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The CHORUS Database on Patient Clinical Care
-- and Interview with Stephen Becker, M.D.
by John S. James
CHORUS is a research database which is enrolling about 6,000
patients in four major U.S. HIV practices; over 4,000 have
volunteered already. This longitudinal study does not change
peoples' treatment in any way, nor require additional doctor
visits; instead, when patients give consent, the data
generated during their regular medical care is also recorded
anonymously for research. In addition, patients fill out a
quarterly questionnaire. They can withdraw from the database
at any time.
CHORUS (Collaborations in HIV Outcomes Research -- U.S.) began
in fall 1997. We are covering it now because of the growing
interest in side effects of antiretroviral drugs, especially
the body-shape changes and metabolic effects which have been
seen in some patients using protease inhibitors. The CHORUS
database is one tool for studying such problems; many people
are thinking about how to research these side effects, and
they should know that this database is available, and that
persons outside the program can suggest questions for
research.
CHORUS is funded by Glaxo Wellcome Inc., but an independent
scientific board of physicians and other HIV experts,
including community advocates, will decide what research is
conducted and published. Database housing and management is
being provided by Research Triangle Institute, of Research
Triangle Park, North Carolina.
Two reports from the CHORUS database have already been
presented.(1, 2)
How It Works
CHORUS collects data at only four sites (listed below; a
fifth site may be added). Therefore, only patients at those
practices can enter the program. Their medical records are
maintained by computer. At the end of each day, new
information about the patients who have consented to enter
the program is copied in an "anonymized" form, using a unique
identifier without the patient's name or other identifying
information. All CHORUS data, identified by this number, is
transmitted securely to Research Triangle Institute and added
to the database. The research data can be analyzed by site,
but individuals cannot be identified.
The four medical practices where patients can volunteer for
the CHORUS database (and the principal investigators on the
project there) are:
Pacific Horizon Medical Group, San Francisco (Stephen
Becker, M.D.);
Pacific Oaks Medical Group, Los Angeles (Anthony Scarsella,
M.D.);
Comprehensive Care Center, Nashville (Stephen Raffanti,
M.D.); and
Liberty Medical, New York (Douglas Dieterich, M.D.).
Anyone can submit questions through a member of the
scientific advisory board. The current co-chairs are Stephen
Becker, M.D., Pacific Horizons Medical Group in San
Francisco, and Richard Moore, M.D., Johns Hopkins University
in Baltimore. Other board members include the principal
investigators at the four CHORUS sites (listed above),
community representatives Robert Frost at the American
Foundation for AIDS Research (AmFAR) and Dawn Averitt,
outside consultants, and scientists from Glaxo-Wellcome.
Interview with Stephen Becker, M.D.
We asked co-chair Dr. Stephen Becker why the CHORUS database
is important.
Dr. Becker: I believe that observational databases will
become increasingly useful in our understanding of HIV
disease, and in answering many clinical questions.
Historically they have played a major role, for example the
MACS data [Multicenter AIDS Cohort Study, which has
contributed to hundreds of publications], and data from Johns
Hopkins finding no different clinical course of HIV disease
by race or by gender.
Observational data will become more important because of the
limitations of doing randomized controlled trials. These
trials for HIV now need to be much longer, because clinical
events are pushed out further. Adverse events are not
completely seen during the duration of clinical trials. And
these studies are increasingly expensive to run, particularly
if they enroll large numbers of people.
Randomized trials will certainly remain important, but our
understanding will be complemented by the larger number of
patients, the longer duration, and perhaps the more real-world experience that observational databases will give us.
Observational databases follow patients for years. The CHORUS
database will have 6,000 patients, after we add a fifth site.
And the issue of real-world experience is important. There is
a selection bias in many trials done by referral of patients
to a study site, because highly motivated patients are the
ones that tend to enroll. They may behave differently: they
may be more compliant, they may be willing to tolerate more
side effects, they may be a sicker patient population. A
community-based observational database such as CHORUS
includes almost all the patients in the practices, and
therefore reflects prevailing medical practice.
AIDS Treatment News: There is much interest today in adverse
effects being seen in some patients -- the lipodystrophy or the
body-shape changes, abnormal cholesterol and triglyceride
values, and problems in glucose metabolism. To what extent is
the CHORUS database tracking these?
Dr. Becker: We are certainly following adverse events.
Lipodystrophy is difficult, because until we have a working
definition that we can all agree upon, it will be hard for
doctors to code for it and have it be retrievable in large
numbers through any automated system. It would be difficult
to get this information from any database until we have
uniformity of definition.
The CHORUS database includes clinical outcomes, various blood
counts, viral loads, diagnoses, CDC demographic criteria,
epidemiological information like the risk factor and how the
patient likely acquired HIV; these are entered daily from the
clinical records into the database. But free-text entries are
not recorded; they would need to be coded in a standard way.
ATN: What about the triglycerides, cholesterol, and blood
glucose?
Dr. Becker: All of those lab data are in the system, and we
are beginning to look at them. For example, we counted
patients with cholesterol above 240, and those with
triglyceride levels above 350. We can ask about trends -- how
many patients had high values at certain dates? And we can
often match this information with dates when particular
therapies were started. We can ask how many patients with
these side effects have never been on protease inhibitors or
other drugs or classes of drugs.
With observational databases we can look at these problems in
a more systematic way than with anecdotal case reports. Large
observational databases can help advance our understanding by
showing phenomena that are happening; however, they do not
answer the question of why. Randomized clinical trials are
still needed to prove cause and effect.
ATN: Could these results help guide studies of the
mechanisms -- of adverse drug effects for example?
Dr. Becker: Absolutely. They should be seen as hypothesis-generating studies, as well as to help our understanding. For
example, we could look at a large number of patients who
started therapy with protease-inhibitor or protease-
inhibitor-sparing regimens, and look at the duration of
response -- for much longer times and with larger numbers of
patients than in clinical trials. And we can match the
durability of virological response to treatment with quality
of life -- to give people more information about balancing the
pros and cons of particular regimens.
ATN: One question is, since we have observed that many people
on regimens with protease inhibitors are still doing well
clinically even after viral load returns, will that be true
for other classes of drugs as well?
Dr. Becker: We have set up the means to do just that
analysis -- distinguishing between the virologic (viral load),
the immunologic (CD4 count), and clinical duration of
therapies.
Also, when we start or stop therapy, we have to provide a
reason for doing so. We are going to code a new reason,
"immune reconstitution," to help study stopping treatment or
prophylaxis for opportunistic infections. Instead of reports
from just a handful of patients, there could be analysis of
several hundred.
The database includes a validated questionnaire on compliance
(adherence), and two questionnaires on quality of life. We
will also be studying economic aspects: frequency of visits,
frequency of laboratory use, ordering of various tests, the
need for consultants, to try to understand better what the
costs of HIV care actually are.
ATN: How is CHORUS different from other observational
databases?
Dr. Becker: What distinguishes this database from some of the
others is that CHORUS is community-based [meaning that it is
based in physicians' offices] and therefore closer to real
life medical practice. Also, the data from the charts are
entered daily -- rather than charts being abstracted every six
months or so -- with the database linked to automated medical
records that the doctors use in their offices. Also, CHORUS
includes data on quality of life, economics, and
epidemiology.
ATN: What steps are taken to make sure that the data are
entered correctly?
Dr. Becker: Quality control is essential, and CHORUS has a
robust and overlapping quality control program to ensure that
all data is accurate. I cannot comment on other observational
studies, but the CHORUS quality control program is very
inclusive.
ATN: How can people submit research ideas to the CHORUS team?
Dr. Becker: Through a member of the advisory board. The board
prioritizes the questions, based on our view of their
importance, because we only have so many analysts and
biostatisticians. We welcome ideas for database queries,
including those from outside industry or academia.
Comment
In a better world, everybody could choose whether or not to
make data from their medical record available anonymously for
research. The cost to the healthcare system would be small,
since there are many reasons to computerize charts anyway for
better patient management -- and development costs could be
spread among millions of patients. Privacy concerns are
greatly reduced if the data is anonymous and even the
anonymous individual patient records are never released from
the research center. We would all benefit, since such
databases would make possible many research projects to
improve the quality of care. For example, physicians could
look for predictors of who is likely to do well with certain
treatments or strategies, and who should avoid them.
With 6,000 patients when fully enrolled, the CHORUS database
is large enough to be useful. It can also be a prototype for
larger systems which computerize medical charts, extract
anonymous information for research, and keep the research
database current through daily updates.
References
1. Bigley JW, Becker S, Raffanti S, and others. Patterns of
protease inhibitor use by healthcare coverage in the U.S.:
Results from the CHORUS observational database. 12th World
AIDS Conference, Geneva, June 28 - July 3, 1998 [abstract
#42310].
2. Bigley JW, Raffanti S, Becker S and others. Viral
detectability & CD4 levels in patients receiving protease
inhibitors in clinical practice: Results from the CHORUS
observational database. 12th World AIDS Conference, Geneva,
June 28 - July 3, 1998 [abstract #42403].
Retroviruses Conference, Jan. 31 - Feb. 4, 1999, Chicago
Abstract Deadline October 1
The 6th Conference on Retroviruses and Opportunistic
Infections, January 31 to February 4 at the Sheraton Chicago,
may be the largest and most important scientific conference
on AIDS in 1999. Although this meeting has been expanded to
3200 people, space is limited and it is likely, as in
previous years, that some who want to go will not be able to
get in. The conference has published upcoming deadlines; if
you want to attend, mark the appropriate dates on your
calendar now.
October 1 is the deadline for abstract submission, if you
want to present research at the conference. Applicants will
be told at the end of October if their presentation was
accepted. (For the late-breaker deadline, see below.)
Accepted authors can apply for preferential registration
and housing -- but only between November 2 and November 20.
Those who apply in this time will almost certainly be able to
register.
For other researchers and clinicians, registration opens
November 23 -- and closes when registration reaches 3,200, or
on December 31. This means that the November 23 date is the
most important for researchers and clinicians who want to
attend but either did not submit an abstract, or were
rejected. It is possible that the remaining slots could fill
within days.
The late breaker abstract deadline is January 5. Late
breaker submission is only for new information which was not
available at the October 1 regular deadline. In addition, it
is usually much more difficult to get a late-breaker
submission accepted.
For press, community, and scholarship applicants, deadlines
are not yet available; check occasionally on the Web site
below.
"A limited number of slots have been reserved for: (1) press, (2) community advocates, and (3) senior marketing personnel
who provide liaison functions within their companies (please
consult the Preliminary Program available in August for
further details on these categories)...
"A limited number of scholarships will be available for
fellows-in-training and community advocates. Please consult
the conference Web site in August for further information."
(Quotes are from conference brochure.)
The 6th Conference on Retroviruses and Opportunistic
Infections is "sponsored by The Foundation for Retrovirology
and Human Health, in scientific collaboration with the
National Institute of Allergy and Infectious Diseases and the
Centers for Disease Control and Prevention."
For more information check the Web site at
www.retroconference.org; or use the faxback service at 800-510-0319 or 703-716-7348 (you need to call from a fax machine, to receive the information by fax); or call the
conference secretariat, Westover Management Group, 703-684-4876, fax 703-684-4841, email info@retroconference.org.
International Healthcare Resource Allocation Conference
November 15-18 Cancun, Mexico
The Second International Conference on Healthcare Resource
Allocation for HIV/AIDS and Other Life-Threatening Illnesses
will take place November 15-18, in Cancun, Mexico.
This conference is chaired by The Most Rev. Desmond Tutu, and
prominent Mexican pediatrician Patricia Uribe Zuniga.
Sponsors include International Association of Physicians in
AIDS Care, Consejo Nacional para la Prevencion y Control del
SIDA, Harvard AIDS Institute, Joint United Nations Programme
on HIV/AIDS, Pan American Health Organization/World Health
Organization, and The World Bank. Funders include Abbott
Laboratories, Bristol-Myers Squibb, Glaxo Wellcome, Roche
Laboratories, Agouron Pharmaceuticals, Roche Diagnostics,
DuPont Merck, and Ortho Biotech.
Objectives are: "To discuss the human right to healthcare and
harm reduction strategies that can reduce unnecessary
suffering and death; to examine the economic and ethical
challenges faced by a global community of individuals,
governments, and nongovernment entities in their efforts to
reduce unnecessary suffering and death; and to propose
solutions to reduce unnecessary suffering and death."
More information is available at http://www.iapac.org; or contact the conference secretariat, International Association
of Physicians in AIDS Care, 225 W. Washington Street, Suite
2200, Chicago, IL 60606-3418, phone 312-419-7078.
Herbal Medicine Safety Workshop, National Institutes of Health
Research Triangle Park September 23 and 24
A two-day workshop, open to the public, will "evaluate what
research may be needed to assure the safety of medicinal
herbs." It will be held at the National Institute of
Environmental Health Sciences, and is sponsored by NIEHS, the
National Institutes of Health Office of Dietary Supplements,
the FDA's Office of Special Nutrition, and the Society for
the Advancement of Women's Health Research.
The sessions are from 8:30 a.m. to 5:00 p.m. each day and are
open to the public, if space is available; advance
registration is recommended. Members of the public will be
able to speak.
The keynote address, by Dr. Norman R. Farnsworth of the
University of Chicago, is "Science, Politics, Public Opinion
and Herbal Dietary Supplements."
To register, "submit name, address, institutional
affiliation, department and address, telephone, fax and email
address (when available) to Jaime Edge, NIEHS, Box 12233,
Research Triangle Park, NC 27709, or by fax to 919-541-0295,
or email to edge@niehs.nih.gov."
Medical Marijuana: Strong Support in Oakland
by John S. James
On August 12 the city of Oakland, California agreed to
designate members of the Oakland Cannabis Buyers Cooperative
as officers of the city. The action was taken under an
ordinance passed by unanimous vote of the Oakland City
Council on July 28.
The measure is intended to shield the club from continuing
Federal efforts to prevent medical marijuana distribution
under California's Proposition 215, the voter-approved
initiative to allow medical marijuana under California law.
Legal experts agree that Federal law takes precedence over
state law. But the same Federal legislation being used to
attack medical marijuana in California -- the Federal
Controlled Substances Act -- also provides that officers will
not be prosecuted for possessing or selling drugs as part of
their duties under local laws.
Legal experts differ on whether this argument will be upheld
by the courts; the next Federal hearing against the
Cooperative is August 31. But Oakland's action leaves no
doubt about the strength of local support for an organization
which, by all accounts, has been outstandingly well run and
is performing a vital public service.
San Francisco: Forum on Body Composition Changes
September 1
"International AIDS Conference 1998: Update on Wasting and
Body Composition Changes," a talk by Richard Cazen, M.D.,
Division of Gastroenterology, California Pacific Medical
Center -- Davies Campus (formerly Davies Medical Center), will
be given Tuesday September 1, 6:30 p.m. to 8:30 p.m., Josie's
Cabaret and Juice Joint, 3853 16th Street at Market. This
forum is sponsored by an educational grant from BTG
Pharmaceuticals. Persons attending are requested to reserve
space by Friday, August 28; call 800-284-2480 x511.
San Francisco: Intensive Seminar on Benefits
September 10-11
"Benefits & HIV: Navigating the Systems with (and for)
Clients," a two-day seminar for AIDS service providers, will
be held September 10 and 11, 9 a.m. to 4 p.m., at the UCSF
Laurel Heights Conference Center, San Francisco; the cost is
$75 each day. AIDS Benefits Counselors is sponsoring this
event, which is partly funded by the San Francisco Department
of Public Health.
Day one, Benefits Overview, will cover employment benefits,
SSDI/SSI/SDI, health and life insurance, Medicare and
MediCal. Day 2, Advanced Session, examines public benefits
and immigrant clients, social security and substance using
clients, building a disability claim, and working while
disabled. Both days include practice sessions.
For more information contact AIDS Benefits
Counselors/Positive Resource Center, 415-558-9845, fax 415-703-9942.
Help Wanted: Assistant Director, Forum for Collaborative HIV Research
The Forum for Collaborative HIV Research, housed at the
Center for Health Policy Research at George Washington
University in Washington, D.C., is looking for a person with
policy experience in "drug development, clinical research
policy, and/or medical information transfer. Experience in
HIV preferred. Applicants should have M.P.H., and/or J.D.
post-graduate degree, and excellent written, oral, and
administrative skills."
The official job title is "research scientist" -- which can be
confusing since the Forum does not run clinical trials. For
more information, interested applicants can contact David
Barr, 202-530-2307, or ihodxb@gwumc.edu.
Or mail a résumé and cover letter to:
Sherry Wilder-Ramirez
Institute for Health Policy Outcomes and Human Values
The George Washington University Medical Center
2021 K St. NW
Suite 800
Washington, DC 20006
Major Email Security Flaws Discovered
How to Protect Your Data
by John S. James
In the last month, serious email security flaws which could
affect millions of users have been discovered and publicized.
AIDS organizations particularly should pay attention because
of the need to maintain confidentiality of client
information. If not corrected, these flaws could allow an
email message to run a hidden program which could steal email
addresses or other confidential information, and/or destroy
all data on hard disks running on the computer. Experts are
worried because there are millions of computers with the
defective software, and many of them will not be fixed.
According to reports in the San Jose Mercury News, The New York Times, and the software publishers' Web sites listed below, the programs affected are:
Eudora Pro for windows, but only the new versions 4.0,
4.0.1, and some 4.1;
Microsoft Outlook 98 and Microsoft Outlook Express 4.x
(including Outlook Express 4.1 on the Macintosh and the
Solaris);
Netscape Communicator for windows, versions 4.01, 4.05, and
4.5 Preview Release 1.
There may also be similar problems in other software. The
recent discoveries have led to an intensive search.
If you are running email software that may be affected, make
sure that important data is backed up so that it will not be
lost if all data on the hard disks is destroyed. Also, the
companies involved are providing instructions on how to fix
their software; sometimes a temporary fix is as easy as
turning off an option, and sometimes a patch or an upgrade is
required (but only use a patch or upgrade from a trusted
source -- not one which arrives unsolicited by email). Check
the following Web sites:
Some computer users may be reluctant to believe these
warnings, because they sound like email security hoaxes which
have been distributed like chain letters on the Internet. But
this report was first published July 28 on page 1 of the San Jose Mercury News -- probably the best general newspaper in the
country for coverage of the computer industry. The New York Times picked it up two days later; and a team at the U.S.
Department of Energy called the problem extremely serious.
(The Eudora flaw is somewhat different from the others and
was discovered later; it affects only a minority of users.)
In some cases it might not even be necessary to open the
malicious email; just receiving it may be enough. A
sophisticated program which searched target computers for
email addresses and used them to replicate itself could
affect millions of users very rapidly, and existing anti-virus software would not protect against it. As of mid-August
we have not heard of any malicious use of these security
flaws; but that could change quickly now that the
vulnerability is widely known.
Older email programs are not likely to be affected, because
each email message is only a text which is displayed; no
matter what the content, it cannot run any program. New
software often allows email messages to do more than just
display a text -- creating a trade-off of convenience vs.
security.
Since AIDS Treatment News does not use any of the software
known to be affected, we could not easily test the fixes
provided at the above Web sites. Unfortunately the software
industry is notorious for poor usability and maintainability
of its products. If you cannot get the provided instructions
to work, other options are to wait until a software upgrade
is available, or switch at least temporarily to a different
email program.
ISSN # 1052-4207
Copyright 1998 by John S. James. Permission granted for noncommercial reproduction, provided that our address
and phone number are included if more than short quotations are used.
