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Vol. LXII, No. 20
October 1, 2010
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Pay Attention to Potential Tension
Grady Points Out Ethical Challenges Where Clinical Research, Practice Meet

On the front page...

Clinical care and clinical research are not the same. Mostly around NIH we know this, but even the most seasoned medical research veterans can find themselves facing a potential ethics crash at the intersection of care and research. At a recent Grand Rounds for Clinical Fellows, Dr. Christine Grady, acting chief of the Clinical Center’s department of bioethics, offered a crash course on preventing collisions.

“There are strong reasons that clinical research and clinical care are distinct, and the reasons are very ethically significant,” she began. That doesn’t mean there’s no overlap between the two, but each has its own goals, methods, justifications for risks and levels of uncertainty.

Continued...


  Dr. Christine Grady  
  Dr. Christine Grady  

Distinct, Not Mutually Exclusive

“The goal of clinical practice is to provide personal or individualized care to people…to benefit them, to improve their condition in some way,” Grady said. “This is distinct from the goal of clinical research, which is to produce useful knowledge through systematic investigation about human health and illness for the benefit of future patients.”

That’s not to say that individuals don’t benefit from clinical research, because they often do, she pointed out. However, “the goal…is not to benefit the individuals who are in it.”

Another area where the two part ways: Research uses different methods than care. Randomizing treatments, double-blinding and placebos, for example, are all typical in research, but not what you want to encounter in a standard care environment.

“It would be very unusual—perhaps even unacceptable—to walk into a physician’s office for treatment and have the doctor say, ‘I’m going to flip a coin to decide what to give you today for your condition’ or ‘I’m going to give you a drug but I don’t know which one it is,’” Grady said. “Yet these are common methods in clinical research.”

In clinical care, treatment decisions are based on what is known through evidence and experience, Grady said. That’s very different from clinical research, where scientists have a hypothesis they are attempting to prove.

“In clinical research,” she stressed, “the starting point is uncertainty. You don’t do a research project if you already know the answer to it. The investigator asks a question to decrease the uncertainty, to gather knowledge about what’s safe or what works or what happens physiologically.”

Competing Commitments Meaningful

So, why do the differences matter?

“It’s critically important—and ethically important— to recognize the distinctions between clinical care and clinical research in order to negotiate the tensions inherent and inevitable in conducting” either, and particularly when one individual has dual roles as care provider and investigator, Grady explained.

If “competing commitments” are not recognized and managed, she argued, they become distractions that can affect study design, recruitment and other procedures. “

“In clinical research, the starting point is uncertainty. You don’t do a research project if you already know the answer to it.”

Clinicians are worried about referring their patients to clinical studies because they don’t like randomization or they’re afraid that their “In clinical research, the starting point is uncertainty. You don’t do a research project if you already know the answer to it.”patient will not benefit from the study,” she acknowledged.

According to a 2009 study published in IRB: Ethics and Human Research by Charles Lidz and colleagues, 70 percent of 780 physicians and nurses surveyed said that at least once they did not refer an eligible patient for a study because it did not appear that the patient would benefit. In addition, 90 percent thought ignoring a minor entry requirement was okay if they felt a patient would benefit from being in the study.

In the first instance, study recruitment could suffer. In the second, study data would be skewed.

Grady made a strong case for would-be investigators—and everyone else in the clinical research setting, from study designers to study protocol recruiters to referring physicians to nurses—to consider the various built-in competing ethics forces involved with conducting clinical research and providing clinical care.

Grady made a strong case for would-be investigators—and everyone else in the clinical research setting, from study designers to study protocol recruiters to referring physicians to nurses—to consider the various built-in competing ethics forces involved with conducting clinical research and providing clinical care.

Coming to Terms

Citing a 2003 New England Journal of Medicine paper by Rosenstein and Miller, she described therapeutic orientation—approaching clinical research through the lens of clinical care without appreciating the distinction—as one source of ethical tensions in research.

“Conflating the ethics of clinical care and research can result in problems in recruitment, determining eligibility, informed consent, monitoring of participants during a trial, dose modifications and withdrawal from a research study,” she noted, providing examples of each. One example is the tension a physician with a therapeutic orientation may experience over giving one patient the trial drug, which the doctor-turned-researcher believes will help the patient’s condition, and giving another patient a placebo. Clinical equipoise, a phrase coined in 1987 by Canadian scientist Dr. Benjamin Freedman and adopted widely by the biomedical research community since then, deals with that dilemma.

Grady said Freedman reasoned that an individual scientist who wants to compare two therapies in a randomized clinical trial can do so if there is genuine uncertainty among other authorities in the field that neither therapy is better than the other. “But clinical equipoise assumes a therapeutic orientation, does not take into consideration the value of the research and provides little direction for critical questions such as statistical design and when to stop the research,” Grady pointed out.

Communication Key to Navigating Perceptions

In her hour-long presentation, followed by a Q&A period, Grady made a strong case for would-be investigators—and everyone else in the clinical research setting, from study designers to study protocol recruiters to referring physicians to nurses—to consider the various built-in competing ethics forces involved with conducting clinical research and providing clinical care.

“Clinical research is socially valuable but ethically challenging,” she said in conclusion. “Ethical clinical research requires balancing rigorous science and protection of research participants” as well as “clarity about how clinical research differs from clinical care.”

Grady recommended “education and support of investigators, clinicians and related others regarding the differences between research and care as well as strategies for managing the tensions, thoughtful oversight of clinical research and greater transparency for research participants.”

To view the full lecture online, go to Past Events at http://videocast.nih.gov/. NIHRecord Icon

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