Jostling for a seat in the last
chance cancer saloon

Patients believe those in clinical trials get better care.
Outcomes suggest they're wrong

By Owen Dyer

Clinical trials were created to advance science, but nowadays there's another side to the story. Many savvy cancer patients are actively trying to get into these trials, seeing them as a way to improve their own chances of survival, and help out future sufferers. What's attracting them is the possibility of getting access to the newest treatments, and also the encouraging belief of many oncologists that even when treatments are equal, patients enrolled in trials do better than those who are not. Welcome to the world of the fabled "trial effect." The theory of the trial effect makes a good deal of sense. First, it's generally believed that patients in trials are monitored with exceptional care. Secondly, the perception that trial subjects receive superior treatments and closer attention is naturally conducive to optimism, and may bring a psychological advantage similar to the placebo effect. And the fact that the trial patients have often taken an active role in seeking treatment could help them overcome feelings of helplessness and passivity that engulf many people diagnosed with advanced cancer.

RAIN ON THE PARADE
A study in the January 24 issue of The Lancet, however, appears to throw cold water on the excitement over clinical trials. Dr Steven Joffe of the Dana-Farber Cancer Institute in Boston and his co-authors analyzed 26 comparisons from 24 published articles involving cancer patients in both mainstream treatment and clinical trials.

Of these, 14 provided some evidence that patients enrolled in trials had improved outcomes. In some cases, the benefit was limited to selected subgroups of the study population, or to some endpoints but not others.

But the authors found that in many of these studies, strategies to control for potential confounding factors were inconsistent and frequently inadequate. Only eight comparisons restricted non-trial patients to those meeting trial eligibility criteria. Of these, three noted better outcomes in trial patients than in non-trial patients.

The study found that children with cancer, patients with hematological malignant disease, and patients treated before 1986 were disproportionately represented in studies, which did point to a positive trial effect. The suggestion that children may benefit from the trial effect is significant, because while the proportion of adults with cancer who participate in clinical trials is still just 5%, among children it is close to 75%.

The authors' conclusion is cautionary: "In sum, we found little generalizable evidence to support the contention that trial participation directly improves outcomes for cancer patients. Until more convincing evidence for a trial effect is available, recruitment messages to patients considering trials should focus on their contribution to advances in treatment."

INTERNET TRIAL SHOPPING
So what about the many cancer patients surfing the net for trials to get involved in? There can be little doubt that the internet is a driving force behind this current trend of patients shopping for clinical trials. Word has spread among a new breed of well-informed, web-surfing patients that clinical trials are the way to go. There are now at least 40 websites in North America devoted to tracking down trials. The family doctor and even the specialist can be cut out of the equation altogether if a determined patient feels they are too conservative.

The US government has now published internet advice for patients browsing the web in search of a trial. Look at study size, they caution, and avoid websites that don't name study sponsors. They also warn against websites that list separately each centre of a multicentre trial to increase the chances of getting a hit on that trial.

Current and former cancer patients who have learned how to navigate the choppy waters of clinical trials have set up their own websites offering advice. The non-profit site Cancerguide.org offers Steve's Strategic Clinical Trial Guide, advice from one patient who's seen it all. Avoid Phase I trials, Steve warns, as the doses are too conservative. Phase III trials would be ideal, were it not for the danger of being randomized into the conventional treatment group. The holy grails, says Steve, are the Phase II trials.

ALTRUISM AND DESPAIR
All is not lost for the trial effect, however. The study authors argue that "[d]e-emphasising direct benefits to patients need not compromise accrual or coverage. We remain optimistic that strong support for trials can flourish on the basis of their unquestioned role in improving options and outcomes for patients with cancer. Many patients find it rewarding to know that they are contributing to the larger fight against cancer."

Dr Richard Sullivan is head of clinical programs for Cancer Research UK, one of the world's largest cancer charities, which oversees hundreds of clinical trials. He agrees that trials can recruit patients without having to promise the moon. "People underestimate the altruism of cancer patients. A great majority of them draw comfort from the knowledge that they are helping others in the future."

The authors of The Lancet study do not claim, however, to have disproved the trial effect: "Although about half the studies provided some evidence for a trial effect, and none found trial participation to be harmful, methodological difficulties with most studies suggest the need for cautious interpretation." That is good science, no doubt, but pretty unlikely to convince a cancer patient desperate for a cure and fast running out of time.