Don't be wary of discussing clinical trials with patients

Patients frequently ask physicians about clinical trials they have seen advertised. What ethical obligation do physicians have to patients who meet the trial eligibility criteria and are interested in participating?

Reply: Consider this: It's late Monday morning. Dr. James is running at least an hour behind. All her emergency slots are booked, and her inbox with the weekend's phone messages has now doubled with incoming morning messages.

She is finishing her visit with Mr. Smith, 59, who has diabetes, hypertension and renal insufficiency. The new blood pressure medication prescribed has not been successful. His home blood pressure readings are better, but today's labs show that his kidney function has worsened.

Dr. James is wrapping up the visit with a plan to taper off the new medicine and then return to consider a different medication. Mr. Smith agrees. But as she steps toward the door, Mr. Smith produces a newspaper clipping from his shirt pocket.

"Say, Dr. James, what about this study over at the U hospital. I hear they're trying a new medicine for blood pressure. Looks pretty promising, and all medication is free. What do you think?"

Dr. James checks her watch. She wishes he had forgotten about that clipping.

Should discussing clinical trials be part of a primary care physician's responsibilities? Dr. James has dedicated her career to caring for her patients. This care is grounded in trust that what she recommends to each patient is in that patient's best interests. Because research exposes participants to risks and burdens that are not part of personal care, what obligation, if any, does a busy doctor like Dr. James have to engage her patients in the pros and cons of enrolling in research?

The answers to this question come out of Dr. James' practice. Much of what she does relies upon research results. Evidence-based medicine is only as good as the available evidence. Much of the progress in the treatment of common and chronic diseases of adulthood has benefited from the results of valid and well-designed clinical trials that enrolled thousands of patients like Mr. Smith. Dr. James can have a role in shaping that evidence.

For patients like Mr. Smith who have reached the limits of benefiting from current therapies, a clinical trial may be among his best options. He could be on the cutting edge of accruing evidence to support the best care for his complicated and interconnected chronic diseases. In some sense, trying Mr. Smith on yet another medication is itself an "n-of-1" research study. This approach will generate useful data, but not the best data on which to determine the standard of care. Dr. James may not be a skilled clinical trialist, but she has a keen sense of what studies will advance the standard of care.

The question for physicians like Dr. James is: How should busy clinicians guide a patient in deciding whether to become a research participant? The discussion actually fits well into the clinical care setting. Clinicians are skilled at teaching patients how to make informed decisions. Physicians can direct patients like Mr. Smith who are considering a clinical trial to the National Institutes of Health's website at clinicaltrials.gov. That site and the U.S. National Library of Medicine have tutorials that explain what a clinical trial is. Clinicaltrials.gov also provides a searchable registry of clinical trials. Dr. James can easily look up the study at the university to learn whether it is a promising one whose results could advance the standard of care for patients like Mr. Smith.

Though informed consent for research is the responsibility of the clinical investigator, clinicians like Dr. James can help their patients make decisions that are not only informed but also in line with their goals and values. Of course, if Dr. James has a relationship with a study sponsor, such as compensation for screening and referring potential participants, she should disclose that to her patients.

Most research participants have three reasons to justify the risks and burdens of research: an expectation of a possible benefit to their health, trust in the researcher and a desire to contribute to the greater good. To discuss these issues, Dr. James should consider the following questions:

Does the trial offer participants a reasonable prospect of direct benefit to their health? Some research studies, such as a clinical trial that follows the results of a successful safety study of an intervention, offer participants a reasonable prospect of direct benefit to their health. But other studies do not have any therapeutic components; for example, studies designed to examine a new diagnostic test or the metabolism of a drug. Unfortunately, most informed consent forms focus on a long litany of risks and offer few, if any, details about the benefits and their likelihood. Researchers may be reluctant to supply this information during the informed consent session. This leaves patients susceptible to false hopes and exaggerated expectations of benefit. Clinicians can serve as honest judges whether the study is designed in a manner that a participant might benefit.

How will this study advance the standard of care? A fundamental reason why society accepts research is that it produces important knowledge. In medical research that involves patients, important knowledge means results that can advance how we diagnose and treat diseases. This is a critical social contract. The more important the knowledge to be gained from the research, the more research risk society is willing to tolerate.

When the study is over, will patients learn what group they were in -- the experimental treatment or the placebo? Will they learn the results of the study -- whether the drug worked? As personal care is set aside in the service of the routines of the research protocol, the day-to-day experiences of being in research can wear on a person's sense of dignity. One way to restore this dignity is to treat the research participants as co-equals by disclosing, at the end of the study, what the researchers discovered and, more intimately, how each participant performed and what intervention they received.

When the study is over, and if it's successful, how long will it take for the drug to make it into clinical practice? Patients need to know where the study they are considering fits in the continuum of research design and translation. Some studies are testing drugs that are available for other clinical uses or are late in the phases of new development. In either case, at the end of the study, a patient may stand a reasonable chance of reaping the fruits of his research labors. Other studies, though, are in an early phase of development. Years may pass before the drug is available. "Open-label" extension studies help gather further safety and efficacy data while clinical trials are ongoing. But this is not a guarantee.

How important is the money and the promise of "free medication"? Some patients considering research may have motivations other than health benefits, trust and altruism. The ad Mr. Smith produced promised "free treatment." The motivation for free medication needs careful scrutiny. A study that is testing a medication a treating physician could prescribe may be a reasonable way to defray medication costs, but Dr. James ought to counsel her patient to learn if the study design assigns some participants to a no-treatment arm. She should also insist that a study testing an unproven drug is stretching the claim that the "free medicine" is in fact a medicine.

Studies also provide compensation. Participants ought to receive some compensation for their time, and some patients use clinical trials, especially early phase trials, as a way to earn money. But a patient needs to understand that these monetary benefits come with a price: namely, exposure to research risks.

Competent, professional medicine relies on progressive consensus that good evidence supports an intervention. Clinicians who recommend studies that are valuable, and also discourage enrolling in ones that are not, can help to shape this consensus one patient at a time.

Jason Karlawish, MD, professor of Medicine and Medical Ethics, University of Pennsylvania