Hews News
Therapy Controversial
Dr. W. French Anderson
tering TNF to humans and to improve TI1VIL-2 therapy. In the December 22, 1988 New England Journal of Medicine, Rosenberg reported that TIL/IL-2 can cause tumor regressions in about half of the advanced melanoma patients treated.
TNF Toxidty When committee members voiced concern about the potential toxicity of TNF, Rosenberg listed possible methods for reversing TNF toxicity should that occur. One strategy, proved effective in other trials, would be withdrawal of IL2, a critical requirement for the maintenance of TILs. A second approach is administration of steroids such as dexamethasone, which can abrogate tenacities due to IL-2. "Alternatively, there is the possibility that an anti-TNF antibody will soon be available. Some pharmaceutical companies have tested such an antibody that shows promise in animal studies," Rosenberg said. The ADA deficiency disease trial would be conducted under the leaderVol. 82, No. 17, September 5, 1990
Gene therapy has been controversial and a number of groups have resisted its implementation. To ensure that the research is conducted with the greatest safety and that no social, moral, or medical ethics are violated, the NIH has subjected these trials to the most comprehensive and thorough reviews possible. There comes a time to test a good idea, said NIH review committee member Charles J. Epstein, M.D., of the University of California, San Francisco. He remarked, "We're at a point where we'd like to see if it works or not." —By Florence S. Antoine
Experts Debate Quality of Life as Clinical Trial Endpoint Cancer researchers are taking steps toward incorporating measures of how treatment affects patients' quality of life as a routine part of evaluating new therapies in cancer clinical trials. An invited group p of 70 rHnirifins, social scientists, and officials of the Food and Drug Administration met recently to pool the experiences of cancer centers nationwide in inserting quality of life measurement into select clinical trials. Participants grappled with what questionnaires, or tools, best measure cancer patients' emotional and social well-being and debated how such data mesh with traditional clinical trial endpoints of survival and toxicity. "The mix of disciplines represented brought skeptics and optimists of quality of life measurement head on," said workshop organizer Anne Bavier, of the National Cancer Institute. "The workshop was intended [to allow] people in the field to roll up their sleeves and talk through the tough issues," Bavier said. Recommendations produced by four working groups at the meeting will be published this fall, she added.
Downloaded from http://jnci.oxfordjournals.org/ at Emory University on August 17, 2015
ship of Blaese, along with Anderson, Rosenberg and another NCI scientist, Kenneth Culver, M.D. Transfusion of lymphocytes transduced with the ADA gene may trigger the production of ADA, thus rescuing the child's immune system. Because white blood cells usually live no longer than a few months, the patients will have to receive repeated infusions of the transduced cells.
Some Surprises
Dr. R. Michael BUese
While quality of life is not a new consideration in cancer therapy, largescale measurement of it is still evolving. "Promoting patients' quality of life is axiomatic to the health care professions," said John Ferguson, M.D., director of the National Institutes of Health Office of Medical Applications of Research, in his opening address. "But it NEWS 1381
News News The assessment working group also emphasized minimi7ing the time burden on the patient. Questionnaires, preferably answered by the patient directly, should be short enough that the patient can finish them in a few minutes, but long enough to be statistically valid, they said. "We don't need psychometric overkill," Ware added.
Missing Data The working group making recommendations on data collection methods focused on the problem of missing data. "These types of [psychometric]
No Gold Standard Despite the various cancer centers' cumulative experience in measuring quality of life, no "gold standard" measurement tool has emerged. This, however, should not be a stumbling block to incorporating such measures into clinical trials, quality of life expert John Ware, PhJ)., senior scientist at the Institute for the Improvement of Medical Care and Health in Boston, told workshop participants. "There are excellent measurement systems that are ready off-the-shelf and that are practical to use. Methodological constraint is no longer an excuse for not gathering this data," he said. The working group charged with assessing currently available tools concurred. Instead of endorsing one tool, the group recommended that existing reliable patient questionnaires be tailored to problems expected with specific cancer sites and types of treatment being tested in the trial.
1382
drop out of treatment should not be dropped out of the quality of life study, Cella said "Patients who drop out of a trial are generally sicker. If a treatment is so toxic that half the patients drop out, but the half that stays on does well, excluding data from the dropped patients will make the treatment look better than it really is," Cella explained. To ensure institutions collect data efficiently and thoroughly, Cella's group recommended designating a central data coordinator. The group also suggested requiring a description of quality of life concerns in all cancer clinical trial proposals, similar to a statement used by the National Cancer Institute of Canada. "The statement would compel investigators to at least address the issue of quality of life without forcing them to measure it in their particular study," Cella said.
Future Challenge
Dr. John Ware
measures are unforgiving in terms of losing data," said group leader David Cella, Ph.D., professor of psychology at Rush-Presbyterian-St. Luke's Medical Center in Chicago. "Once you've missed a data point, there's no way to go back and measure it." To prevent missed data at the patient level, the group recommended limiting the number of data points within a trial. In many cases two data points, baseline and post-treatment, are sufficient, with the caveat that patients who
But while increased patient and institutional compliance may improve quality of life data, it does not guarantee its acceptance as an endpoint on par with survival and toxicity. FDA officials at the workshop, for example, expressed willingness to approve therapies based on quality of life endpoints, but are unconvinced of the validity of the measurement tools. As a result, no therapy has yet been approved on the basis of improved quality of life. Cella sees much of the future challenge as attitudinal. "We need to recognize that quality of life and survival are not competing endpoints. We need continuing dialogue between clinicians and social scientists to gain insight on how each can improve patient care," he said. "Rarely do the two groups get together — this was a rare event." -By Jill Woolen
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at Emory University on August 17, 2015
has only been in the last two decades that we've attempted to quantify it." Some of these attempts have had surprising results. An example cited by workshop chairman Patricia Ganz, M.D., medical oncologist at UCLA, was a study in which she and her colleagues compared breast cancer patients who had modified radical mastectomies to patients treated with segmental mastectomies. In the year following surgery, the investigators found no significant difference in the overall quality of life of the two groups, although patients with the more radical surgery scored lower in certain components such as clothing and body image. These types of intangible factors give physicians and patients an additional database for choosing between therapies. The data are valuable as prognostic tools as well, Ganz said.
Therapy Controversial
Dr. W. French Anderson
tering TNF to humans and to improve TI1VIL-2 therapy. In the December 22, 1988 New England Journal of Medicine, Rosenberg reported that TIL/IL-2 can cause tumor regressions in about half of the advanced melanoma patients treated.
TNF Toxidty When committee members voiced concern about the potential toxicity of TNF, Rosenberg listed possible methods for reversing TNF toxicity should that occur. One strategy, proved effective in other trials, would be withdrawal of IL2, a critical requirement for the maintenance of TILs. A second approach is administration of steroids such as dexamethasone, which can abrogate tenacities due to IL-2. "Alternatively, there is the possibility that an anti-TNF antibody will soon be available. Some pharmaceutical companies have tested such an antibody that shows promise in animal studies," Rosenberg said. The ADA deficiency disease trial would be conducted under the leaderVol. 82, No. 17, September 5, 1990
Gene therapy has been controversial and a number of groups have resisted its implementation. To ensure that the research is conducted with the greatest safety and that no social, moral, or medical ethics are violated, the NIH has subjected these trials to the most comprehensive and thorough reviews possible. There comes a time to test a good idea, said NIH review committee member Charles J. Epstein, M.D., of the University of California, San Francisco. He remarked, "We're at a point where we'd like to see if it works or not." —By Florence S. Antoine
Experts Debate Quality of Life as Clinical Trial Endpoint Cancer researchers are taking steps toward incorporating measures of how treatment affects patients' quality of life as a routine part of evaluating new therapies in cancer clinical trials. An invited group p of 70 rHnirifins, social scientists, and officials of the Food and Drug Administration met recently to pool the experiences of cancer centers nationwide in inserting quality of life measurement into select clinical trials. Participants grappled with what questionnaires, or tools, best measure cancer patients' emotional and social well-being and debated how such data mesh with traditional clinical trial endpoints of survival and toxicity. "The mix of disciplines represented brought skeptics and optimists of quality of life measurement head on," said workshop organizer Anne Bavier, of the National Cancer Institute. "The workshop was intended [to allow] people in the field to roll up their sleeves and talk through the tough issues," Bavier said. Recommendations produced by four working groups at the meeting will be published this fall, she added.
Downloaded from http://jnci.oxfordjournals.org/ at Emory University on August 17, 2015
ship of Blaese, along with Anderson, Rosenberg and another NCI scientist, Kenneth Culver, M.D. Transfusion of lymphocytes transduced with the ADA gene may trigger the production of ADA, thus rescuing the child's immune system. Because white blood cells usually live no longer than a few months, the patients will have to receive repeated infusions of the transduced cells.
Some Surprises
Dr. R. Michael BUese
While quality of life is not a new consideration in cancer therapy, largescale measurement of it is still evolving. "Promoting patients' quality of life is axiomatic to the health care professions," said John Ferguson, M.D., director of the National Institutes of Health Office of Medical Applications of Research, in his opening address. "But it NEWS 1381
News News The assessment working group also emphasized minimi7ing the time burden on the patient. Questionnaires, preferably answered by the patient directly, should be short enough that the patient can finish them in a few minutes, but long enough to be statistically valid, they said. "We don't need psychometric overkill," Ware added.
Missing Data The working group making recommendations on data collection methods focused on the problem of missing data. "These types of [psychometric]
No Gold Standard Despite the various cancer centers' cumulative experience in measuring quality of life, no "gold standard" measurement tool has emerged. This, however, should not be a stumbling block to incorporating such measures into clinical trials, quality of life expert John Ware, PhJ)., senior scientist at the Institute for the Improvement of Medical Care and Health in Boston, told workshop participants. "There are excellent measurement systems that are ready off-the-shelf and that are practical to use. Methodological constraint is no longer an excuse for not gathering this data," he said. The working group charged with assessing currently available tools concurred. Instead of endorsing one tool, the group recommended that existing reliable patient questionnaires be tailored to problems expected with specific cancer sites and types of treatment being tested in the trial.
1382
drop out of treatment should not be dropped out of the quality of life study, Cella said "Patients who drop out of a trial are generally sicker. If a treatment is so toxic that half the patients drop out, but the half that stays on does well, excluding data from the dropped patients will make the treatment look better than it really is," Cella explained. To ensure institutions collect data efficiently and thoroughly, Cella's group recommended designating a central data coordinator. The group also suggested requiring a description of quality of life concerns in all cancer clinical trial proposals, similar to a statement used by the National Cancer Institute of Canada. "The statement would compel investigators to at least address the issue of quality of life without forcing them to measure it in their particular study," Cella said.
Future Challenge
Dr. John Ware
measures are unforgiving in terms of losing data," said group leader David Cella, Ph.D., professor of psychology at Rush-Presbyterian-St. Luke's Medical Center in Chicago. "Once you've missed a data point, there's no way to go back and measure it." To prevent missed data at the patient level, the group recommended limiting the number of data points within a trial. In many cases two data points, baseline and post-treatment, are sufficient, with the caveat that patients who
But while increased patient and institutional compliance may improve quality of life data, it does not guarantee its acceptance as an endpoint on par with survival and toxicity. FDA officials at the workshop, for example, expressed willingness to approve therapies based on quality of life endpoints, but are unconvinced of the validity of the measurement tools. As a result, no therapy has yet been approved on the basis of improved quality of life. Cella sees much of the future challenge as attitudinal. "We need to recognize that quality of life and survival are not competing endpoints. We need continuing dialogue between clinicians and social scientists to gain insight on how each can improve patient care," he said. "Rarely do the two groups get together — this was a rare event." -By Jill Woolen
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at Emory University on August 17, 2015
has only been in the last two decades that we've attempted to quantify it." Some of these attempts have had surprising results. An example cited by workshop chairman Patricia Ganz, M.D., medical oncologist at UCLA, was a study in which she and her colleagues compared breast cancer patients who had modified radical mastectomies to patients treated with segmental mastectomies. In the year following surgery, the investigators found no significant difference in the overall quality of life of the two groups, although patients with the more radical surgery scored lower in certain components such as clothing and body image. These types of intangible factors give physicians and patients an additional database for choosing between therapies. The data are valuable as prognostic tools as well, Ganz said.
