Handle with Care
by Heidi Moore
June 2007
Although full disclosure of early phase clinical trial results is lauded for the sake of transparency, data must be disseminated carefully and responsibly to avoid raising false hopes.
Since the Abigail Alliance for Better Access to Developmental Drugs petitioned the U.S Food and Drug Administration (FDA) in 2003 for access to unproven, early phase investigational drugs for terminally ill patients not enrolled in clinical trials, patient advocacy groups and medical ethicists have been struggling to answer the question: How early is too early?
Early phase clinical trials generate preliminary results that mainly relate to safety and, in some therapeutic areas, efficacy. Drugs tested in such trials often abruptly exit the research stage for safety or tolerability reasons, and fail to proceed to later phase studies. In cases where efficacy data from early phase clinical trials exists, the data usually is just the first indication of whether a compound is tolerated by patients, and often comes only from a one-week or 10-day study, says Dr. Charles Farthing, the Los Angeles, Calif., USA-based chief of medicine for the AIDS Healthcare Foundation.
Proceed with Caution
In early phase trials, there isn’t much data that is relevant to the general public, Farthing says. Promising trial results won’t necessarily lead to the development of a specific compound within a particular class of drugs, although early results may suggest that a certain therapeutic platform will prove effective after further research. In other words, researchers should exercise restraint before releasing the results of early phase trials, he says. Positive initial data can be misleading and may encourage false hope in an already vulnerable population.
For this reason, trial sponsors should guard against premature dissemination of early phase clinical trial data, says Dr. Lainie Friedman Ross, associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago, in Chicago, Ill., USA. “There’s a real conflict of interest here when pharmaceutical companies try to get data out earlier,” she says.
Divulging trial information to the media too soon can result in unwarranted hype and the “wonder drug” phenomenon, which touts a particular agent as a cure for cancer or AIDS, despite the limited data on which the claim is based. “No matter when [a trial] gets published, you must remind people that in later phase trials—when it goes out to the public—we’ll find things we didn’t find in those earlier trials,” Ross says. “But to use the media [to disseminate] preliminary safety data based on a very small sample seems socially irresponsible.”
The conflict of interest inherent in the release of preliminary trial data to the media goes beyond mere unwarranted hype, says Arthur Caplan, Ph.D., director of the Center for Bioethics at the University of Pennsylvania, in Philadelphia, Pa., USA. During the early clinical development stage, companies often are looking for investors and trying to convince people that their therapeutic platform is worth putting money behind, he says. Many of these scenarios involve “small companies desperate to attract capital,” Caplan says, and for some, the desire to generate buzz for the sake of gaining financial backing may win out over the need to offer realistic and balanced projections about the drug’s efficacy.
Hope or Hype?
Because accurate interpretation of trial data requires specialized knowledge, caution when releasing results is necessary to avoid misinterpretation. There are many different types of drugs being tested in Phase I, and they have vastly different contexts and expected outcomes, Caplan says.
One of the main reasons pharmaceutical companies and university research departments release early phase data is to recruit participants for future clinical trials. Drug researchers depend on volunteer subjects to determine safety and sometimes efficacy, and in some cases these patients may benefit from access to new drug compounds that end up saving or dramatically improving their lives. The problem arises when patients who are in need of a cure read an over-hyped or incorrectly contextualized story about the latest wonder drug and pin their hopes on accessing it. “You certainly have desperate people who have used up every other option and are looking at [results from] Phase I studies and say, ‘I have to get that, it’s my best chance,’ and it might be no chance,” Caplan says.
False hope stems from what Caplan calls the “therapeutic misconception” of clinical trials—patients’ mistaken belief that the primary goal of a trial is not to generate scientific knowledge but to make them better. “Usually Phase I is not useful for putting forward hope of any kind, and doctors want to give hope,” he says.
To avoid the creation of false hope, early-phase data should undergo an independent review prior to its release, preferably undertaken by an outside researcher with no relationship to the trial, Caplan says. “Have someone not affiliated with the study evaluate the data and see what they think,” he says. Following the review, trial sponsors should make the information available in a standardized format on the Web as well as in peer-reviewed journals, he says.
Focus on Patients
One critical but often overlooked reason for the responsible release of early phase clinical trial data is the trial participants themselves. “You have to be very careful when giving results to participants,” says Dr. Ann Partridge, medical oncologist at the Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, both in Boston, Mass., USA. “Many patients don’t really understand clinical trials, and certainly not the actual goal of a Phase I clinical trial. So when you give results with an explanation, they’re certainly more informed about the clinical results.”
Trial participants who know and understand trial results are more likely to feel positive about the experience of participating in clinical research, Partridge says. Therefore, researchers must be careful when delivering trial results to patients because they can have a strong emotional response, she says.
For example, if a compound does very well in a trial, and early data indicates a blockbuster drug in the making, patients whose conditions improved with the drug would be understandably pleased by the outcome. But other patients who had a bad experience with the treatment—whether they experienced toxicity or just failed to have a good therapeutic response—might feel anxious and upset when hearing about the majority of positive responses. These participants might feel as if they “drew the short straw,” Partridge says.
When patients exit a clinical trial feeling let down by the experience, they’re unlikely to participate in future investigations. This kind of negative response can have broader ramifications when these trial participants voice their disappointment to the media or even just to friends and family, Partridge says. In the worst-case scenario, trial participants might feel misled by the clinical trial process. “That doesn’t mean that we shouldn’t be offering results,” she says. “We just need to do the best job we can explaining the goals to patients as well as the actual results, and offer support and explanations when results are shared.”
“[Participants] may be giving up a lot to be in a trial,” Partridge says. “They give up their time. They give up their body to a degree. As such, trial participants should be treated as partners in the research process as much as possible, and sharing study results is one small piece of the clinical trial process that would show appreciation and respect for their participation, and might improve communications with clinical trial participants.”
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