentum to pay the consulting fees
necessary to be taken seriously by the AIDS research
establishment. Could new possibilities be abandoned in favor of
still more research on products like AZT, which are already on
the market and therefore have the cash flow necessary to buy
their way into the professional community?

Many researchers, not surprisingly, have a very different
view. They see their decisions as reflecting only the higher
worlds of Science and Medicine, independent of such mundane
matters as who pays the bill. Many are angry that anyone would
think otherwise. They feel that such ideas challenge their
integrity.

One middle-ground position acknowledges that the large
majority of researchers do remain independent of undue financial
influence. It sees the problem instead in the narrow outlook
which develops when people interact constantly with small groups
of others who have the same viewpoints they do. Activists as well
as researchers face this problem.

But research costs much more than activism, so research
cliques will seldom come into being except where there is money
to support them. Money builds influence which brings in more
money, leading to increasing concentrations of power in small and
narrow groups, whose members quite correctly do not see
themselves as being bought off, but as doing what they sincerely
believe is right. Yet new treatments may be abandoned just the
same, shut out as the groups which have coalesced around cash-
rich commercial products compete for increasingly scarce Federal
funds. The issue is not personal integrity, but the fact that the
system does not work.

Publication Embargos: A Different Conflict of Interest

An issue usually considered separately from conflict of
interest, because it does not directly involve money, is the
common requirement that scientists conceal their work for months
or years, from the public and often from scientific colleagues as
well, in order to enhance the news value of journals or
conferences. (The common news embargos which last only a few
days, and are intended to allow orderly release of information
which does not depend on whose mail is delivered first, present
much less serious problems.)

A recent article in The New York Times (May 22, 1990)
reported one particularly serious example. The Times interviewed
the former head of the U. S. National Cancer Institute concerning
a large 1981 study which found that breast cancer in women could
often be treated as well by removing a small lump as by removing
the entire breast. "But the data were kept secret for 14 months
while the paper was considered at The New England Journal of
Medicine. During that time...some 100,000 American women were
found to have breast cancer and were unaware that complete
removal of the breast was unnecessary." The article did not
estimate how many thousands of women had their breasts removed
needlessly so that the researchers could publish in the most
prestigious journal, and so that the Journal could have a scoop
to further its business interests.

Recently The New England Journal of Medicine and some other
major journals have allowed early release of information with
urgent public-health importance; The New York Times article
included several examples. But areas like AIDS, complex
emergencies without a single solution, present a more fundamental
problem. Scientists build on each other's work; long pre-
publication secrecy, even when not immediately life- threatening,
slows the entire research process and delays the ultimate
development of better treatments, costing lives eventually
although not immediately.

A recent book (Covering the Plague: AIDS and the American
Media, by James Kinsella, Rutgers University Press, 1989) traces
the history of pre-publication secrecy to the large increase in
the number of scientists, beginning in the early 1970s, which
allowed The New England Journal of Medicine to be very selective.
"The surplus of manuscripts at the Journal allowed then-editor
Dr. Franz Inglefinger to demand an 'exclusive' on every article
that appeared in the Journal. The publication would run no
manuscript that had been reported in detail anywhere else,
including the popular press." Since there was a backlog of
articles, scientific results were regularly withheld from the
public, and from many scientific colleagues, for months. Hundreds
of other journals followed and imposed the notorious "Inglefinger
rule," but others (such as the Lancet, according to Kinsella)
have not.

It might be hoped that the Sixth International Conference on
AIDS would take the lead against this destructive system, but it
has failed to do so. Authors had to certify that their abstract
"has not been published elsewhere or submitted for presentation
at another national or international meeting." Technically this
wording does not require pre-publication secrecy -- authors could
present the material elsewhere after they signed the
certification, which, with the abstracts themselves, was due in
January. But in fact researchers have been tight-lipped about
what they plan to present, maintaining the five-month "shadow"
which each annual Conference casts before it -- the time each year
when researchers are most reluctant to talk about their latest
results. (The Sixth International Conference also threatened
journalists with loss of credentials, and therefore expulsion
from the meeting, if they did not honor a press embargo on the
Advance Program by withholding "all information related to
program content...for release only after presentation at the
Conference.")

Early public discussion of results to be presented would
improve the Conference, by letting participants orient themselves
before the whirlwind of events begins. The value of this meeting
is not in the release of scoops -- let us hope that nothing truly
important was concealed for five months to be presented in San
Francisco -- but rather in status reports from leading researchers.
Good business meetings provide information in advance, so that
participants can have in-depth discussions instead of spending
their time figuring out what is going on.

Unfortunately, next year's Seventh International Conference
on AIDS, June 16-21, 1991, in Florence, Italy, already has
similar restrictions on its form for submission of abstracts.

What Can Be Done?

The initial attempt to control conflict of interest in NIH-
funded research (mentioned above) has been rejected, after
vehement opposition by many scientists. Efforts are now
continuing to develop milder standards -- perhaps not forbidding
certain practices but only requiring disclosure. According to an
assistant in the office of Congressman Ted Weiss, Democrat from
New York, who has long pushed NIH to develop such standards,
nothing will be in place for at least a year. (Congressman Weiss'
subcommittee will soon publish recommendations on what it
believes should be done. It has few specific examples of conflict
of interest, however, and none concerning AIDS research. Anyone
with a documented case -- clear evidence of something, not just
suspicion -- should call or write to Weiss' office.)

Dr. Janet Newburgh, of the Institutional Liaison Office at
NIH, told AIDS TREATMENT NEWS that development of proposed
conflict of interest rules is proceeding in two parts. The faster
track concerns commercial products, or items close to being
commercial products. The slower track concerns invention
development, ideas farther from commercialization.

Unfortunately it seems clear that if we have a major
problem, these NIH efforts will not solve it in the time frame
needed. Nothing is likely to be done for over a year. And then if
anything happens to restrain conflict of interest, and if it is
successful, it will only gradually lead to improvement in
government research priorities, which in turn will gradually lead
to improvement in research and then to better treatments. This
effort must be pursued, but we cannot hold our breath.

Another approach that we can take now is to investigate the
problems around conflict of interest, understand the situation
better ourselves, and increase awareness within the professional
community and the public. Better awareness, and the resulting
informal pressures and influences, may bring effective change
faster than formal regulation can. Activists and investigative
reporters can make a critical contribution, by informing the
public about the dimensions of the problem.

Still another approach, suggested in the article below, is
to continue to strengthen the ability of PWA, activist, and
front- line physician organizations to work together to develop
the community's own priorities for treatment research. Developing
consensus on a few treatments which most deserve public help to
shepherd them through the research system will also build the
constituency to overcome the obstacles blocking their progress.