University Of Califoria, San Francisco
School of Medicine
Please address reply to the undersigned at:
UCSF AIDS Program
San Francisco General Hospital
995 Potrero Avenue
Building 80, Ward 84
San Francisco, California 94110
April 28, 1995
Alan I. Leshner, Ph.D
Director
National Institute on Drug Abuse
5600 Fishers Lane
Rockville, Maryland 20857
Dear Dr. Leshner,
I am writing in response to your letter of April 19 regarding my
request that NIDA consider supplying marijuana for the Community
Consortium's proposed study in patients with HIV-related wasting
syndrome. I was not only disappointed by the flat out rejection of
the request, but also by the way this matter has been handled by your
Institute from the onset. To receive the first communication from
your office nine months after we sent the initial submission is
offensive and insulting. I realize that this has been a very
difficult decision for you to make because of all the nonscientific
issues involved, but I am certainly not used to having no
communication at all for nine months from someone with whom I had
corresponded on an official matter. The apparent abscence of any
possibility to discuss your concerns and to modify the protocol
appropriately so that we may work together for the benefit of our
patients is also unacceptable in my opinion.
The National Institute on Drug Abuse has not been the first body to
review our proposed pilot study. It has been reviewed and approved
by the Committee on Human Research of the University of California,
San Francisco, as well as by our own Scientific Advisory Committee
and Community Advisory Forum. In addition, the study has been
approved (pending location of the source of inhaled marijuana) by the
California Research Advisory Panel. The US Food and Drug
Administration has also been involved since the onset in developing
the trial and has strongly influenced the study's design. The
General Clinical Research Center at San Francisco General Hospital
has agreed to collaborate in the study by providing dietary
counseling and monitoring of patients, as well as performing the
state-of-the-art composition measurements we intend to perform.
Collaborating investigators at Chiron Corporation were also eager to
participate in this study by donating their newly developed
technology to assess HIV viral burden in patients randomized to
receive marijuana. Hence, your concerns about the scientific merit
of the study have not been shared by a number of competent reviewers
and investigators.
To respond to your concerns in a timely manner, I will address each
issue you raise in turn. However, it is important to stress that
this trial was designed as a pilot study to determine the feasibility
of conducting a larger study and, in particular, the sample size
required to evaluate the efficacy of inhaled marijuana. As you know,
the use of a pilot study in clinical research is a well-established
procedure. I am sure you would agree that it is a prudent strategy
to conduct a small pilot trial of inhaled marijuana prior to launching
the definitive efficacy trial that would require a much larger sample
size.
We fully appreciate that the current pilot study would not be
adequate to "make any inferences regarding the dose-effect
relationship." However, we would be able to determine whether a dose
was associated with an intolerable rate of side effects, and that
dose would then be eliminated from a larger efficacy trial. As
indicated in the protocol, we plan to do intensive monitoring of
pulmonary and immune function as well as HIV viral load in our
patients. If we saw that inhalation of marijuana was detrimental to
any of these parameters, that information would be crucial to share
with others in order to protect the safety of patients who are
already using inhaled marijuana (from other sources). The current
pilot study certainly should be large enough (with 30 patients
smoking marijuana) to assess such possible detrimental effects.
The Community Consortium conducts community-based clinical trials of
treatments that are being widely used by the patient population and,
as I am sure you are aware, individuals with access are currently
utilizing inhaled marijuana. Our aim is to assess the impact of
treatments that we study in "real world" situations. As you know,
with whatever drug one studies in a clinical trial, we can never be
truly certain that patients are consuming 100% of their assigned
doses. Even for treatment of Pneumococcal pneumonia, very few
patients treated actually complete their full course of penicillin.
Similarly, zidovudine (AZT) was approved as the first antiretroviral
agent for treating HIV infectioin, and we know that compliance in
those trials was not 100%. In our study, we plan to ask patients to
quantitate how much of their allotted marijuana they smoked on any
given day. We also plan to have patients return any unused marijuana
so we can assess how much they actually usilized. Whether they
actually smoked all that they were given at each visit is irrelevant
when an intent-to-treat analysis is utilized for data analysis.
Your concerns about total daily caloric intake and "the percentages
of the composition of the foodstuffs" are a bit extreme, in my
opinion, but do not present insurmountable problems for us. As the
General Clinical Research Center at San Francisco General Hospital is
our collaborating site where patients will go to be taught how to use
the water pipe for inhalation, and where they will return for all of
their follow-up evaluations, obtaining this dietary information is
certainly possible. In fact, this is the sort of information that
the GCRC specializes in collecting! Though we could add this
requirement, it would be a major inconvience to these already ill
patients to ask them to collect this information on a daily basis
during the trial. Of course, another option is to admit all patients
on the study to the GCR for the duration of their participation in
the study, so that all intake and output can be accurately assessed.
Once again, however, that is not how patients would be living while
they utilized the intervention in the real world, so the value of
data obtained in this fashion is, in my mind, unclear. It certainly
does not reflect the "real world" usage.
As an AIDS investigator who has worked closely with National
Institutes of Health and the US Food and Drug Administration for the
past 14 years of this epidemic, I must tell you that dealing with
your Institute has been the worst experience of my career! The lack
of any official communication for nine months is unheard of, even in
the most cumbersome of government bureaucracies. In fact, I was so
shocked to finally receive your communication that I failed to detach
the green postcard to verify receipt. I apologize to you, and to
your staff who called for three consecutive days to make sure the
letter had arrived.
Finally, the "sincerity" with which you share my "hope that new
treatments will be found swiftly" feels so hypocritical that it makes
me cringe. Believe it or not, I wish I had never needed to approach
NIDA with this request. The Community Consortium had a source of
marijuana established for this study from the onset. Unfortunately,
the source was foreign and the FDA advised us that the DEA was having
difficulty with the importation issue and suggested we contact you.
(The DEA has also been less than forthcoming in responding to my
request for a Schedule I license sent to them April 15, 1994.)
Obviously, your letter leaves no door open for further discussion as
to how this pilot study could be modified so that we could work
together. Hence, I will not bother you further. Your letter will be
widely distributed. You had an opportunity to do a service to the
community of people living with AIDS. You and your Institute failed.
In the words of the AIDS activist community: SHAME!
Sincerely,
[signed]
Donald I. Abrams, M.D.
Chairman, Community Consortium
Assistant Director, AIDS Program
San Francisco General Hospital
Professor of Clinical Medicine
University of California San Francisco
cc: Philip R. Lee, MD
Harold E. Varmus, MD