AIDS Trestment News
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:
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?
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.
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.
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].
"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 email@example.com.
International Healthcare Resource Allocation Conference
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
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 firstname.lastname@example.org."
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
"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.
"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 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 email@example.com.
Or mail a résumé and cover letter to:
Major Email Security Flaws Discovered
How to Protect Your Databy 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:
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.
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.