Conclusions of this study by The University of Texas M. D. Anderson Cancer Center, published in the September 15 issue of the Journal of Clinical Oncology, suggests that some patients who follow the medical media are sophisticated enough to understand the purpose and limitations of the clinical trials process -- even in the face of what researchers see as optimistic reporting.
"We thought patients who wanted to enter a clinical trial because of what the media reported would have unrealistically high hopes and would be misinformed about Phase I testing, but some turned out to be almost ideal Phase I participants," said the study's lead author, Rebecca Pentz, Ph.D, a professor of hematology and oncology in research ethics at Emory University's Winship Cancer Institute.
"They were hopeful, as all patients wishing to enter a Phase I trial tend to be, yet well informed and realistic -- the kind of patients that researchers want," says Pentz, who conducted the study while she worked at M. D. Anderson, before her move to Emory. The research was funded in part by the National Cancer Institute.
"Contrary to our expectations, the media coverage was helpful because the patients it brought in appeared to be better informed than those who came in through the standard referral process via their physicians," agreed the study's principal investigator, James Abbruzzese, M.D., professor and chairman of M. D. Anderson's Department of Gastrointestinal Medical Oncology. "This is a small study, but it is reassuring."
This study was launched 18 months after The New York Times ran a landmark, front page story on May 3, 1998, that heralded the discovery and development of an agent called recombinant human endostatin (rh-Endo), an angiogenesis inhibitor designed to dry up a tumor's source of blood, starving it. In the article, researchers predicted endostatin might quickly prove to be a cure for cancer. The media blitz that followed was unusual in medical reporting because the drug had not been formally tested in humans.
When M. D. Anderson researchers geared up to run a small Phase I clinical trial of rh-Endo -- one of three centers in the country to conduct such a study -- they were ethically concerned that such "hyperbolic" coverage both in 1998 and at the launch of the clinical trials might draw patients who had little understanding of the purpose of a Phase I clinical trial, but were solely focused on the drug's ability to save their lives. Patients admitted into this beginning phase of testing have no curative treatment options, yet these trials are designed to determine safety and optimal dose, and monitor effectiveness -- it is not intended to prove clinical benefit.
To see if their worries were justified, they asked patients who were referred to the trial from physicians at M. D. Anderson to participate in a survey. Some of these patients were not being cared for at M. D. Anderson, but subsequently contacted the cancer center in the hopes of being seen and referred to the trial.
The seven-member ethics research team analyzed media coverage of the agent from 1997 to 2000 in three newspapers known for medical reporting -- The New York Times, Boston Globe and Chicago Tribune. They found that the majority of coverage was generally positive on the promise of endostatin -- only 25 percent of the articles gave what researchers called a "factual account."
They then surveyed 100 patients referred to the endostatin trial between October 1999 and November 2000. Almost half of survey participants (47 percent) had heard about endostatin from media sources, and 51 percent of these patients had then contacted their physicians to start the process of entering the trial.
The patients were then divided into two groups. The "pre-IC" group included the majority of patients, 79 percent, who had not yet met with endostatin investigators to discuss the trial, and thus had not entered an informed consent (IC) process that formally presents the goals and limitations of the trial. The other 21 percent of patients were the "post-IC group" because they had met with endostatin investigators by the time they took the survey.
The researchers first looked at whether the patients surveyed knew the purpose of a Phase I clinical trial, and found that across both groups, 33 percent had the right understanding.
Comparing the pre-IC and post-IC groups, the study team found that patients who had met with trial investigators were no more likely than patients who had not to identify the purpose of a trial correctly, says Pentz. Many patients already had decided to enter the trial, if they could get in, even before they had met with the endostatin researchers. Eighty percent of 99 patients said they had decided to join the study if offered a chance, while 45 percent said they had no concerns about participating.
"For patients who talked to the trial coordinators, new information may not have led to an understanding of what the trial was designed to do, because they had already decided they wanted to be in it," says Pentz. "This lack of understanding is typical of what has been found in other studies like this," she says. "We were a bit surprised, though, that so many people had decided to participate before meeting with trial investigators."
But a difference emerged when the survey team examined the pre-IC group (those who had not met endostatin researchers) for their understanding of clinical trial. Of pre-IC patients who got their information first from media, 47 percent correctly understood the purpose of the trial. In fact, they were five times more likely to understand the process than pre-IC patients who heard about the trial from other sources. The knowledgeable patients tended to be younger, college educated, "media consumers," says Pentz.
Finally, the researchers measured the patients' motivation for joining the study, and almost without exception (99 percent), patients in both groups agreed that one factor contributing to their decision to seek the clinical trial was that "joining the study gives me hope." Seventy-four percent (70 of 95) of the patients cited hope for personal benefit as the main reason for their willingness to enroll, and those who first heard about endostatin from the media were no more motivated by hope of personal benefit (77 percent) than those who first heard from other sources (71 percent).
It is understandable that patients want to benefit from the study, but it is problematic if they believe such benefit is the purpose of the trial, the researchers contend. But patients who understand that personal benefit is not the purpose of the trial but who remain hopeful "constitute an ethically desirable Phase I research population, for this group avoids both false hope and hopelessness," the researchers say in their study publication.
In this study, media coverage didn't inflate hope -- "everyone had hope," says Pentz -- but did increase understanding of the purpose of the trial, she says.