Reliability and validity of the instrument for scoring clinical outcomes of research for epidermolysis bullosa (iscorEB).

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare and currently incurable genetic blistering disorders. As more pathogenic-driven therapies are being developed, there is an important need for EB-specific validated outcomes measures designed for use in clinical trials. OBJECTIVES: To test the reliability and construct validity of an instrument for scoring clinical outcomes of research for EB (iscorEB), a new combined clinician- and patient-reported outcomes tool. METHODS: We conducted an observational study consisting of independent 1-day assessments (six assessors) at two academic hospitals. The assessments consisted of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity (BEBS) and global severity assessment for physicians; and iscorEB patient (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's Dermatology Life Quality Index for patients. Construct validity and intraclass correlation coefficients (ICCs) for interobserver, intraobserver and test-retest reliability were calculated. RESULTS: Overall, 31 patients with a mean age of 19·5 years (1·8-45·2) were included. Disease severity was mild in 42% of cases, moderate in 29% and severe in 29%. The interobserver ICC was 0·96 for both the clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver reliability was 0·91 and 0·70 for the skin and mucosal domains of iscorEB-c, respectively. Cronbach's alpha for iscorEB-c was 0·89. The test-retest reliability of iscorEB-p was 0·97 and Cronbach's alpha was 0·84. The clinical score differentiated between subjects with mild, moderate and severe disease, and both clinical and patient subscores discriminated between recessive dystrophic EB and other EB subtypes. CONCLUSIONS: iscorEB has robust reliability and construct validity, including strong ability to distinguish EB types and severities. Further studies are planned to test its responsiveness to change.

The functional assessment of cancer therapy-BRM (FACT-BRM): a new tool for the assessment of quality of life in patients treated with biologic response modifiers.

PURPOSE: This paper reports on the development and validation of two biologic response modifier (BRM) subscales for use with the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire. METHODS: Using the FACT-G as a base, 17 additional questions related to symptoms common to interferon and retinoid therapy were developed. Data collected at baseline (n = 191) and week 2 (n = 168) in a randomized trial of interferon +/- 13-cis-retinoic acid in advanced renal cell carcinoma patients were used to validate this measure. RESULTS: Using a combined empirical and conceptual approach, the 17 questions were reduced to 13 questions consisting of two subscales: 'BRM-physical' (7 items; baseline coefficient alpha(alpha) = 0.70; week-2 alpha = 0.75) and 'BRM-mental' (6 items; baseline alpha = 0.79; week-2 alpha = 0.78). Internal consistency of the trial outcome index (TOI) combining physical well-being, functional well-being and the BRM subscales, was 0.91 for baseline assessments and 0.92 for week 2. Discriminant validity was demonstrated for the TOI by its ability to differentiate among prognostic risk groups, and for the total FACT-G, TOI and total FACT-BRM scores by their ability to distinguish between groups differing in performance, response and toxicity status. CONCLUSIONS: The 'BRM-physical' and 'BRM-mental' subscales can be combined with the FACT-G to form the 'FACT BRM' scale, useful for measuring QOL in cancer patients who are receiving treatment with biologic response modifiers.

Evaluation of quality of life in a clinical trial with nonrandom dropout: the effect of epoetin alfa in anemic cancer patients.

Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of anemic cancer patients treated with nonplatinum-containing chemotherapy who received epoetin alfa or placebo were subjected to a sensitivity analysis. Three QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the SF-36 physical and mental component summary scales. Lower QOL scores were reported for patients who discontinued early, suggesting a nonrandom dropout process. Significant correlations (ranging from 0.37 to 0.77) between individual rates of change and the time to early termination of therapy or death supported this conclusion. Estimates of within-treatment-arm QOL change over time are more conservative with the missing not at random (MNAR) assumption as compared with the more optimistic estimates with the assumption that missing QOL data are missing at random (MAR). However, the between-treatment-arm comparisons were consistent across analyses, demonstrating statistically significant differences in favor of the epoetin alfa arm for four of the seven outcome measures.

Understanding the experience of pain in terminally ill patients.

BACKGROUND: Terminally ill patients commonly experience substantial pain. Unresolved pain has been cited as evidence that end-of-life care is of poor quality. However, the data on which that conclusion is based are limited. We aimed to provide additional data on the experience of pain in such patients. METHODS: We interviewed 988 terminally ill patients from six randomly selected US sites. We asked them who had treated their pain in the previous 4 weeks (primary-care physician, pain specialist, or both), and whether they wanted more pain medication than they were receiving, or why they did not want more. FINDINGS: 496 (50%) terminally ill patients reported moderate or severe pain. 514 (52%) individuals had seen a primary-care physician for treatment of pain in the previous 4 weeks and 198 (20%) saw a pain specialist. Of those who had been treated by their primary-care physician, 287 (29%) wanted more therapy, 613 (62%) wanted their pain therapy to remain the same, and 89 (9%) wanted to reduce or stop their pain therapy. Several reasons for not wanting additional therapy were offered-fear of addiction, dislike of mental or physical side-effects, and not wanting to take more pills or injections. We saw no association between disease and amount of pain between disease and the desire for more treatment. Black patients were more likely to seek additional pain therapy, see a pain specialist, and refuse additional medication because of fear of addiction than other populations. INTERPRETATION: Although half of terminally ill patients experienced moderate to severe pain, only 30% of them wanted additional pain treatment from their primary-care physician. The number of patients experiencing pain remains too high. However, the number is not as large as perceived. Additionally, most are willing to tolerate pain. Furthermore, the experience of pain is constant across major terminal diseases.

Attitudes and practices among pediatric oncologists regarding end-of-life care: results of the 1998 American Society of Clinical Oncology survey.

PURPOSE: In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications for care of children dying from cancer. METHODS: The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which was completed by 228 pediatric oncologists. Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year. RESULTS: Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as a barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control. CONCLUSION: Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge.

Attitudes and desires related to euthanasia and physician-assisted suicide among terminally ill patients and their caregivers.

CONTEXT: Euthanasia and physician-assisted suicide (PAS) are highly controversial issues. While there are studies of seriously ill patients' interest in euthanasia and PAS, there are no data on the attitudes and desires of terminally ill patients regarding these issues. OBJECTIVE: To determine the attitudes of terminally ill patients toward euthanasia and PAS, whether they seriously were considering euthanasia and PAS for themselves, the stability of their desires, factors associated with their desires, and the proportion of patients who die from these interventions. DESIGN: Prospective cohort of terminally ill patients and their primary caregivers surveyed twice between March 1996 and July 1997. SETTING: Outpatient settings in 5 randomly selected metropolitan statistical areas and 1 rural county. PARTICIPANTS: A total of 988 patients identified by their physicians to be terminally ill with any disease except for human immunodeficiency virus infection (response rate, 87. 4%) and 893 patient-designated primary caregivers (response rate, 97. 6%). MAIN OUTCOME MEASURES: Support for euthanasia or PAS in standard scenarios; patient-expressed considerations and discussions of their desire for euthanasia or PAS; hoarding of drugs for suicide; patient death by euthanasia or PAS; and patient-reported sociodemographic factors and symptoms related to these outcomes. RESULTS: Of the 988 terminally ill patients, a total of 60.2% supported euthanasia or PAS in a hypothetical situation, but only 10. 6% reported seriously considering euthanasia or PAS for themselves. Factors associated with being less likely to consider euthanasia or PAS were feeling appreciated (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.52-0.82), being aged 65 years or older (OR, 0.52; 95% CI, 0.34-0.82), and being African American (OR, 0.39; 95% CI, 0. 18-0.84). Factors associated with being more likely to consider euthanasia or PAS were depressive symptoms (OR, 1.25; 95% CI, 1.05-1. 49), substantial caregiving needs (OR, 1.09; 95% CI, 1.01-1.17), and pain (OR, 1.26; 95% CI, 1.02-1.56). At the follow-up interview, half of the terminally ill patients who had considered euthanasia or PAS for themselves changed their minds, while an almost equal number began considering these interventions. Patients with depressive symptoms (OR, 5.29; 95% CI, 1.21-23.2) and dyspnea (OR, 1.68; 95% CI, 1.26-2.22) were more likely to change their minds to consider euthanasia or PAS. According to the caregivers of the 256 decedents, 14 patients (5.6%) had discussed asking the physician for euthanasia or PAS and 6 (2.5%) had hoarded drugs. Ultimately, of the 256 decedents, 1 (0.4%) died by euthanasia or PAS, 1 unsuccessfully attempted suicide, and 1 repeatedly requested for her life to be ended but the family and physicians refused. CONCLUSIONS: In this survey, a small proportion of terminally ill patients seriously considered euthanasia or PAS for themselves. Over a few months, half the patients changed their minds. Patients with depressive symptoms were more likely to change their minds about desiring euthanasia or PAS. JAMA. 2000;284:2460-2468.

Factors that contribute to positive perceived health in an older population.

This study explored the extent to which factors commonly associated with negative outcomes of aging also predicted positive perceived health in a group of community-dwelling older people. Questionnaires originally administered during a randomized trial of HMO's outpatient group visit program supplied data from approximately 700 participants. Stepwise modeling identified significant factors within categories of predictors of perceived health. Hierarchical multiple linear regression then modeled the incremental importance of theoretically-derived categories of factors. Many but not all of the factors previously associated with negative outcomes of aging also predicted positive perceived health, accounting for 38% of the variation. The most important predictors were fewer chronic conditions and no worsening of those conditions, mobility and better physical performance status, and the absence of depression. Gender, limitations in daily living activities, dementia, and utilization of services had little effect. The categories of f factors associated with positive perceived health had cumulative, interdependent effects.

Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma.

PURPOSE: A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Two hundred eighty-four patients were randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a alone. IFNalpha2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless >/= grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed. RESULTS: Complete or partial responses were achieved by 12% of patients treated with IFNalpha2a plus 13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P =.03). Nineteen percent of patients treated with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNalpha2a alone (P =.05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy. CONCLUSION: Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.

Understanding economic and other burdens of terminal illness: the experience of patients and their caregivers.

BACKGROUND: Terminal illness imposes substantial burdens--economic and otherwise--on patients and caregivers. The cause of these burdens is not understood. OBJECTIVE: To determine the mechanism for economic and noneconomic burdens of terminal illness and to identify potential ameliorating interventions. DESIGN: In-person interviews of terminally ill patients and their caregivers. SETTING: Six randomly selected U.S. sites: Worcester, Massachusetts; St. Louis, Missouri; Tucson, Arizona; Birmingham, Alabama; Brooklyn, New York; and Mesa County, Colorado. PARTICIPANTS: 988 terminally ill patients and 893 caregivers. MEASUREMENTS: Needs for transportation, nursing care, homemaking, and personal care; subjective perception of economic burden; expenditure of more than 10% of household income on health care costs; caregiver depression and sense of interference with his or her life; and patient consideration of euthanasia or physician-assisted suicide. RESULTS: Of all patients, 34.7% had substantial care needs. Patients who had substantial care needs were more likely to report that they had a subjective sense of economic burden (44.9% compared with 35.3%; difference, 9.6 percentage points [95% CI, 3.1 to 16.1]; P = 0.005); that 10% of their household income was spent on health care (28.0% compared with 17.0%; difference, 11.0 percentage points [CI, 4.8 to 17.1]; P < or = 0.001); and that they or their families had to take out a loan or mortgage, spend their savings, or obtain an additional job (16.3% compared with 10.2%; difference, 6.1 percentage points [CI, 1.4 to 10.6]; P = 0.004). Patients with substantial care needs were more likely to consider euthanasia or physician-assisted suicide (P = 0.001). Caregivers of these patients were more likely to have depressive symptoms (31.4% compared with 24.8%; difference, 6.6 percentage points [CI, 0.4 to 12.8]; P = 0.01) and to report that caring for the patients interfered with their lives (35.6% compared with 24.3%; difference, 11.3 percentage points [CI, 5.0 to 17.7]; P = 0.001). Caregivers of patients whose physicians listened to patients' and caregivers' needs had fewer burdens. CONCLUSIONS: Substantial care needs are an important cause of the economic and other burdens imposed by terminal illness. Through empathy, physicians may be able to ameliorate some of these burdens.

Stability of attitudes regarding physician-assisted suicide and euthanasia among oncology patients, physicians, and the general public.

PURPOSE: Attitudes regarding the ethics of physician-assisted suicide (PAS) and euthanasia have been examined in many cross-sectional studies. Stability of these attitudes has not been studied, and this is important in informing the dialog on PAS in this country. We evaluated the stability of attitudes regarding euthanasia and PAS among three cohorts. METHODS: Subjects included 593 respondents: 111 oncology patients, 324 oncologists, and 158 members of the general public. We conducted initial and follow-up interviews separated by 6 to 12 months by telephone, regarding acceptance of PAS and euthanasia in four different clinical vignettes. RESULTS: The proportion of respondents with stable responses to vignettes ranged from 69.2% to 94.8%. In comparison to patients and the general public, physicians had less stable responses concerning the PAS pain vignette (69.1% v 80.8%; P =.001) and more stable responses for all euthanasia vignettes (P <.001) except for pain. Over time, physicians were significantly more likely to change toward opposing PAS and euthanasia in all vignettes (P <.05). Characteristics previously associated with attitudes regarding PAS and euthanasia, such as Roman Catholic religion, were not predictive of stability. CONCLUSION: Up to one third of participants changed their attitudes regarding the ethical acceptability of PAS and euthanasia in their follow-up interview. This lack of consistency mandates careful interpretation of referendums and requests for physician-assisted suicide. Furthermore, in this study, we found that physicians are becoming increasingly opposed to PAS and euthanasia. The growing disparity between physicians and patients regarding the role of these practices is large enough to suggest possible conflicts in the delivery of end-of-life care.

Age-related differences in the quality of life of breast carcinoma patients after treatment.

BACKGROUND: The objective of this study was to compare the quality of life (QOL) of younger (< or =50 years) versus older (>50 years) women on recent completion of treatment of breast carcinoma. METHODS: Data reported herein were obtained from a baseline assessment of 304 breast carcinoma patients. These patients were enrolled in a multiinstitutional, randomized trial testing a psychosocial telephone counseling intervention for breast carcinoma patients immediately after treatment. The assessment was made using a self-administered (mail) questionnaire, with an overall response rate of 86%. Included in this questionnaire were standardized measures of QOL using the Functional Assessment of Cancer Therapy-Breast instrument, the Center for Epidemiologic Studies Depression Scale, and the Impact of Event Scale. RESULTS: Comparisons of baseline data analyzed according to age approximating menopausal status (< or =50 years and >50 years) indicated that younger women reported significantly greater QOL disturbance. QOL was significantly worse for younger women globally (P = 0.021), and with regard to domains of emotional well-being (P = 0.0002) and breast carcinoma specific concerns (P = 0.022). Furthermore, symptoms of depression (P = 0.041) and disease specific intrusive thoughts (P = 0.013) were significantly worse for younger women. No significant sexual dysfunction or body image differences were noted. CONCLUSIONS: Results from this analysis suggest that younger women with breast carcinoma should be considered to be at high risk for QOL disruption and significant clinical distress. Targeted interventions for this cohort are recommended.

A test strip for diamines in tuna.

This study describes the production of a solid-phase assay (test strip/dipstick test) for putrescine and cadaverine in tuna based on the coupling of an amine oxidase to a peroxidase/dye system. The assay was linear to 75 microM in phosphate buffer, and the minimum detectable concentration was 0.5 microM (< 0.1 ppm), corresponding to 0.01 mg% in spiked extracts. Intra- and interassay precisions were < 20%. Test strips were stable at 4 degrees C for at least 12 months. Lysine, ornithine, and histidine did not react with the assay, and histamine reacted only minimally. Sixteen fish samples were tested by test strip and the standard AOAC protocol, and results were in good agreement.

Assistance from family members, friends, paid care givers, and volunteers in the care of terminally ill patients.

BACKGROUND: In addition to medical care, dying patients often need many types of assistance, including help with transportation, nursing care, homemaking services, and personal care. We interviewed terminally ill adults and their care givers in six randomly selected areas of the United States (five metropolitan areas and one rural county) to determine how their needs for assistance were met and the frequency with which they received such assistance from family members and paid and volunteer care givers. METHODS: The patients, whose physicians estimated them to have less than six months to live and who had clinically significant illness other than human immunodeficiency virus infection or the acquired immunodeficiency syndrome, were referred to the study by their physicians. Of the 1131 eligible patients, 988 (87.4 percent) consented to a detailed in-person interview conducted in English, as did 893 of the 915 eligible primary care givers (97.6 percent). RESULTS: Of the 988 terminally ill patients, 59.4 percent were over the age of 65 years, and 51.5 percent were women. The most frequent terminal illness was cancer (in 51.8 percent of the patients), followed by heart disease (18.0 percent) and chronic obstructive pulmonary disease (10.9 percent). Four percent of the patients were in an institution, such as a nursing home, residential hospice, or hospital; the rest were living in a private residence. A need for assistance was reported by 86.8 percent of the patients; they required help with transportation (reported by 62.0 percent), homemaking services (55.2 percent), nursing care (28.7 percent), and personal care (26.0 percent). Of the care givers, 72.1 percent were women. Primary care givers were family members in 96.0 percent of cases; only 4.0 percent were unrelated. Most patients relied completely on family members and friends for assistance. A total of 15.5 percent of patients relied only on paid assistance for more than half of the types of care that they needed. Volunteers (that is, unpaid helpers who were not family members or friends) provided less than 3 percent of all care. CONCLUSIONS: In our survey of terminally ill patients, family members, usually women, provided the majority of assistance with nonmedical care. Although many people received assistance from paid care givers, very few had assistance from volunteers.

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.

The practice of euthanasia and physician-assisted suicide in the United States: adherence to proposed safeguards and effects on physicians.

CONTEXT: Despite intense debates about legalization, there are few data examining the details of actual euthanasia and physician-assisted suicide (PAS) cases in the United States. OBJECTIVE: To determine whether the practices of euthanasia and PAS are consistent with proposed safeguards and the effect on physicians of having performed euthanasia or PAS. DESIGN: Structured in-depth telephone interviews. SETTING AND PARTICIPANTS: Randomly selected oncologists in the United States. OUTCOME MEASURES: Adherence to primary and secondary safeguards for the practice of euthanasia and PAS; regret, comfort, and fear of prosecution from performing euthanasia or PAS. RESULTS: A total of 355 oncologists (72.6% response rate) were interviewed on euthanasia and PAS. On 2 screening questions, 56 oncologists (15.8%) reported participating in euthanasia or PAS; 53 oncologists (94.6% response rate) participated in in-depth interviews. Thirty-eight of 53 oncologists described clearly defined cases of euthanasia or PAS. Twenty-three patients (60.5%) both initiated and repeated their request for euthanasia or PAS, but 6 patients (15.8%) did not participate in the decision for euthanasia or PAS. Thirty-seven patients (97.4%) were experiencing unremitting pain or such poor physical functioning they could not perform self-care. Physicians sought consultation in 15 cases (39.5%). Overall, oncologists adhered to all 3 main safeguards in 13 cases (34.2%): (1) having the patient initiate and repeat the request for euthanasia or PAS, (2) ensuring the patient was experiencing extreme physical pain or suffering, and (3) consulting with a colleague. Those who adhered to the safeguards had known their patients longer and tended to be more religious. In 28 cases (73.7%), the family supported the decision. In all cases of pain, patients were receiving narcotic analgesia. Fifteen patients (39.5%) were enrolled in a hospice. While 19 oncologists (52.6%) received comfort from having helped a patient with euthanasia or PAS, 9 (23.7%) regretted having performed euthanasia or PAS, and 15 (39.5%) feared prosecution. CONCLUSIONS: Intractable pain or poor physical functioning seem to be nearly absolute requirements for physicians to perform euthanasia or PAS. Only one third of cases are performed consistently with proposed safeguards. For some patients, end-of-life care that includes opioid analgesia and hospice care does not obviate their desire for euthanasia or PAS. While the majority of physicians seem comforted by their actions, some experience adverse consequences from having performed euthanasia or PAS.

Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study.

PURPOSE: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. PATIENTS AND METHODS: A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. RESULTS: At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. CONCLUSION: The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.

Missing data in quality of life research in Eastern Cooperative Oncology Group (ECOG) clinical trials: problems and solutions.

Incorporation of quality of life (QOL) investigation into Eastern Cooperative Oncology Group (ECOG) multi-centre clinical trials has led to innovative strategies for protocol design and high quality data collection. A scientific advisory committee reviews protocol design components, measurement selection, timing of assessments and compliance issues. Extensive educational programmes provide information about the scientific and clinical relevance of QOL protocols, as well as practical strategies for data collection and management. Compliance with QOL data collection standards is prospectively monitored and evaluated. Preliminary results from eight ECOG-run protocols found overall compliance to be approximately 85 per cent (94 per cent at baseline and 73 per cent during treatment). Selected patient and institutional factors were evaluated for their association with compliance.

Statistical analysis of quality of life with missing data in cancer clinical trials.

We summarize issues that arise when considering quality of life (QOL) data in cancer clinical trials, especially those related to missing data. We describe different types of missing data mechanisms, and discuss ways of assessing and testing missing data mechanisms. A section on presentation of study design and results describes how graphical displays can effectively document the extent of the missing data problem, as well as describe its impact on interpretation of results. Finally, we describe several different statistical methods used to analyse repeated measures, with an emphasis on their properties and their ability to adequately handle different types of missing data mechanisms. We make recommendations as to the most appropriate methods, and suggest important directions for future research.