| 1. |
- Raices Cruz, Ivette, et al.
(författare)
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A robust Bayesian bias-adjusted random effects model for consideration of uncertainty about bias terms in evidence synthesis
- 2022
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Ingår i: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 41:17, s. 3365-3379
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Tidskriftsartikel (refereegranskat)abstract
- Meta-analysis is a statistical method used in evidence synthesis for combining, analyzing and summarizing studies that have the same target endpoint and aims to derive a pooled quantitative estimate using fixed and random effects models or network models. Differences among included studies depend on variations in target populations (ie, heterogeneity) and variations in study quality due to study design and execution (ie, bias). The risk of bias is usually assessed qualitatively using critical appraisal, and quantitative bias analysis can be used to evaluate the influence of bias on the quantity of interest. We propose a way to consider ignorance or ambiguity in how to quantify bias terms in a bias analysis by characterizing bias with imprecision (as bounds on probability) and use robust Bayesian analysis to estimate the overall effect. Robust Bayesian analysis is here seen as Bayesian updating performed over a set of coherent probability distributions, where the set emerges from a set of bias terms. We show how the set of bias terms can be specified based on judgments on the relative magnitude of biases (ie, low, unclear, and high risk of bias) in one or several domains of the Cochrane's risk of bias table. For illustration, we apply a robust Bayesian bias-adjusted random effects model to an already published meta-analysis on the effect of Rituximab for rheumatoid arthritis from the Cochrane Database of Systematic Reviews.
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| 2. |
- Raices Cruz, Ivette, et al.
(författare)
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A suggestion for the quantification of precise and bounded probability to quantify epistemic uncertainty in scientific assessments
- 2022
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Ingår i: Risk Analysis. - : Wiley. - 0272-4332 .- 1539-6924. ; 42:2, s. 239-253
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Tidskriftsartikel (refereegranskat)abstract
- An honest communication of uncertainty about quantities of interest enhances transparency in scientific assessments. To support this communication, risk assessors should choose appropriate ways to evaluate and characterize epistemic uncertainty. A full treatment of uncertainty requires methods that distinguish aleatory from epistemic uncertainty. Quantitative expressions for epistemic uncertainty are advantageous in scientific assessments because they are nonambiguous and enable individual uncertainties to be characterized and combined in a systematic way. Since 2019, the European Food Safety Authority (EFSA) recommends assessors to express epistemic uncertainty in conclusions of scientific assessments quantitatively by subjective probability. A subjective probability can be used to represent an expert judgment, which may or may not be updated using Bayes's rule to integrate evidence available for the assessment and could be either precise or approximate. Approximate (or bounded) probabilities may be enough for decision making and allow experts to reach agreement on certainty when they struggle to specify precise subjective probabilities. The difference between the lower and upper bound on a subjective probability can also be used to reflect someone's strength of knowledge. In this article, we demonstrate how to quantify uncertainty by bounded probability, and explicitly distinguish between epistemic and aleatory uncertainty, by means of robust Bayesian analysis, including standard Bayesian analysis through precise probability as a special case. For illustration, the two analyses are applied to an intake assessment.
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| 3. |
- Raices Cruz, Ivette, et al.
(författare)
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Iterative importance sampling with Markov chain Monte Carlo sampling in robust Bayesian analysis
- 2022
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Ingår i: Computational Statistics and Data Analysis. - : Elsevier BV. - 0167-9473. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- Bayesian inference under a set of priors, called robust Bayesian analysis, allows for estimation of parameters within a model and quantification of epistemic uncertainty in quantities of interest by bounded (or imprecise) probability. Iterative importance sampling can be used to estimate bounds on the quantity of interest by optimizing over the set of priors. A method for iterative importance sampling when the robust Bayesian inference relies on Markov chain Monte Carlo (MCMC) sampling is proposed. To accommodate the MCMC sampling in iterative importance sampling, a new expression for the effective sample size of the importance sampling is derived, which accounts for the correlation in the MCMC samples. To illustrate the proposed method for robust Bayesian analysis, iterative importance sampling with MCMC sampling is applied to estimate the lower bound of the overall effect in a previously published meta-analysis with a random effects model. The performance of the method compared to a grid search method and under different degrees of prior-data conflict is also explored.
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| 4. |
- Raices Cruz, Ivette
(författare)
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Robust analysis of uncertainty in scientific assessments
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Uncertainty refers to any limitation in knowledge. Identifying and characterizing uncertainty in conclusions is important to ensure transparency and avoid over or under confidence in scientific assessments. Quantitative expressions of uncertainty are less ambiguous compared to uncertainty expressed qualitatively, or not at all. Subjective probability is an example of a quantitative expression of epistemic uncertainty, which combined with Bayesian inference makes it possible to integrate evidence and characterizes uncertainty in quantities of interest. This thesis contributes to the understanding and implementation of robust Bayesian analysis as a way to integrate expert judgment and data into assessments and quantify uncertainty by bounded probability. The robust Bayesian framework is based on sets of probability for epistemic uncertainty, where precise probability is seen as a special case. This thesis covers applications relevant for scientific assessments, including evidence synthesis and quantitative risk assessment.Paper I proposes to combine two sampling methods: iterative importance sampling and Markov chain Monte Carlo (MCMC) sampling, for quantifying uncertainty by bounded probability when Bayesian updating requires MCMC sampling. This opens up for robust Bayesian analysis to be applied to complex statistical models. To achieve this, an effective sample size of importance sampling that accounts for correlated MCMC samples is proposed. For illustration, the proposed method is applied to estimate the overall effect with bounded probability in a published meta-analysis within the Collaboration for Environmental Evidence on the effect of biomanipulation on freshwater lakes.Paper II demonstrates robust Bayesian analysis as a way to quantify uncertainty in a quantity of interest by bounded probability, and explicitly distinguishes between epistemic and aleatory uncertainty in the assessment and learn parameters by integrating evidence into the model. Robust Bayesian analysis is described as a generalization of Bayesian analysis, including Bayesian analysis through precise probability as a special case. Both analyses are applied to an intake assessment.Paper III describes a way to consider uncertainty arising from ignorance or ambiguity about bias terms in a quantitative bias analysis by characterizing bias with imprecision. This is done by specifying bias with a set of bias terms and use robust Bayesian analysis to estimate the overall effect in the meta-analysis. The approach provides a structured framework to transform qualitative judgments concerning risk of biases into quantitative expressions of uncertainty in quantitative bias analysis.Paper IV compares the effect of different diversified farming practices on biodiversity and crop yields. This is done by applying a Bayesian network meta-analysis to a new public global database from a systematic protocol on diversified farming. A portfolio analysis calibrated by the network meta-analyses showed that uncertainty about the mean performance is large compared to the variability in performance across different farms.
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| 5. |
- Zhu, Yajing, et al.
(författare)
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The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer : biomarker analysis from the swedish phase ii randomized predix HER2 trial
- 2024
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 204:2, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.Methods: In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.Results: No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.Conclusion: sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.Trial registration: ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.
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| 6. |
- Zhu, Yajing, et al.
(författare)
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The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer : biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial
- 2024
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 204:2, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.MethodsIn the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.ResultsNo association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.ConclusionsTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.Trial registrationClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.
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