SPECIAL ARTICLE
`Outcomes of Cancer Treatment for Technology
`Assessment and Cancer Treatment Guidelines
`
`Adopted on July 24, 1995 by the American Society of Clinical Oncology*
`
`In 1993, the Health Services Research Committee of
`the American Society of Clinical Oncology (ASCO)
`charged an Outcomes Working Group with defining the
`outcomes of adult and pediatric cancer treatment to be
`used for technology assessment and development of can(cid:173)
`cer treatment guidelines.
`The Working Group defined by consensus outcomes
`for technology assessment and guideline development,
`focusing on cancer treatments. The Working Group con(cid:173)
`sidered a variety of perspectives on outcomes, including
`those of patients, physicians, clinical investigators,
`ASCO, and policy makers. Because ASCO's guidelines
`will define what constitutes the best treatment and not
`whether that treatment should be paid for, the Working
`Group gave higher priority to the clinical and clinical
`research perspectives than to the health policy perspec(cid:173)
`tive.
`Survival is the most important outcome of cancer treat(cid:173)
`ment. An improvement in at least disease-free survival
`is a prerequisite for recommending adjuvant therapy. In
`the case of metastatic cancer, treatment can be recom(cid:173)
`mended even without an improvement in survival, if it
`improves quality of life.
`Quality of life includes global quality of life, as well as
`its physical, psychologic, and social dimensions. To be
`an outcome of cancer treatment, quality-of-life measures
`must be sensitive to clinically meaningful changes pro-
`
`duced by treatment; evaluations must control for placebo
`effects and determinants of quality of life not related to
`cancer or its treatment.
`Toxicity, both short and long term, is vitally important,
`with the latter being particularly critical in children.
`The value of cancer outcomes like tumor response (eg,
`complete or partial response) and biomarkers (eg, CA·
`125) for technology assessment and guideline develop·
`ment depends on their ability to predict patient outcomes
`(survival and quality of life) or to influence decisions
`about treatment. Complete response is an important out(cid:173)
`come when it predicts survival. Progression is important
`because it signals the need to change or stop treatment.
`Cost-effectiveness is an especially important outcome
`to consider when the benefits of treatment are modest
`or the costs are high.
`Patient outcomes (eg, survival and quality of life)
`should receive higher priority than cancer outcomes (eg,
`response rate), but both types of outcomes are important
`in technology assessment and guideline development.
`Multiple outcomes should be considered because no sin(cid:173)
`gle outcome adequately describes the results of cancer
`treatment. In general, there is no minimum benefit above
`which treatments are justified; rather, benefits should be
`balanced against toxicity and cost.
`J Clin Oncol 14:671-679. © 1996 by American So(cid:173)
`ciety of Clinical Oncology.
`
`HEALTH SERVICES RESEARCH COMMITTEE
`
`I N 1993, the American Society of Clinical Oncology
`
`(ASCO) formed a Health Services Research Commit(cid:173)
`tee to perform technology assessment and to develop
`guidelines for cancer treatment. The Committee was
`formed so that ASCO could address the value of emerging
`technologies and of new and established cancer treatment.
`The Health Services Research Committee was formed
`in response to input from ASCO's members. As part of
`its recent long-range planning effort, ASCO surveyed its
`members about possible future directions of the Society.
`A significant majority indicated that ASCO should be
`
`more involved in areas of technology assessment and
`development of treatment guidelines.
`The Health Services Research Committee is composed
`of clinical researchers and clinicians from academic cen(cid:173)
`ters and private practice (Appendix I). A number of Com(cid:173)
`mittee members are involved in health services research
`or quality improvement efforts.
`The Health Services Research Committee will perform
`technology assessment after hearing from expert advisors.
`The Committee will not develop guidelines; instead, it will
`assemble expert panels to develop guidelines. Expert panels
`will be given direction by the Health Services Research
`
`See Appendixes for Health Service Committee members and Out(cid:173)
`comes Working Group.
`From the Outcomes Working Group, Health Services Research
`Committee, American Society of Clinical Oncology.
`Submitted October 19, 1995; accepted October 19, 1995.
`Address reprint requests to the American Society of Clinical On(cid:173)
`cology, 225 Reinekers Lane, Suite 650, Alexandria, VA 22314.
`*ASCO sincerely appreciates the contributions of the ASCO
`Health Services Research Outcomes Working Group, who devoted
`much time and effort to this project: Chair: John Fetting; and Panel
`
`Members: Paul Anderson, Harrison Ball, John Benear, Katy Benja(cid:173)
`min, Charles Bennett, Susan Braun, Harmar Brereton, John Bur(cid:173)
`rows, Charles Cobau, Alfred Cohen, Leslie Ford, Michael Friedman,
`Patricia Ganz, Richard Gelber, Holcombe Grier, Gerald Hanks,
`Robert Justice, Patricia Legant, Mark Levine, Susan Parsons, Peter
`Raich, Sandra Schafer, Thomas Smith, Collier Smyth, A. T. van Oost(cid:173)
`erom, James Wade, Jane Weeks, Rodger Winn, and Janet Wood(cid:173)
`cock.
`© 1996 by American Society of Clinical Oncology.
`0732-l 83X/96!1402-0049$3.00!0
`
`Journal of Clinical Oncology, Vol 14, No 2 (February), 1996: pp 671 -679
`
`671
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`Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
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`672
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`Committee, one or more members of the Committee will
`serve on each panel, and the report of the expert panels will
`be approved by the Health Services Research Committee.
`Final approval of technology assessments and practice
`guidelines comes from the Board of Directors.
`
`THE OUTCOMES WORKING GROUP
`The Health Services Research Committee charged an
`Outcomes Working Group with defining the outcomes of
`cancer treatment that should be considered for technology
`assessment and cancer treatment guidelines. The Out(cid:173)
`comes Working Group is composed of selected members
`of the Health Services Research Committee, representa(cid:173)
`tives of organizations involved in the development and
`delivery of cancer treatment, and additional experts in
`health services research (Appendix II). A core group pro(cid:173)
`duced the preliminary drafts of this report for comment
`by the entire Working Group. This report of the Outcomes
`Working Group provides an introduction on the outcomes
`to be considered for technology assessment and guideline
`development, as well as evaluations of the effectiveness
`of cancer treatment in clinical practice.
`
`WORKING GROUP DELIBERATIONS
`
`The Working Group believed that ASCO should focus
`its initial efforts on therapies that produce tumor regres(cid:173)
`sion and related technologies, rather than other aspects
`of the care of cancer patients. Thus, a guideline for the
`treatment of metastatic lung cancer should focus on che(cid:173)
`motherapy and radiation therapy and not on the more
`general issue of the care of patients with metastatic lung
`cancer. By focusing on therapies that produce tumor re(cid:173)
`gression, ASCO will concentrate its available resources
`on an area that it is uniquely qualified to evaluate. 1
`Patients, physicians, researchers, payors, and policy
`makers all have different ideas about which outcomes of
`cancer are most important. The Working Group recog(cid:173)
`nized that broad acceptance of ASCO's technology as(cid:173)
`sessments and guidelines would require that all of these
`perspectives be considered. However, the main purpose
`of ASCO's technology assessments and guidelines is to
`define what constitutes the best cancer treatment, not to
`inform policy development and payment decisions. The
`Working Group, therefore, considered outcomes primar(cid:173)
`ily from the perspectives of the clinical investigators who
`produce evidence for the guidelines, the individual doc(cid:173)
`tors and patients who make decisions about treatment,
`and the health services researchers who will evaluate the
`quality and cost of care produced by the guidelines. Be(cid:173)
`cause it recognized the health policy implications of
`ASCO's technology assessments and guidelines, the
`Working Group also took into consideration the outcomes
`
`AMERICAN SOCIETY OF CLINICAL ONCOLOGY
`
`that would convince health policy makers and payors
`that ASCO's technology assessment is sound and that its
`guidelines represent worthwhile cancer treatment.
`Outcomes were defined by the Working Group as the
`products, both good and bad, of cancer treatment. The
`Working Group distinguished between cancer outcomes
`and patient outcomes. Cancer outcomes were defined as
`measures of the effect of treatment on cancer, eg, com(cid:173)
`plete and partial response, response duration, time to pro(cid:173)
`gression, and tumor markers. Patient outcomes were de(cid:173)
`fined as measures of the effect of treatment on the patient,
`eg, survival, toxicity, and quality of life.
`The Working Group identified the most important out(cid:173)
`comes of cancer treatment, but limited its consideration of
`their measurement to clinical trials and effectiveness re(cid:173)
`search. It did not consider measurement of these outcomes
`as part of the day-to-day care of patients in clinical practice.
`The Working Group did not attempt to define the uni(cid:173)
`verse of outcomes for clinical trials, because clinical trials
`are conducted for other reasons than to provide evidence
`for guidelines. For example, phase I and II trials are
`conducted to develop new and improved treatments. It is
`unnecessary to routinely collect quality-of-life and cost(cid:173)
`effectiveness data until early trials demonstrate real prom(cid:173)
`ise. On the other hand, laboratory correlative studies are
`an important part of these trials, but are not important for
`technology assessment or guideline development.
`The Working Group did not attempt to define the uni(cid:173)
`verse of outcomes for effectiveness research either. For
`example, patient satisfaction is increasingly used to evalu(cid:173)
`ate the effectiveness of health care delivery, but it is not
`important in technology assessment and guideline devel(cid:173)
`opment, which are shaped by evidence from clinical trials
`on the benefits and risks. 2
`The Working Group also addressed how outcomes
`should be used to make guidelines. It considered the prior(cid:173)
`ity of outcomes including whether any one outcome (eg,
`survival) was ever so important that it overshadowed the
`others. The Working Group also considered the minimal
`amount of benefit that justified recommending treatment,
`since some cancer treatment produces so little benefit that
`it is not clear whether it should be administered at all. In
`the case of cancers for which treatment is more effective,
`the question is not whether treatment should be started,
`but when it should be stopped. For both types of cancer,
`the critical question is the same: Does the expected benefit
`justify recommending the treatment?
`
`OUTCOMES FOR TECHNOLOGY ASSESSMENTS AND
`GUIDELINE DEVELOPMENT
`
`Survival
`Survival, whether measured overall, disease-free, pro(cid:173)
`gression-free, or event-free, is the most important out-
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`Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
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`CANCER TREATMENT: OUTCOMES AND GUIDELINES
`
`come in cancer treatment. Nevertheless, survival alone is
`not sufficient; the quality of survival and cost of main(cid:173)
`taining or improving it must also be assessed. Disease(cid:173)
`free survival is especially important in the adjuvant set(cid:173)
`ting, as is progression-free survival in metastatic disease. 3
`Event-free survival has been used to denote survival free
`of any bad outcome, including failure to attain a complete
`remission, relapse, or death due to toxicity.4 Although an
`improvement in overall survival is desired, an improve(cid:173)
`ment in disease-free, progression-free, or event-free sur(cid:173)
`vival can also justify recommending treatment, as long
`as the quality of that survival is good and the cost of
`producing it compares favorably to the cost of no treat(cid:173)
`ment or of alternative treatment.
`Survival outcomes can be represented in several ways,
`including percent surviving at a particular time, median
`survival, and percent reduction in the odds of death over a
`time interval or at a particular point in time. 5 Representing
`survival benefits in more than one way permits physicians
`and patients to evaluate thoroughly the value of treatment;
`for example, although chemotherapy for non-small-cell
`lung cancer has minimal long-term effect on survival
`(seven of 100 treated patients alive at 1 year), and a
`modest effect on mean or median survival times (6 to 8
`weeks), the short-term risk reduction (20 of 100 patients
`alive at 6 months due to chemotherapy) may be im(cid:173)
`portant.6·7
`The choice between alternative treatment approaches
`often involves a trade-off between length and quality of
`life; survival alone may not answer the question of
`whether gains in survival justify the toxicity. Quality(cid:173)
`adjusted survival adjusts the absolute length of life to
`reflect the patient's quality of life. Quality-adjusted sur(cid:173)
`vival provides a framework within which trade-offs that
`influence treatment choices can be explicitly defined, as
`in decision and cost-effectiveness analyses, to assess the
`effectiveness of alternative therapies.8·9 The quality-ad(cid:173)
`justed time without symptoms of disease and toxicity
`(Q-TWIST) methodology is one example of a quality(cid:173)
`adjusted survival calculated from observed survival in
`11 Practical methods for esti(cid:173)
`randomized clinical trials. 10
`•
`mating the appropriate utility weights, or value given to
`time in a health state, are still experimental. In particular,
`estimation of utility weights in children is a particularly
`formidable conceptual and methodologic challenge, and
`relatively little has been done to address this problem.
`
`Quality of Life
`Cancer-related quality of life has been defined as a
`multidimensional concept that considers the impact of
`cancer and its treatment on the physical, psychologic,
`and social components of patients' lives. 12·14 Even in the
`
`673
`
`Dimension
`
`Physical
`
`Psychologic
`
`Social
`
`Table 1. Dimensions of Quality of Life
`
`Examples
`
`Symptoms commonly caused by cancer and the toxicities of
`treatment, eg, the activities of daily living, walking, and
`climbing stairs.
`Effects of cancer and cancer treatment on cognitive
`function and the emotional state, eg, anxiety, optimism,
`and depression.
`Effects of cancer and its treatment on interpersonal
`relationships, school, work, and recreation.
`
`absence of consensus regarding the definition and mea(cid:173)
`surement of this complex concept, the Working Group
`was in agreement that quality of life is an important out(cid:173)
`come of cancer treatment because it reflects how patients
`feel. 15·16 The Working Group viewed cancer-related qual(cid:173)
`ity of life as a family of outcomes (including the global
`quality of life, as well as its physical, psychologic, and
`social dimensions), each one of which is a potentially
`separate outcome (Table 1).
`Because of its subjective nature, assessment of quality of
`life should generally include an evaluation by the patient.12·14
`In pediatrics, an evaluation by the patient is often problematic
`because of the developmental limitations of the child. Other
`observers ( eg, parents) can contribute to the evaluation, but
`it is important to note that their evaluation is likely to differ
`from that of the patient.17
`Little research has been conducted to determine which
`dimensions of cancer-related quality of life are most im(cid:173)
`portant to patients. 18·19 The research that has been done
`suggests that patients believe that the effects of cancer
`and its treatment on all three dimensions of quality of
`life are important.19
`Quality-of-life measures should have basic types of
`reliability and validity. 12·14 They should be relatively
`brief, easy to read, and easy to complete; when used to
`evaluate cancer treatment, they should be administered
`before, during, and after treatment. 12·14 Some quality-of(cid:173)
`life measures are listed in Table 2. Measures used in
`pediatric patients should be developmentally appropriate.
`Quality-of-life measures must also be responsive (eg,
`sensitive to change).20 The more specific a quality-of-life
`measure is to a particular treatment situation, the more
`responsive it generally is.21 Several approaches can be used
`to enhance specificity. One is to develop an entire quality(cid:173)
`of-life measure for a particular treatment situation.22 An(cid:173)
`other approach is to develop a module for a particular
`disease or treatment situation that augments the informa(cid:173)
`tion obtained by a more general measure. 23·24 Yet another
`approach is to measure only the dimension of quality of
`life that is most likely to change with treatment, eg, the
`
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`Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
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`674
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`Table 2. Some Quality-of-Life Measures
`
`Eponym
`
`Measure
`
`Functional Living Index, Cancer
`FLIC
`Functional Assessment of Cancer Treatment
`FACT
`EORTC QLQ-C30 European Organization on Research and Treatment of
`Cancer Quality-of-Life Questionnaire
`Medical Outcomes Survey Short Form 36
`Spitzer Quality of Lile Index
`
`SF-36
`QLI
`
`physical dimension by using the physical symptom and
`physical functioning subscales of a quality-of-life measure
`or by using a symptom checklist. 23
`26 The limitation of this
`·
`selective approach is that it fails to capture the effects of
`treatment on the other dimensions of quality of life.
`Quality-of-life outcomes are affected by more than can(cid:173)
`cer and its treatment, eg, the physical dimension of can(cid:173)
`cer-related quality of life is affected by comorbid condi(cid:173)
`tions and their treatments, and improvement in quality of
`life with treatment can reflect the placebo effect. Optimal
`control of these factors is found in randomized (ie, phase
`III) clinical trials. 14 Quality-of-life outcomes can also be
`measured in nonrandomized (phase I and II) trials, as well
`as in descriptive studies of clinical practice (ie, medical
`effectiveness research), but appropriate controls (eg, eval(cid:173)
`uation of comorbidity, measures of cancer response, and
`toxicity assessments) are required before inferences can
`be drawn about the relationship between cancer treatment
`and quality-of-life outcomes. 14
`Currently available quality-of-life measures have been
`used primarily for research and their suitability for day(cid:173)
`to-day patient care in clinical settings has not been estab(cid:173)
`lished. There is a pressing need to develop quality-of-life
`measures for clinical practice.
`
`Toxicity
`Treatment toxicity is an important outcome for technol(cid:173)
`ogy assessment and guideline development because it re(cid:173)
`duces the quality of life and can be life-threatening. Many
`toxic effects can be minimized or avoided if treatment
`toxicity is carefully evaluated. Management of treatment
`toxicity also raises the cost of treatment and can reduce
`its cost-effectiveness.
`Both the short-term and long-term toxicity of all treatment
`modalities deserve careful consideration. The latter is partic(cid:173)
`ularly important in pediatric patients because of the effects
`of treatment on growth and development. Three toxicity
`dimensions need to be evaluated: frequency, severity, and
`duration. 27 For instance, when anthracycline cardiotoxicity
`is being evaluated, the assessment should distinguish the
`various cardiac toxicity syndromes (ie, acute toxicity should
`be distinguished from the late effects that may develop long
`
`AMERICAN SOCIETY OF CLINICAL ONCOLOGY
`
`after anthracyclines are administered). The frequency of
`each syndrome should also be determined, including the
`frequencies observed at different doses. In addition, the de(cid:173)
`gree of cardiac dysfunction and the duration of each type
`of cardiotoxicity should be assessed.
`Toxicities are subjective, objective, or both. Subjective
`toxicities are symptoms (eg, nausea) that are often not
`associated with overt signs or laboratory abnormalities;
`evaluation of these toxicities rests with the patient's re(cid:173)
`port. The evaluation of a subjective toxicity is begun
`by asking the patient whether the toxicity occurred. Just
`because the patient does not report toxic symptoms volun(cid:173)
`tarily does not mean that they did not occur. If the toxicity
`has occurred, patients should next be asked to describe
`the severity and duration of the toxicity. Subjective toxici(cid:173)
`ties can be evaluated by patient interview or a reliable,
`valid patient-completed questionnaire. 28
`Quality-of-life instruments typically evaluate some
`symptoms of common toxicities, but these instruments
`do not evaluate all of the potentially important subjective
`toxicities or evaluate any thoroughly enough to substitute
`26
`for a formal evaluation of toxicity. 22
`-
`Objective toxicities are measured by physical examina(cid:173)
`tion or laboratory tests. The reliability and validity of
`laboratory tests commonly used to evaluate treatment tox(cid:173)
`icity have generally been well established; the physical
`examination has been less rigorously evaluated.
`The common toxicity criteria (CTC), a system for cate(cid:173)
`gorizing toxicities of cancer treatment according to their
`severity, are widely used in cooperative group trials. 29
`For some toxicities (eg, WBC count and liver function
`tests), the CTC do not specify the methods of toxicity
`evaluation, but only how to categorize the data. In these
`cases, the reliability and validity of the toxicity data de(cid:173)
`pend on the method of toxicity evaluation. For other tox(cid:173)
`icities (eg, nausea and vomiting, and mucositis), the CTC
`actually suggest the form in which the data should be
`collected. The reliability and validity of toxicity data col(cid:173)
`lected in these ways have not been established.
`
`Measures of Cancer Response
`
`Measures of cancer response have long been used as
`outcomes of cancer treatment. These include measures of
`tumor response (ie, complete response, partial response,
`response duration, and time to progression), biomarkers
`(eg, CA-125), and cancer-induced abnormalities in com(cid:173)
`mon blood tests (eg, alkaline phosphatase). The use(cid:173)
`fulness of cancer response measures for technology as(cid:173)
`sessment and guideline development depends on their
`ability to predict patient outcomes (eg, survival and qual(cid:173)
`ity of life) and to assist clinicians in making decisions
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`Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
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`CANCER TREATMENT: OUTCOMES AND GUIDELINES
`
`about whether to continue treatment. Only some of these
`measures will be useful for technology assessment and
`guideline development. The complete response rate is an
`important intermediate outcome because it often predicts
`the potential of a drug or regimen to effect a significant
`improvement in survival or even a cure; lesser degrees
`31
`30
`of response do not.3
`•
`•
`Some studies have demonstrated a positive relation(cid:173)
`ship between response rate and quality of life; others
`35 Whether a responding patient experiences
`have not. 32
`-
`improvement in quality of life is probably dependent on
`the extent to which that patient was symptomatic before
`treatment, the completeness of response of the cancer, and
`the toxicity of the treatment. The tumor response is likely
`to be positively correlated with improvement in quality of
`life when a patient is symptomatic from the cancer before
`treatment, the complete response rate of the tumor is rela(cid:173)
`tively high, and the treatment toxicity is modest.
`It is important to distinguish between the use of cancer
`response rates for technology assessment and guidelines,
`on the one hand, and drug development, on the other.
`While lesser degrees of response ( eg, partial response and
`minimal response) are unlikely to be important for the
`former, they are often important indicators of promising
`treatment activity in the latter.
`Cancer progression is an important negative outcome
`because it indicates that a treatment has stopped working,
`even if the patient has not declined symptomatically.
`Therefore, recommendations on how to monitor cancer
`progression are an important part of guidelines on cancer
`treatment. Freedom from progression, on the other hand,
`may not be a convincing indication of the benefits of
`treatment if it does not predict significantly improved
`survival or cure. By itself, freedom from progression is
`not an adequate measure of quality of life.
`Much of the evidence available for technology assess(cid:173)
`ment and guideline development will be related to tumor
`response. Expert panels must bear in mind the limitations
`of tumor response as an outcome measure and remember
`that tumor response is not always easy to measure reli(cid:173)
`ably. 36,37
`Because they lack adequate sensitivity and specificity
`biomarkers are not likely to be among the outcome-re(cid:173)
`lated evidence to be considered in the development of
`guidelines. Biomarkers have not been established as good
`predictors of survival, and there have been virtually no
`studies of the relationship between biomarkers and quality
`of life. Biomarkers might be incorporated into guidelines
`as measures of disease progression. The more sensitive
`and specific the biomarkers and the more effective the
`treatment available after progression, the more useful the
`biomarkers will be. For example, biomarkers are very
`
`675
`
`useful in stage I testis cancer when alpha-fetaprotein and
`beta-human chorionic gonadotropin can be used to moni(cid:173)
`tor for disease recurrence after surgery. 38 Less useful, but
`still potentially valuable, are some markers for common
`epithelial cancers (eg, prostate-specific antigen, CA-125,
`and CA 15-3).3942
`
`Cost-Effectiveness
`
`Cost per se is not an outcome; it is what we expend
`to produce an outcome. Cost-effectiveness, on the other
`hand, is an increasingly important outcome. 1 Cost-effec(cid:173)
`tiveness is often reported in terms of cost per year of life
`saved (LY) or cost per quality-adjusted year of life saved
`(QAL Y). Cost-effectiveness is a way to evaluate cancer
`treatment and also to compare the benefits of cancer treat(cid:173)
`ment with the benefits of other kinds of medical treatment
`(eg, dialysis) that are competing for the same health-care
`dollar. Because interest in this outcome is recent, there
`have been relatively few evaluations of the cost-effective(cid:173)
`ness of cancer technologies and treatments. 1
`How do cost-effectiveness studies add to the evaluation
`of cancer treatment? In some cases, not much. In the case
`of first-line chemotherapy for germ cell cancer, survival
`benefits are large and long-term toxicity is modest; cost(cid:173)
`effectiveness adds relatively little to the treatment evalua(cid:173)
`tion. On the other hand, cost-effectiveness analysis can
`provide an important perspective when treatment costs
`are high and benefits are small (eg, in high-dose chemo(cid:173)
`therapy for cisplatin-refractory germ cell cancer), or when
`treatment benefits are modest (eg, in adjuvant chemother(cid:173)
`apy for breast or colon cancer).
`All clinical practice guidelines, including ASCO' s,
`must be informed by cost-effectiveness considerations, or
`they risk being ignored. When the information is avail(cid:173)
`able, cost-effectiveness should be considered in technol(cid:173)
`ogy assessment and in the development of cancer treat(cid:173)
`ment guidelines. When cost-effectiveness analyses are not
`available, cost-consciousness should be a part of technol(cid:173)
`ogy assessment and guideline development. For example,
`if two chemotherapy regimens produce the same patient
`outcomes but one costs more than the other, the less
`costly regimen should be preferred. However, a cost com(cid:173)
`parison is more than a simple comparison of the charges
`for the drugs and their administration. Costs associated
`with the ease or difficulty of administration, the treatment
`facility, concomitant medications, and adverse events
`must also be considered_ 1
`The Working Group recommends that cost-effective(cid:173)
`ness be measured when appropriate and feasible and that
`it be considered as an outcome of cancer technology and
`treatment under these circumstances. If cost-effectiveness
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`Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
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`676
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`data from clinical trials are to be generalizable to clinical
`practice, future trials will need to approximate clinical
`practice as closely as possible with less restrictive eligibil(cid:173)
`ity criteria, minimal monitoring costs, and outpatient
`rather than inpatient care. Of all clinical trial settings,
`phase III trials are the most appropriate for economic
`analysis, especially when the drugs or technologies that
`are being evaluated are well established and stable. Yet
`there is concern about the generalizability of economic
`data from phase III trials to clinical practice because of
`variations in practice patterns and economic outcomes
`among participating centers, and because trial participa(cid:173)
`tion affects physician practice patterns.43
`
`SUGGESTIONS ON HOW TO USE OUTCOMES FOR
`TECHNOLOGY ASSESSMENTS AND GUIDELINE
`DEVELOPMENT
`
`The Priority of Patient Outcomes
`
`In the final analysis, patient outcomes are more im(cid:173)
`portant than cancer outcomes for technology assessment
`and development of cancer treatment guidelines. If a tech(cid:173)
`nology or cancer treatment is not ultimately shown to
`make patients live longer or feel better, its use cannot be
`justified. Although it gave priority to patient outcomes,
`the Working Group believed that selected cancer out(cid:173)
`comes will also be imporiant.
`
`The Need to Use Multiple Outcomes
`
`No single outcome, even survival, adequately repre(cid:173)
`sents the results of cancer treatment. Each outcome pro(cid:173)
`vides a unique perspective on treatment, but each also
`has its own conceptual and methodologic limitations.
`Therefore, multiple outcomes should be used for technol(cid:173)
`ogy assessment and guideline preparation.
`
`The Benefit Required to Justify Treatment
`
`The amount of benefit required to justify treatment is
`different for patients, physicians, payors, and policy makers.
`Patients generally require less benefit than the other groups
`and a small fraction of patients requires almost no benefit
`at all.44 Payors and policy makers, on the other hand, require
`more substantial benefits. Which perspective(s) should ex(cid:173)
`pert panels adopt when performing technology assessment
`and developing guidelines? Panels should recall that the
`purpose of ASCO's technology assessment and guidelines
`is to make recommendations about what is the best medical
`care. The concept of best medical care takes into account
`the fact that the quality of life of some few patients is better
`maintained by trying a treatment with very little chance of
`benefit than by not trying it. However, the Working Group
`
`AMERICAN SOCIETY OF CLINICAL ONCOLOGY
`
`did not believe that treatments with very limited benefits
`should be routinely recommended just because they improve
`the quality of life of a minority of patients. Routine recom(cid:173)
`mendation of such treatments ignores the fact that the major(cid:173)
`ity of patients not only receive no benefit, but also suffer
`toxicity. Moreover, if treatments with marginal benefits are
`very toxic or very costl