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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2005
    In:  BMC Medical Research Methodology Vol. 5, No. 1 ( 2005-12)
    In: BMC Medical Research Methodology, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2005-12)
    Type of Medium: Online Resource
    ISSN: 1471-2288
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2005
    detail.hit.zdb_id: 2041362-2
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  • 2
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 671-671
    Abstract: Background: When randomized clinical trials (RCTs) are conducted there should be some reasonable expectations that the trials will provide the answer to the questions they were design to address. Failure to do so i.e. completing trials that will result in inconclusive results represents an avoidable waste of precious resources and ethical breach of contracts with patients who expect that definitive answers will help future patients. Two main factors are thought to be responsible for generating inconclusive findings in clinical research: poor patient accrual and expectation bias or ‘optimism bias’ - an unwarranted belief in the efficacy of new therapies. (Lancet.2006; 367:449) Objectives: Our objective was to determine which of the two factors, poor patient accrual or expectation bias, is the main culprit for producing inconclusive clinical research results in the trials focusing on hematological cancers. Methods: We extracted data from the original protocols and publications related to 210 hematological cancer trials conducted by the 8 NCI sponsored Cooperative Groups conducted and published from year 1955 to 1998. A priori effect size used in the power calculation for the trial’s pre-defined primary outcome (expected differences) was compared with those observed in the final reports. All treatment effects were expressed as either HR [hazard ratio] or OR [odds ratio] . We also analyzed the planned accrual vs. actual patient accrual. The question whether “negative”/inconclusive i.e. statistically non-significant results were due to poor accrual or due to “optimism” bias was addressed. We defined inconclusive results as those in which treatment was consistent with no difference between treatment effects, or experimental treatment being superior to the standard treatments, or vice verse. Operationally, this was defined as the point estimate of the treatment effect and its 95% confidence intervals (CI) crossing the lines of equivalence on either side of the no-treatment effect from 0.77 to 1.3. Results: Data on primary outcomes were available for 105 out of 210 total hematological cancer studies. 71% of the studies had non-significant results (75/105). The vast majority of these trials (92%, 69/75) were inconclusive i.e. 95% CI of their treatments had crossed both limits of equivalence. Overall, the investigators enrolled more patients than actually planned [Nplanned: median: 220, mean: 280, range: 40–1100; Nactual: median: 250, mean: 336, range: 40–1606; p=0.1203]. However, the expected effect size was considerably greater than actually observed differences in treatment effects: [Expected: mean=47% (range: 17% to 74%) vs. Observed: mean=12% (range: −88% to 83%; p=0.000). The median ratio between the expected and the observed HR/OR was 1.77 [range: 0.34–6.41] , meaning that observed HR/OR fell short of the expected HR/OR values by 1.77 times on average. Conclusion: Unrealistic expectations in treatment effects appear to be a major culprit for continuing generation of large number of “negative”/inconclusive results in the field of hematological malignancies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2011
    In:  BMC Medical Research Methodology Vol. 11, No. 1 ( 2011-12)
    In: BMC Medical Research Methodology, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2011-12)
    Type of Medium: Online Resource
    ISSN: 1471-2288
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
    detail.hit.zdb_id: 2041362-2
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2012
    In:  BMC Medical Research Methodology Vol. 12, No. 1 ( 2012-12)
    In: BMC Medical Research Methodology, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2012-12)
    Type of Medium: Online Resource
    ISSN: 1471-2288
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2041362-2
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5799-5799
    Abstract: Background: Therapy-related heart failure (HF) is a leading cause of morbidity and mortality in patients who undergo successful HCT for hematological malignancies. To eventually help improve management of HF, timely and accurate diagnosis of HF is crucial. Currently, no established method for diagnosis of HF exist. One approach to help improve diagnosis and management of HF is to use predictive modeling to assess the likelihood of HF, using key predictors known to be associated with HF. Such models can, in turn, be used for bedside management, including implementation of early screening approaches. That said, many techniques for predictive modeling exist. Currently, it is not known if Artificial Intelligence machine learning (ML) approaches are superior to standard statistical techniques for the development of predictive models for clinical practice. Here we present a comparative analysis of traditional multivariable models with ML learning predictive modeling in an attempt to identify the best predictive model for diagnosis of HF after HCT. Methods: At City of Hope, we have established a large prospective cohort ( 〉 12,000 patients) of HCT survivors (HCT survivorship registry). This registry is dynamic, and interfaces with other registries and databases (e.g., electronically indexed inpatient and outpatient medical records, national death index [NDI]). We utilized natural language processing (NLP) to extract 13 key demographics and clinical data that are known to be associated with HF. For the purposes of this project, we extracted data from 1,834 patients (~15% sample) who underwent HCT between 1994 to 2004 to allow adequate follow-up for the development of HF. We fit and compared 6 models [standard logistic regression (glm), FFT (fast-and-frugal tree) decision model and four ML models: CART (classification and regression trees), SVM (support vector machine), NN (neural network) and RF (random forest)] . Data were randomly split (50:50) into training and validation samples; the ultimate assessment of the best algorithm was based on its performance (in terms of calibration and discrimination) in the validation sample. DeLong test was used to test for statistical differences in discrimination [i.e. area under the curve (AUC)] among the models. Results: The accuracy of NLP was consistently 〉 95%. Only the standard logistic regression model LR (glm) resulted in a well-calibrated model (Hosmer-Lemeshow goodness of fitness test: p=0.104); all other models were miscalibrated. The standard glm model also had best discrimination properties (AUC=0.704 in training and 0.619 in validation set). CART performed the worst (AUC=0.5). Other ML models (RF, NN, and SVM) also showed modest discriminatory characteristics (AUCs of 0.547, 0.573, and 0.619, respectively). DeLong test indicated that all models outperformed CART model (at nominal p 〈 0.05 ), but were statistically indistinguishable among each other (see Figure). Power of analysis was borderline sufficient for the glm model and very limited for ML models. Conclusions: None of tested models showed optimal performance characteristics for their use in clinical practice. ML models performed even worse than standard logistic models; given increasing use of ML models in medicine, we caution against the use of these models without adequate comparative testing. Figure Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4707-4707
    Abstract: Background: Clinical practice guidelines (CPGs) represent a key mechanism for optimizing health care decision making. CPGs are a product of discussion by a group of, typically, 10-20 individuals with varying expertise. Little is known how CPG panels actually make their recommendations. Objective: In a study of real-life decision making, we investigated the factors considered by members of panels convened by the American Society of Hematology (ASH) to develop guidelines, when using the widely accepted formal GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. Methods: To account for panel level factors and individual level factors, we employed two level hierarchical, random-effect, multivariate logistic and ordered logistic regression analysis. Results: 101 participants taking part in 8 CPGs panels issued 1,289 recommendations. Association of GRADE (normative) factors with the strength of recommendations (SOR) dominated the findings over the non-GRADE (descriptive) factors. In the main analysis certainty in evidence (regardless of direction for or against intervention) [OR=1.83 (95CI% 1.45 to 2.31;p 〈 0.0001)], balance of benefits and harms [OR=1.49 (95CI% 1.30 to 1.69;p 〈 0.0001)] and variability or uncertainty in the patients' values and preferences [OR=1.47 (95CI% 1.15 to 1.88;p 〈 0.002)] were the strongest predictors of SOR coded as "neither for nor against" , "weak for or against" or "strong for or against" health intervention. Greater judgment of certainty of evidence proved highly associated with a strong recommendation [OR=3.60 (95% CI 2.16 to 6.00;p 〈 0.00001] when panel members were issuing recommendation "for" interventions. When, however, panels made recommendations "against" intervention, certainty in evidence was not associated with probability of issuing strong recommendation [OR=0.98 (95%CI: 0.57 to 1.8; p=0.94)] . Two panelist characteristics were associated with strong recommendations: age (per decade) [OR=1.79 (95 CI% 1.2 to 2.84; p 〈 0.005)], and greater intolerance of uncertainties [OR=0.57 (95 CI% 0.37 to 0.86; p 〈 0.008)]. Agreement between individual panel members and the group ranged from very poor (average kappa of -0.01 in one panel) to moderate (kappa=0.64 in another panel), with most panels in an intermediate range. We also found that the panel members who were asked by the ASH to recuse themselves from voting due to high risk of conflict of interest (COI) would have voted differently if they were allowed to do so. Conclusion: Factors associated with GRADE's conceptual framework proved, in general, highly associated with strong versus weak recommendations and with the direction of recommendation. However, some non-GRADE factors of importance for decision-making were also identified. Findings that panel members with high risk of COI made different judgments than those without COI provide empirical support for the importance of managing conflict of interest. The low agreement between individual panel members and group consensus, and failure of certainty of evidence to be associated with strength of recommendations against an intervention, suggest the need for improvements in the process. Disclosures Cuker: Synergy: Consultancy; Genzyme: Consultancy; Kedrion: Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2010
    In:  BMC Medical Informatics and Decision Making Vol. 10, No. 1 ( 2010-12)
    In: BMC Medical Informatics and Decision Making, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2010-12)
    Abstract: Decision curve analysis (DCA) has been proposed as an alternative method for evaluation of diagnostic tests, prediction models, and molecular markers. However, DCA is based on expected utility theory, which has been routinely violated by decision makers. Decision-making is governed by intuition (system 1), and analytical, deliberative process (system 2), thus, rational decision-making should reflect both formal principles of rationality and intuition about good decisions. We use the cognitive emotion of regret to serve as a link between systems 1 and 2 and to reformulate DCA. Methods First, we analysed a classic decision tree describing three decision alternatives: treat, do not treat, and treat or no treat based on a predictive model. We then computed the expected regret for each of these alternatives as the difference between the utility of the action taken and the utility of the action that, in retrospect, should have been taken. For any pair of strategies, we measure the difference in net expected regret. Finally, we employ the concept of acceptable regret to identify the circumstances under which a potentially wrong strategy is tolerable to a decision-maker. Results We developed a novel dual visual analog scale to describe the relationship between regret associated with "omissions" (e.g. failure to treat) vs. "commissions" (e.g. treating unnecessary) and decision maker's preferences as expressed in terms of threshold probability. We then proved that the Net Expected Regret Difference, first presented in this paper, is equivalent to net benefits as described in the original DCA. Based on the concept of acceptable regret we identified the circumstances under which a decision maker tolerates a potentially wrong decision and expressed it in terms of probability of disease. Conclusions We present a novel method for eliciting decision maker's preferences and an alternative derivation of DCA based on regret theory. Our approach may be intuitively more appealing to a decision-maker, particularly in those clinical situations when the best management option is the one associated with the least amount of regret (e.g. diagnosis and treatment of advanced cancer, etc).
    Type of Medium: Online Resource
    ISSN: 1472-6947
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2046490-3
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Journal of Clinical Epidemiology Vol. 152 ( 2022-12), p. 298-299
    In: Journal of Clinical Epidemiology, Elsevier BV, Vol. 152 ( 2022-12), p. 298-299
    Type of Medium: Online Resource
    ISSN: 0895-4356
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1500490-9
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  • 9
    In: Journal of Clinical Epidemiology, Elsevier BV, Vol. 136 ( 2021-08), p. 1-9
    Type of Medium: Online Resource
    ISSN: 0895-4356
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1500490-9
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  • 10
    In: Cochrane Database of Systematic Reviews, Wiley
    Type of Medium: Online Resource
    ISSN: 1465-1858
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2038950-4
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