March 10, 2003
| TERRY SISK is fighting for his life. The 60-year-old Dallas real estate developer has follicular non-Hodgkin's lymphoma, and the cancer has spread beyond his lymph nodes. In the 51/2 years since his disease was diagnosed, Sisk has tried 11 different drug regimens and is running out of options. His doctors recommend a bone-marrow transplant, but Sisk is leery. "I don't like the odds," he says.
In a desperate search for alternatives, Sisk scoured the Internet. There he recently came upon a Web site run by EmergingMed.com Inc., a three-year-old Manhattan company that acts as a matchmaker between cancer patients and pharmaceutical companies. The drug makers have an urgent need of their own: finding enough patients to participate in clinical trials.
Sisk filled out an online questionnaire about his medical history. Within 10 minutes, he got a phone call from a representative at EmergingMed, who then conferenced in a nurse at the M.D. Anderson Cancer Center in Houston. Researchers there are conducting a clinical trial for which Sisk might be eligible.
People like Sisk, willing to volunteer as research subjects, are in short supply. That has created a major bottleneck in the development of new drugs. According to data gathered by the medical publishing and research company CenterWatch, nearly 80 percent of clinical trials today do not meet their enrollment targets. For the average drug, each day of delay costs $1.3 million in lost sales.
EmergingMed is among a handful of young companies trying to recruit trial participants online. From EmergingMed's perspective, the Web is the perfect tool for reaching the large numbers of patients required by companies testing new drugs, therapies, and medical devices: Millions of Americans already use it to hunt for health and medical information. E-recruitment, as it's called, simply bridges the gap between Web surfers and academic medical centers.
So far, however, these electronic matchmaking services have failed to significantly boost participation in clinical trials. Some of EmergingMed's competitors, such as HopeLink, have already gone out of business. Efforts to recruit patients via AOL and Yahoo! have fallen by the wayside. "The Internet isn't the panacea that everyone promised," says Kenneth Getz, president of CenterWatch.
Even so, clinical trial experts like Getz think technology can help relieve the chronic headache of patient recruitment. In the United States alone, thousands of clinical trials are in progress every day. The approval of a single new drug requires an average of 37 separate clinical trials, according to the Tufts Center for the Study of Drug Development. Meanwhile, the number of prospective new drugs is rising with advances in biotechnology. And statistical concerns about getting valid, high-quality data also require late-stage trials to have more patients than in the past.
Complications abound, too. Many clinical trials have very specific requirements for participation. The protocol for each study not only spells out criteria for demographics and medical condition but also includes a long list of inclusions and exclusions. Women pregnant or nursing, for instance, are automatically excluded from most trials. An "inclusion," on the other hand, might specify that only patients who are taking insulin will be accepted into a particular diabetes study. Finding patients who fit all the requirements can take months or years. "You're looking for a needle in a haystack," says Courtney Hudson, CEO and founder of EmergingMed.
Symptomatic Lack of Awareness
The solution, everyone agrees, is to make more patients aware of clinical trials. A survey done in 2001 by the market research company Harris Interactive found that about 85 percent of the 6,000 cancer patients interviewed were either unaware or unsure that participation in clinical trials was an option. About 75 percent of those people said they would have been willing to enroll had they known it was possible.
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Currently only 3 percent to 5 percent of all cancer patients participate in clinical trials. If that number could be increased to 10 percent, promising new cancer therapies might be brought to market in as little as one year, according to US Oncology Inc., a network of oncologists. US Oncology has partnered with Internet consulting company Molecular.com of Boston to create a clinical trial matching system that enables doctors to enroll patients online.
Other patients turn to CenterWatch. The grandfather of trial listings at nine years old, it sees its role as a publisher rather than a matchmaker, providing data to patients, doctors, and organizations sponsoring studies. Before CenterWatch began publishing trial information online, the only listings available were government registries. The federal databases don't include many industry-sponsored trials because the government requires sponsors to post study details that could be considered proprietary. And the government listings have been difficult for many patients to understand, although sites such as Clinicaltrials.gov and Cancer.gov have become more user friendly.
CenterWatch got around the usability problem by translating detailed protocols into simpler language. The site currently lists more than 9,000 industry-sponsored trials, as well as trials sponsored by the National Cancer Institute and the National Institutes of Health. Users select from a menu of diseases, enter a location, and hit "search" to generate a list of available trials. If a patient wants to learn more, he can send e-mail directly to the study site. "A patient might not feel comfortable picking up the phone and talking with someone at the research center, so sending an e-mail with questions is sometimes a better solution," explains Dan McDonald, director of Internet services at CenterWatch. The company says an estimated 800,000 people visit the site each month. The site is linked to almost 6,000 other organizations, notes McDonald.
Patient, Refer Thyself
According to CenterWatch statistics, more patients are referring themselves to clinical trials than ever before. In 1993, McDonald says, 65 percent of all study volunteers were referred by a doctor or a nurse. By 2000, the majority of all patients in trials — close to 60 percent — had referred themselves.
Some companies aim to facilitate referrals using online questionnaires. CenterWatch has joined forces with one of these companies, Veritas Medicine, to offer a personalized trial matching service. Such matching services are typically free to patients. (One exception is Cancer Advisors Inc.'s Canceradvisors.org, which charges $400 for a personalized report that lists recommended clinical trials.)
|Reluctance by many patients to share personal medical data may be holding back companies that offer personalized matching services.
Most matching services work like this: The patient provides some basic information about his or her condition and gets a listing of available trials, then fills out a registration form and identifies himself or herself so that he or she can be referred to a research site. For example, a breast cancer patient who visits the Veritas Medicine site fills out — anonymously — a questionnaire that asks such things as age, geographic location, the stage of the cancer, whether the patient has had a lumpectomy or mastectomy, and what drugs the patient has taken. The questionnaire also asks more technical questions that could require checking lab reports, such as whether the patient's tumor has an elevated level of the HER2 receptor.
Like virtually all companies offering trial-matching services, Veritas relies on an Oracle database, the de facto standard in the pharmaceutical industry. An in-house development staff uses ColdFusion MX software, from Macromedia, to create and deploy applications for the site.
When a pharmaceutical client submits its protocol for a clinical trial, operations staffers at Veritas (most of whom have medical backgrounds) enter the study criteria into their database. They then work with a medical editor who heads each disease area (e.g., diabetes) to "toggle" the study criteria with the questionnaires used to screen patients. In essence, they decide which questions should be asked on the questionnaire to address the inclusions and exclusions specified by the study protocol. Once a week, the newly toggled questionnaires are pushed out to the Web site. To protect patient confidentiality, Veritas encrypts all communications end-to-end with SSL (Secure Sockets Layer, the protocol used by most commercial sites to safeguard credit card transactions, for example). Referrals are sent to research sites by e-faxes rather than e-mails, because the FDA regards faxes as a more secure form of transmission.
Low on Money, Short on Time
E-recruitment companies are guarded on the question of how many patients they're referring, or what percentage is actually getting into trials. To many observers, that suggests the technology hasn't yet significantly boosted patient recruitment.
Matchmaking services are "running low on money and can't afford to wait too much longer for the technology to catch on," says Michael Barrett, a senior analyst at Forrester Research, who gave low marks to e-recruiters in an April 2001 report. Barrett would like to see a consortium of drug and device firms join forces and build a Web site with solid brand recognition and content. That consortium could then outsource some functions back to existing e-recruiters.
Some alliances are already happening. EmergingMed uses a product called iSyndicator, sold by WebCollage, to syndicate its content and services to the American Cancer Society and OncoLink, a cancer information center sponsored by the University of Pennsylvania. Veritas Medicine has a network of 65 channel partners, including the American Diabetes Association. And the Holy Grail of both companies is a giant database containing every clinical trial and every eligible patient, which would enable them to make more matches than currently possible.
Surprisingly, however, a few e-recruiters are having better luck with study-specific Web sites. The Dallas-based recruitment company D. Anderson and Co., for instance, recently used a site dubbed DryEye.com to recruit patients for a study of Sjögren's syndrome, a chronic disease that affects moisture-producing glands. More than half of the 1,400 patients who visited were prequalified for the study after filling out an application, says Diana Anderson, president and CEO of the firm.
Reluctance by many patients, however, to share personal medical data may be holding back companies that offer personalized matching services. It doesn't seem to matter that most sites let visitors return and remove, or "scrub," personal information. "Patients just aren't ready to provide detailed information about their health to pharmaceutical companies," says McDonald of CenterWatch. "They're not sure how the information will be used."
Even when online matching succeeds, some patient-recruitment experts question whether the information collected by matching services is sufficient to fill clinical trials with the right patients. "We don't have the metrics to support these Internet-based strategies yet," Anderson says. "It doesn't matter if you get 50,000 hits and you refer 20,000 of those to sites, if none end up in the research study."
CenterWatch's Getz adds that certain eligibility criteria can never be fully automated. A questionnaire cannot tell researchers, for instance, whether a patient is truly willing to have an invasive intervention performed.
Internet in the Middle
E-recruitment needn't revolutionize the world of clinical trials; filling only a portion of the patient shortage could be significant. "It's fine if e-recruitment contributes only 20 percent of the total patients needed in a given trial," notes Barrett of Forrester Research. "We're not looking for a panacea, just a significant contribution."
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But Barrett says the industry has yet to really figure out the role of the Internet and traditional advertising media such as television and direct mail. Such channels are essential for raising the public's awareness of clinical trials, he says, and personal contact with a doctor is also a key part of any decision to participate. "The Internet's role is in the middle," Barrett says. "Someone has to put the total strategy together, and give the Internet its proper role and no more."
"What most patients want is basic information," says Getz, "but then they want to be interacting with professionals who can help them answer the tough questions." He believes there's a role for matchmaking, but mainly for patients like Terry Sisk who are suffering from terminal illnesses and are motivated to seek out clinical trials on their own.
Even for tech-savvy patients like Sisk, however, finding the right trial to join is still difficult. "There are many, many people who'd like to be in a clinical trial but don't know how to do it," Sisk says. "It'd be nice if it was easier."
Dawn Stover is an editor at Popular Science. She may be reached at firstname.lastname@example.org.