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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 11588-11588
    Kurzfassung: 11588 Background: Women have more adverse events (AEs) from chemotherapy than men, but few studies have explored sex differences in biologic/immunotherapies (BIs) or targeted therapies. We examined subjective (symptomatic) and objective AEs by sex across different treatments. Methods: We analyzed drug-related severe (grade 3) or worse AEs by sex in SWOG phase II and III clinical trials conducted between 1980-2018, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events (CTCAE). Subjective or symptomatic toxicities were defined as those aligned with the NCI’s new Patient-Reported Outcome (PRO) CTCAE; lab-based or physician-determined AEs were designated as objective. Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 19 objective AE categories were examined. Results: In total, 36,397 patients (women, 13,907 [38.2%]; men, 22,490 [61.8%] ) experiencing 522,835 AEs on 297 trials with 385 treatment arms were analyzed. Overall, 29.1% (n = 10.860) had severe or worse toxicity. Women experienced an increased risk of severe symptomatic AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p 〈 .0001), chemotherapy (OR = 1.31, 95% CI: 1.24-1.39, p 〈 .0001), and targeted therapies (OR = 1.23, 95% CI: 1.06-1.43, p = .008). Women also had an increased risk of severe objective AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p 〈 .0001), chemotherapy (OR = 1.35, 95% CI: 1.28-1.43, p 〈 .0001), but not targeted therapies (OR = 1.08, 95% CI: 0.94-1.25, p = .28). Across all treatments, sex differences were greater for hematologic (OR = 1.29, 95% CI: 1.24-1.35, p 〈 .0001) v. non-hematologic (OR = 1.13, 95% CI: 1.08-1.18, p 〈 .0001) objective AEs. Conclusions: The greater severity of both symptomatic and objective – especially hematologic – AEs in women across multiple treatment paradigms indicates broad-based sex-differences exist. This could be due to AE reporting, pharmacogenomics of drug metabolism and disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving BIs, suggesting studying AEs from these agents is a priority.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2019
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 8038-8038
    Kurzfassung: 8038 Background: Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients (pts) with lymphoma on clinical trials. We evaluated 2 prior data sets and concluded that BMB impact response assessment in a minority of pts with follicular lymphoma (FL) (Rutherford BJH 2017; Rutherford ASH abstract 1605, 2018). We sought to establish if BMB add value in assessing response or identify distinct progression free (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort. Methods: Data were pooled from 7 trials of 580 pts with untreated FL conducted through the Alliance for Clinical Trials in Oncology and SWOG from 2002-2016. The proportion of pts with positive (+) baseline BMB, CR on imaging after treatment, and (+) repeat BMB was calculated using total pts enrolled as the denominator. We tested against the null hypothesis that the proportion was = 10%, the threshold below which BMB would be considered irrelevant for response assessment, versus (vs) the alternative hypothesis that this proportion was 〈 10%, using 1-sided exact binomial test. Response criteria were CT-based. Imaging was not used to assess BM involvement. Because confirmatory BMB were not completed in all indicated pts, landmark survival analyses compared PFS/OS of pts with CR on imaging and negative (-) BMB vs pts with CR on imaging without repeat BMB. Pts with CR on imaging were categorized as having (-) repeat BMB or no repeat BMB within 60 days of first CR on imaging. PFS and OS were calculated from time of first CR and estimated using Kaplan-Meier and Cox models adjusting for age, sex, stage, Follicular Lymphoma International Prognostic Index (FLIPI) score, and treatment type (targeted vs chemotherapy plus targeted therapy), and stratified by treatment arm. Results: Median age was 55 with 51% male, 96% stage III-IV, and 88% grade I-II. FLIPI scores were 113 low, 265 intermediate, and 199 high risk. 67% received chemotherapy-based regimens. Baseline BMB was (+) in 321 (55%). Only 5/580 (0.8%) had (+) baseline BMB, CR on imaging, and subsequent (+) BMB (p 〈 0.0001). Of pts with CR on imaging, PFS and OS were not different among pts with (-) BMB vs pts without repeat BMB (PFS: HR = 1.08, 95%CI 0.61-1.93, p = 0.783; OS: HR = 0.52, 95%CI 0.20-1.40, p = 0.199). Conclusions: BMB requirements may discourage pt participation in trials and add pain, expense and time without providing necessary information. We recommend eliminating BMB for response assessment from FL clinical trials. Clinical trial information: NCT00553501, NCT01145495, NCT01190449, NCT01286272, NCT01829568, NCT00822120, and NCT00770224 .
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2020
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 6604-6604
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 6604-6604
    Kurzfassung: 6604 Background: National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying new antineoplastic regimens. However, the clinical impact of their trials has not been systematically examined. We analyzed the influence of network group cancer clinical trials on clinical guidelines and new drug approvals. Methods: We evaluated Phase III cancer clinical trials which the SWOG Cancer Research Network coordinated or participated in (1980-2017). Included trials were completed and its results published. A documented practice influential (DPI) trial was one with verified influence on National Comprehensive Cancer Network (NCCN) clinical guidelines (available starting in 1996) or on U.S. Food and Drug Administration (FDA)-approved package inserts. We estimated the rate of DPI trials overall and over time. The total federal investment supporting the set of trials was also determined based on public data. Results: In total, 182 trials comprising 148,028 patients were studied. We identified 79 DPI studies (43.4%); 73 influenced NCCN guidelines, 12 influenced new drug approvals, and 6 influenced both. The rate of DPI trials was 72.3% (47/65) among formally positive trials (i.e., achieved their protocol specified endpoint) and 27.4% (32/117) among negative trials. Thus 40.5% (32/79) of DPI trials were based on negative studies, half of which (16/32 = 50.0%) reaffirmed standard of care over experimental therapy. There were no differences between DPI and non-DPI trials in key study design characteristics. Total federal investment for the programs conducting the trials was $1.36 billion (USD2017), a rate of $7.5 million per trial, or $17.2 million per DPI trial. Conclusions: Nearly half of all phase III trials by one of the NCTN’s largest groups had documented practice influence on clinical care guidelines or new drug approvals. Even many negative trials impacted guideline recommendations. Compared to the costs of a new drug approval in pharmaceutical companies – typically estimated at 〉 $1 billion – the amount invested by federal funders to provide this valuable evidence was modest. These findings highlight the major role of the NCTN’s clinical trial program in advancing oncology practice.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2019
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 6527-6527
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 6527-6527
    Kurzfassung: 6527 Background: Reducing unplanned Emergency Room (ER) visits and hospitalizations is an important strategy for improving value. Patients enrolled in clinical trials are treated per protocol. While demographic factors have been associated with increased healthcare utilization, less is known about measures of socioeconomic deprivation (SD), which may be a proxy for structural barriers to access. We tested whether ER and hospital stays are more common among trials participants who live in areas of SD or have Medicaid insurance (MI). Methods: We examined ER visits and hospitalizations among cancer patients ≥65 years treated on SWOG clinical trials from 1999-2018 using trial data linked to Medicare claims. Neighborhood socioeconomic deprivation (NSD) was measured using patients’ zip code linked to the Area Deprivation Index (ADI), measured on a 0-100 scale and categorized into tertiles (T1-T3). Higher ADI (T3) denotes areas of higher deprivation. Type of insurance was classified as Medicare alone or with Commercial, versus Medicare + MI. Outcomes were ER visits, hospital stays, and costs, all in the first year. Demographic, clinical, and prognostic factors were captured from trial records. Generalized estimating equations (GEE) were used, accounting for clustering by cancer type. Regression models were adjusted for age, race, and a study-specific prognostic risk score, and stratified by study and treatment. ADI and Insurance were considered separately to reflect neighborhood-level and individual-level measures of SD. Results: In total, N = 3,027 participants from 27 trials in bladder, breast, colorectal, lung, myeloma, and prostate cancers were analyzed. Median age was 71 years, 3% had Medicare + Medicaid and 22.3% were in the Highest ADI tertile. In all, 983 (32%) patients experienced hospitalization, and 1094 (36%) visited the ER. In multivariate GEE, patients living in more deprived areas were more likely to experience hospitalization (OR for ADI T3 compared to T1: 1.36, 95% CI, 0.95-1.94, p=.09) and to visit an ER (OR for ADI T3 compared to T1: 1.33, 95% CI, 1.08-1.63, p=.008). Overall, patients from the most deprived areas had a 61% increase in risk of either ER visit or hospitalization (OR for ADI T3 compared to T1: 1.61, 95% CI, 1.23-2.10, p 〈 .001). Patients with MI were 86% more likely to visit an ER in the first year (OR 1.86, 95% CI, 1.49-2.33, p 〈 .001. No increased risk of hospitalization was observed. Conclusions: Despite participation in cancer clinical trials, patients living in areas with higher deprivation or those with Medicare + MI had an increased risk of unplanned ER visits. These findings suggest that neighborhood deprivation and economic disadvantage may increase ER visits for socioeconomically vulnerable older patients with cancer. Efforts are needed to ensure adequate resources to prevent unplanned use of acute care in vulnerable populations.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2023
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 1551-1551
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 1551-1551
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2018
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9576-9576
    Kurzfassung: 9576 Background: S1400, a BDMP, was designed to address an unmet need in sqNSCLC, run within the National Clinical Trials Network of the National Cancer Institute using a public-private partnership (PPP). The goal of was to establish an infrastructure for biomarker-screening and rapid evaluation of targeted therapies in biomarker-defined groups leading to regulatory approval. Methods: S1400 included a screening part using the FoundationOne assay and a clinical trial part with biomarker-driven studies (BDS) and “non-match” studies (NMS) for patients not eligible for any BDS. Patients could be screened (SaP) at progression or pre-screened (PreS). Results: Between June 2014 and January 2019, 1864 patients enrolled (711 PreS, 1079 SaP), 1674 with biomarker results, and 653 registered to a study with 217 to BDS and 436 to NMS. Six BDS and 3 NMS were initiated in small subsets with all BDS and 2 NMS completed within 2-3 years (see Table). Completed BDS have not demonstrated activity with 0-2 responses. On S1400I, Nivolumab and ipilimumab did not improve survival. Response with durvalumab (S1400A) was 16%. Conclusions: Lung-MAP met its goal to quickly answer targeted and other novel therapy questions in rare sqNSCLC subpopulations, answering questions that likely would not have been otherwise feasible, thereby demonstrating value. Activated just prior to the success of PD-(L)1 therapies in sqNSCLC, the trial had to undergo major design changes. Lessons learned include the need to update based on new science and that the PPP collaboration was essential to success. Lung-MAP continues now with new BDS and NMS in all NSCLC as of January 2019. Clinical trial information: NCT02154490 . [Table: see text]
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2020
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1541-1541
    Kurzfassung: 1541 Background: The cooperative cancer research groups of the National Cancer Institute’s National Clinical Trials Network have a history of successful conduct of large randomized phase III trials of prevention for cancer. An important question for funding agencies is whether the conduct of large prevention trials provides strong scientific return on investment. Methods: We used study data from a single NCI-sponsored cooperative group (SWOG) over a 20-year period (1990-2009, inclusive). During this time, SWOG conducted two large prevention trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial) and numerous treatment trials. Scientific impact for prevention and treatment trials was examined using citation analysis. Average annual citation counts were compared using t-tests. Scientific impact was also assessed as a function of trial costs. Results: Twenty-six treatment trials with 16,391 patients and two prevention trials with 54,415 patients were examined. The mean annual citation rate for primary articles was higher for prevention trials compared to treatment trials (173.6 vs. 41.7, p = .003). For both primary and secondary article publications, mean annual citations for articles associated with prevention trials were also higher (557.2 vs. 67.6, p 〈 .0001). Large prevention trials were estimated to provide 70% greater scientific impact on a cost-adjusted basis. Conclusions: Based on these criteria, the scientific impact of large phase III cancer prevention trials was very high in absolute terms and after accounting for trial costs. For appropriate scientific questions, large prevention trials provide a strong scientific return on investment for federal funding agencies.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2017
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 27_suppl ( 2019-09-20), p. 119-119
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 27_suppl ( 2019-09-20), p. 119-119
    Kurzfassung: 119 Background: Very few new treatments tested in randomized phase III cancer clinical trials show an overall survival (OS) benefit. Understanding whether the benefits are consistent among all patient groups is critical for informing guideline care. However, within trials, there is limited power to examine demographic or insurance subsets, especially in under-represented groups. Here we systematically examine whether positive treatment effects apply to all demographic and insurance groups. Methods: We examined all SWOG treatment trials completed from 1985-2014, and pooled data from trials with a statistically significant (p 〈 .05) OS benefit for the experimental treatment. We conducted multivariable Cox regression analyses adjusting for clinical risk level and stratifying by study-specific 2-year OS probability ( 〈 25% vs. 25-75% vs. 〉 75%). Interaction tests determined whether OS hazard ratios (HRs) differed by 5 prespecified factors including age ( 〈 65 vs. ≥65), race (black vs. other), sex, ethnicity (Hispanic vs. non-Hispanic), and insurance status in patients 〈 65 years (private insurance vs. Medicaid/no insurance). Results: We identified 16 trials, containing 9,328 patients, with statistically significantly better OS in the experimental arm. The OS HR did not differ by sex (p = .60), race (p = .68), or ethnicity (p = .66). However, patients ≥65 years had a smaller treatment benefit than patients 〈 65 (HR = 1.24 vs HR = 1.37, p = .03), and patients with Medicaid/no insurance had a smaller treatment benefit than private insurance patients (HR = 1.22 vs. HR = 1.70, p = .03). Conclusions: The magnitude of the OS benefit from experimental treatments may not be uniform among demographic and insurance status groups. Older age patients and those with suboptimal insurance are at greater risk of experiencing competing risks of death, which can reduce power to identify the benefits of new experimental therapies. Trial designs should account for the risk of non-cancer deaths in important patient groups. Future research should examine whether reduced treatment impact is due to a higher comorbid burden in older patients, and to worse adherence to protocol care in those with limited financial resources.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2019
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS8067-TPS8067
    Kurzfassung: TPS8067 Background: Treatment for pediatric cHL varies considerably from that in adult cHL. Hence there are gaps in risk prediction and optimal therapy for de-novo advanced stage disease across the adolescent and young adult (AYA) age spectrum. Early access to novel agents for AYA could be facilitated via collaboration with adult research groups through the U.S. National Cancer Institute’s National Clinical Trials Network (NCTN). The PD-1 inhibitor Nivolumab (Nivo) has safety and efficacy in relapsed and refractory disease in children and adults, but has not been evaluated in de-novo disease to date. Methods: North American cooperative group lymphoma chairs, Cancer Therapy Evaluation Program (CTEP) representatives and patient advocates met to establish consensus on the comparison arms and study design, based on recent historical approaches across adult and pediatric groups. Study champions were identified across North American cooperative groups and include expertise in imaging, radiation oncology, biology and patient-reported outcomes. A therapeutic study was designed with the primary aim being to compare progression-free survival with novel targeted agents in advanced stage cHL. S1826 (NCT03907488), led by SWOG Cancer Research Network, opened to accrual in July 2019. Eligibility criteria include age 〉 12 years, and Stage III or IV cHL. Patients are randomized (1:1) to 6 cycles of either Nivo-Adriamycin, Vinblastine, Dacarbazine (AVD) or Brentuximab vedotin (Bv)-AVD. Enrollment is stratified by age, baseline International Prognostic Score, and provider intent to use involved site radiation therapy (ISRT). Protocol-prescribed ISRT is response-adapted, based on end of therapy imaging. The primary endpoint is a comparison of progression-free survival between arms. Secondary clinical endpoints include comparison of: overall survival, metabolic response at the end of therapy, physician-reported adverse events, patient-reported adverse events, and health-related quality of life (overall, and specific to fatigue and neuropathy). This unique intergroup collaboration demonstrates the process and the feasibility of consensus study designs toward early adoption of targeted therapies and harmonization of treatment approaches for AYA populations. Clinical trial information: NCT03907488 .
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2020
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 26_suppl ( 2016-10-09), p. 44-44
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 26_suppl ( 2016-10-09), p. 44-44
    Kurzfassung: 44 Background: In 1997, OR enacted a voter initiative allowing terminally ill residents to self-administer physician-prescribed medication to end their lives. Statute requires prescriptions written for lethal medications be reported; the state also collects demographic and intended use data. We wished to to evaluate and report participation trends. Methods: OR's Public Health Division gathers compliance forms from prescribing/consulting physicians, pharmacists, and psychiatrists, prescribing physician follow-up forms, and death certificates. Data from 1998-early 2016 were reviewed, collated, and interpreted. Results: 1,545 prescriptions were written; 991 pts died from legally-prescribed lethal medication. The % of prescription recipients dying from drug use per yr ranged from 48-82, with no significant trend (logistic regression 2-sided p = .90) The prescribing rate increased 12%/yr on average through 2013, with a 28% increase in 2014 and 40% in 2015, not explainable by growth in population. Characteristics of 991 pts dying from drug: Most recipients had cancer (77%); 8% had ALS, 4.5% lung disease, 2.6% heart disease, and 0.9% HIV. 5.3% were sent for psychiatric evaluation. M/F (%) 51.4/48.6; median age (years) 71 (range 25-102); race white/black/asian/hispanic (%) 97/0.1/1.3/1; hospice Y/N (%) 90.5/9/5. 94% died at home. Estimated median time between intake and coma (min): 5 (range 1-38); to death (min): 25 (range 1-6240). 3.3% had known complications. Reasons for DWD (%): ADL not enjoyable 90; loss of autonomy 92, dignity 79, or bodily functions 48; inadequate pain control 25; financial 3. Conclusions: The number of prescriptions written for ORDWDA medications increased annually since enactment. The % of recipients self-administering drugs has varied. Very few pts are referred for psychiatric consultation prior to DWD. Most pts dying from lethal medications have cancer, and the overwhelming majority expire at home. Medications used are effective and rapidly acting. Little evidence exists disadvantaged pts are disproportionally using DWD. Pts use DWD for reasons related to QOL, autonomy, and dignity, and relatively rarely because of inadequate pain palliation. Future studies should evaluate why many pts prescribed lethal drugs choose not to take them.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2016
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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