Consumers can be central to the [medical] research endeavor. We can be a catalyzing force for translating research into the services we desperately need, such as treatments, technologies to alleviate suffering, and clinical methods of dealing with the conditions.

-Sharon Terry

As more and more patients gather, process, and publish their own medical data and coordinate recruitment for clinical studies, the relationships between researchers and patients will change dramatically.

-Gilles Frydman

CHAPTER FIVE (See Summary)

e-Patients as Medical Researchers

In a research laboratory at Tulane Medical School, Andy Martin studied tissue samples of sinonasal undifferentiated carcinoma (SNUC), one of the most malignant and poorly understood cancers. The same type of cancer was growing inside his head. ^[1] On his Web site, ^[2] Martin explained why he decided to forego the usual duties of a third-year medical student to do what he could to further our understanding of the disease.

When Martin first decided that he wanted to do research on sinonasal undifferentiated carcinoma, Dr. Tyler Curiel, Tulane's chief of Hematology/Oncology, hesitated. All previous attempts to grow SNUC cells in the laboratory had failed. And Martin was already critically ill. But Curiel was so impressed by Martin's commitment that he helped raise funds for his research.

In the limited time he's had to spend on the project, Martin has exceeded everyone's expectations. He's figured out a way to grow SNUC cells in the laboratory, something none of the world's thousands of cancer researchers, most with M.D.s, Ph.D.s, or both, had been able to do. And growing cells in culture could be the first step toward finding a cure. ^[3] When Martin, after a number of failed attempts, finally succeeded in getting the tumor cells to grow, "It was one of the greatest moments of my scientific career," Dr. Curiel recalls. "I just sat right down on the lab floor next to the microscope, speechless." ^[4]

Martin felt lucky because other SNUC patients don't have the "extraordinary opportunity…to undertake a project that might have lasting benefit." ^[5] Dr. Curiel is now seeking funding to help other cancer patients to study their own tumors. "It's therapeutic for patients, especially those with hard-to-treat cancers," he says. ^[6]

From Passive Patients to Active Researchers

Andy Martin is just one of many patients who have made important contributions to medical science. But he's one of the few who have received credit for doing so. Many previously unexplained medical phenomena were first noticed by patients. But in most cases, professionals got credit for the patients' discoveries.

The sexual effects of Viagra (sildenafil) were originally discovered by patients. The British researchers who developed the drug were hoping that it would increase the cardiac blood supply in angina patients. Not until a number of patients took them aside to report the dramatic side effect for which the drug is now well known did the researchers begin to wonder whether the drug might increase another kind of blood flow. Thanks to this patient-provided intelligence, Pfizer soon found itself with a spectacular new pharmaceutical bestseller. ^[7]

The researchers can hardly be blamed for taking the credit. Before the Internet, the idea that patients might help advance scientific knowledge was almost unthinkable. And their opportunities to contribute were few. Most could play only a passive role, serving as subjects for clinical trials designed and conducted by professionals. Few if any researchers had considered the possibility that patients might be able to do real medical research-conducting experiments, collecting and analyzing data, and reporting significant and valid conclusions. Not until the Internet made it possible for large groups of patients with the same health concern to share their clinical experiences did the potential role of e-patients in medical research become apparent.

The Life Raft Group: A Research-Oriented Online Support Community

The man many consider the George Washington of e-patient-directed medical research is Norman Scherzer, a tall, graying public health professional who, until recently, worked with 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 his online group's research efforts, speaking soothingly yet authoritatively to worried cancer patients, and juggling 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. ^[8]

In 1994, Scherzer's wife, Anita, developed an abdominal tumor. "The first doctor we saw told us she had a rare type of cancer called leiomyosarcoma," Scherzer recalls. "So, I joined an online support group ^[9] for that disease. I found the mailing list discussions a little unwieldy at first. There were many different conversations going on. It was all so different from the carefully organized information I knew from the world of public health. There was a lot 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. 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. The Scherzers' own doctor knew nothing about it, so Norman took his wife to see this new physician. It was only then that Anita's cancer was correctly diagnosed as gastrointestinal stromal tumor (GIST).

At the time, no effective treatment for this condition existed. A few months later, however, 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 30-patient clinical trial. After only 30 days of this new therapy, now known as Gleevec, his wife's tumor had shrunk by more than 50 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. It started to get a bit awkward, but by this time, I'd gotten to know Gilles Frydman, who runs ACOR (Association for Cancer Online Resources). With his help, we started a new mailing list for GIST patients. Since we would be 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 groups are open to anyone," Scherzer explains, "patients, family members, professionals, researchers, and anyone else who's interested. But our group meets privately and only GIST patients and their family caregivers can apply. We pre-screen them carefully, making sure they actually have this disease and understand that they'll be expected to share their medical experiences. We operate as a highly organized, networked scientific work group.

"The only health professionals admitted to the group are GIST patients and their family caregivers. Not even the top GIST specialists or the researchers who conduct the clinical trials in which many of our members are enrolled are admitted to the group," Scherzer says. "We publish an online newsletter ^[10] 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. In 2004 Scherzer explained, "We have our own medical librarian, who collects regular medical updates from each member and stores them on an Excel spreadsheet. 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 Life Raft Group's Science Team is comprised of approximately ten highly committed members who regularly review the medical literature, speak with leading GIST specialists, interact with top medical researchers, keep up-to-date on the latest drug company information, and check in with other support groups in an ongoing attempt to understand the current state-of-the-art GIST therapy."

"It's quite a remarkable crew," Scherzer reflected. "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. We operate at a level of technical complexity many professionals would have trouble keeping up with. We provide other members-and our newsletter readers-with an up-to-date, high-level review of the latest developments in GIST treatment, often based on a growing understanding of the molecular and genetic components of the disease." Science Team members communicate via their own private list.

I asked Scherzer how he collected 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, 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 said. "We can get lifesaving information out to the people who need it right away, much faster than professional researchers, who must go through many time-consuming steps. First you design your study. Then you arrange for funding. Then you must get everything approved-sometimes by several different committees. Then you recruit your subjects. So at last you can begin. Then you must wait for your results to trickle in. But that's only the beginning.

"Next you must analyze and interpret your data. You must write everything up. After all that, you'll need to find a peer-reviewed journal to publish your work. And if you're lucky enough to find one, you must go through even more long rounds of reviews, revisions, corrections, and proofing-as well as possible editorial or production 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 everybody knows.

"As a result of this delay, 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 to five years, or even more. Physicians are subject to this delay just like everyone else. 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 GIST patients."

Publishing Their Own Research Studies

In June 2001, the group used its newsletter to publish its first formal study of Gleevec's effectiveness for GIST patients In October 2001, the group published its first comprehensive study of Gleevec side effects. 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 sparticipants 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 clinical trial toxicity standards established by the National Cancer Institute.

This last point requires some explanation. Scherzer, trained to conduct population studies, looked for the existing instruments used to report the severity of side effects. They were available from the National Cancer Institute, but Scherzer was surprised to find that side effect measurements were focused exclusively upon toxicity as opposed to quality of life. For example, a patient who developed diarrhea several times a day, every day, on an indefinite basis would be rated a one on the NCI Toxicity Scale of one through five, with five being death and one being the mildest rating.As an alternative Scherzer adapted a common pain-management rating scale of one to ten, with one being the mildest and ten the most intolerable and then asked Gleevec patients to rate a number of possible side effects using this scale. A situation like the one described above would rank as an eight or higher using this scale.

To account for the fact that there was no placebo in the Gleevec clinical trial, Scherzer asked the survey participants to rank their side effects in the quarter prior to starting Gleevec in addition to each quarter following it. By doing so, he was able to document that some side effects were in fact pre-existing conditions. In addition, by rating side effects over several contiguous quarters he discovered that actual side effects got better over time. Finally, Scherzer correlated side effects by a number of demographic factors and discovered that they were generally worse in females, particularly those side effects that affected skin, and that the more severe they were at onset the more they improved over time.

When Scherzer presented the Life Raft Group findings on Gleevec side effects to the team that had just reviewed the results from the official clinical trial, the health care professionals could hardly believe what they had just witnessed. The results and the methodology were both extraordinary. This two-hour presentation was clearly a watershed; it resulted in significant funding for continued Life Raft Group patient-centered and patient-directed research.

"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, where he conducts clinical trials with GIST patients. "I predict that we'll be seeing a lot more of this sort of thing in the years to come." Dr. Daniel Vasella, CEO of Novartis, describes the research as follows: "The Life Raft Group … has provided various people, patients, doctors, investigators with a unique kind of data bank that cannot be replicated anywhere else, not even in patient trials."

In 2007, The Life Raft Group website states: "Today, the Life Raft Group conducts its own patient-based research to ensure that it provides the most timely and relevant information that GIST patients need to survive. This internal research is designed to provide all of us with information that is not currently available from clinical trials, either because we are waiting for the trial to reach its research end point and for the researcher to share the information or because the perspective of the trial is just not geared to what patients need to know in order to survive. If you have problems with finding a reliable essay service that offers assistance not only with creating essays but term and research paper writing as well, I highly recommend you to visit BestWritingService.Com. If you have problems with finding a reliable essay service that offers assistance not only with creating essays but term and research paper writing as well, I highly recommend you to visit BestWritingService.Com. The process of essay writing will be much easier with MarvelousEssays.Com as there are a lot of highly professional and talented writers who are always eager to help you out with any sort of academic assignments regardless of the complexity levels. I do know what I�m talking about! We cannot completely depend upon the profit drive of the normal drug development marketplace and traditional research funding to ensure patient survival". ^[11]

Parent-Initiated Research on Reflux

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 disease (GERD), one with severe complications. Her doctor assured her that the condition could not be passed on from parent to child. The odds of her new baby having GERD were, he insisted, "a million to one against it." Eight months later, Caroline gave birth to twins. Both had GERD. And even though there was nothing in the medical literature to suggest that this trait was genetic, Caroline was convinced that it was. So she set out to prove it.

She joined forces with Elizabeth Pulsifer-Anderson, who had recently started PAGER (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 succeeded 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 GERD sufferers spanning several generations. The researchers were able to evaluate both affected and unaffected family members, obtaining their detailed medical histories and performing genome-wide DNA scans. Finally, in the July 19, 2000 issue of the Journal of the American Medical Association, McGraw and Pulsifer-Anderson published the first study to demonstrate the patterns by which GERD is inherited and to map the responsible gene. ^[12] Caroline and Elizabeth, along with the key members of the medical research team, were listed as co-authors.

Jannine and Liz Cody

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-). Individuals with the condition are typically hard of hearing and mentally retarded. The doctor told Cody that there were only a few dozen known cases of 18- and that no treatments were available. He then opened a medical textbook, showed her photographs of a typical 18- patient, lying immobile in a froglike position and vegetative state, and told her that she must go home and persevere. Instead, Cody went to the medical library and started reading everything she could find on her daughter's condition.

At age four, Liz experienced a dramatic improvement in 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 people 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 individuals with 18-.

When Cody told medical researchers at the University of Texas Health Science Center at San Antonio about her theory, they were impressed enough with it to test it. They found 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 with 18-, who would otherwise have grown up mentally retarded, can now have normal IQs. The following year, Cody started a support group called the Chromosome 18 Registry & Research Society and began corresponding with affected families around the globe. She also 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.

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. In addition to serving as president of the Chromosome 18 Registry & Research Society, Cody also serves as assistant professor of genetics and pediatrics at the University of Texas Health Science Center in San Antonio.

Portia Iversen Tackles Autism

In 1989, Portia Iversen won an Emmy as art director of the Tracey Ullman Show. Since 1995, when her firstborn son Dov was diagnosed with autism, she has become a major player in autism advocacy and research.

In the beginning, Iversen spent many long nights online, searching for information about 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 [autism]. 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 the researchers weren't about to turn their hard-earned results over to their competitors. "They had their own agenda. And it didn't always lead to getting new treatments out to the people who needed them ASAP," Iversen says. After running into a brick wall again and again, Iversen and her husband decided to establish 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. "We hope that something good for Dov will come out of it."

"Portia's gene-bank idea has been extraordinarily effective in stimulating new work in this badly neglected area," says Daniel Geschwind, M.D., Ph.D., director of UCLA's neurogenetics program. "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."

On February 18, 2007, The Autism Genome Project Consortium (AGP), of which AGRE is a primary partner, published its report on a link between autism spectrum disorders and a site on chromosome 11. ^[13] This project involved researchers from 19 countries examining genes from 1,168 families. The work that Portia Iversen initiated years ago has evolved into a significant research collaboration hailed by NIH Director, Elias Zerhouni, MD: "This is the most ambitious effort yet to find the location of genes that may confer vulnerability to autism. The AGP is revealing clues that will likely influence the direction of autism research for years to come." ^[14]

Parent Expertise on PXE

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 and told Terry that her daughter had pseudoxanthoma elasticum(PXE), a rare genetic disorder that affects connective tissues throughout the body. He then glanced down at her son Ian, age five, who'd accompanied his mother and sister to the clinic. "Ah, he has it too," the doctor said.

Terry set out to photocopy and read every article about PXE in the medical library at the University of Massachusetts at Worcester. "Popular medical resources such as the Merck Manual described the condition in dire terms, including the possibility that our kids would die at age thirty," Terry recalls. "What most jarred us was the realization that the research-medical system was not a well-oiled machine. We began to understand that we could not expect accurate information or a course of treatment." ^[15] Then she and her husband contacted all major PXE researchers 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. "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. The worst part was that our doctors seemed to know almost nothing about it. "In the beginning, my husband, Patrick, and I didn't know a gene from a hubcap,'" she says. "But we didn't let that stop us. 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." ^[16]

"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. "But Pat and I had a lot 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, the Terrys decided to set up a registry and tissue bank to support genetic research. Within the next few months, the Terrys visited 24 countries, collecting more than a thousand tissue samples from PXE patients. Their playroom soon became the headquarters of PXE International, which now boasts 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, our efforts paid off," Terry recalls. "The University of Hawaii researchers we were collaborating with, and two other research groups we'd been supporting, identified the gene that causes PXE." ^[17] In August 2004, Sharon Terry did something no parent had ever done: she received a patent on the gene that caused her children's disorder. ^[18] "In other cases, when patients have helped researchers like this, the researchers 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."

"My work with PXE International has taught me that consumers can be central to the research endeavor," Terry concludes. Health "We can be a catalyzing force for translating research into the services we desperately need, such as treatments, technologies to alleviate suffering, and clinical methods of dealing with the conditions. I now serve as president of the Genetic Alliance. ^[19] This role enables me to work with other groups so that we leverage each other's capacities to make a difference for our loved ones." ^[20]

e-Patients' Role in Future Medical Research

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. But as e-patients become more capable researchers-and research partners-a wider range of approaches to medical research are becoming realistic.

Research-oriented online support groups can design and conduct their own studies, collect and analyze their own data, and publish their own results. Online groups can provide researchers with access to perfectly targeted study populations at little or no cost. But whatever role they play, once they begin to wield real power in the research enterprise, patient groups will want to have a voice in shaping the future directions and strategies of medical research studies.

The Life Raft Group's entire cash budget for its first year of operation was $225.00 , yet this group has accomplished extraordinary results. e-Patients are motivated to find answers and they are willing to donate massive amounts of time - something most researchers don't have. And while such e-patient initiatives may encounter some resistance, in the end, it seems likely that the financially strapped medical research establishment will decide that such e-patient initiatives represent an offer contemporary healthcare can't afford to refuse.

"It's so exciting to be involved in this new initiative, to try to figure out how online groups can collect and disseminate good information," Scherzer says. "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 PXE medical researchers," 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. 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 advised: "There is an important lesson for medical professionals in all this: Families were the ones who first noticed a pattern of inherited reflux, and families were the ones who sought out researchers who were 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."

"As these examples show, patient-driven research will become more and more important," says ACOR's Frydman. "As more patient groups begin gathering and publishing their own medical data, it will change the relationships between researchers and patients in dramatic ways. Researchers will increasingly depend on patients, not the other way around. These groups have been phenomenally successful in recruiting new patients for needed clinical trials. And I can assure you that e-patients' potential role in medical research is not lost on the drug companies."

In the chapters that follow, we suggest that initiating and conducting medical research is not the only major healthcare contribution our new generation of e-patients is now ready, willing, and able to make-if we will only let them. n