Dataset Information

The Complementary Nature of Patient-Reported Outcomes and Adverse Event Reporting in Cooperative Group Oncology Clinical Trials: A Pooled Analysis (NCCTG N0591).

ABSTRACT: CONTEXT:Clinical trials use clinician-graded adverse events (AEs) and patient-reported outcomes (PROs) to describe symptoms. OBJECTIVES:The aim of the study was to examine the agreement between PROs and AEs in the clinical trial setting. METHODS:Patient-level data were pooled from seven North Central Cancer Treatment Group, two Southwest Oncology Group, and three Radiation Therapy Oncology Group lung studies that included both PROs and AE data. Ten-point changes (on a 0-100 scale) in PRO scores were considered clinically significant differences (CSDs). PRO score changes were compared to AE grade (Gr) categories (2+ yes vs. no and 3+ yes vs. no) using Wilcoxon rank-sum or two-sample t-tests between Gr categories. Incidence rates and concordance of CSD in PRO scores and AE Gr categories were compiled. Spearman correlations were computed between PRO scores and AE severity. RESULTS:PROs completed by patients (n = 1013) were the Uniscale, Lung Cancer Symptom Scale (LCSS), Functional Assessment of Cancer Therapy-Lung (FACT-L), Symptom Distress Scale, and/or Functional Living Index-Cancer. Significantly worse PRO score changes were found for the FACT-L in patients with Gr 2+ AEs. Worse scores were seen for the Uniscale for patients with Gr 2+ AEs (P = 0.07) and LCSS for patients with Gr 3+ AEs (P = 0.09). Agreement between incidence of any Gr 2+ (Gr 3+) AE and a CSD in PROs ranged from 27% to 67% (36%-61%). Correlations between PRO scores and AE severity were low: -0.06 Uniscale, -0.03 LCSS, 0.10 FACT-L, -0.11 Symptom Distress Scale, and -0.51 Functional Living Index-Cancer. CONCLUSION:These results support previous work and an a priori hypothesis that AEs and PROs measure differing aspects of the disease experience and are complementary.

SUBMITTER: Atherton PJ

PROVIDER: S-EPMC4657556 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Complementary Nature of Patient-Reported Outcomes and Adverse Event Reporting in Cooperative Group Oncology Clinical Trials: A Pooled Analysis (NCCTG N0591).

Atherton Pamela J PJ Watkins-Bruner Deborah W DW Gotay Carolyn C Moinpour Carol M CM Satele Daniel V DV Winter Kathryn A KA Schaefer Paul L PL Movsas Benjamin B Sloan Jeff A JA

Journal of pain and symptom management 20150530 4

<h4>Context</h4>Clinical trials use clinician-graded adverse events (AEs) and patient-reported outcomes (PROs) to describe symptoms.<h4>Objectives</h4>The aim of the study was to examine the agreement between PROs and AEs in the clinical trial setting.<h4>Methods</h4>Patient-level data were pooled from seven North Central Cancer Treatment Group, two Southwest Oncology Group, and three Radiation Therapy Oncology Group lung studies that included both PROs and AE data. Ten-point changes (on a 0-100 ...[more]

PMID: 26031708

Similar Datasets

Project description:BackgroundSerious cardiovascular adverse events (SCAEs) associated with intravenous sedatives remain poorly characterized.ObjectiveThe objective of this study was to compare SCAE incidence, types, and mortality between intravenous benzodiazepines (i.e., diazepam, lorazepam, and midazolam), dexmedetomidine, and propofol in the USA over 8 years regardless of the clinical setting where it was administered.MethodsThe Food and Drug Administration's MedWatch Adverse Event Reporting System was searched between 2004 and 2011 using the Evidex® platform from Advera Health Analytics, Inc. to identify all reports that included one or more of ten different SCAEs (package insert incidence???1%) and where an intravenous benzodiazepine, dexmedetomidine, or propofol was the primary suspected drug.ResultsAmong the 2326 Food and Drug Administration's MedWatch Adverse Event Reporting System cases reported, 394 (16.9%) were related to a SCAE. The presence of a SCAE (vs. a non-SCAE) is associated with higher mortality (34 vs. 8%, p?<?0.001). The percentage of cases with one or more SCAE, the case mortality rate (%), and the incidence of each SCAE (per 106 days of sedative exposure), respectively, were benzodiazepines (14, 26, 13) [diazepam (13, 23, 31); lorazepam (15, 43, 14); midazolam (14, 20, 11)]; dexmedetomidine (40, 15, 13); and propofol (17, 39, 7). Propofol (vs. either a benzodiazepine or dexmedetomidine) was associated with more total SCAEs (268 vs. 126, p?<?0.001) but a lower incidence (per 106 days of sedative exposure) of SCAE (7 vs. 13, p?=?0.0001) and cardiac arrest [6.3 (benzodiazepine) vs. 6.7 (dexmedetomidine) vs. 1.4 (propofol), p?<?0.0001].ConclusionsSerious cardiac adverse events account for nearly one-fifth of intravenous sedative Food and Drug Administration's MedWatch Adverse Event Reporting System reports. These SCAEs appear to be associated with greater mortality than non-cardiac serious adverse events. Serious cardiac events may be more prevalent with either benzodiazepines or dexmedetomidine than propofol.

Project description:Traditional methods of reporting adverse events in clinical trials are inadequate for modern cancer treatments with chronic administration. Conventional analysis and display of maximum grade adverse events do not capture toxicity profiles that evolve over time or longer lasting, lower grade toxic effects; we aimed to address this shortcoming in this study.We developed an analytic approach and standardised, comprehensive format, the Toxicity over Time (ToxT) approach, which combines graphs and adverse event tabular displays with multiple longitudinal statistical techniques into a readily applicable method to study toxic effects. Plots visualising summary statistics or individual patient data over discrete timepoints were combined with statistical methods including the following longitudinal techniques: repeated measures models that describe the changes in adverse events across all cycles of treatment; time-to-event analyses of first and worst grade toxicity; and area under the curve (AUC) analyses summarising adverse event profiles over the entire course of a study, including chronic low-grade events. We applied ToxT analysis to adverse event data from two completed North Central Cancer Treatment Group (NCCTG/Alliance) trials: N9741 (NCT00003594), in which different combinations of oxaliplatin, 5-fluorouracil, and irinotecan were investigated for metastatic colorectal cancer, and 979254, in which survivors of breast cancer were given venlafaxine or placebo for control of hot flashes.In trial NCCTG 979254 there was a higher incidence of late-occurring dry mouth in patients who were given venlafaxine than in those given placebo (week 1 [baseline]: 13% [six incidence in 48 patients, SD 5] vs 22% [11/49, SD 6]; p=0·20; week 5: 49% [24/49, 7] vs 2% [1/46, 2]; p<0·0001). In trial NCCTG N9741 there was an increased incidence of early nausea for patients given irinotecan plus oxaliplatin (IROX) compared with those given 5-fluorouracil plus oxaliplatin (FOLFOX; cycle 1 mean grade nausea 1·1 [SD 1·0] vs 0·6 [0·7]; p<0·0001). Event charts showed earlier occurrences of higher grades of diarrhoea for patients given IROX compared with those given FOLFOX, and the AUC analysis shows a higher magnitude of diarrhoea consistently over time throughout the study in patients given IROX versus those given FOLFOX (mean AUC 4·2 [SD 5·2] vs 2·9 [4·2]; p<0·0001).The ToxT analytical approach incorporates the dimension of time into adverse event assessment and offers a more comprehensive depiction of toxic effects than present methods. With new, continuously administered targeted agents, immunotherapy, and maintenance regimens, these improved longitudinal analyses are directly relevant to patients and are crucial in cancer clinical trials.National Cancer Institute of the National Institutes of Health and the Mayo Comprehensive Cancer Center.

Project description:BackgroundAntibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database.MethodsData were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated.ResultsA total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26-1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2-24.58)], dry eye [ROR = 9.69, 95% CI (8.81-10.66)], night blindness [ROR = 259.87, 95% CI (228.23-295.89)], vision blurred [ROR = 1.78, 95% CI (1.57-2.02)], photophobia [ROR = 10.45, 95% CI (9.07-12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88-27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3-178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66-156.69)], eye disorder [ROR = 2.71, 95% CI (2.21-3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days.ConclusionADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.

Project description:BackgroundTaxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world.MethodsTaxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson's χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI).ResultsA total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09).ConclusionsThe results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.

Dataset Information

The Complementary Nature of Patient-Reported Outcomes and Adverse Event Reporting in Cooperative Group Oncology Clinical Trials: A Pooled Analysis (NCCTG N0591).

Publications

The Complementary Nature of Patient-Reported Outcomes and Adverse Event Reporting in Cooperative Group Oncology Clinical Trials: A Pooled Analysis (NCCTG N0591).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets