Bootstrap AIDS Research Giving Patients Active Role
It is a sad and oft-told tale: AIDS patients, frustrated by a dearth of federally approved drugs, popping unproven pills and potions in a desperate fight to stay alive.
But a more hopeful story about people with AIDS taking matters into their own hands is starting to emerge from the offices and clinic of an organization called the Community Research Initiative in an old loft building in Chelsea.
There, up a rickety flight of stairs, people with AIDS and their community doctors have launched a remarkable experiment in grass-roots research.
Impatient with the traditional system of academic research’s efforts to deliver a cure, the people on the front lines of the epidemic have taken it upon themselves to conduct clinical trials of experimental drugs to treat or prevent acquired immune deficiency syndrome and its complications.
The Community Research Initiative and the County Community Consortium in San Francisco are the prototypes for so-called community-based AIDS research programs, which are designed to take advantage of the dedication of local AIDS doctors and their patients in the search for treatments. Last month, the federal government unveiled a $6-million program to promote community-based AIDS research throughout the country.
Both organizations are backed by professional staffs and advisers to ensure the scientific validity of their work. They are also breaking new ethical ground as they strive to reconcile the sometimes conflicting needs of experimental subjects with those of scientific investigators.
The novel approach, if successful, could lead to faster and more humane testing of experimental therapies for cancer, heart disease and any number of other illnesses.
“The AIDS activists have done us a great service by pointing up flaws in the (traditional research) system,” said Dr. Burton Lee, a cancer researcher at Memorial Sloan-Kettering Cancer Center and a member of President Reagan’s Commission on the Human Immunodeficiency Virus Epidemic.
“Community-based trials give us an opening to speed things up across-the-board: in cancer, in heart disease, in diabetes,” Lee said. “They are not as gummed up by red tape and paper work.”
“If we can’t make AIDS go away, we can at least make the ride a little smoother,” Community Research Initiative co-founder Michael Callen said.
Academic researchers such as Dr. Robert T. Schooley of Massachusetts General Hospital have questioned the value of research data gathered by community physicians outside the rigidly controlled environment of major medical centers.
Backing Won
But the unprecedented effort has also won the backing of many prominent scientists and drug companies. The Community Research Initiative’s scientific advisory board boasts representatives from the major academic medical centers in New York. The organization has conducted clinical trials for such companies as Johnson & Johnson’s Ortho Pharmaceutical unit.
In part, such blue-chip support reflects growing ferment in mainstream medicine over the sluggish federal drug-approval process, as well as the urgent need to increase the number of clinical drug trials for people with AIDS and HIV infection. Up to 1.5 million Americans are infected with the virus and will likely develop AIDS unless effective treatments are made available.
“The current (federal) system is designed to be cautious. It’s designed to stop bad drugs--not to hurry up good drugs,” said Carol Levine, a medical ethicist and a member of the Community Research Initiative’s institutional review board, which under federal health regulations is charged with protecting the rights of study subjects.
Scientific Rationale
There is also a scientific rationale for community-based trials. Researchers now believe that they will never find a single “magic bullet” to cure AIDS and its many complications. Rather, they hope to find a combination of agents to keep the virus inactive and revitalize the immune system. As a result, they must test scores of drugs, in varying doses and combinations, in patients at varying stages of illness.
“It is clear that the traditional way of doing things will not be able to handle the the tens of thousands of volunteer subjects we will need to test dozens of new drugs now emerging from the laboratories,” said Dr. Mathilde Krim, founding chair of the American Foundation for AIDS Research and a member of the Community Research Initiative’s governing board.
In addition to the federal initiative, the American Foundation for AIDS Research last month said it would put up $1 million to fund pilot community-research programs throughout the country. Thirty-nine groups are vying for the grants.
Model for Applicants
The New York group, an outgrowth of the local People With AIDS Coalition, is a model for many of the applicants. The San Francisco group, which has close ties to UC San Francisco, is also considered a model but is in a much more preliminary stage of research. It began as a forum for doctors who treat AIDS patients to exchange information and keep tabs on the latest developments on treatments. It is only now beginning to gear up to conduct trials.
Krim believes that both types of groups can overcome the most common objections to community-based drug trials--that local doctors lack the time and expertise to conduct research. “They can be taught,” Krim said. “They can be assisted in the collection and processing of data. And they can be compensated for their time.”
Another criticism, voiced by Massachusetts General’s Schooley, is that patients participating in community trials will try several therapies at once, confounding investigators testing the effectiveness of a particular drug. But advocates of community-based research say such cheating already occurs in academic settings--and that subjects in community-based trials are more likely to comply with instructions from their own doctors.
‘Enforce Quality Control’
“The fact is, there are very bad studies done in academic centers, and very good studies done by physicians in the field,” Lee said. “All they need is for someone who runs the show to enforce quality control.”
Even the federal research establishment has acknowledged the promise of the approach, as evidenced by the $6 million it is devoting to community-based trials. “It makes absolute sense to draw on the experience and enthusiasm of community physicians and their patients,” said Dr. Anthony S. Fauci, director of AIDS Research at the National Institutes of Health and director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
Fauci hopes that the new federal program can address the growing clamor for access to experimental drugs by AIDS activists. A recent congressional report titled “AIDS Drugs: Where Are They?” found that 0.3% of Americans infected with HIV have participated in National Institutes of Health-directed clinical trials.
‘Time Has Come’
Fauci said he is especially anxious for the community-based trials to enroll large numbers of HIV-infected women, minority group members and intravenous drug abusers--groups that have been under-represented in academic clinical research.
“Clearly, this a movement whose time has come,” said Dr. Thomas F. Mitchell, project director of the County Community Consortium in San Francisco.
Even the most ardent backers of community-based research acknowledge that the approach has its limits. Some potential AIDS therapies require sophisticated technological equipment for monitoring patients and thus do not lend themselves to being tested in doctors’ offices.
Another possible pitfall is that some physicians who care for AIDS patients are already overburdened and may not have time to take on the additional role of researcher.
Paper Work Problem
“Who will help me do the paper work, which undoubtedly will be horrible?” Los Angeles AIDS physician Dr. Neil Schram asked. San Francisco’s County Community Consortium has tried to solve the paper work problem by devising data-collection forms that double as patients’ medical records.
Above all, experts stress the importance of preserving the scientific integrity of the trials. Said Fauci: “The purpose of this is to collect scientific information so that decisions can be made about the safety and efficacy of experimental drugs. . . . A study that does not give you an answer is not a good study, or even worth doing.”
Given such constraints, the two-year-old Community Research Initiative’s accomplishments have been impressive. The New York group was hailed as a “model” and a “prototype” by a congressional committee and was cited favorably in the report of the President’s AIDS Commission.
Five Trials
Already, the group has conducted five trials, three of them sponsored by drug companies and thus subject to pre-approval by the Food and Drug Administration. Its biggest trial, involving 225 patients, has amassed data that could speed the licensing of LyphoMed’s Pentamidine in aerosol form to prevent the virulent pneumonia that kills most AIDS patients.
Patients in that trial are drawn from the practices of the Community Research Initiative’s 60 participating physicians and come to the organization’s clinic in Chelsea every two weeks. There, they are hooked up to a machine by one of four staff nurses and breathe a fine mist of the drug for about 30 minutes.
“Everyone at LyphoMed is extremely pleased with the relationship with CRI, and with the quality of their data,” said Cynthia Yost, a product manager for the company, which funded the trial. Others say they have been impressed by the group’s speedy recruitment of research subjects.
‘Underground’ Treatments
Besides sponsored research for drug companies, the Community Research Initiative can launch quick studies to monitor the effects of unproven “underground” treatments used by many AIDS patients.
“If people are taking it, that’s almost reason enough to study it,” Associate Administrator Tom Hannan said. “If something works, great. If it is ineffective or harmful, we want to get the word out.”
The concept of community-based AIDS research has come a long way since the idea was first floated by Dr. Joseph Sonnabend, a Greenwich Village physician and former academic researcher.
“I was out there in private practice, and this extraordinary mystery that we now know as AIDS came my way,” Sonnabend said. “I quickly realized that my patients constituted an untapped and valuable resource.”
Doors ‘Began to Open’
The turning point came when Sonnabend and Michael Callen, former president of New York’s People With AIDS Coalition, secured the support of Krim, the well-connected scientist who had left her position as head of Memorial Sloan-Kettering’s interferon laboratory in 1985 to work full time on raising money and public consciousness in the fight against AIDS.
“With Mathilde on board, doors that had been closed to us began to open,” said Callen, who has battled AIDS since he was first diagnosed as having the disease in 1982. The founders rapidly recruited a scientific advisory committee and an institutional review board.
The review board is made up of scientists, doctors, lawyers, medical ethicists and clergymen--as well as Callen and Hannan, who also has AIDS. Their presence ensures that the interests of people with AIDS will be addressed.
‘Collaborative Spirit’
“We are developing a new ethical sense of what is appropriate in an emergency,” review board member Levine said. She said the “collaborative spirit” between patients and scientists “is one of the most beneficial impacts of AIDS on the ethics of human-subjects research.”
The Community Research Initiative employs a dozen paid staffers, including nurses, bio-statisticians, computer operators and office workers. The group hopes to raise $700,000 for operations next year from contracts with drug companies, grants and donations, $200,000 more than its budget now. Nevertheless, the group has come a long way since it began with only a personal computer and a file cabinet in a corner of Hannan’s apartment. “What is amazing,” said J. David Seaman, co-director of research, “is that this growth has occurred in the context of constant death and illness.”
‘They Will Not Give Up’
Giorgia Herington, the group’s office manager, said many friends mistakenly assume her work is depressing. “Just the opposite,” she said. “Most of the people with AIDS that I meet have not given up--they will not give up.”
When Hannan was recently hospitalized with tuberculosis, he spent much of his time working to persuade his doctor to test a new experimental drug called CD4 through the Community Research Initiative.
Such demonstrations of pluck suggest that, at least on one level, the Community Research Initiative is already a success. Said New York community physician Dr. Nathaniel Pier: “You cannot underestimate the therapeutic value of feeling like a soldier in the war against AIDS.”
