Quality-of-Life End Points in Oncology Drug Trials

Measurement of the quality of life (QOL) of patients, particularly those with cancer, has recently become a major scientific endeavor. The rapid growth of the hospice movement throughout the world during the past half-century has underscored the importance of palliation when a cure no longer seems possible.

In 1990, the World Health Organization (WHO) published a report on the value of palliative care, defining it as “the active total care of patients whose disease is not responsive to curative treatment.”According to the WHO expert committee, “the goal of palliative care is the achievement of the best quality of life for patients and their families.”[1] Control of pain and other symptoms and amelioration of psychological, social, and spiritual problems are paramount.

Cohen et al recently proposed that, “if palliative care providers wish to evaluate the full impact of their care, they must measure changes in quality of life (QOL) as well as improvements in areas specifically targeted by particular interventions (eg, pain, depression). Since palliative medicine considers the family as the unit of care (WHO, 1990) patient QOL, family QOL, and QOL of the family unit are all primary outcomes of palliative care. While problems in specific areas are important to address with specific interventions and specific measures, the best indicator of the quality of whole person care is the QOL of the care recipients.”[2]

This is certainly a worthy goal, but it is not yet feasible. We do not have the necessary tools to evaluate all of the dimensions of QOL in patients, let alone family members and the “family unit.”

What Constitutes QOL?

Recently, the term “quality of life” has become a source of considerable debate. In its broadest sense, QOL encompasses the spiritual richness of life, as well as the more obvious dimensions, such as pain, anxiety, and physical mobility. The current debate,[1,3] as I understand it, is due to a failure to recognize that QOL is a multidimensional concept that must incorporate all of these aspects. One single index certainly will not suffice, and we must seek multiple dimensions and measures.

Views of QOL range from Cella’s contention that “health-related QOL refers to the extent to which one’s usual or expected physical, emotional, and social well-being are affected by a medical condition or its treatment”[3] to Cohen’s et al view that “... adding the word ‘health’ before QOL does not allow us to disregard some aspects of the person such as spiritual well-being if we consider that people with cancer and HIV disease define health as a sense of personal integrity consisting of physical, psychological, and spiritual domains.”[2] Obviously, both viewpoints are valid.

Cohen et al wish to include the broadest concept of QOL. In contrast, Cella believes, for pragmatic reasons shared by Beitz in her review article, that measuring pain and several other dimensions of QOL are presently sufficient for estimating at least one domain of the QOL of a patient who has cancer but is not terminal. Living without pain, anxiety, or nausea is a highly desirable goal. However, says Beitz, we need reliable, meaningful tests, validated in placebo-controlled, double-blind studies, to enable the physician to offer such relief to the patient. If that can be accomplished, it is reasonable to assume that the patient’s QOL will be improved as a result.

Quality of life has sensory (such as pain), emotional (such as depression), and cognitive (such as spiritual) dimensions. We can avoid fruitless arguments that are certain to become more rancorous by recognizing that QOL is a multidimensional, personal, subjective experience comprising—at a minimum—physical, psychological, familial, social, and spiritual dimensions. Moreover, each major dimension consists of additional dimensions; for example, the psychological dimension includes the dimensions of pain, fear, anxiety, and a sense of personal insecurity.

Pain provides an example of a multidimensional experience that can be measured with valid, reliable tools.[4,5] Similarly, tools are available to examine many other dimensions of QOL. Our understanding of the complexity of the dimensions will grow as our tools become more varied and reliable.

“Quality of life” is a useful phrase that is meant to provide an index of the richness, value, and meaning of a human life. As important as the labels we use to describe the multidimensional qualities of our experience is our need to carry out trials of drugs or other treatments in order to determine their effectiveness in improving one or more of the major dimensions. Moreover, as Beitz notes, the design of our trials must take into consideration the power of the placebo effect and the need for double-blinding.

Value of a Multidimensional View of QOL

All human subjective experience is multidimensional. Pain, for example, involves sensory qualities, emotion, the meaning of the pathology in terms of its threat to life, and, in special circumstances, a sense of spirituality. Attempts have been made to measure many of the dimensions of pain perception and behavior.[6,7]

Nausea also can be measured with the McGill Nausea Questionnaire, a tool similar to the McGill Pain Questionnaire.[8,9] Nausea can be induced by a wide variety of causes, including chemotherapy and radiation therapy, various drugs given for different purposes (such as morphine for the alleviation of pain), anxiety and fear, and even a deep sense of grief or loss. The McGill Nausea Questionnaire is a simple measuring tool that, in the case of chemotherapy at least, has been shown to be valid and reliable.[8,9] Further research is needed, however, to examine its usefulness for measuring nausea induced by other causes.

Summary

We must expand our concept of QOL in order to incorporate changes in the criteria for “quality” that occur with the progression of illness.[10] We need to know the QOL of (1) people in good health and without illness, (2) people who have a brief illness, (3) people with chronic illnesses besides cancer, (4) people with cancer during treatment or in remission, and (5) people in the terminal stages of cancer. We must develop valid, reliable measuring tools that are appropriate for particular stages of an illness. Finally, we need to use these tools in well-designed experiments to determine how best to use drugs (both new and old) in order to enhance the largest number of dimensions that comprise a positive, desirable QOL.

References:

1. WHO Expert Committee: Cancer Pain Relief and Pallative Care. WHO technical report series 804. Geneva, Switzerland, World Health Organization, 1990.

2. Cohen SR, Mount BM, Bruera E, et al: Validity of the McGill Quality of Life Questionnaire in the palliative care setting: A multi-centre Canadian study demonstrating the importance of the existential domain. Palliat Med 11:3-20, 1997.

3. Schipper H: Guidelines and caveats for quality-of-life measurement in clinical practice and research. Oncology 4:51-57, 1990.

4. Melzack R: The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1:277-299, 1975.

5. Melzack R: The Short-Form McGill Pain Questionnaire. Pain 30:191-197, 1987.

6. Melzack R, Katz J: Pain measurement in persons in pain, in Wall PD, Melzack R (eds): Textbook of Pain, 4th ed, pp 337-351. Edinburgh, Scotland, Churchill Livingstone, 1999.

7. Melzack R, Katz J: The McGill Pain Questionnaire: Appraisal and current status, in Turk DC, Melzack R (eds): Handbook of Pain Assessment, pp 152-168. New York, Guilford Press, 1992.

8. Melzack R, Rosberger Z, Hollingsworth ML, et al: New approaches to measuring nausea. Can Med Assoc J 133:755-759, 1985.

9. Melzack R: Measurement of nausea. J Pain Symptom Manage 4:157-160, 1989.

10. Chaturvedi SK: What’s important for quality of life to Indians—in relation to cancer. Soc Sci Med 33:91-94, 1991.