A comparison of visual analogue and numerical rating scale formats for the Lung Cancer Symptom Scale (LCSS): does format affect patient ratings of symptoms and quality of life?

PROBLEM AND PURPOSE: The Lung Cancer Symptom Scale (LCSS), a site-specific health-related quality of life measure for patients with lung cancer, was originally developed using a Visual Analogue Scale (VAS) format. However, the VAS format is not readily compatible with data management and software programs using scanning. The primary aim of this study was to evaluate the convergence of ratings obtained with a Numerical Rating Scale (NRS), with an 11-pt response category format, to those obtained with a VAS format. The intent was to determine the degree of agreement between two formats to generalize the existing psychometric properties for the original measure to the new presentation. DESIGN/SETTING: This methodological study evaluated the feasibility, reliability, and validity of a NRS format for the LCSS. The study was conducted at two cancer centers in New York City. PATIENTS/PROCEDURES: Sixty-eight patients with non-small cell lung cancer (NSCLC) completed both versions of the LCSS along with demographic and feasibility questions on a single occasion. The VAS form was administered first, followed by the NRS form to prevent bias. The intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), and Bland-Altman plots were used to evaluate agreement and to characterize bias. RESULTS: Cronbach's alpha for the NRS format total score was 0.89 for the 68 patients with NSCLC. Agreement was excellent, with both the ICC and CCC > or = 0.90 for the two summary scores (total score and average symptom burden index) for the LCSS. Only five of the nine individual items showed this level of strict agreement. An agreement criterion of > or = 0.80 (representing excellent) was observed for seven of the nine individual items (all but appetite loss and hemoptysis). Mean differences tended to be slightly lower for the VAS format compared to the NRS format (more so for the appetite and hemoptysis items), with evidence of scale shift for the same two items. The summary measures showed good concordance as measured by the ICC and CCC, but did display mean differences (VAS - NRS) of -2.7 and -3.1, respectively. CONCLUSIONS: Overall, the NRS format for the LCSS suitable for scanning has good feasibility, reliability (internal consistency), and convergent validity. The complete set of concordance evaluation measures supports the reproducibility of VAS scores by NRS scores, particularly for the two summary scores.

Development, feasibility and compliance of a web-based system for very frequent QOL and symptom home self-assessment after hematopoietic stem cell transplantation.

We believe that many adverse events following hematopoietic stem cell transplantation (HSCT), particularly relapse and chronic graft-versus-host disease (CGVHD), are preceded by a subclinical period of development that is accessible by frequent psychometric assessment. Documenting these associations could improve future clinical care by extending the potential window for intervention. However, conventional methods of assessing quantity of lite (QOL) in patients in their homes, typically by mailed self-assessment questionnaires, are impractical for very frequent administration. We have developed and implemented a web-based system for measuring short-term (dynamic) changes in QOL by employing brief, online, daily QOL assessments and more extensive, monthly online assessments from patients' homes. Here we report the feasibility of collecting very frequent patient home self-assessments of QOL via the web for a 52 week participation period; we detail incidence of home web access, accrual, compliance, and satisfaction with the system in an HSCT patient sample. We also describe our integrated web-systems for administering patient recruitment, scheduling, monitoring, and analysis. Our results suggest that very frequent routine collection of QOL outcomes is entirely feasible using our web-based home assessment tool, with good patient compliance and high user satisfaction. We believe our methodology shows great promise for use with other cancer and health populations.

Health-related quality of life in female long-term colorectal cancer survivors.

Although the number of women who survive treatment for colorectal cancer is growing, little is known about the quality of life of long-term survivors. The purpose of analyses presented in this paper is to describe the overall health-related quality of life of female long-term colorectal cancer survivors and the factors that may modify their levels of quality of life. A population-based sample of 726 Wisconsin women diagnosed with colorectal cancer from 1990-1991 was recontacted. Of the 443 women alive in 1999, 307 (69%) completed a follow-up questionnaire including the Medical Outcomes Study Short-Form 36 Health Status Survey, which is comprised of 36 items that generate nine domain scale scores and two summary scores: the Physical Component Summary score and the Mental Component Summary score. The mean follow-up was 9 years (range 7-11), and the mean age at follow-up was 72 years (range 43-85). The mean Physical Component Summary score was lower for participants with greater ages, greater numbers of comorbidities, and greater body masses at the time of follow-up. The mean Mental Component Summary score also was lower for participants with greater numbers of comorbidities. Differences associated with degree of comorbidity were observed for all eight domain scales. Female long-term survivors of colorectal cancer appear to report health-related quality of life comparable with that of similarly aged women in the general population. These data suggest that, over the long term, factors attributable to aging, body weight, and chronic medical conditions play more dominant roles in determining physical and mental health than factors related to the initial colorectal cancer diagnosis.

Quality of life in advanced non-small-cell lung cancer: results of a Southwest Oncology Group randomized trial.

PURPOSE: The main purpose of this paper is to present the results of a randomized trial comparing the effects of two chemotherapy regimens on the Quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). Trials in advanced stage disease represent an important treatment context for QOL assessment. A second purpose of this paper is to examine methods for handling the level of missing data commonly observed in the advanced stage disease context. METHODS: Patients were randomized to receive cisplatin plus vinorelbine or carboplatin plus paclitaxel. The QOL of 222 patients was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) prior to randomization; follow-up assessments occurred at 13 and 25 weeks. Three methods were used to analyze the QOL data: (1) cross-sectional analysis of four patient categories (improved, stable, missing, and declined) based on changes in the FACT-L score, (2) a mixed linear model, and (3) a pattern mixture model. The longitudinal analyses addressed two potential data biases. RESULTS: Questionnaire submission rates were 91% at baseline, 68% at 13 weeks, and 47% at 25 weeks. The cross-sectional and mixed linear model analyses did not show significant differences by treatment arm in patient-reported QOL. The pattern mixture model analysis, more appropriate given non-ignorable missing data, also found no statistically significant effect of treatment on patient QOL. CONCLUSION: We present a sensitivity analysis approach with multiple methods for analyzing treatment effects on patient QOL in the presence of substantial, non-ignorable missing data in an advanced stage disease clinical trial. We conclude that the two treatment arms did not differ statistically in their effects on patient QOL over a 25-week treatment period.

Phase II trial of bicalutamide in patients with advanced prostate cancer in whom conventional hormonal therapy failed: a Southwest Oncology Group study (SWOG 9235).

OBJECTIVES: To determine the efficacy and tolerability of bicalutamide in patients with advanced prostate cancer with progression after conventional hormonal therapy. METHODS: Fifty-two patients received bicalutamide, 150 mg once daily, as second-line therapy after progressing following treatment with orchiectomy or luteinizing hormone-releasing hormone analogue or diethylstilbestrol, alone or in combination. Patients had measurable (n = 8) or assessable (n = 44) disease, a Southwest Oncology Group performance status of 0 to 2, and no prior antiandrogen therapy or chemotherapy. The objective response to treatment was assessed every 12 weeks; symptoms and pain were assessed monthly with questionnaires for 6 months. RESULTS: There was evidence of palliation with three measures of pain and, to a lesser extent, with a measure of overall symptom status after 3 months of taking bicalutamide. No complete or partial responses occurred. However, 9 (20%) of 44 subjects with adequate prostate-specific antigen data had a 50% or higher decrease in their prostate-specific antigen levels, which did not correlate with symptom improvement. The median survival time was 15 months. The most common side effects were hot flashes (23%) and nausea (21%). CONCLUSIONS: These data suggest that bicalutamide decreases pain and improves symptom status in patients with prostate cancer in whom first-line hormonal therapy failed.

Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial.

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

Association of African-American ethnic background with survival in men with metastatic prostate cancer.

BACKGROUND: African-American men have earlier onset of prostate cancer, higher prostate-specific antigen (PSA) levels, more advanced stage at diagnosis, and higher mortality than white men. It is not known whether the poorer survival of African-American men with prostate cancer reflects their later stage at diagnosis or differences in the basic biology of their disease. To evaluate this question, we examined outcomes of African-American and white men with metastatic prostate cancer in the context of a randomized clinical trial. METHODS: Southwest Oncology Group Study 8894 was a randomized phase III trial that compared orchiectomy with or without flutamide in men with metastatic prostate cancer. Using data from 288 African-American and 975 white men in the trial, we conducted a proportional hazards regression analysis to determine if ethnicity was an independent predictor of survival. All statistical tests were two-sided. RESULTS: African-American men were more likely than white men to have extensive disease and bone pain and had poorer performance status, younger age at study entry, higher Gleason score, and higher PSA levels. After adjustment for these prognostic variables, the hazard ratio (HR) for all-cause mortality for African-American men relative to white men was 1.23 (P: =.018). Further adjustment for initial quality-of-life assessments also resulted in higher HRs associated with African-American ethnicity relative to white ethnicity (HR = 1.39; P: =.007). CONCLUSIONS: African-American men with metastatic prostate cancer have a statistically significantly worse prognosis than white men that cannot be explained by the prognostic variables explored in this study. These data should give increased impetus for efforts to detect the disease early in African-American men and for the development of more effective therapies based on potential biologic differences in this ethnic group.

Impact of a randomized, controlled trial of liberal vs conservative hospital discharge criteria on energy, protein, and fluid intake in patients who received marrow transplants.

OBJECT: To determine if adult patients who received marrow transplants had faster resumption of oral energy and nutrient intake and shorter duration of intravenous (i.v.) fluid requirement if discharged from the hospital earlier than is customary. DESIGN: Randomized, controlled trial of patients remaining hospitalized because of inadequate oral intake. Consenting patients were assigned randomly to remain hospitalized (hospital group) or be discharged to an ambulatory setting (ambulatory group). SUBJECTS: Seventy-eight patients of the Fred Hutchinson Cancer Research Center who were consuming less than 33% of estimated energy requirement and requiring up to 3,000 mL of fluids per day intravenously. INTERVENTION: Participants received nutrition counseling by a registered dietitian to promote resumption of oral intake. Daily oral intake records were analyzed to determine energy and nutrient content. MAIN OUTCOME MEASURES: Days after study enrollment to consume 33% of energy and protein requirements and total number of days of i.v. fluid support were analyzed by group until discharge from the center, approximately 100 days after transplantation. STATISTICAL ANALYSES: Demographic data were defined by group means. Differences between treatment procedures were determined by Cox regression analysis. No variables were confounding. RESULTS: The hospital group took fewer days than the ambulatory group to resume oral energy intake (4.5 vs 8.0, P = .004) and to discontinue i.v. fluids (30.5 vs 48.5, P = .019). There was no difference between groups in days of parenteral nutrition support (P = .817) or days to resume oral protein intake (P = .470). APPLICATIONS/CONCLUSIONS: Oral and gastrointestinal complications delay resumption of oral energy and protein intakes after transplantation. Earlier hospital discharge can achieve cost savings but may delay resumption of oral energy intake. Because of continued high-risk nutrition status and potential for rapid change in medical status, nutrition assessment and counseling are necessary in both the hospital and ambulatory setting to promote resumption of oral intake and discontinuation of i.v. fluids.

Substituting proxy ratings for patient ratings in cancer clinical trials: an analysis based on a Southwest Oncology Group trial in patients with brain metastases.

In studies of the effect of cancer treatment in the advanced disease setting, researchers have attempted to avoid missing data for quality of life (QOL) assessments by either substituting proxy for patient assessments from the outset or by interspersing proxy measures when patients are unable to respond. Although poor agreement between patient and proxy assessments has been amply demonstrated in the literature, interest in using proxy measures persists. Completion of the Spitzer QL-Index by a small sample of patients with brain metastases and family member proxies provided data for evaluating the ability to substitute proxy for patient QOL assessments. These data cannot address treatment efficacy due to the modest sample size. Rather, the analyses serve to alert researchers to the important distinction (in a clinical trial setting) between agreement and the use of the proxy as a surrogate. We present several methods for evaluating the accuracy of proxy measures and for identifying other sources of error and bias that may vary with time or with treatment arm. Lin's concordance correlation coefficient suggests that proxies are generally a poor substitute for capturing a patient's perspective of his/her QOL. A longitudinal analysis suggests that the use of proxy rather than patient responses could lead to different conclusions concerning radiation therapy's effect on QOL.

Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.

Profile of men randomized to the prostate cancer prevention trial: baseline health-related quality of life, urinary and sexual functioning, and health behaviors.

PURPOSE: To describe men who agreed to be randomized to the Prostate Cancer Prevention Trial (PCPT), a 7-year, double-blind placebo-controlled study of the efficacy of finasteride in preventing prostate cancer. METHODS: Comprehensive health-related quality-of-life data are presented for 18,882 randomized PCPT participants. RESULTS: PCPT participants are highly educated, middle to upper income, and primarily white (92%). Participants reported healthy lifestyles. The mean American Urological Association Symptom Index score was well below the maximum entry score of less than 19; existing urinary symptoms were generally not bothersome. The scores for two sexual functioning scales could range from 0 to 100, with higher scores reflecting worse sexual functioning. The mean score for the Sexual Problem Scale was 19.2 out of 100, and the mean Sexual Activities Scale was 44.1 out of 100. Scores for seven of the eight Medical Outcomes Study 36-item Short-Form Health Survey scales (higher scores are better) were 10 to 20 points higher than those reported by a general population sample and differed minimally by race but not by age. Previously reported associations between sexual dysfunction and hypertension, diabetes, and depression were also observed. Men who never smoked reported less sexual dysfunction than did those who either had quit or still smoked. CONCLUSION: Individuals who are likely to enroll in primary prevention trials have a high socioeconomic status, healthy lifestyle behaviors, and better health than the general population. These data help oncologists design chemoprevention trials with respect to the selection of health-related quality-of-life assessments and recruitment strategies.

Quality of life in survivors of colorectal carcinoma.

BACKGROUND: Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer-related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community-based samples of cases across stage and survival times from diagnosis. METHODS: Subjects with colorectal carcinoma were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry. Subjects completed two self-administered surveys: the Functional Assessment of Cancer Therapy Scales for Colorectal Cancer (FACT-C) and the Health Utilities Index (HUI) Mark III. RESULTS: One hundred seventy-three respondents (average age: 70.4 years, 71.4% female) completed the survey. In the first 3 years after diagnosis, quality of life was lower and varied substantially among respondents. After 3 years, respondents in all TNM stages of disease except Stage IV reported a relatively uniform and high quality of life. Pain, functional well-being, and social well-being were affected most substantially across all stages and times from diagnosis. Low income status was associated with worse outcomes for pain, ambulation, and social and emotional well-being. Only emotional well-being scores improved significantly over time in both surveys. CONCLUSIONS: Those individuals who achieve a long term remission from colorectal carcinoma may experience a relatively high quality of life, although deficits remain for several areas, particularly in those of low socioeconomic status. Sampling design may have excluded the most severely ill patients.

Minority recruitment in the prostate cancer prevention trial.

PURPOSE: African American men have a higher prostate cancer risk profile than that of other men in the United States. The purpose of this manuscript is to summarize the challenges associated with enrolling and randomizing African American and other minority participants in the Prostate Cancer Prevention Trial (PCPT). METHODS: The PCPT is a randomized trial of finasteride versus placebo for preventing prostate cancer in healthy men age 55 years and older; it is coordinated by the Southwest Oncology Group. The manuscript describes demographic and lifestyle characteristics of the PCPT randomized sample (18,882 men) by four racial and ethnic groups (Caucasian, African American, Hispanic, and other). African American men comprised 4% of the total randomized sample compared to our goal of 8%. Minority recruitment was emphasized through the Study Manual and training that occurred at trial activation. Supplemental minority recruitment activities were initiated a year after study activation and continued through the end of the accrual period. Minority recruitment was emphasized as follows: minority recruitment presentations at PCPT training seminars (held during twice yearly Southwest Oncology Group meetings); distribution of additional minority recruitment materials; engagement of four consultants for minority recruitment; production of a Minority Recruitment Manual; and a small pilot study involving minority outreach recruiters at five PCPT sites. RESULTS: The consultants were helpful in implementing the pilot project and in suggesting and reviewing materials for minority recruitment. The five-site pilot project did not increase either enrollment or randomization of minorities (with a possible exception at one site). CONCLUSIONS: We suggest that a long-term perspective is required for successful recruitment of minority participants in clinical trials. Likewise, extensive minority recruitment efforts must be ready to implement at trial activation.

Practice and policy of measuring quality of life and health economics in cancer clinical trials: a survey among co-operative trial groups.

BACKGROUND: Co-operative groups have played an important role in the advance of health-related quality of life (HRQL) research. However, definitions of the concept, criteria for selection of existing instruments and methods for data collection and interpretation remain poorly defined in the literature. A survey was conducted amongst the major cancer co-operative groups in order to gain a better understanding of their current policy and processes to ensure optimal HRQL data collection within cancer clinical trials. The topic of health economics was similarly addressed. METHODS: A written questionnaire was addressed to 16 major European and North American cancer co-operative groups. Eleven groups responded (response rate: 69%). however, one group could not provide information for the survey, thus ten questionnaires were available for analysis. RESULTS: The results from this survey among co-operative groups show that HRQL (more than health economics) is recognized as an important, although usually secondary, outcome measure in oncology trials. On the whole, co-operative groups have a rather flexible policy towards the inclusion of HRQL (and HE) into their clinical trials, and practice is very much on a case-by-case basis, but use standard practice guidelines and internal procedures is to ensure well-defined study protocols and enhance good quality studies.

Inclusion of black Americans in oncology clinical trials: the Louisiana State University Medical Center experience.

Recruitment of patients from diverse ethnic, racial, and socioeconomic backgrounds for clinical trials is desirable for both scientific and ethical reasons. Participation rates in clinical trials are low for minorities and especially for black Americans. This report summarizes the experience at Louisiana State University Medical Center in Shreveport, Louisiana, in enrolling black Americans in oncology treatment and prevention trials. Barriers to enrollment are identified and discussed. Although major strides must still be made in the area of cancer prevention, the university's experience demonstrates that black Americans can be encouraged to participate in and can be enrolled in cancer clinical trials.

Physician participation in research surveys. A randomized study of inducements to return mailed research questionnaires.

The authors randomly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information. In a two-factor completely randomized factorial design, the 400 physicians were assigned to receive mailed surveys with either no compensation or a $5 check and either no follow-up call or a follow-up call 3 weeks after mailing. Overall, 51.5% of the physicians returned the mailed surveys. Comparison of logit models showed that inclusion of a $5 check in the mailer significantly (p = .016) increased the probability of returning the surveys (57.5% vs. 45.5%). In contrast, the telephone follow-up had no overall effect. The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective.

Quality of life and quality adjusted survival for breast cancer patients receiving adjuvant therapy. Eastern Cooperative Oncology Group (ECOG).

PURPOSE: The objective was to compare health related quality of life (QOL) in hormone receptor negative, node-positive breast cancer patients receiving adjuvant chemotherapy to determine whether a more intensive chemotherapy regimen has an adverse effect upon QOL that is not balanced by improvements in disease control or survival. Increased physical symptoms, including fatigue and the inconvenience of the dose intensive 16-week regimen, were expected to have a negative impact on QOL. DESIGN: QOL was measured in 163 patients, randomized to either a standard cyclophosphamide, doxorubicin and 5-flurouracil (CAF) or a 16-week multidrug regimen, using the Breast Chemotherapy Questionnaire (BCQ). The 30 item BCQ was self-administered prior to therapy, during therapy, and 4 months post treatment. RESULTS: BCQ scores decreased (worsened) more during therapy on the 16-week regimen, median change -1.4, than on CAF, median change -0.8 (p < 0.001). By 4 months post treatment, BCQ scores were higher than pre-treatment and equal in the two arms (CAF: 8.1 and 16 weeks: 8.2, p = 0.6). Over a period of 48 months, patients on the 16-week regimen averaged 1.4 fewer months of treatment with toxicity, 4.0 more months without symptoms and 0.7 fewer months post recurrence compared to patients on the CAF regimen. Given typical values for these health states, the gain in Q-TWiST observed for the CAF regimen during treatment shifted to the 16-week regimen after 1 year, with a gain of 2.0 to 2.4 months after 4 years. CONCLUSIONS: The hypothesized negative impact of the dose intensive 16-week regimen was confirmed by the BCQ assessments. However, Q-TWiST analysis suggests a small gain for the 16-week regimen. The later results should be interpreted with caution with the limited follow-up of 4 years.

Quality of life in advanced prostate cancer: results of a randomized therapeutic trial.

BACKGROUND: For patients with metastatic prostate cancer, treatment is primarily palliative, relying mainly on the suppression of systemic androgen hormone levels. To help document the achievement of palliation and to characterize positive and negative effects of treatment, we evaluated quality-of-life (QOL) parameters in patients with metastatic prostate cancer who were randomly assigned to two methods of androgen deprivation. METHODS: Patients (n = 739) with stage M1 (bone or soft tissue metastasis) prostate cancer were enrolled in a QOL protocol that was a companion to Southwest Oncology Group INT-0105, a randomized double-blind trial comparing treatment with bilateral orchiectomy (surgical castration) plus either flutamide or placebo. Patients completed a comprehensive battery of QOL questionnaires at random assignment to treatment and at 1, 3, and 6 months later. Data were collected on three treatment-specific symptoms (diarrhea, gas pain, and body image), on physical functioning, and on emotional functioning. All P values are two-sided. RESULTS: Questionnaire return rates for this study never dropped below 80%; only 2% of the patients did not submit baseline QOL assessments. Cross-sectional analyses (corrected for multiple testing) identified statistically significant differences that favored orchiectomy plus placebo for two of the five primary QOL parameters as follows: patients receiving flutamide reported more diarrhea at 3 months (P = .001) and worse emotional functioning at 3 and 6 months (both P<.003). Longitudinal analyses replicated these findings. Other analyzed QOL parameters favored the group receiving placebo but were not statistically significant after adjustment for multiple testing. CONCLUSIONS: We found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo.

Missing quality of life data in cancer clinical trials: serious problems and challenges.

Measurement of quality of life (QOL) in cancer clinical trials has increased in recent years as more groups realize the importance of such endpoints. A key problem has been missing data. Some QOL data may unavoidably be missing, as for example when patients are too ill to complete forms. Other important sources are potentially avoidable and can broadly be divided into three categories: (i) methodological factors; (ii) logistic and administrative factors; (iii) patient-related factors. Logistic and administrative factors, for example, staff oversights, have proven to be most important. Since most QOL measurements require patient self-report, it is usually not possible to rectify the failure to collect baseline data or any follow-up assessments. There is strong evidence that such data are not 'missing at random', and cannot be ignored without introducing bias. Although several approaches to the analysis of partly missing data have been described, none is entirely satisfactory. Prevention of avoidable missing data is better than attempted cure. In July 1996, an international conference on missing QOL data in cancer clinical trials reported the experience of most major groups involved. This paper will serve as an introduction to the problem and provide an estimation of its magnitude, and approaches to its prevention and solution.