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© 2001 American Society for Clinical Oncology
Hazards of Quality-of-Life Data for Clinical Decision MakingAmerican Society of Clinical OncologyAlexandria, VANOTE. The opinions expressed herein are those of the author and do not necessarily reflect those of the American Society of Clinical Oncology. To the Editor:Jatoi et al’s article, "On Appetite and Its Loss,"1 published in the August 2000 issue of the Journal of Clinical Oncology, illustrates the challenges of evidence-based clinical oncology as applied to the management of weight loss in cancer. Jatoi et al begin their article with an exchange between two physicians, an oncology fellow and an attending oncologist, who discuss the evidence support for the use of megestrol acetate to treat appetite loss in a woman, Ms Jones, with an unspecified cancer. The major focus of this exchange is the lack of an empirically demonstrated effect of megestrol acetate on quality of life (QOL). I found myself both gratified and alarmed by this exchange. As someone with an abiding interest in psychosocial oncology, I was gratified that the clinicians in the exchange were considering QOL data in arriving at a patient management decision. I was alarmed, however, that these clinicians were taking seriously QOL data from studies that relied solely on measures of global QOL. As I argue below, exclusive reliance on global QOL measures to study cancer QOL is misguided and likely to yield inconsistent and, for the clinician, generally confusing results. Jatoi et al themselves highlight concerns over the use of global QOL data as the basis for prescribing megestrol acetate. They cite methodologic criticisms of global QOL studies in an effort to explain the lack of evidence for a QOL effect of megestrol acetate. Here I would like to argue against the use of global QOL measures from a broader conceptual perspective in hopes of more convincingly pointing up the futility of using these measures to study the effectiveness of most clinical oncology interventions. In this connection, I will argue for the use of more disease- or condition-specific measures of QOL to supplement more generic measures. This is not a new argument by any stretch,2 but it is one that has been slower to catch on than many of us in the psychosocial oncology arena would have liked. The conceptual case for including disease- or condition-specific QOL measures in cancer research draws from Brenner et al’s proximal-distal continuum of health outcome measures.3 In clinical research, the outcomes considered range from the more proximal (signs and symptoms) to the more distal (role functioning, general well-being). According to Brenner et al, proximal outcomes are those clinical indicators of disease that are influenced most directly and powerfully by an effective intervention. Distal outcomes are more removed from the illness per se and are usually the product of a multitude of nonillness or "external" factors; as such, distal outcomes tend to be influenced less directly and less powerfully by even very effective health inverventions.3 Global QOL is among the most distal of the indicators in the continuum of outcomes usually considered in cancer clinical trials and therefore requires the greatest number of external factors for its explanation. In contrast to Jatoi et al’s statement that "we cannot totally discount the possibility that megestrol acetate does improve global quality of life but that our measurement tools are not detecting it," the tenets of the proximal-distal continuum would suggest that megestrol acetate does not improve global QOL because global QOL is too far removed from the immediate effects of megestrol acetate for an effect to be detected reliably. Jatoi et al actually seem to be saying this when they argue that "global quality of life subsumes appetite [and] is far more intricate and intangible," but they also imply that a better measure of global QOL might be the solution to the lack of an empirical effect. In fact, the effects of megestrol acetate on QOL are much more likely to be detected through the use of a symptom-specific QOL measure4 that is responsive to the QOL correlates of appetite and weight gain, which megestrol acetate has been shown to increase.5,6 Cella et al4 have developed a brief visual analog measure of the subjective QOL benefits of appetite and weight gain in the treatment of anorexia/cachexia. This measure has demonstrated validity among people with acquired immune deficiency syndrome7 and is being tested in an ongoing study of cancer-related anorexia/cachexia. Of note, QOL researchers are concerned that disease- and symptom-specific QOL measures will supplant—rather than supplement—more generic QOL measures. This can result in an incomplete picture of the impact of cancer and its treatment. As Moinpour et al8 have pointed out, if the Southwest Oncology Group trial comparing orchiectomy plus placebo with orchiectomy plus flutamide in the treatment of prostate cancer had included just a symptom measure, the negative impact on emotional functioning in the latter arm would have been missed. This underscores the often-cited need for a modular approach to QOL assessment that combines disease- or symptom-specific measures with more generic measures. In terms of the proximal-distal continuum described above,3 an important analytic strategy to explore would evaluate indirect causal relations between the treatment and the more distal outcome of generic QOL. Thus, the effect of megestrol acetate on generic QOL may operate through the more proximal measure of subjective QOL benefits of appetite and weight gain. In conclusion, the literature on megestrol acetate and global QOL supports the suggestion that having some QOL data is not necessarily better than having no QOL data, particularly if QOL data of limited validity are used to make patient management decisions. It is heartening that the oncology fellow in Jatoi et al’s scenario decided to prescribe megestrol acetate even after considering the overwhelmingly negative and null QOL studies. Given the quality of the QOL data they were considering, it is more appropriate in this instance, as Jatoi et al argue passionately, to rely on humanity as a guide to patient management and to discount the placebo-controlled, randomized data. REFERENCES
1.
Jatoi A, Kumar S, Sloan JA, et al: On appetite and its loss. J Clin Oncol 18: 2930-2932, 2000 2. Cella DF, Bonomi AE: Measuring quality of life: 1995 update. Oncology 9: 47-60, 1995 (suppl)[Medline] 3. Brenner MH, Curbow B, Legro MW: The proximal-distal continuum of multiple health outcome measures: The case of cataract surgery. Med Care 33: AS236-AS244, 1995 (suppl)[Medline] 4. Cella DF, Von Roenn J, Lloyd S, et al: The Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI): A brief assessment of patients’ subjective response to treatment for anorexia/cachexia. Qual Life Res 4: 221-231, 1995[Medline]
5.
Loprinzi CL, Lugler JW, Sloan JA, et al: Randomized comparison of megestrol acetate verus dexamethasone verus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 17: 3299-3306, 1999 6. Bruera E, Macmillan K, Hanson J, et al: A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. Cancer 66: 1279-1282, 1990[Medline]
7.
Von Roenn JH, Armstrong D, Kotler DP, et al: Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med 121: 393-399, 1994 8. Moinpour C, Ganz P, Rowland J, et al: The value of quality of life data in judging patient benefit: Experts respond to ODAC. Cancer Letter 25: 1-5, 1999
Response
Mayo ClinicRochester, MN In Reply:We thank Dr Somerfield for his comments. He makes a critical point with eloquence: global measures of quality of life should sometimes be supplemented with symptom-specific ones. He draws on the article by Brenner et al on cataract surgery to discuss proximal and distal measures of quality of life.1 Somerfield suggests a range of quality-of-life tools that might be used in cancer symptom control research, as shown in Fig 1.
We believe our review of 15 placebo-controlled trials of megestrol acetate in cancer patients illustrates Somerfield’s point well.2 Improvement in appetite, a proximal measure, occurred in 13 of 15 of these studies, whereas improvement in global quality of life, a distal measure, occurred in only one (see Table 1 in Jatoi et al2). Had these 13 studies not measured this proximal symptom, justification for prescribing megestrol acetate for cancer-associated anorexia would be sparse. Although we agree with Somerfield’s comments on methods of measurement, we ourselves continue to struggle with the meaning behind these measurements. As alluded to in the article by Brenner et al,1 cataract surgery allows individuals to drive, read, and look people in the eye. The meaning of such proximal quality-of-life measurements is obvious. In contrast, appetite stimulation in patients with advanced cancer carries limited consequences. Patients may eat more, but they do not live longer, tolerate chemotherapy better, or become more functional. As discussed in our article,2 it is from Meares’ article,3 as well as from Holden’s,4 that we begin to find meaning behind these proximal measurements: "Food, from time immemorial, is part of the nurturing process ... ." Somerfield’s comments remind us of the challenge of measuring quality of life in cancer clinical trials and of the challenge of including both proximal and distal measures in cancer symptom control research. Yet, there is another part to that challenge: finding meaning behind these measurements. Therein lies the art of oncology. REFERENCES 1. Brenner MH, Curbow B, Legro MW: The proximal-distal continuum of multiple health outcome measures: The case of cataract surgery. Med Care 33: AS236-AS244, 1995 2. Jatoi A, Kumar S, Sloan JA, et al: On appetite and its loss. J Clin Oncol 18: 2930-2932, 2000 3. Meares CJ: Primary caregiver perceptions of intake cessation in patients who are terminally ill. Oncol Nurs Forum 24: 1751-1757, 1997[Medline] 4. Holden CM: Anorexia in the terminally ill cancer patient: The emotional impact in the patient and the family. Hosp J 7: 73-84, 1991[Medline]
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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