The increasing complexity and specificity of clinical trials, widely publicized research scandals and major advances in psychopharmacology have created a dilemma for academic institutions and private research organizations alike--how to find appropriate volunteers to participate in clinical drug trials.
A major obstacle to patient recruitment is finding patients who are protocol-appropriate, said Nancy Hashim, affiliated with the Feighner Research Institute in San Diego.
"Some of the protocols we are seeing now are very specific as to inclusion/exclusion criteria. The gate is very narrow, making it difficult for us to find people who fit through it," she said. "Another problem is that the patient population we are targeting includes a number of prospective patients who are self-medicating with drugs or alcohol(Drug information on alcohol). Almost every drug protocol we're involved in requires that the patient be clean for at least six months. So there are huge numbers of patients we cannot include."
Indirectly, the success of the pharmaceutical industry in developing safer and more efficacious psychotropic medications has impacted patient recruitment, according to Shannon Baker, M.A., a study coordinator at the University of Texas Southwestern Medical Center.
"Lots of times, people prefer not to go through the trouble of participating in a study," she said, explaining that because many of the newer treatments for psychiatric disorders are much safer, physicians feel comfortable prescribing them, and patients prefer to get help from their personal physicians. Patients don't want to risk problems with an experimental drug or the possibility that they will receive a placebo in a drug trial.
Charles Wilcox, Ph.D., executive director of Pharmacology Research Institute (PRI) in California, warned that there is now a stigma connected with clinical trials that "for some people can be dissuasive."
"[There are] increasing amounts of negative press and exposes resulting from some of the actions and shortcomings of clinical trial sites, particularly those that are university-based, that cut corners or didn't play by the rules...It is unfortunate for all of us who are in the majority, who play by the rules, to have to overcome that stigma, because the press can be pretty powerful," he said.
Another barrier to recruitment, according to Wilcox, is the commitment required on the patient's part.
"What I've seen over the years is that studies have become much more complex and labor-intensive, not only for us, but for the patients as well," he said. "So now, we are not only asking them...to volunteer, but to be a volunteer who is committing a substantial amount of time away from work [and] family...which has costs for people."
To explore why individuals volunteer for clinical trials, PRI conducted a series of focus groups.
"We asked if they know that on most, but not all studies, there is a probability that participants will get a placebo then what can we as a research site do for them to make them feel that volunteering and participating is a worthwhile endeavor?" Wilcox said. "Across the board, people said they participate for five reasons. First and foremost, care is free. We had a couple here yesterday who decided to do a little research before coming to PRI. Their primary care physician had told them that if he were to do for them what we were doing over a six-month basis, the bill would be between $6,000 and $8,000."
A second reason is that volunteers have the potential of being exposed to something new that they hope will have a better risk/benefit ratio than anything else on the market. A third reason is that their involvement in the study is confidential. The fourth reason, Wilcox said, is altruism, particularly among some of the older volunteers.
"On an Alzheimer's disease study, a loved one, be it a spouse, a child or a good friend, will tell us "My loved one and I are participating in this study, knowing that we cannot reverse this process. We hope the drug will help, but of equal importance to us is that we feel we are doing something to help battle this terrible disease,'" Wilcox told Psychiatric Times. "I keep coming back to the word 'altruism,' even though it seems a little flowery, because I believe for a number of people, that is a significant component of their motivation."
The fifth reason, Wilcox said, is personalized attention. Participants like the "old-fashioned primary care model that we have here...where patients are able to come in and learn a little bit about their illness, have an experienced professional listen to them and give them some degree of attention and care, not only during the study, but in programs that fall in the category of aftercare as well."Recruiting Via the Internet
Over the years, many clinical research sites have relied on newspaper and radio advertising to recruit patients, but now many are combining that with the new technology of the Internet, along with more targeted marketing techniques.
Some 6,000 clinical trials where investigators are actively recruiting patients are posted in CenterWatch Clinical Trials Listing Service, an international listing of clinical research trials, said Ann Kennon, CenterWatch's Web manager. All of the information provided on the listing service is free to anyone with Internet access.
"The majority of trials posted on CenterWatch have been placed there by some 75 pharmaceutical companies sponsoring research...They post a patient recruitment ad on behalf of all of research centers participating in a study. The fee is $20 per research center per month," she said.
CenterWatch is visited by approximately 80,000 people per month, Kennon said, adding that she estimates that "70% to 75% are patients looking to participate in clinical trials." Others visiting the Internet site include health care professionals such as physicians, clinical research study coordinators and professionals in pharmaceutical companies.
Patients find the Web site through Internet search engines and through referrals from health associations and patient advocacy groups. Once the CenterWatch site has been located at <www.centerwatch.com>, a patient can click on the listing of clinical trials in the patient resources section. The trials are organized by disease category. If a patient were looking for a clinical trial involving an antidepressant, for example, he or she would click on psychiatry and then on the subcategory of depression.
"All the trials are broken down by geographical area; patients will only look for a study in their own geographic region, because most cannot afford to travel," Kennon said.
Once a clinical trial is located, the patient can then click on it and read a more detailed description of the study, typically including the inclusion/exclusion criteria, as well as a profile of the research center, a summary of the clinical research experience, a listing of staff expertise and the name of a person at the research center to contact for more information. Oftentimes, an e-mail address is provided so that the patient can respond directly to the center.
Usually, Phase II to Phase IV trials are posted at CenterWatch. Along with pharmaceutical company-sponsored trials, there are also some government agency-sponsored trials. Examples of recent psychiatry-related postings on CenterWatch are a study to compare the antidepressant efficacy and tolerability of two marketed medications with placebo in treating geriatric outpatients, a study to evaluate the safety and efficacy of research medications for patients with bipolar disorder, and a Phase III, double-blind, placebo-controlled study to test the safety and efficacy of two active doses of a medication used in patients with alcohol dependency.
When a patient cannot find a trial, CenterWatch provides the option of a free and confidential patient notification service.
"Patients register their e-mail address and therapeutic areas of interest, so if they were interested in depression, for example, they would enter that into the database," Kennon said. "Anytime we post a new study in that area, we would send the requester an e-mail message. We have 16,000 patients registered in our database. The database is very diverse in terms of disease area. Oncology is the largest group; 20% of those registered are cancer patients. About 10% [of those registered] are psychiatric patients."
The patient notification service also provides the requesters with the option of being notified about drugs newly approved by the U.S. Food and Drug Administration in a particular therapeutic area.
Not only are some of the clinical trials centers listed on CenterWatch, many have established their own Web sites or are posting trials on the sites of others, such as patient advocacy groups. The response results have been mixed.
"The biggest problem of listing on the Internet is you can't really control where your replies are coming from," said Hashim. "We are getting replies from people who are not necessarily in our area, so we really can't do anything for them if they are out of the San Diego area. We're not presently getting many viable study participants from the Internet, but we expected that. We went online as a look to the future rather than what it would generate for us today."
When the pharmaceutical company Organon posted information via CenterWatch regarding a clinical trial that the University of Texas Southwestern Medical Center was conducting on the use of mirtazapine(Drug information on mirtazapine) (Remeron) for people who had failed to respond to serotonin reuptake inhibitors, Baker said several people volunteered to participate. Unfortunately, most of the volunteers were from other states or cities.
"We did notice, however, that lots of the respondents did send us via e-mail extensive information about themselves," she said.
Wilcox pointed out that about two and one-half years ago, PRI started recruiting study participants via the Internet for several research studies involving treatment of depression, anxiety, migraine, panic attacks and memory loss due to Alzheimer's disease. The company has its own Web site, <www.priresearch.com>, as well as postings on CenterWatch.
"We've gotten an overwhelming response from recent college graduates looking for employment, foreign-trained medical graduates looking for employment and a somewhat significant response from people overseas, wondering if we can--via grants--bring their relatives here to treat them for certain illnesses, usually Alzheimer's disease. In terms of viable study participants, I believe we have enrolled one patient suffering from migraine headaches," he said, adding that he is personally convinced that with regard to patient recruitment for clinical trials, the Internet is not "ready for prime time."Other Avenues for Recruitment
PRI, Wilcox said, relies heavily on print advertising in major newspapers and on some radio spots.
"Those venues seem to be the most effective for us," he said. "We also receive some referrals from practitioners in the community...because they know that we have been around for a long time, that we have five board-certified physicians and nine masters-degreed nurses and a fairly low turnover...We also receive a fair number of referrals from friends and relatives of former study participants."
At the University of Texas Southwestern Medical Center, Baker said patients are also recruited through media advertising and referrals from physicians and clinics on campus.
"Because recruitment is becoming difficult, we really need to broaden our resources," she said. That broadening process encompasses sending letters and information to local mental health clinics and to nonprofit organizations that provide counseling on a sliding scale.
Recently, the center developed a brochure that lists every current study it is conducting, including several on depression, several on anxiety disorders and some exploring different routes of administration, such as patches to administer psychotropic drugs. The brochure also describes a grant-funded brain imaging project that Madhukar Trivedi, M.D., assistant professor of psychiatry, is involved with.
Baker added that the center staff is trying to get the brochure to different community agencies such as libraries, college campus health clinics and job fairs.
"We have been invited by representatives of employee assistance programs to have our materials available in their offices to hand out to employees when they seek help," she said. "Those are some of the newer things we are trying to do, because the advertising in itself is not sufficient any longer."
At Feighner Research Institute, Hashim said, "We've tried to build up a physician referral base in our area and to do direct mailings to physicians, therapists and other health care professionals. We do a lot of advertising in newspapers, on television and radio."
John Feighner, M.D., institute director, also has produced some television advertisements, according to Hashim.
"Looking very dignified, Dr. Feighner comes on and explains the symptoms of a specific psychiatric disorder, the availability of the research study and the basic requirements for study participation, such as age and general good health. This is followed by a telephone number to call," Hashim said. "We have used this technique in recruiting patients for clinical trials involving depression, anxiety, migraines and Alzheimer's disease."
Feighner, who has been in the San Diego area for 25 years, is also sought out by television news reporters to comment on events involving psychiatric issues.
"When he is on the news as an expert on some psychiatric disorder, we are absolutely deluged with calls from people volunteering for our studies," she said.
Individuals volunteering for studies are carefully screened by telephone, and even those who are not found to be appropriate for the clinical trial are referred to community resources for help.
Other clinical research sites also provide referrals to sources of help. CenterWatch, too, has links to general and specific health resources, associations and patient advocacy groups. Overall, patients, whether they are appropriate for clinical drug trials or not, are given some help.