Benefit of Clinical Trials to Participants Questioned

Writing in The Lancet (2004;363:263–270), researchers from the Dana-Farber Cancer Institute say there's not much evidence patients participating in cancer clinical trials have better outcomes than those who do not participate. 

Figure  .

Clinical trial enrollment efforts should emphasize benefit to future, rather than current, patients.

Jeffrey Peppercorn, MD, MPH, and colleagues reviewed 24 published studies describing 26 comparisons of outcomes for patients who participated in clinical trials with those who did not to determine whether there was a discernible “trial effect”—a measurably better outcome for those who participated. Fourteen of these 26 comparisons showed some evidence of better outcomes among trial participants. However, only eight comparisons limited the control group to individuals who met eligibility criteria for the trials in question. Of these eight comparisons, only three showed a benefit to those enrolled in the study. Studies showing a trial effect were more likely to involve pediatric cancers and hematologic malignancies and were more often from the period before 1986. No studies showed worse outcomes for people who participated compared with other patients.

“We found a few instances in which cancer trial participants may have had better outcomes than nonparticipants, but the limitations of the data we reviewed made it difficult to establish a definitive link between trial participation and improved outcome,” said coauthor Steven Joffe, MD, MPH, in a statement.

Most of the comparisons were retrospective cohort analyses, and few controlled adequately for potentially confounding factors like comorbidities, socioeconomic status, or treatment differences like hospital volume or care in a specialized cancer center, the authors wrote.

However, that doesn't mean cancer patients should be discouraged from participating in trials. “Clinical trials are critical to the advancement of cancer care, but it is important that people who enroll in a study understand that their participation is intended primarily to benefit future patients,” said Peppercorn, a clinical fellow at the Dana-Farber Cancer Institute.

“It is important that we not overpromise the potential results and outcomes of participation [in clinical trials],” agreed Harmon J. Eyre, MD, Chief Medical Officer of the ACS and CA Editor-in-Chief.

But Eyre questioned whether doctors really are giving patients false hope, and he worried that the study might discourage some patients from taking part in critical research. “This study may lead patients, their families, and even health care providers to the faulty conclusion that participating in clinical trials has no benefit,” he said.

Although no two trials are the same, Eyre noted that many do offer participants certain advantages. Patients may get access to treatments that aren't otherwise available and that may be safer or more effective than standard treatment, for instance. Patients in trials may be more carefully monitored for changes in their condition and for side effects of treatment. Participants may also be offered a greater number of treatment options, even if they haven't exhausted standard options.

“Treatment offered in most trials is equivalent to or incrementally more effective than the current standard of care, and there are numerous examples of real advances that led to dramatic improvements in survival and quality of life among participating patients,” Eyre said. “We should not lead participants to believe that trial participation is likely to improve their survival, but it is true that participating patients have small chance of substantial benefit from a new therapy.”

Eyre pointed out that Peppercorn and colleagues noticed a trial effect for childhood and hematologic cancers, areas of rapid progress during the time these data were collected. During such a period, trial participants may benefit from access to new treatments; when little progress is being made, a trial effect is less likely. The problem facing both patients and oncologists, he said, is that it's often difficult to predict which trials provide access to the next big breakthrough.

There is also evidence that trial participation has a positive impact on quality of life for some patients, even in Phase 1 oncology trials, which are designed to study safety rather than efficacy (JAMA 2003;290:1,075–1,082). Participating in a trial that offers even a relatively small chance of direct benefit is an important coping strategy for some patients, Eyre said. For others, the opportunity to help future patients is a source of pride and comfort.

Finally, trial participation offers some patients the opportunity to receive their care from leaders in academic oncology who might not currently be accepting many new patients outside of certain trials, Eyre noted.

Of course, there are downsides to trials, also. Patients in randomized trials do not have a choice concerning which treatment they receive, insurers may not cover the cost of participation, and patients may be inconvenienced by more frequent testing or time and travel commitments associated with participation.

Nevertheless, Eyre said clinical trials are crucial. “Because clinical trials often benefit tomorrow's patients and sometimes help today's patients, the ACS will continue to promote participation in these trials.”