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  Key Concepts in Online Health:
e-Patients as Medical Researchers

The sexual effects of Viagra (sildenafil) were first discovered by patients. The British researchers who developed the drug were hoping that sildenafil would increase the cardiac blood supply in angina patients. It was not until a number of patients reported the dramatic side effect for which the drug is now well known that they realized that it might increase another kind of blood flow. Thanks to this patient-provided intelligence, Pfizer soon found itself with a spectacular new pharmaceutical bestseller.

In the world of Industrial Age medical research, patients played a completely passive role, serving as subjects for clinical trials designed and conducted by professionals. There was no place in the Industrial Age medical paradigm for the idea that patients could discover, analyze, and report important medical phenomena. It was not until the Internet made it possible for large groups of patients with the same health concern to share their clinical experiences that the potential role of e-patients in medical research became apparent.

The man many consider the George Washington of e-patient-directed medical research is Norman Scherzer, a tall, graying, 60-ish public health professional who until recently worked at the Centers for Disease Control and the New York City Department of Health. Working from a tiny office in his New Jersey home, Scherzer now spends 50 hours a week coordinating the research efforts of his online group. He answers calls from frantic cancer patients in a calm, soothing, voice and juggles a constant stream of incoming e-mails from group members, drug company executives, and cancer researchers, while a noisy fax machine clatters in the background.

In 1994, Scherzer's wife, Anita, developed an abdominal tumor. "The first doctor we saw told us she had a type of cancer called Leiomyosarcoma," Scherzer recalls. "So I joined an online support group-sponsored by the Association of Cancer Online Resources (www.acor.org) for that disease."

"I found the mailing list discussions a little unwieldy at first. There were a lot of different conversations going on. It was all so different from the carefully organized information I'd grown accustomed to in the world of public health. There was lots of information available. But there wasn't much organization or quality control. It was a needle-in-the-haystack situation. But I persevered, and soon figured out how to find what I was looking for. So in the end I was able to locate the needle we really needed."

Through the list, Scherzer heard that a cancer specialist at New York's Columbia-Presbyterian Medical Center was using a newly developed enzyme test to help diagnose tumors like Anita's. Their own doctor knew nothing about it, so he took his wife to see this new physician. Anita's cancer was correctly diagnosed as gastrointestinal stromal tumor (GIST).

At the time, there was no effective treatment for this condition. But a few months later, Scherzer heard that a promising new drug called STI-571-which had produced excellent results with other cancers-would be tested on GIST patients. With the help of Anita's new oncologist, Scherzer enrolled her as patient number seven in an early ten patient clinical trial. After a year of this new therapy-now known as Geevec-his wife's tumors had shrunk by 75 percent.

"After Anita was correctly diagnosed, I got in touch with some other GIST patients who'd started an online mailing list," Scherzer recalls. "There were only five of us at first, so we communicated by e-mail. But the group kept growing, and before we knew it, there were more than 50 members, so it started to get a bit awkward. By this time, I'd gotten to know Gilles Frydman, who runs the Association of Cancer Online Resources (ACOR.org). With his help, we started a new mailing list for GIST patients, the Life Raft Group (liferaftgroup.org). But since we were thinking of using the new list to collect information on the drug's effectiveness, we decided to make it a closed group.

"No Doctors Allowed"

"Most online support groups are open to anyone who's interested," Scherzer explains, "But the Life Raft Group meets privately and only GIST patients and their family caregivers can join. Prospective members must apply for admission. And we check them out carefully to make sure they actually have this disease and understand that they'll be expected to share their medical experiences. Health professionals are not admitted to the group, not even the top GIST specialists or the researchers conducting the clinical trials in which many of our members are enrolled.

"Most online support groups offer casual conversations among whoever shows up. But we operate as a highly-organized networked work group," Scherzer says. "And since we're a closed group, we felt that we should publish a monthly newsletter at our Web site (www.liferaftgroup.org) to share the things we're learning with the larger world."

While Scherzer is acknowledged as the leader, he is by no means the only one who makes this complex process work. "We have our own medical librarian, who collects regular medical updates from each member and stores them on an Excel spreadsheet," he explains. "We have a membership director who processes new applications and registers new members. We have an editor, a professional newspaperman who puts out a lovely newsletter every month. We have a webmaster, a treasurer, a list manager, and a government relations coordinator. And of course we have our Science Team."

The Science Team is composed of ten highly committed members. "We review the medical literature and speak regularly with the leading GIST specialists," Scherzer says. "We keep up to date on the latest information available from drug companies and check in with other support groups in an ongoing attempt to understand the current state of the art of GIST therapy." Science Team members communicate via their own private list.

"It's quite a remarkable crew," Scherzer reflects. "We have a virologist, a microbiologist, a physician-surgeon, and a physicist who works at Los Alamos. One guy is a key player at the human genome project. The team is headed by a self-taught caregiver who never acquired any professional credentials, but is nonetheless one of the three smartest people I've ever known. We operate at a level of technical complexity many professionals would find challenging. And we provide other members-and our newsletter readers-with an up-to-date, high-level review of the latest developments in GIST treatment."

I ask Scherzer how he managed to collect such a capable cast of characters. "People who survive a life-threatening disease-one that should have killed them years ago-are often extraordinary people," he explains. "When someone figures out how to defy the odds and stay alive long enough to find a promising new clinical trial, either the patient or the caregiver or both usually turn out to be truly remarkable individuals."

Bypassing the "Lethal Lag Time"

"One of the great benefits of patient-initiated research is its speed," Scherzer says. "We can get lifesaving information out to the people who need it right away. If you're a professional researcher, you must go through many time-consuming steps: First you must design your study. Then you must arrange for funding. Then you must get everything approved. Then you must recruit your subjects. So at last you can begin. Then you must wait for all your results to trickle in. But that's only the beginning.

"Next you must analyze and interpret your data. You must write everything up. And after all that, you'll still need to find a peer reviewed journal to publish your work. And if you're lucky enough to find one, you must go through the long process of reviews, revisions, corrections, and proofing-as well as possible editorial delays. This can take several years. So professional research has a built-in lethal lag time-a period of delay between the time some people know about an important medical breakthrough and the time everyone knows. And as a result, many patients who could have been saved by the latest treatments die unnecessarily. In my experience this lethal lag time is rarely less than two to three years. And it can sometimes be four or five years or even more. Physicians are just as much a victim of this lethal lag time as their patients. That's why we're so delighted that our newsletter mailing list is now growing just as fast among the medical community as it is among those with GIST and their caretakers."

Publishing Their Own Research Studies

In June 2001, the Life Raft Group published its first formal study-an evaluation of Gleevec's effectiveness for GIST patients. Although results were available a month earlier, Scherzer and friends decided to wait until a team of professional researchers, who'd conducted a similar study, had reported their results. "We didn't want to steal their thunder," he explains. "And we wanted to avoid a confrontational relationship."

In October 2001, the group published a review of Gleevec's side effects. And in addition to collecting the usual data, the Life Raft Group's study broke new ground in several areas:

  • It provided data on the quality of the clinical care available to study participants at each of the centers conducting clinical trials.
  • It attempted to evaluate the information sources patients relied upon.
  • It developed a methodology by which patients could, in effect, serve as their own control group.
  • It introduced a new scale for rating the severity of side effects from the patient's point of view, as opposed to the toxicity standards established for clinical trials by the National Cancer Institute.

"The new research model pioneered by the Life Raft group is making it possible for patients and family members to contribute to clinical research for their diseases in unprecedented ways," says George Demetri, medical director of the Center for Sarcoma and Bone Oncology at Boston's Dana-Farber Cancer Institute. "I predict that we'll be seeing a lot more of this sort of thing in the years to come."

"A Million to One Against It"

Scherzer and his colleagues are not alone. Other e-patients have also found innovative ways of contributing to medical research. Support groups for the parents of children with genetic conditions have been responsible for several recent breakthroughs in medical research.

When Caroline McGraw discovered that she and her husband Tom were going to have their third baby, she began to worry. Her two older children both had severe cases of gastroesophageal reflux disorder (GERD), and one had experienced severe complications. Her doctor assured her that the condition was not passed on from parent to child. When she asked about the odds of her new baby having GERD, he insisted that they were "A million to one against it."

Eight months later, Caroline gave birth to twins. Both had the disorder. And even though there was nothing in the medical literature to suggest that this trait was genetic, Caroline was convinced that it was. And she set out to prove it.

She joined forces with Elizabeth Pulsifer-Anderson, who had recently started PAGER (for Pediatric/Adolescent Gastroesophageal Reflux Association) which offers an online support group and web site (www.reflux.org) for this condition. Together the two mothers took their idea of genetically transmitted heartburn to a number of medical research teams.

When the first researchers they met with turned them down, they gathered more evidence and tried again-and again. They finally hit pay dirt with a research team headed by Christopher Post and Garth Ehrlich at Allegheny General Hospital's Center for Genomic Sciences. With the help of group members and an online screening process, the PAGER team found five families with multiple members with GERD spanning several generations. The researchers were able to evaluate both affected and unaffected family members, obtain detailed medical histories, and perform genome-wide DNA scans. Finally, in the July 19, 2000 issue of the Journal of the American Medical Association, they published the first-ever study to demonstrate that GERD is genetic, and to map the gene responsible. Caroline and Elizabeth, along with the key members of the medical research team, were listed as co-authors.

From Parent to Professor

In 1985, Jannine Cody's daughter Liz was born with a cleft palate and her feet turned in. Her pediatrician told Cody that her baby had a rare genetic defect called Chromosome 18 deletion (usually written as 18-). Children with this condition are often hard of hearing and may be mentally retarded. Cody's doctor told her that there were only a few dozen known cases of 18- worldwide and that no treatments were available. He then opened a medical textbook, showed her photos of a typical 18- patient, lying immobile in a froglike, vegetative state, and told her that she must go home and make the best of it. Instead, Cody want to the medical library and read everything she could find on Chromosome 18 deletion.

At age 4, Liz, experienced a dramatic improvement in her hearing. Cody attributed this to the fact that she had arranged for her daughter to begin taking human growth hormone (HGH) the year before. When her doctors told her that no such effects were known, Cody went back to the medical literature. After reviewing hundreds of scientific articles, she came across a study in which researchers had reported that cells from the brains of fetal rats responded to HGH by producing myelin, the protein that insulates the nerves. In children with 18-, this insulating nerve sheath is abnormal. Cody suspected that in addition to improving hearing, HGH might also help prevent the lowered IQ often seen in 18- children.

When Cody told medical researchers at UT San Antonio about her theory, they were impressed enough to put it to the test. They discovered that she was right. Not only does HGH improve hearing, it increases IQ as well-by as much as 47 points. An increase of this magnitude means that with proper treatment, children who might otherwise have grown up mentally retarded could have normal IQs.

The following year, Cody started a support group called the Chromosome 18 Registry and Research Society, and began corresponding with affected families around the world. She then enrolled at the University of Texas, pursuing a doctorate in genetics. Her group now sponsors the definitive web site for the parents of children with Chromosome 18 abnormalities. And in 1994, while still a graduate student, she developed and began offering the first effective treatment for 18- children.

Today, Cody's professional bibliography includes more than three dozen peer-reviewed scientific articles, abstracts, and papers on Chromosome 18 abnormalities. And in addition to serving as President of the Chromosome 18 Registry and Research Society, Cody is also an Assistant Professor of Genetics and Pediatrics at the University of Texas Health Science Center in San Antonio.

"We Decided to Set Up Our Own Gene Bank"

In 1989, Portia Iversen won an Emmy as art director of the Tracey Ullman Show. In 1995, her firstborn son, Dov, was diagnosed with autism, and she spent many long nights online, searching for information on her son's condition. "I'd spend hours and hours working my way through these complicated neuroscience Web sites," she remembers. "No one knew what caused it. The only thing they all agreed on was that there was no treatment. There was no cure. There was little ongoing research. And the few active researchers weren't even telling other researchers what they'd found."

At first Iversen and her husband, Jon Shestack, tried to persuade autism researchers to share their DNA samples with other scientists. "But they weren't about to turn their hard-earned results over to their competitors," she explains. "They had their own agenda. And it didn't always lead to getting new treatments out to the people that needed them." After running into a brick wall again and again, Iversen and her husband decided to open their own gene bank.

The couple established the Autism Genetic Resource Exchange (AGRE) a databank of tissue samples collected from families with two or more autistic children. It is now the world's largest autism gene bank, supplying tissue samples and biomedical records from 500 families to more than 40 medical research teams. Researchers who use the gene bank must agree to share their results openly with other scientists.

"We felt that this would be a great way to speed up the progress of current autism research and attract prospective researchers to the field," Iversen says. Dr. Daniel Geschwind, Director of UCLA's Neurogenetics Program, agrees with this assessment. "Portia's gene bank idea has been extraordinarily effective in stimulating new work in this badly neglected area," he says. "The work her group has done has motivated dozens of new researchers to study the genetics of autism. As recently as three years ago, no researchers were addressing this badly neglected area. Today, there are dozens of research teams. It should be just a matter of time until we're able to identify the key genes responsible-and to come up with effective treatments."

"We learned as we went along."

In 1994, Sharon Terry noticed that her seven-year-old daughter, Elizabeth, had a bumpy rash on both sides of her neck. When she asked her pediatrician about it, he insisted that it was nothing to worry about.

Terry decided to get a second opinion. A dermatologist examined Liz briefly, then told Terry that her daughter had pseudoxanthoma elasticum (PXE), a rare genetic disorder that effects connective tissues throughout the body. He then glanced down at her son Ian, age five. "And so does he," the doctor said.

Terry set out to read and photocopy every article about PXE in the medical library at the University of Massachusetts at Worcester. Then she and her husband contacted every major PXE researcher to request information about their work. But the more she learned, the more alarmed she became.

"PXE could cause heart disease, GI bleeding, and severe vision loss," she remembers. "These children were born with a number of built-in risk factors: Their arteries could harden. They could bleed internally at any time. They could go blind. And they would almost certainly die prematurely of this disorder. And the worst part was that our doctors seemed to know almost nothing about it."

"In the beginning, my husband Patrick and I knew almost nothing about molecular biology," she says. "We became obsessed. The little playroom behind our kitchen became our office. We began reading thick medical textbooks and obscure genetics journals and sticking genetics charts up on our walls. We learned as we went along."

"PXE was so rare that there was no central registry. And virtually no research was being done." So Terry and her husband set out to get medical researchers to pay more attention to this understudied ailment. "Pat and I had lots to learn about the politics of medical research," she recalls. "You can't just walk into some researcher's office and demand that they look into PXE."

Like Jannine Cody, they decided set up a registry and tissue bank to support genetic research. Within the next few months, the Terrys visited 24 countries, collecting over a thousand tissue samples from PXE patients. Their playroom soon became the world headquarters of PXE International, which now has 35 offices worldwide. And they began working side-by-side with a team of medical researchers, advising on symptoms and consulting on research strategies.

"Finally, in 1999, all our efforts paid off," Terry recalls. "The University of Hawaii researchers we were collaborating with identified the gene that causes PXE." And in February of 2001, Sharon Terry, a college chaplain by profession, did something no parent had ever done. In collaboration with the University of Hawaii researchers, she applied for a patent on the gene that caused her children's disorder.

"In other cases, when parents have helped professionals research their children's disorders, the researchers have patented the gene and controlled all rights to it," Terry explains. "But that can impede further research and keep new advances from becoming available and affordable. We wanted to make sure that any genetic tests that result will be inexpensive and widely available. That's why we applied for the patent."

The Future of Medical Research

Such patient-initiated medical research projects turn the traditional medical paradigm upside down. Before the Internet, researchers called the shots, research trials were structured to meet their needs, and the delay between discovery and dissemination was considered an unavoidable part of the process.

The prospect of research-oriented online support groups offers a number of appealing scenarios. Patient groups could design and conduct their own studies, collecting their own data, analyzing their results, and publishing their results. They could provide researchers with access to perfectly targeted study populations at little or no cost. But whatever role they play, once they become active players in medical research, patient groups will demand a voice in deciding what should be studied and how that research will be conducted. And while such e-patient initiatives may encounter some resistance, in the end it seems likely that the financially-strapped medical research establishment will come to consider such e-patient research an offer it can't afford to refuse. The Life Raft Group's entire cash budget for its first year of operation was $225.00.

"It's so exciting to be involved in this new initiative to try to figure out how online groups can collect, process, and disseminate good medical information," Scherzer says. "And we find it extremely encouraging that clinical researchers at the leading drug companies and treatment centers are now beginning to take us seriously. The fact that we've been able to collect, interpret, and publish medically valid studies makes all the difference in the world."

"We now have great relationships with all the medical researchers for PXE," says Sharon Terry. "And while we've learned a lot about biology, chemistry, and molecular genetics, we don't involve ourselves in the competition among professional researchers. We support everyone. And this makes us a very powerful ally." A dozen other self-help organizations have asked Terry's group to teach them how to initiate leading-edge research for their own respective conditions. PAGER's McGraw and Pulsifer-Anderson offer the following advice:

Families were the ones who first noticed a pattern of inherited reflux, and families were the ones who sought out researchers who willing to explore this "wild idea." We strongly encourage other patient groups to be assertive if they see patterns that do not fit the current medical theories. Medical theories change and you can jump-start that change through hard work, persistence and a little luck.

More researchers would do well to realize that patient groups hold a unique and valuable position in a research collaborations because of their sheer numbers and an intense focus on their shared illness. Patient groups typically have contact with larger numbers of disease-specific patients than most physicians. And we have the luxury of spending many hours discussing our similarities and differences. After hundreds of hours of conversation, patterns can begin to emerge, and puzzle pieces start to fit together. Working with patient groups can provide researchers with a wealth of information unavailable from other sources.

"As these examples show, patient-driven research will become more and more important, and will provide an example of the way things will go in the future," says ACOR's Frydman. "As other patient groups begin generating their own medical data, it will change the relationships between research professionals, clinicians, and patients quite dramatically. These groups have been phenomenally successful in recruiting new patients for badly needed clinical trials. And I can assure you that their potential role in medical research is not lost on the drug companies."

Acknowledgement: Many thanks to Sara Solovitch, author of "The Citizen Scientists," WIRED, September 2001, (www.sarasolo.com/wm1.html), from which many of the examples used in this article are drawn. Sara's article was recently awarded the American Society of Journalists and Authors 2002 Writing Award for Outstanding Article of the Year for Reporting on a Significant Topic.

Published in The Ferguson Report, Number 9, September 2002


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