Conversation with Donald Abrams, M.D.

Donald Abrams, M.D., is Assistant Director of the AIDS Division at San Francisco General Hospital, and Assistant
Clinical Professor at the Cancer Research Institute, University of California San Francisco. He also chairs the County
Community Consortium, a group of about 80 San Francisco physicians treating persons with AIDS. At times he has been
controversial in the AIDS community, where some see him as a leading opponent of alternative treatments.

Originally we asked for this interview in order to give our readers the widest range of opinions, by presenting a
viewpoint which we thought would be opposite of our own. But we found that the differences were not as great as we had
expected. Much of the controversy has stemmed from lack of information and communication rather than from fundamental disagreements.

Recently representatives of both parties--AIDS researchers at San Francisco General, and persons with AIDS who have chosen to take an active part in their health care--have made major efforts to improve communication so that each can understand and address the others' concerns. This interview is part of that process.

We asked Dr. Abrams to discuss whatever he wanted. The conversation included several areas: the activities and plans of the County Community Consortium, and background on clinical trials, including how the Imuthiol (DTC) results had been delayed. We edited and rearranged the questions and replies, with Dr. Abrams' permission.

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JJ: What can you tell us about the Consortium, and its future plans?
DA: The County Community Consortium was set up in March of 1985 at the request of Mayor Feinstein, who felt that there should be some mechanism to maintain open communications between physicians here at the "County" hospital, San Francisco General, and physicians in the "community" who were caring for people with AIDS. Originally Paul Volberding called a meeting of the dozen or so physicians who were caring for AIDS patients predominantly at that time (1985), and started a series of now monthly meetings. I became the chairman of the Consortium shortly after it was formed and have been involved in shaping its direction; and I'm certainly gratified by the progress and the enthusiasm around the Consortium.
Initial goals of the County Community Consortium were to inform physicians in the community as to what protocols were ongoing here at SFGH so that they could refer patients; to update physicians on information that we may have heard that they didn't hear about yet--pre-publication from research going on here as well as elsewhere; and also to maintain lines of communication so that patients' care could be transferred most effectively from here to private physicians when necessary.
After a while it became clear as the group became more cohesive that the physicians in the community didn't just want to sit and listen to the clinical investigations that we're doing here. They wanted to participate as well. And they
wanted to participate with their patients in their practices without sending them over here. Se we said, OK, let's think
about something we can do. And in the beginning of 1986 we spent six months together working on a protocol to try to
evaluate the best way to prevent pneumocystis from coming back in people who have a previous episode.
Every physician in the community had their own pet way to prophylax. I used to give no treatment in patients who had had pneumocystis once. I would say, "Let's wait till you get it again, then we can treat it again," because I didn't have any evidence that prophylaxis really prolonged survival. Other physicians were giving septra, others were giving pentamidine on a monthly basis, some people were using dapsone at various dosages on a daily basis, or twice a week, and some were giving fansidar once a month. So we decided to organize and do a realstudy, because we were not collecting data and this information which was potentially very important, not only for us but around the country where physicians didn't have all the experience we had here, was going up in smoke.
So we as a group of physicians worked out a protocol and got it approved by the various Committees on Human Research at the hospitals around San Francisco. And we initiated a four-arm pneumocystis prophylaxis trial in July of 1986.
But then in September of 1986 AZT became available for the same group of patients, people who have had pneumocystis. The stipulation then was that they couldn't take another medicine, so although we put 25 patients on our study very quickly, the study came to a halt because all those people who were eligible for pneumocystis prophylaxis wanted AZT at that time.
So next we decided to set up a mechanism to collect information on patients who were going to be given AZT. But
that never caught on, the physicians didn't really want to participate because that study lacked the drama and glory of
doing a randomized trial; just collecting information is not as exciting.
But during that time the community began, on the basis of information trickling in from New York, to become more
interested in aerosolized pentamidine. A number of respiratory care centers in the community, as you know, began treating patients with aerosolized pentamidine--again, without any attempt to collect data systematically, without any attempt to standardize the dose or the delivery of the drug. So again, the Consortium, with the collaboration of Bruce Montgomery here in San Francisco General, and Gifford Leoung, decided to run a three-arm study of aerosolized pentamidine.
We decided to include not only people who have had an episode of pneumocystis, but also patients at risk to develop pneumocystis, those with KS and those with ARC. So in July of 1987 we opened this study for enrollment. This was a most gratifying experience--we actually had 440 patients onto that trial within two months through the participation of physicians at 20 different centers not only in San Francisco but in the East Bay, Sonoma, Sacramento, a truly regional study.
Extending clinical trials into the community physicians' offices is a fabulous thing and I think it's obvious through
the enthusiasm of the Consortium--every month our meetings have about 70 to 80 physicians. Our mailing list has grown from 12 to 125 physicians who are caring for people with AIDS and coming to the Consortium meetings because they're interested in this community-based clinical research.
It can be quite draining for physicians dealing with AIDS all day in their offices--they're all alone with their office
staff and seeing patients all day, and sometimes they ask what am I really doing to help? By putting patients on clinical
trials, the physician feels like he's doing something not only potentially for that patient but for the people that are coming
down the road. It really lifts some of the burden off the health-care provider, and provides an increased sense of satisfaction.
JJ: I hear everywhere that this is the direction things are moving today, toward clinical trials through physicians'
private practices.
DA: There are problems, however. Physicians in their private practices, or at medical centers, care about their
patients predominantly, and want to provide what they believe is optimal care. When you design a study by committee, it's harder to get everybody to believe that the study is valid. So, for example, on the first pneumocystis prophylaxis trial
physicians used to call up and randomize a patient, and they would hear that their patient was randomized to either fansidar or dapsone or pentamidine or no treatment. But after calling up to put the patient on the trial, if they were told that
their patient was on the "no treatment" arm, the physician would say that they didn't want this patient on the study then.
And so they withdrew.
That's not how one does clinical research. So there is a little bit of a tension in the community health-care provider
between doing clinical investigation and providing first-rate care.
And now in the aerosol pentamidine study we're seeing potential jeopardy of all the valuable data we could get,
because patients in the community and their physicians feel that one particular dose is inferior to the other. That's the
point of doing the study, to determine that. That's the whole purpose, and we have not even begun to really look at the data because it hasn't matured yet to a point were we feel that any significant information can be gained. But because of the activism of the patient community as well as the conflict that some of the physicians have between providing optimal care and doing clinical investigation, our current study is threatened. And that's one of the problems I see in doing clinical studies in the community where some of the community physicians might not really have all their heart into doing the investigation.
(Dr. Abrams explained that a separate team is monitoring the results as they occur, so that if any dose turns out to be
clearly inferior, that arm of the study will be stopped and the patients will be put onto the other doses. There is no placebo in this study; everybody gets some dose of the drug. Dr. Abrams also explained that during the treatment with aerosol pentamidine persons should take a deep breath every 30 seconds to every minute, to help the medicine get to all parts of the lungs.)
JJ: It seems that an extra amount of creativity and prior thought is necessary to bring these two values into harmony.
DA: You're absolutely right and that's what we're trying to do now. Do you have to work out some sort of a contract
with physicians who say, "Yes, I want to participate in this study." Should they sign something saying that if they do
participate in the study they will carry out this agreement?
JJ: But also they should have some input into the study.
DA: Oh yes, they are designing it. Now we have on the burner about five different studies. We have one monthly
meeting for physicians in the community; that's our business meeting where we discuss the protocols and the studies that we want to do and the studies that we are doing; also we have guest speakers. We've had Project Inform, we're having Dr. Ellen Cooper (the head of the AIDS division of the FDA) to our next meeting.
JJ: What kinds of studies are you planning for the Consortium in the future?
DA: I think that some studies, such as testing a brand new drug, an antiviral or immune modulator, need to be done in a medical center that has the necessary research support to collect the information in a standardized, carefully
controlled, quality assured manner, as opposed to having 15 or 20 different physicians trying to do it in their offices.
Private physicians don't have time to do a lot of paperwork and extra studies; I think some things really need to be done at a single center.
Our goal in Consortium trials is to evaluate some of the treatments to prevent infections; to lessen the toxicity of
AZT; to perhaps improve nutrition--studies that are not using the high-tech, brand-new antiviral or immune modulator. We'll need to continue to do those here at SFGH, on a pilot level.
The CRI (Community Research Initiative) in New York is being a little more aggressive, in trying to obtain drugs for
early private-practice trials. That might be a little more than we can do well at this time and obtain quality data. I
think there's a need for centralization of some studies at the AIDS center, if you will, and then other studies certainly are
much more important to decentralize and do out in the community.
Now we are certainly aware that the AIDS Clinic at San Francisco General and the physicians in the community are not the only people who are prescribing therapies, that patients themselves have taken it into their own hands to self-medicate. And this is a constant question that we've been discussing within the Consortium for a long time. What should, what can we do, to monitor that group of people? Can we collect any valuable information if 14 different people are taking 12 different dosages of six different preparations of AL 721, can we obtain any useful information? Can we validate any of the testimonial claims by collecting their T-cells or their clinical status? Can we have a registry that physicians in their offices can fill out for consenting patients, and get honest information from the person on what they are really taking, get all that data and see if a computer can sort any of it out?
JJ: What I hear from talking to people around the CRI in New York is that for such a registry to work, they will need
employees who visit the physicians' offices and collect the information.
DA: Right, and that was our model. That's the grant I wrote, to have itinerant nurse practitioners who would be the
research nurses who would help, because the physicians don't have time to do that, so that's what we applied for government funding for, but we didn't get it.
Just last weekend I wrote the protocol to set up a registry so that we can collect this data because so much
information out there is just going up in smoke. We're still talking about it in the Consortium because this registry idea
hasn't met with overwhelming approval. But that's the beauty of the Consortium, that physicians who are interested in
participating in a study can choose to do so, can offer it to their patients.

(Part II of this interview will appear later.)

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