Taking Advantage of Clinical Trials
According to a research study published in the August 2000 issue of the Journal of Clinical Oncology, worries about higher costs should play no role in a patient's decision on whether to enroll in a clinical trial. Dr. Charles Bennett of the Veterans Administration Chicago Healthcare System-Lakeside and colleagues calculated that the cost of treating cancer patients enrolled in clinical trials is no higher than the cost that would be incurred with conventional treatments.
This conclusion runs contrary to an earlier finding by the Congressional Budget Office which reported that clinical trials cost an average 25 percent more than standard therapies.
The conclusion by Bennett's team is important because cost has often been cited as a significant-but certainly not the only-barrier to more participation by cancer patients in clinical trials. And the end result is that clinical trials are skewing results that may not be relevant to older, minority or even female cancer patients.
Bennett's team based their conclusions on the costs of care for 70 cancer patients treated for 6 months in 5 different cancer centers. Half of the patients were enrolled in phase II cancer clinical trials during the study period and half were not. They calculated that the costs for treating the patients enrolled in clinical trials averaged $57,542, while the costs for the patients receiving standard care was $63,721.
This finding is significant because it comes on the heels of President Clinton's executive order in June that Medicare begin covering the costs of treatment for senior citizens in clinical trials that test medicines and procedures to cure illnesses such as cancer, Alzheimer's and heart disease.
Clinton noted that seniors are "badly underrepresented" in clinical trials, yet they develop a much higher percentage of life-threatening illnesses due to the normal aging process. In his statement, Clinton asserted that only a third of the participants in cancer clinical trials are senior citizens, while more than half of all cancer patients are over 65.
In fact, the situation may actually be worse.
A study published in the New England Journal of Medicine looked at how many patients 65 years of age and older were involved in 164 Southwest Oncology Group (SWOG) cancer treatment trials between 1993 and 1996. Dr. Laura Hutchins of the University of Arkansas for Medical Sciences in Little Rock and colleagues analyzed treatment trials for 15 types of cancer and found that older patients are "substantially underrepresented."
Patients who were 65 years of age or older accounted for only 25 percent of patients in SWOG trials, but they comprised 63 percent of the cancer patients in the U.S. population, they wrote.
They added that the underenrollment of older patients was "particularly striking" for breast cancer trials. In those studies, only 9 percent of participants were 65 years of age or older, versus 49 percent of patients in the general population with breast cancer.
Hutchins echoed what many other researchers have also concluded: Far too many doctors-and even patients themselves-assume that older patients would not be able to tolerate or benefit from many of the most promising treatments under study. However, given that the number of people over the age of 65 is expected to double in the coming decades, such assumptions could be disastrous.
It is not just seniors who are underrepresented; virtually every minority group has traditionally lagged in clinical trial enrollment.
For example, a recent trial that investigated the preventive use of tamoxifen for breast cancer had so few African-American participants that there was insufficient data to show whether tamoxifen could benefit these women. African-American women are known to have estrogen-receptor-negative tumors more often than white women and to develop the disease at a younger age.
In a symposium last year sponsored by the Magic Johnson Foundation, a dais of speakers noted that minorities in general-and African Americans in particular-face unique barriers that limit their participation in clinical trials. Factors cited by the panel included lack of information from physicians, cultural biases, less access to quality medical care, and even patients' lingering mistrust because of the infamous Tuskegee Experiment (in which black patients were unwittingly exposed to syphilis as part of a government research program).
However, the panel emphasized that another barrier to involvement is a basic lack of awareness that clinical trials were available. Until recently, only oncologists who were members of NCI-sponsored cooperative research groups could refer patients to clinical trials. Many outside physicians were simply not aware of pertinent trials for their patients.
In response to a growing number of such findings-and an alarming lack of clinical trial participants-the National Cancer Institute launched the Expanded Participation Project in March. The objective is to extend clinical trial privileges to qualified oncologists beyond those who are members of the major research cooperatives. Any qualified oncologist can now participate in an NCI-sponsored trial.
In announcing the pilot project, Dr. Richard Ungerleider pointed out that 97 percent of U.S. cancer patients have never participated in a clinical study, and this is severely hampering research efforts into promising treatments and even a possible cure.
A panel discussion sponsored by the Susan G. Komen Breast Cancer Foundation reported that only 3 percent of eligible breast cancer patients participate in clinical trials in the United States, while enrollment rates are as high as 70 percent for breast cancer trials in Scandinavia and 50 percent for U.S. pediatric cancer trials.
Reasons cited for this low enrollment rate were: failure by the physician to mention that trials existed, time requirements on physicians, and basic misperceptions about the nature of trials. Furthermore, both patients and physicians may be uncomfortable with randomization, said the panelists, even though cancer patients are randomized either to the best standard therapy or to promising new therapies.
In a presentation to delegates at the recent annual meeting of the American Society for Clinical Oncology, Dr. Robert Comis of the MCP Hahnemann University Clinical Trials Research Center in Philadelphia, said that 84 percent of cancer patients are simply unaware of clinical trials or not sure that they would be an option for them. The findings were based on a survey of 6,000 cancer patients by Harris Interactive.
Only 4 percent of the cancer patients interviewed by Harris Interactive said they had participated in clinical trials, and the majority of them heard about the possibility through their physician. About 58 percent of the respondents said they would never participate in a clinical trial; fear of getting insurance coverage for the trial costs was mentioned as a concern by a majority of these respondents. They also cited worries that they would not get the best treatment or that they would get a placebo instead of a real drug. More than 20 percent said they would feel like a "guinea pig."
Yet, in the same survey 97 percent of the patients who had participated in clinical trials said they received excellent or good quality care and that they were treated with dignity. And the vast majority said they would recommend participating in clinical trials to others. Eighty-six percent of the patients also said they were able to secure insurance coverage for their participation.
Last November, the U.S. General Accounting Office issued a report on the coverage provided by insurers of clinical trials. It found no evidence that insurers were tightening payments on coverage of experimental treatment or impeding participation. While insurers generally excluded clinical trials from coverage, the report said, the plans that were reviewed by the GAO investigators generally made exceptions on a case-by-case basis. "We did not find evidence of widespread limitations on patient access to clinical trials," the GAO concluded.
But the process is burdensome, the investigators noted, and "given the uncertainty about approval and payment levels, patients and physicians can be discouraged from seeking prior approval from insurers." One result, according to the report, is that doctors "submit claims without identifying the services as trial-related. Consequently, insurers may be covering more trial services than they officially approve."
Every successful cancer treatment being used today started as a clinical trial, which is a three-step research process to evaluate the safety and effectiveness of a new treatment. Those patients who participated in these successful trials were the first to benefit from the improved therapy.
All clinical trial participants receive the best care possible, and their reactions to the treatment are watched very closely. If the treatment does not seem to be helping, a doctor can take a patient out of a study. Also, a patient may choose to leave at any time. If a patient leaves a research study for any reason, standard care and treatment are still available.
Experts are unanimous about the dire need to dramatically increase enrollments in cancer clinical trials. As Dr. Nancy Davidson of the Johns Hopkins Oncology Center in Baltimore noted during the Komen Foundation symposium, "Everything we can tell patients today is based on the results of clinical trials that have been done in the past."
SOURCES:
Journal of Clinical Oncology, August 2000; 18: 2805-2810
New England Journal of Medicine, December 30, 1999; 341:2061-2067
"African Americans and Breast Cancer," a symposium sponsored by the Magic Johnson Foundation, Sept. 14, 2000, New York, NY
The National Cancer Institute (http://www.nci.nih.gov)
Abstracts from the annual meeting of the American Society of Clinical Oncology, May 23, 2000, New Orleans, LA
Susan G. Komen Breast Cancer Foundation (http://www.komen.org)
Office of Research on Minority Health, National Institutes of Health
Drug Benefit Trends, 1999; 11(12):17-18
[Table of Contents] [Archived Issues / Search] [The Breast Center]