Selling’ clinical trials goes too far, ethicists say

Corporations hold strings on recruiting methods

Type the phrase "clinical trials" into any Internet search engine, and the responses leap out at you: CenterWatch Clinical Trials Listing Service, Clinical Research Studies Database, AIDS Clinical Trials Information Service — the list goes on.

Increasingly, people with life-threatening conditions do not have to rely on their physicians to inform them about available research studies of new drug regimens or procedures. They can research available studies on their own. In the latest example of this shift, the National Institutes of Health (NIH) and the U.S. Food and Drug Administration have launched their own public Web site, ClinicalTrials.gov, that allows people to search a database of all federally funded clinical trials.

Although this has the potential to open access to the latest therapies to a wider range of people, some ethicists are concerned that such Web sites eventually may function more to recruit study subjects for trials than to inform the public.

"This creates a single outlet, endorsed by the highest authority in the research community. Unlike advertisements in the newspaper or on the radio, which people understand to be true commercials, ClinicalTrials.gov could give people the impression that the trials listed there are somehow endorsed or otherwise better, safer, or, in effect, given the government’s seal of approval," states Jeffrey Kahn, PhD, MPH, director of the Center for Bioethics at the University of Minnesota in Minneapolis. Kahn is author of the "Ethics Matters" column for CNN.com.

Currently, ClinicalTrials.gov, which was created in response to a 1997 congressional law mandating better public information on clinical trials, has several confidentiality protections to guard against misrepresentation. There is no site registration and no requirement for personal identification. People who search the site are not contacted by sponsors of listed studies, although contact information for the studies is listed, and people can call for more information about a particular trial.

Kahn is more concerned about how studies are listed on ClinicalTrials.gov and other informational Web sites, and whether the public understands what clinical trials involve.

"[There should be] clear statements about how research projects get listed on the site, and that the listing carries no endorsement by the listing entity," he says. "There should also be a list of questions potential subjects should always ask about a prospective trial, [as well as] what privacy protections are in place if there are on-line mechanisms for asking for more information about a trial."

Many research studies already advertise in newspapers and on the radio. As long as researchers have adequate informed consent procedures in place before enrolling a subject, does advertising have a harmful effect?

Informed consent is only part of what determines whether a study is conducted in ethical ways, Kahn contends. "Recruitment of subjects is a separate issue, and we need to ask whether recruitment techniques or approaches undermine voluntariness by pressuring potential subjects, or as is more likely in a case like this [the Web site], over-promises benefits or offers undue enticement," he explains.

Actual advertising (not just listing) of research studies is already done in the conventional media, and such ads often pose ethical dilemmas for many institutional review boards (IRBs), explains Gary Chiodo, DMD, director of the Center for Bioethics in Health Care at Oregon Health Sciences University (OHSU) in Portland and chairman of the university’s IRB.

"One of the things we see is advertisements that, rather than couch the approach as We are seeking research subjects for study,’ it is, We are seeking patients for treatment,’" he notes. "There is a very thick line between the investigational study-subject relationship and the doctor-patient relationship that I am not sure is drawn."

Also, advertisements often do not mention the presence of a control group or the chances that a subject participating in the trial will be placed in a group that will not receive the experimental drug or procedure, he adds.

"And one of the things that really drives me crazy is having one centralized phone number to call for more information and having initial screening performed over the telephone," Chiodo states. "When the person calls, the representative on the other end of the line asks them a number of very private, personal questions, and then gets their contact information."

The person calling is then told they will be contacted if they meet the inclusion criteria in the study, he says. "So this other person has all of this sensitive information on an individual — plus the person’s name, telephone number, and address — for further use," Chiodo says.

Initial contact through telephone

For local clinical trials performed at OHSU, potential subjects call a phone number for information, receive a number, and schedule an appointment to come in for initial screening. If the patient is not selected, his or her information is destroyed.

For multicenter trials, which usually offer one centralized telephone number for information and initial screening, the OHSU IRB asks that sponsors either not ask particular questions and/or agree not to ask for identifying information from the person who undergoes the telephone screening. Instead they allow the caller to remain anonymous but call back to find out whether he or she has been accepted.

The OHSU IRB frequently rejects advertisements that do not meet its ethical criteria for informing the public about a study. Those criteria include informing the public of both the possible risks and benefits.

IRBs often face a difficult dilemma when reviewing large multicenter trials that are sponsored by private companies and pharmaceutical corporations, Chiodo says. "For local research studies seeking approval, if we have a problem with the ad, we say, This is not acceptable. Change this, change that.’ The researchers make the changes, and it goes on from there. But in many cases with larger studies, the advertisements are done by the sponsor, and they don’t want to change [them] for one IRB," he says.

In that situation, the IRB at the local center that has investigators wishing to participate in the study must decide not to allow the study to be conducted at the center or allow it to be conducted, but without advertisement.

"This puts the local center at a disadvantage because the other centers with the advertising are going to recruit more participants," he says.

However, the recruiting procedure for a research study should almost be seen as part of the informed consent process, Kahn and Chiodo say. "On the question of informed consent, advertising a clinical trial, either in the newspaper or on a government-sponsored Web site, can create misimpressions or misunderstandings that no amount of informing will undo," Kahn argues. "So, do such potential subjects give adequate informed consent? It’s a question worth asking."

As a result of increased information on the Internet and increased advertising by privately sponsored trials, physicians will face even more pressure from patients who learn about studies themselves.

"The first thing physicians should do [when a patient asks about an unfamiliar clinical study] is research the trial for themselves, then counsel patients accordingly," says Kahn. "This is similar to other information available on the Web to patients, which has created a new task for physicians — reviewing the information brought in by their patients and working to separate wheat from chaff."

Jeffrey Kahn, PhD, MPH, Director, Center for Bioethics, University of Minnesota, N504 Boynton, 410 Church St. S.E., Minneapolis, MN 55455-0346. Also, see Kahn’s "Ethics Matters" column, Shopping for clinical trials: New Web site raises ethical issues. March 6, 2000. http:// www.cnn.com/2000/HEALTH/03/06/ethics.matters/index.html.

Gary Chiodo, DMD, Director, Center for Bioethics in Health Care, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road UHN-86, Portland, OR 97201-3098.

Oregon Health Sciences University. "Research Compliance and Assurance Guidelines on Advertising for Study Subjects" is available on the Web at http://www.ohsu.edu/ra/ad.html.