Subject: Treatments Lists, Ideas; Chinese Medicine 10/23 Date: Oct 7 1988 (487 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 #66, October 7, 1988. CONTENTS: [***** appears here at each new item] Treatment Ideas for Community-Based Trials Grassroots Treatment List; What the Community Wants to Test Potential Treatment List (alphabetical) Decisions for Community-Based Trials Chinese Medicine Symposium October 23 In Long Beach, CA Avoiding the 20 Percent Copayment On Insured Prescription Drugs ***** Treatment Research Ideas for Community-Based Trials by John S. James The U. S. system of testing new treatments against AIDS or other diseases has become so cumbersome that many promising pos- sibilities never even start the testing process. A new system called community-based research, pioneered by the Community Research Initiative in New York and the County Community Consor- tium in San Francisco, organizes scientifically sound drug trials through the practices of private physicians, whose patients can volunteer for the studies. By integrating scientific trials with normal medical prac- tice, community-based trials allow credible testing of treatment options with far less administrative delay than usually involved, and at far less cost; often the main expense is laboratory tests which the patients should be receiving anyway. These trials differ from everyday medical practice in being designed in advance by a research professional, and being approved by scien- tific and by ethical review boards. Criteria for patient selec- tion and for evaluating the success of the therapy are as rigorous as in any other trials. And patient compliance can be better in community-based than in other trials, because of the closer physician-patient relationship, and because community- based trials often test treatments which are already available, meaning that no one is forced into the studies to get treatment, so there is no incentive to cheat; volunteers come forward only for altruistic reasons. The greatly reduced cost of community- based trials encourages research by pharmaceutical companies, and also allows testing of medically attractive treatment options which lack commercial or scientific glamor, and thus would not be studied otherwise. Community-based trials are most suitable for testing poten- tial therapies which already have known safety records in human use -- including most of the treatments which have developed a grassroots following among patients or scientists without commer- cial prompting. Drugs which are unusually dangerous, difficult to use, or untried in humans usually need to be studied in major medical centers, not through private physicians' offices in com- munity trials. Grassroots Treatment List; What the Community Wants to Test Most treatments already being studied in community-based trials are products being developed by pharmaceutical companies. The immediate reason for this focus is of course financial; it has been hard to fund trials of substances which are medically promising -- or used by thousands of people -- but which are unpatentable or otherwise lack commercial potential. Certainly the commercial treatments must be studied; "second generation" HIV drugs can be the most promising possibilities. But we also need trials of the "grassroots" treatments which the public is using, for at least two reasons: (1) to give patients objective assessments of risks and benefits of different options, and (2) because treatments attractive enough to have developed a follow- ing among patients, physicians, or scientists, with little com- mercial or organized promotion, may well have objective benefits which academic research and medicine should consider. While community-based trials clearly should study both the industrial and grassroots treatment possibilities, in our list below we focused on those with a popular interest or following (some also have commercial sponsors). We chose this focus for the practical reason that AIDS Treatment News has better informa- tion about treatments with grassroots support, which usually come to our attention, than about treatments being developed by phar- maceutical companies, which are often kept secret. We selected the treatments listed below because there is public interest in them, they have some medical or scientific rationale, and they appear suitable for community-based research. This list is not nearly complete, and we welcome suggestions for additions. Readers should note that the rationales we present below are necessarily sketchy; we could not research every treatment thoroughly by press time. We published this list to emphasize the wide range of treatment possibilities suitable for testing in community-based research. Potential Treatment List (Alphabetical) **Acidophilus. Acidophilus preparations, available in health-food stores, contain live beneficial bacteria, intended to help crowd out harmful micro-organisms in the gastrointestinal tract. (For more background information, see AIDS Treatment News # 32, May 22, 1987.) A community-based study of acidophilus could begin by asking clinicians experienced with it to specify (a) how to select the patients believed most likely to benefit, and (b) what benefits should occur, and when. While community-based trials would seldom use a placebo, a randomized double-blind placebo trial might be appropriate in this case because: * The placebo would be strictly voluntary, as anyone who wanted could obtain acidophilus outside the study. The only rea- son for volunteering would be to contribute to the advancement of knowledge, not to obtain treatment. * Benefits of acidophilus (if any) are likely to be noticed very rapidly. The placebo phase of the trial would probably need to last for only a few days. * Evaluating the success of this treatment might necessarily be subjective, through patients' reports that they were feeling better. Lack of laboratory measurements of success increases the danger of a false positive outcome of the trial due to "placebo effect", making a double-blind design more necessary. Incidentally, it should be easy to make a placebo which looks and tastes like acidophilus, simply by heat treating the capsules or otherwise making sure the organisms were dead. ** AL 721 or substitutes. The Community Research Initiative in New York is already conducting a community-based trial of egg-lecithin lipids. The study is fully enrolled, and prelim- inary results should be available in a few weeks. ** Aloe vera. Aloe vera preparations are used for medicinal purposes in many cultures. For AIDS/HIV, the most systematic studies are being done by advocates of carrisyn, a chemical found in aloe vera and now being moved through the FDA approval process by Carrington Laboratories in Dallas, Texas. Carrisyn may take months before showing improvement (usually measured in T-cell numbers). It would be difficult to ask patients to stay off other treatments during this time. Therefore the study could be designed not as a test of carrisyn (or other aloe preparation) by itself, but rather of whatever combination therapy patients are most likely to want to try anyway. Such patient-led design should make it easier to recruit patients, reduce any incentive to cheat, and also take advantage of any practical knowledge in the community of patients and front-line physicians on how best to use carrisyn (or other aloe prepara- tions). ** Amino acids. A number of people are using lysine, readily available in health-food stores, as an antiviral for herpes and/or HIV. Some are convinced that at least two other amino acids should be avoided -- not supplemented or used in large amounts -- as they are believed to encourage the growth of viruses. We have heard of this use of lysine from at least three well-informed sources; however one nutritionist who is familiar with the literature on amino acids had never heard of using them in antiviral treatment. The scientific review committee would need to research whether there is credible justification for this therapy, and if so, what patients should be selected and what measurable end- points used to look for beneficial results. ** Antabuse. Thousands of people are using this prescrip- tion drug as a substitute for imuthiol (DTC), an immune modulator developed in France but not easily available in the United States. Much of the antabuse taken becomes imuthiol in the body. The Community Research Initiative in New York is now con- ducting a monitoring study of antabuse. ** Anti-inflammatory therapy. Various published and unpub- lished information suggests that certain anti-inflammatory drugs such as indocin or even aspirin may be helpful to some patients. Others might not be helped or might be harmed by the drugs. By reviewing the literature and interviewing clinicians, some of whom have been using this treatment for years, the scien- tific committee could determine which patients are likely to benefit, what measurable results could be expected, how long it should take to see them, and what is known about risks of long- term use of the drugs by persons with AIDS or ARC (less relevant to the safety of this short-term study than to the usefulness of a positive result). If benefits could be expected very quickly (perhaps within days) it might be feasible to use a placebo and double-blind design for only the first week or two of the test, after which everyone would go on the drug. Only volunteers would risk the placebo; the rest would start open label immediately. This pro- tocol not only eliminates the unethical extortion of withholding treatment to force participation in a placebo study, it also removes any incentive to cheat. Only those who volunteer to help research may get the placebo -- and only for a short time. ** AZT for cryptosporidiosis. At the June Stockholm confer- ence, six researchers at a Paris hospital presented results from 16 patients (poster #3672). Marked improvement was found in 14 of the 16 in the first month; diarrhea disappeared in 10 of the 15 patients who were treated for at least three month. Half and full doses of AZT seemed to work equally well. Unfortunately this poster session received less attention than it deserved, because it was not indexed under cryptosporidium in the abstract book. Other scattered reports have suggested such an effect -- not as surprising as it may seem, since AZT is an antibiotic as well as an antiviral, effective against a number of micro-organisms including at least one intestinal parasite, giardia. An anti- cryptosporidiosis effect of AZT may explain why this disease has been less common than had been feared. It might be hard to find patients for the trial, as most of those ill enough to have cryptosporidiosis would already be using AZT, unless they could not tolerate it. ** BHT. This food preservative is very effective against most lipid-coated viruses in the test tube, and has prevented viral infections in animals. One published human trial found it effective for treating herpes. One laboratory test found partic- ular activity against CMV. (See AIDS Treatment News #10, August 15, 1986). For several years hundreds of people have been using large doses of BHT, about one gram a day, to help control herpes. Few have tried it for AIDS-related conditions. Laboratory results with HIV are mixed, with NIH finding no efficacy. In recent months public interest has greatly increased, perhaps due to widespread publicity about encouraging laboratory results mentioned by RC Aloia and others in the February 1988 Proceedings of the National Academy of Sciences USA (pages 900- 904). This public interest in a readily available chemical makes it even more important to have a trial with medical monitoring to learn more about safety as well as efficacy of this potential treatment. Other Possibilities We had not written annotations for the following by press time. These and others may appear in future issues. ** Bile salts. ** Chinese medicine. ** Chlorophyll. ** Coenzyme Q. ** Dapsone. ** DDI. ** Deficiency testing and supplementation. ** Dextran sulfate. ** DHEA. ** DNCB. ** Fatty acids. ** Ganoderma. ** Garlic. ** Germanium. ** Ginseng. ** Homeopathy. ** Hydrogen peroxide (or chlorine dioxide). ** Imuthiol (DTC) from France. ** Iscador. ** Japanese herbs (over 100 paid for by national health system). ** Lentinan. ** Macrobiotic diet (investigate status of earlier study). ** Milk antibodies (or colostrum, or veterinary antibodies from whey). ** Naltrexone. ** Nutrition improvement. ** Ozone. ** Peptide T. ** Plasmapheresis (and related, eg Prosorba column, packed washed red cells). ** Polio killed-virus vaccine. ** Propolis. ** Selenium. ** Typhoid immunization. ** Vitamins: A, C, E, others. ** Zinc. ***** Decisions for Community-Based Trials Recent conversations with leaders of the Community Research Initiative (CRI) in New York suggested several issues that a community-research organization should consider. We prepared this report, drawn from our phone notes, to help others develop similar research elsewhere. * Is the goal to do monitoring studies, prospective trials, or both? Monitoring studies -- for example, collecting records from physicians offices of patients who have used a particular treat- ment -- are much easier and less expensive. In New York, volunteers have done much of the legwork. Such studies can show trends; but the research community considers them only suggestive that further research should be done, if a treatment looks good. Prospective trials, which are more definitive, ask patients to follow protocols designed in advance by research profession- als, instead of simply recording what the patients are doing any- way. The New York CRI has both kinds of trials under way. * There is a major shortage of principal investigators to design and manage AIDS treatment trials. NIH and pharmaceutical companies have a big problem finding qualified people, the CRI has had major problems, and for a new organization it could be even more difficult. The principal investigator (PI) does not need to be an M. D. ; many are Ph.D., although the combination of both degrees is strongest for getting published. The PI does need to know about AIDS, know how to design clinical trials, and have the time; it often takes about 20 hours a week to manage a study: write the protocol, get it approved by committees, negotiate among all the parties, recruit subjects, manage the data collection, analysis, writing and publication, etc. Often the PI trusts someone with less training, such as a research nurse, to draft the protocol and change it as required, make phone calls when possible, etc. The PI must sign off on the result, of course. Perhaps the ten to 20 hours a week could be reduced to two or three this way, making it much easier for top people to serve as the PI. * Pharmaceutical companies are very unhappy with the NIH clinical research system, because it is too slow and for other reasons, so they are looking for alternative ways to test their drugs. The New York CRI has had a number of requests from both large and small companies to run trials for them. If a community-based research organization is credible, and is an attractive site for testing pharmaceutical-industry drugs, it will probably be able to do this work. On the down side, such organizations might be seen as a bread-and-butter threat by other researchers, making it harder to get the effort off the ground. * Promoters with money have also approached the New York CRI, trying to get favorable publicity for dubious products. Any research organization must be careful. * New York had much difficulty getting funding to study non-commercial treatment options (like most of those listed below). Therefore it had to focus on what pharmaceutical com- panies wanted to test. CRI had to live for a long time on its $5,000 seed money from the PWA Coalition. But now it should be possible to raise money much more quickly, because the community-research concept has become well known and established. * If such funding is available, an organization could build a reputation for doing quality research on grassroots treatments. Clearly this work should be done -- we need to study what people are in fact using -- but because of lack of funding, this research is now largely neglected. * A typical community-based prospective study with 10-20 people lasting several months might cost $30,000 to $70,000. Much of the expense is for laboratory testing. Also, someone needs to be hired for "keeping the books" on the data. There is also the cost of physician examinations. And of course there is overhead -- rent, staff, telephone, etc. for the organization. * What about minimizing expenses by building the study around laboratory tests which patients will be doing anyway? CRI considered this approach. Two potential difficulties are (1) community objection that only those insured or who can pay for their care could participate, and (2) concern that insurance com- panies should not be billed for research (against which others say that if the blood tests are going to be done anyway for treatment, there is no ethical imperative to waste the data). These issues were discussed in the CRI, but not resolved. It may be possible to conduct scientifically sound, credible research ultra-cheap -- by carefully designing studies which organize elements of patient care which already exist and are paid for. But if funding is available, it should be used to assure faster results by following more conventional, better tested procedures. * The CRI obtained space for a clinic -- to facilitate administering aerosol pentamidine, drawing blood to be sent to the same lab, and data collection. Physical examinations, how- ever, are still done at the offices of individual physicians, who then send a form to the CRI. * Community-research organizations need to involve many pro- fessional people besides physicians in support of their effort -- for example, fundraisers, statisticians, and attorneys. The clergy can be helpful in making connections. Many people in the business community would be ready to help but have not yet been asked. * In New York, the CRI has developed many procedures and documents that others can use. For example, its IRB (institu- tional review board) recently approved a set of documents provid- ing a flow sheet of what the IRB must do for a trial. New efforts for community-based research can benefit from the experi- ence of the CRI, and of other organizations that want to help. ***** Chinese Medicine Symposium October 23 in Long Beach, CA A one-day symposium, "AIDS, Immunity, and Chinese Medicine", will be presented by the Oriental Healing Arts Institute, on Sun- day, October 23 from 9 AM to 5 PM, at the Marriott Hotel, near the Long Beach, CA airport. Speakers include well-known herbalist Subhuti Dharmananda, orthopedist and traditional Chinese doctor Qing-Cai Zhang, M. D., Dr. Misha Cohen, clinical director of the Quan Yin Acupuncture and Herbal Center of San Francisco, Keith Barton, M. D., a Berke- ley, CA physician who is also a certified acupuncturist, and H. W. Yeung, Ph.D., Director of the Department of Microbiology and Biochemistry, Chinese University of Hong Kong, and co-author of "Inhibition of Growth of Human Immunodeficiency Virus By Crude Extracts of Chinese Medicinal Herbs", published in Antiviral Research, and reviewed in AIDS Treatment News issue # 61, July 29, 1988. Continuing education credit is available. For fees or other information, call the Oriental Healing Arts Institute, (213) 425-5210. ***** Avoiding the 20 Percent Copayment On Insured Prescription Drugs Since running our earlier article on the prices of prescrip- tion drugs, the following information was brought to our atten- tion by Ron English, whom we know through his work as a major fundraiser for the Community Research Initiative in New York. Mr. English is also working for Preferred Rx, of Independence, OH, the company discussed below. Most patients who have insurance coverage for the cost of prescription drugs still have to pay 20 percent of the price; the insurance pays 80 percent (after any deductible has been met). Preferred Rx offers a plan which allows patients to avoid this 20 percent. It fills the prescription through its arrangement with a mail-order supplier, and accepts an insurance payment of 80 percent or more as payment in full. The plan works by taking advantage of the difference between common retail prices of prescription drugs, and the lower prices available through mail-order pharmacies. Insurance companies can- not force patients to use the cheapest way to fill their prescriptions, as long as the price is reasonable. Preferred Rx bills the prescription at a reasonable price, receives 80 percent of that, and profits by filling the prescription for less. There is an annual $25.00 dues for using this system -- waived in certain cases such as for Medicare patients. If you do not have insurance coverage of prescription drugs, Preferred Rx is comparable to other mail-order pharmacies. For more information, contact Preferred Rx at 5755 Granger Road, Suite 305, Independence, OH 44131, 216/661-1977 or 800/365-2646. ***** [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display