Subject: Treatments, Delays, Urgent Message Date: Apr 8 1988 (514 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1988 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS, Issue #54, April 8, 1988 CONTENTS: [***** appears here at each new item] Conversation with Donald Abrams, M. D. Urgent: California AIDS Research Initiative Needs Help Treatment Issues On Dextran Sulfate, Imuthiol/Antabuse, and "German Enzymes" Why AIDS Treatment Delay? ***** Conversation with Donald Abrams, M. D. Donald Abrams, M. D., is Assistant Director of the AIDS Division at San Francisco General Hospital, and Assistant Clini- cal 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 alterna- tive 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 communi- cation 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 tri- als, including how the Imuthiol (DTC) results had been delayed. We edited and rearranged the questions and replies, with Dr. Abrams' permission. ***** 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 send- ing 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 previ- ous 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 phy- sicians 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 real study, 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 informa- tion 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 random- ized 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 aero- solized 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 aerosol- ized 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 grati- fying 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 poten- tially 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 poten- tial jeopardy of all the valuable data we could get, because patients in the community and their physicians feel that one par- ticular 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 informa- tion 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 investiga- tion, 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 Consor- tium 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 med- ical 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 physi- cians 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 impor- tant to decentralize and do out in the community. Now we are certainly aware that the AIDS Clinic at San Fran- cisco General and the physicians in the community are not the only people who are prescribing therapies, that patients them- selves 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 mon- itor that group of people? Can we collect any valuable informa- tion 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 con- senting patients, and get honest information from the person on what they are really taking, get all that data and see if a com- puter 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.) ***** Urgent: California AIDS Research Initiative Needs Help Persons living anywhere can help make available $180 million additional money for AIDS research. But you must act in the next four weeks. The AIDS Tax Credit Initiative will allow a California tax credit of up to $25. per year for contributions to a new state AIDS-research fund ($5000. each for corporations, trusts, and estates). Virtually certain to pass in November if it gets on the ballot, this initiative is expected to raise $180,000,000 for AIDS research over the next three years. The money will be espe- cially valuable because California law allows researchers to bypass the U. S. Food and Drug Administration and obtain state approval instead. (See "Why AIDS Treatment Delay?", below.) Although the initiative applies only to California taxpayers and finances research within this state, the knowledge and treat- ments developed will of course benefit people everywhere. Per- sons with other diseases will benefit too, since new understand- ing of the immune system promises treatment breakthroughs against many other conditions. The problem is that to get on the ballot, the AIDS Tax Credit Initiative needs over 400,000 valid signatures of registered voters before May 20 -- less than five weeks away -- and it has less than half of them so far. To get the rest in time, the campaign for the initiative must use paid petition cir- culators. It must raise $300,000 within the next four weeks to have a comfortable margin. This AIDS tax credit proposal passed both houses of the Cal- ifornia legislature unanimously -- but Governor George Deukmejian vetoed it, and Republican legislators refused to help override the Republican governor's veto. Legislation to place the measure on the ballot has been stalled, making the signature campaign necessary. Lack of $300,000 now will lose $180,000,000 for AIDS research. People anywhere can contribute money to this campaign, and share the benefit. California voters can also help by collecting signatures. If you can help in any way, please contact either office below immediately. Northern California: AIDS Initiative Committee 10 United Nations Plaza, Suite 400 San Francisco, CA 94102 (415) 621-6164 Southern California: AIDS Initiative Committee 8235 Santa Monica Blvd., Suite 306 West Hollywood, CA 90046 (213) 654-9094 ***** Treatment Issues On Dextran Sulfate, Imuthiol/Antabuse, and "German Enzymes" We continue to recommend Treatment Issues, a newsletter pub- lished by the Gay Men's Health Crisis and edited by Barry Gingell, M. D. The current issue (volume 2 number 2) includes a short update on dextran sulfate, and a long article on Imuthiol (DTC) and Antabuse. The article "German Enzyme Therapy" may be particularly interesting. This treatment, used in Germany for several diseases including AIDS, is believed to reduce excessive levels of circulating immune complexes, which may cause much of the dam- age in certain autoimmune conditions. Comparable preparations are available in the United States as health supplements. For more information, see the article in Treatment Issues. To subscribe to Treatment Issues, send your name and address to: GMHC, Department of Medical Information, 132 West 24th St., Box 274, New York, NY 10011. GMHC distributes the newsletter without charge, but contributions are appreciated. ***** Why AIDS Treatment Delay? by John S. James (ACT UP Los Angeles newsletter (213-668-2357) asked us for this article. It is appearing simultaneously in ACT UP Los Angeles, and in AIDS Treatment News.) Today we know that hundreds of thousands of people will die of AIDS in the United States alone over the next several years -- unless effective treatments become available. Yet government, business, the general public, and the AIDS community alike have failed to mobilize to assure that solid treatment leads get prompt attention and research, and become accessible to patients when they should be. Far more attention has gone to supporting the dying process than to making it unnecessary. Dozens of serious, promising treatment possibilities exist. For almost all of them, virtually nothing effective is being done. We won't be any closer next year than now to knowing if and when they work. A look at the promising treatments of two years ago -- such as ribavirin, isoprinosine, AL 721, DNCB, foscarnet, HPA-23, len- tinan, gamma globulin, plasmapheresis, AZT -- shows that in two years nothing decisive has happened, except for AZT. The rest are still in the same limbo they were then, still on the same promising-treatment list two years later, still neither in nor out. Some have suffered vituperation or neglect in the shifting political winds, but none has been rejected (or accepted either) on rational grounds based on evidence. The research just was not done. And it isn't being done today. The much-touted spectacular progress in "AIDS research" concerns high-tech, basic science which could not possibly produce practical treatments for years. Treatment research can be done right. For example, some European physicians noticed spectacular improvement in one AIDS patient treated with an antibiotic, fusidic acid. Small trials with ten to twenty patients each were quickly started in Denmark and England; apparently they showed that the drug is ineffective. Although the drug failed, the research which tested it succeeded excellently. It showed how practical trials can be done. Similar immediate, no-nonsense trials could test not only single drugs, but drug combinations, in fact any reasonable therapeutic plan or protocol. Recently the head of San Francisco's Department of Public Health offered to start trials immediately in City facilities; he called the current clinical trials "leaden-footed". Virtually never has quick but workable testing of any other AIDS treatment possibility (besides fusidic acid) been carried out. In the United States, the rules of the Food and Drug Administration (FDA) would not allow it. These rules often require, for example, "phase I" dosage and toxicity tests even for drugs in common use for years and well known to be safe. Even such well-known drugs can take a year or more of negotia- tions and paperwork just to crank up a phase I trial even after financing has become available -- as it almost never does unless the drug happens to fit into the commercial plans or scientific preconceptions of the day. "Phase II" -- efficacy testing -- takes years longer. AIDS experts have agreed for years that drug combinations will probably be necessary for treatment. But the FDA refuses to allow human testing of combinations of two or more unapproved drugs. Except for combinations with AZT -- which is approved, but unsuitable for many patients -- this rule alone adds several years delay before testing can even begin on any promising AIDS therapy. U. S. rules and procedures also delay drug trials abroad in Europe and elsewhere, even if privately financed by foreign com- panies with no U. S. support. How can the U. S. government affect AIDS research conducted elsewhere without U. S. funding? The answer is that the U. S. AIDS market so dwarfs all others that pharmaceutical companies fear doing anything anywhere in the world, until the FDA has given its blessing to their research plans. We have heard that a handful of people at the FDA -- one report said only two, both young physicians recently out of training -- constitute the bottleneck which all proposed AIDS drugs must go through. Almost every AIDS drug trial anywhere in the world waits in line for permission at this door. U. S. medical planners can confidently predict hundreds of thousands of deaths, because there is no way an effective drug could get through this system in time. The FDA's much touted "new rules" -- supposed to allow faster access to treatments for serious or life-threatening diseases -- apply only late in phase II, have no constituency within the FDA, and have had practically no effect on AIDS treatment availability in almost a year of their existence. The official U. S. drug-research system may find a cure in five to ten years, but meanwhile it has nothing to offer but death. An alternative-treatment movement is growing explosively and doing some of the most useful AIDS-treatment research -- the only AIDS research in the United States at least designed to get quick results. Now it faces increasing attacks through government, corporate, and even international sabotage -- actions taken solely to deny treatment access to persons with AIDS, or to harass research efforts by private physicians. For example, at least fifteen companies in Japan sell dextran sulfate -- avail- able there as a non-prescription drug for 20 years, and now one of the most promising experimental AIDS treatments -- but within the last two months every one of these companies started refusing to sell it to Americans. And when the old Salk killed-virus polio vaccine showed good results as an AIDS/ARC treatment, the only company in the world which manufactures it refused to sell it to physicians for that purpose. We don't yet know where the pressures came from, or why. But no one involved has even pre- tended that concern for patients' safety or welfare led to these decisions. For the first six years of the epidemic, practically every AIDS organization slept on treatment and research issues, refus- ing to inform itself or have anything to do with the matter. This utter lack of treatment advocacy allowed horrors like those outlined above to come into being. Now the community is awaken- ing. The faster it awakens, the more lives will be saved. ***** [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display