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1.
Stat Med ; 43(13): 2592-2606, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38664934

ABSTRACT

Statistical techniques are needed to analyze data structures with complex dependencies such that clinically useful information can be extracted. Individual-specific networks, which capture dependencies in complex biological systems, are often summarized by graph-theoretical features. These features, which lend themselves to outcome modeling, can be subject to high variability due to arbitrary decisions in network inference and noise. Correlation-based adjacency matrices often need to be sparsified before meaningful graph-theoretical features can be extracted, requiring the data analysts to determine an optimal threshold. To address this issue, we propose to incorporate a flexible weighting function over the full range of possible thresholds to capture the variability of graph-theoretical features over the threshold domain. The potential of this approach, which extends concepts from functional data analysis to a graph-theoretical setting, is explored in a plasmode simulation study using real functional magnetic resonance imaging (fMRI) data from the Autism Brain Imaging Data Exchange (ABIDE) Preprocessed initiative. The simulations show that our modeling approach yields accurate estimates of the functional form of the weight function, improves inference efficiency, and achieves a comparable or reduced root mean square prediction error compared to competitor modeling approaches. This assertion holds true in settings where both complex functional forms underlie the outcome-generating process and a universal threshold value is employed. We demonstrate the practical utility of our approach by using resting-state fMRI data to predict biological age in children. Our study establishes the flexible modeling approach as a statistically principled, serious competitor to ad-hoc methods with superior performance.


Subject(s)
Computer Simulation , Magnetic Resonance Imaging , Humans , Child , Brain/diagnostic imaging , Models, Statistical , Autistic Disorder
3.
Stud Health Technol Inform ; 310: 1404-1405, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38269668

ABSTRACT

Quality indicators serve as a tool to measure and improve evidence-based health care. Often the transition from inpatient to outpatient care is not sufficiently included. The focus of this work was to develop and to evaluate methods to define relevant cross-sector quality indicators based on Austrian claims data, using myocardial infarction as tracer.


Subject(s)
Myocardial Infarction , Quality Indicators, Health Care , Humans , Ambulatory Care , Inpatients , Myocardial Infarction/therapy
4.
Biom J ; 66(1): e2200222, 2024 Jan.
Article in English | MEDLINE | ID: mdl-36737675

ABSTRACT

Although new biostatistical methods are published at a very high rate, many of these developments are not trustworthy enough to be adopted by the scientific community. We propose a framework to think about how a piece of methodological work contributes to the evidence base for a method. Similar to the well-known phases of clinical research in drug development, we propose to define four phases of methodological research. These four phases cover (I) proposing a new methodological idea while providing, for example, logical reasoning or proofs, (II) providing empirical evidence, first in a narrow target setting, then (III) in an extended range of settings and for various outcomes, accompanied by appropriate application examples, and (IV) investigations that establish a method as sufficiently well-understood to know when it is preferred over others and when it is not; that is, its pitfalls. We suggest basic definitions of the four phases to provoke thought and discussion rather than devising an unambiguous classification of studies into phases. Too many methodological developments finish before phase III/IV, but we give two examples with references. Our concept rebalances the emphasis to studies in phases III and IV, that is, carefully planned method comparison studies and studies that explore the empirical properties of existing methods in a wider range of problems.


Subject(s)
Biostatistics , Research Design
5.
Eur Heart J ; 45(1): 45-53, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37769352

ABSTRACT

BACKGROUND AND AIMS: Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and guidelines suggest extended-phase anticoagulation. Many patients never experience recurrence but are exposed to bleeding. The aim of this study was to assess the performance of the Vienna Prediction Model (VPM) and to evaluate if the VPM accurately identifies these patients. METHODS: In patients with unprovoked VTE, the VPM was performed 3 weeks after anticoagulation withdrawal. Those with a predicted 1-year recurrence risk of ≤5.5% were prospectively followed. Study endpoint was recurrent VTE over 2 years. RESULTS: A total of 818 patients received anticoagulation for a median of 3.9 months. 520 patients (65%) had a predicted annual recurrence risk of ≤5.5%. During a median time of 23.9 months, 52 patients had non-fatal recurrence. The recurrence risk was 5.2% [95% confidence interval (CI) 3.2-7.2] at 1 year and 11.2% (95% CI 8.3-14) at 2 years. Model calibration was adequate after 1 year. The VPM underestimated the recurrence risk of patients with a 2-year recurrence rate of >5%. In a post-hoc analysis, the VPM's baseline hazard was recalibrated. Bootstrap validation confirmed an ideal ratio of observed and expected recurrence events. The recurrence risk was highest in men with proximal deep-vein thrombosis or pulmonary embolism and lower in women regardless of the site of incident VTE. CONCLUSIONS: In this prospective evaluation of the performance of the VPM, the 1-year rate of recurrence in patients with unprovoked VTE was 5.2%. Recalibration improved identification of patients at low recurrence risk and stratification into distinct low-risk categories.


Subject(s)
Pulmonary Embolism , Venous Thromboembolism , Male , Humans , Female , Venous Thromboembolism/epidemiology , Prospective Studies , Anticoagulants/therapeutic use , Recurrence , Risk Factors
6.
Kidney Int ; 104(5): 885-887, 2023 11.
Article in English | MEDLINE | ID: mdl-37863637

ABSTRACT

Accurate estimation of chronic kidney disease (CKD) progression risk is vital for clinical decision-making. Existing risk equations lack validation in pediatric CKD populations. Ng et al. developed new risk equations using the CKD in Children and European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients cohorts. The elementary model, incorporating estimated glomerular filtration rate, urine protein-creatinine ratio, and diagnosis, exhibited excellent discrimination and calibration at external validation. External validation of enriched models is pending. The equations have the potential to aid pediatric CKD centers in patient counseling and care planning.


Subject(s)
Renal Insufficiency, Chronic , Humans , Child , Glomerular Filtration Rate , Kidney Function Tests , Renal Insufficiency, Chronic/diagnosis , Creatinine , Disease Progression , Kidney
7.
Front Cardiovasc Med ; 10: 1219744, 2023.
Article in English | MEDLINE | ID: mdl-37576114

ABSTRACT

Objective: This retrospective study evaluates the performance of UK National Institute for Health and Care Excellence (NICE) Guidelines on management of ruptured abdominal aortic aneurysms in a "real world setting" by emulating a hypothetical target trial with data from two European Aortic Centers. Methods: Clinical data was retrospectively collected for all patients who had undergone ruptured endovascular aneurysm repair (rEVAR) and ruptured open surgical repair (rOSR). Survival analysis was performed comparing NICE compliance to usual care strategy. NICE compliers were defined as: female patients undergoing rEVAR; male patients >70 years old undergoing rEVAR; and male patients ≤70 years old undergoing rOSR. Hemodynamic instability was considered additionally. Results: This multicenter study included 298 patients treated for rAAA. The majority of patients were treated with rOSR (186 rOSR vs. 112 rEVAR). Overall, 184 deaths (68 [37%] with rEVAR and 116 [63%] with rOSR) were observed during the study period. Overall survival under usual care was 69.2% at 30 days, 56.5% at one year, and 42.4% at 5 years. NICE compliance gave survival outcomes of 73.1% at 30 days, 60.2% at 1 year and 42.9% at 5 years. The risk ratios at these time points, comparing NICE-compliance to usual care, were 0.88, 0.92 and 0.99, respectively. Conclusions: We support NICE recommendations to manage men below the age of 71 years and hemodynamic stability with rOSR. There was a slight survival advantage for NICE compliers overall, in men >70 years and women of all ages.

8.
Oncogene ; 42(33): 2473-2484, 2023 08.
Article in English | MEDLINE | ID: mdl-37402882

ABSTRACT

TP53 is the most commonly mutated gene in cancer and has been shown to form amyloid-like aggregates, similar to key proteins in neurodegenerative diseases. Nonetheless, the clinical implications of p53 aggregation remain unclear. Here, we investigated the presence and clinical relevance of p53 aggregates in serous ovarian cancer (OC). Using the p53-Seprion-ELISA, p53 aggregates were detected in 46 out of 81 patients, with a detection rate of 84.3% in patients with missense mutations. High p53 aggregation was associated with prolonged progression-free survival. We found associations of overall survival with p53 aggregates, but they did not reach statistical significance. Interestingly, p53 aggregation was significantly associated with elevated levels of p53 autoantibodies and increased apoptosis, suggesting that high levels of p53 aggregates may trigger an immune response and/or exert a cytotoxic effect. To conclude, for the first time, we demonstrated that p53 aggregates are an independent prognostic marker in serous OC. P53-targeted therapies based on the amount of these aggregates may improve the patient's prognosis.


Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Humans , Female , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ovarian Neoplasms/metabolism , Prognosis , Carcinoma, Ovarian Epithelial , Cystadenocarcinoma, Serous/genetics , Biomarkers , Mutation
9.
Nephrol Dial Transplant ; 39(1): 36-44, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37403325

ABSTRACT

BACKGROUND: Kidney transplantation is the preferred treatment for eligible patients with kidney failure who need renal replacement therapy. However, it remains unclear whether the anticipated survival benefit from kidney transplantation is different for women and men. METHODS: We included all dialysis patients recorded in the Austrian Dialysis and Transplant Registry who were waitlisted for their first kidney transplant between 2000 and 2018. In order to estimate the causal effect of kidney transplantation on 10-year restricted mean survival time, we mimicked a series of controlled clinical trials and applied inverse probability of treatment and censoring weighted sequential Cox models. RESULTS: This study included 4408 patients (33% female) with a mean age of 52 years. Glomerulonephritis was the most common primary renal disease both in women (27%) and men (28%). Kidney transplantation led to a gain of 2.22 years (95% CI 1.88 to 2.49) compared with dialysis over a 10-year follow-up. The effect was smaller in women (1.95 years, 95% CI 1.38 to 2.41) than in men (2.35 years, 95% CI 1.92 to 2.70) due to a better survival on dialysis. Across ages the survival benefit of transplantation over a follow-up of 10 years was smaller in younger women and men and increased with age, showing a peak for both women and men aged about 60 years. CONCLUSIONS: There were few differences in survival benefit by transplantation between females and males. Females had better survival than males on the waitlist receiving dialysis and similar survival to males after transplantation.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Humans , Male , Female , Middle Aged , Renal Dialysis , Kidney Failure, Chronic/surgery , Retrospective Studies , Sex Characteristics
10.
Diagn Progn Res ; 7(1): 9, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37127679

ABSTRACT

BACKGROUND: The performance of models for binary outcomes can be described by measures such as the concordance statistic (c-statistic, area under the curve), the discrimination slope, or the Brier score. At internal validation, data resampling techniques, e.g., cross-validation, are frequently employed to correct for optimism in these model performance criteria. Especially with small samples or rare events, leave-one-out cross-validation is a popular choice. METHODS: Using simulations and a real data example, we compared the effect of different resampling techniques on the estimation of c-statistics, discrimination slopes, and Brier scores for three estimators of logistic regression models, including the maximum likelihood and two maximum penalized likelihood estimators. RESULTS: Our simulation study confirms earlier studies reporting that leave-one-out cross-validated c-statistics can be strongly biased towards zero. In addition, our study reveals that this bias is even more pronounced for model estimators shrinking estimated probabilities towards the observed event fraction, such as ridge regression. Leave-one-out cross-validation also provided pessimistic estimates of the discrimination slope but nearly unbiased estimates of the Brier score. CONCLUSIONS: We recommend to use leave-pair-out cross-validation, fivefold cross-validation with repetitions, the enhanced or the .632+ bootstrap to estimate c-statistics, and leave-pair-out or fivefold cross-validation to estimate discrimination slopes.

11.
JAMA Netw Open ; 6(4): e231870, 2023 04 03.
Article in English | MEDLINE | ID: mdl-37017968

ABSTRACT

Importance: Type 2 diabetes increases the risk of progressive diabetic kidney disease, but reliable prediction tools that can be used in clinical practice and aid in patients' understanding of disease progression are currently lacking. Objective: To develop and externally validate a model to predict future trajectories in estimated glomerular filtration rate (eGFR) in adults with type 2 diabetes and chronic kidney disease using data from 3 European multinational cohorts. Design, Setting, and Participants: This prognostic study used baseline and follow-up information collected between February 2010 and December 2019 from 3 prospective multinational cohort studies: PROVALID (Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers), GCKD (German Chronic Kidney Disease), and DIACORE (Diabetes Cohorte). A total of 4637 adult participants (aged 18-75 years) with type 2 diabetes and mildly to moderately impaired kidney function (baseline eGFR of ≥30 mL/min/1.73 m2) were included. Data were analyzed between June 30, 2021, and January 31, 2023. Main Outcomes and Measures: Thirteen variables readily available from routine clinical care visits (age, sex, body mass index; smoking status; hemoglobin A1c [mmol/mol and percentage]; hemoglobin, and serum cholesterol levels; mean arterial pressure, urinary albumin-creatinine ratio, and intake of glucose-lowering, blood-pressure lowering, or lipid-lowering medication) were selected as predictors. Repeated eGFR measurements at baseline and follow-up visits were used as the outcome. A linear mixed-effects model for repeated eGFR measurements at study entry up to the last recorded follow-up visit (up to 5 years after baseline) was fit and externally validated. Results: Among 4637 adults with type 2 diabetes and chronic kidney disease (mean [SD] age at baseline, 63.5 [9.1] years; 2680 men [57.8%]; all of White race), 3323 participants from the PROVALID and GCKD studies (mean [SD] age at baseline, 63.2 [9.3] years; 1864 men [56.1%]) were included in the model development cohort, and 1314 participants from the DIACORE study (mean [SD] age at baseline, 64.5 [8.3] years; 816 men [62.1%]) were included in the external validation cohort, with a mean (SD) follow-up of 5.0 (0.6) years. Updating the random coefficient estimates with baseline eGFR values yielded improved predictive performance, which was particularly evident in the visual inspection of the calibration curve (calibration slope at 5 years: 1.09; 95% CI, 1.04-1.15). The prediction model had good discrimination in the validation cohort, with the lowest C statistic at 5 years after baseline (0.79; 95% CI, 0.77-0.80). The model also had predictive accuracy, with an R2 ranging from 0.70 (95% CI, 0.63-0.76) at year 1 to 0.58 (95% CI, 0.53-0.63) at year 5. Conclusions and Relevance: In this prognostic study, a reliable prediction model was developed and externally validated; the robust model was well calibrated and capable of predicting kidney function decline up to 5 years after baseline. The results and prediction model are publicly available in an accompanying web-based application, which may open the way for improved prediction of individual eGFR trajectories and disease progression.


Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Male , Adult , Humans , Diabetes Mellitus, Type 2/complications , Glomerular Filtration Rate , Prospective Studies , Disease Progression
12.
Article in English | MEDLINE | ID: mdl-36833877

ABSTRACT

Randomization is an effective design option to prevent bias from confounding in the evaluation of the causal effect of interventions on outcomes. However, in some cases, randomization is not possible, making subsequent adjustment for confounders essential to obtain valid results. Several methods exist to adjust for confounding, with multivariable modeling being among the most widely used. The main challenge is to determine which variables should be included in the causal model and to specify appropriate functional relations for continuous variables in the model. While the statistical literature gives a variety of recommendations on how to build multivariable regression models in practice, this guidance is often unknown to applied researchers. We set out to investigate the current practice of explanatory regression modeling to control confounding in the field of cardiac rehabilitation, for which mainly non-randomized observational studies are available. In particular, we conducted a systematic methods review to identify and compare statistical methodology with respect to statistical model building in the context of the existing recent systematic review CROS-II, which evaluated the prognostic effect of cardiac rehabilitation. CROS-II identified 28 observational studies, which were published between 2004 and 2018. Our methods review revealed that 24 (86%) of the included studies used methods to adjust for confounding. Of these, 11 (46%) mentioned how the variables were selected and two studies (8%) considered functional forms for continuous variables. The use of background knowledge for variable selection was barely reported and data-driven variable selection methods were applied frequently. We conclude that in the majority of studies, the methods used to develop models to investigate the effect of cardiac rehabilitation on outcomes do not meet common criteria for appropriate statistical model building and that reporting often lacks precision.


Subject(s)
Cardiac Rehabilitation , Humans , Models, Theoretical , Models, Statistical
13.
Diagn Progn Res ; 6(1): 22, 2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36384641

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. METHODS: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. RESULTS: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09). CONCLUSION: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended.

14.
JAMA Netw Open ; 5(10): e2234971, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36205998

ABSTRACT

Importance: Kidney transplant is considered beneficial in terms of survival compared with continued dialysis for patients with kidney failure. However, randomized clinical trials are infeasible, and available evidence from cohort studies is at high risk of bias. Objective: To compare restricted mean survival times (RMSTs) between patients who underwent transplant and patients continuing dialysis across transplant candidate ages and depending on waiting time, applying target trial emulation methods. Design, Setting, and Participants: In this retrospective cohort study, patients aged 18 years or older appearing on the wait list for their first single-organ deceased donor kidney transplant between January 1, 2000, and December 31, 2018, in Austria were evaluated. Available data were obtained from the Austrian Dialysis and Transplant Registry and Eurotransplant and included repeated updates on wait-listing status and relevant covariates. Data were analyzed between August 1, 2019, and December 23, 2021. Exposures: A target trial was emulated in which patients were randomized to either receive the transplant immediately (treatment group) or to continue dialysis and never receive a transplant (control group) at each time an organ became available. Main Outcomes and Measures: The primary outcome was time from transplant allocation to death. Effect sizes in terms of RMSTs were obtained using a sequential Cox approach. Results: Among the 4445 included patients (2974 men [66.9%]; mean [SD] age, 52.2 [13.2] years), transplant was associated with increased survival time across all considered ages compared with continuing dialysis and remaining on the wait list within a 10-year follow-up. The estimated RMST differences were 0.57 years (95% CI, -0.14 to 1.84 years) at age 20 years, 3.01 years (95% CI, 2.50 to 3.54 years) at age 60 years, and 2.48 years (95% CI, 1.88 to 3.04 years) at age 70 years. The survival benefit for patients who underwent transplant across ages was independent of waiting time. Conclusions and Relevance: The findings of this study suggest that kidney transplant prolongs the survival time of persons with kidney failure across all candidate ages and waiting times.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Renal Insufficiency , Adult , Aged , Humans , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Male , Middle Aged , Renal Dialysis , Retrospective Studies , Young Adult
15.
Kidney Int ; 102(4): 939, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36150767
16.
BMC Med Res Methodol ; 22(1): 206, 2022 07 26.
Article in English | MEDLINE | ID: mdl-35883041

ABSTRACT

BACKGROUND: Variable selection for regression models plays a key role in the analysis of biomedical data. However, inference after selection is not covered by classical statistical frequentist theory, which assumes a fixed set of covariates in the model. This leads to over-optimistic selection and replicability issues. METHODS: We compared proposals for selective inference targeting the submodel parameters of the Lasso and its extension, the adaptive Lasso: sample splitting, selective inference conditional on the Lasso selection (SI), and universally valid post-selection inference (PoSI). We studied the properties of the proposed selective confidence intervals available via R software packages using a neutral simulation study inspired by real data commonly seen in biomedical studies. Furthermore, we present an exemplary application of these methods to a publicly available dataset to discuss their practical usability. RESULTS: Frequentist properties of selective confidence intervals by the SI method were generally acceptable, but the claimed selective coverage levels were not attained in all scenarios, in particular with the adaptive Lasso. The actual coverage of the extremely conservative PoSI method exceeded the nominal levels, and this method also required the greatest computational effort. Sample splitting achieved acceptable actual selective coverage levels, but the method is inefficient and leads to less accurate point estimates. The choice of inference method had a large impact on the resulting interval estimates, thereby necessitating that the user is acutely aware of the goal of inference in order to interpret and communicate the results. CONCLUSIONS: Despite violating nominal coverage levels in some scenarios, selective inference conditional on the Lasso selection is our recommended approach for most cases. If simplicity is strongly favoured over efficiency, then sample splitting is an alternative. If only few predictors undergo variable selection (i.e. up to 5) or the avoidance of false positive claims of significance is a concern, then the conservative approach of PoSI may be useful. For the adaptive Lasso, SI should be avoided and only PoSI and sample splitting are recommended. In summary, we find selective inference useful to assess the uncertainties in the importance of individual selected predictors for future applications.


Subject(s)
Biomedical Research , Computer Simulation , Humans
17.
BMC Med Res Methodol ; 22(1): 168, 2022 06 09.
Article in English | MEDLINE | ID: mdl-35681120

ABSTRACT

BACKGROUND: In binary logistic regression data are 'separable' if there exists a linear combination of explanatory variables which perfectly predicts the observed outcome, leading to non-existence of some of the maximum likelihood coefficient estimates. A popular solution to obtain finite estimates even with separable data is Firth's logistic regression (FL), which was originally proposed to reduce the bias in coefficient estimates. The question of convergence becomes more involved when analyzing clustered data as frequently encountered in clinical research, e.g. data collected in several study centers or when individuals contribute multiple observations, using marginal logistic regression models fitted by generalized estimating equations (GEE). From our experience we suspect that separable data are a sufficient, but not a necessary condition for non-convergence of GEE. Thus, we expect that generalizations of approaches that can handle separable uncorrelated data may reduce but not fully remove the non-convergence issues of GEE. METHODS: We investigate one recently proposed and two new extensions of FL to GEE. With 'penalized GEE' the GEE are treated as score equations, i.e. as derivatives of a log-likelihood set to zero, which are then modified as in FL. We introduce two approaches motivated by the equivalence of FL and maximum likelihood estimation with iteratively augmented data. Specifically, we consider fully iterated and single-step versions of this 'augmented GEE' approach. We compare the three approaches with respect to convergence behavior, practical applicability and performance using simulated data and a real data example. RESULTS: Our simulations indicate that all three extensions of FL to GEE substantially improve convergence compared to ordinary GEE, while showing a similar or even better performance in terms of accuracy of coefficient estimates and predictions. Penalized GEE often slightly outperforms the augmented GEE approaches, but this comes at the cost of a higher burden of implementation. CONCLUSIONS: When fitting marginal logistic regression models using GEE on sparse data we recommend to apply penalized GEE if one has access to a suitable software implementation and single-step augmented GEE otherwise.


Subject(s)
Models, Statistical , Bias , Computer Simulation , Humans , Likelihood Functions , Logistic Models
18.
Entropy (Basel) ; 24(6)2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35741566

ABSTRACT

There is an increasing interest in machine learning (ML) algorithms for predicting patient outcomes, as these methods are designed to automatically discover complex data patterns. For example, the random forest (RF) algorithm is designed to identify relevant predictor variables out of a large set of candidates. In addition, researchers may also use external information for variable selection to improve model interpretability and variable selection accuracy, thereby prediction quality. However, it is unclear to which extent, if at all, RF and ML methods may benefit from external information. In this paper, we examine the usefulness of external information from prior variable selection studies that used traditional statistical modeling approaches such as the Lasso, or suboptimal methods such as univariate selection. We conducted a plasmode simulation study based on subsampling a data set from a pharmacoepidemiologic study with nearly 200,000 individuals, two binary outcomes and 1152 candidate predictor (mainly sparse binary) variables. When the scope of candidate predictors was reduced based on external knowledge RF models achieved better calibration, that is, better agreement of predictions and observed outcome rates. However, prediction quality measured by cross-entropy, AUROC or the Brier score did not improve. We recommend appraising the methodological quality of studies that serve as an external information source for future prediction model development.

19.
Health Qual Life Outcomes ; 20(1): 99, 2022 Jun 24.
Article in English | MEDLINE | ID: mdl-35751092

ABSTRACT

BACKGROUND: Some capability dimensions may be more important than others in determining someone's well-being, and these preferences might be dependent on ill-health experience. This study aimed to explore the relative preference weights of the 16 items of the German language version of the OxCAP-MH (Oxford Capability questionnaire-Mental Health) capability instrument and their differences across cohorts with alternative levels of mental ill-health experience. METHODS: A Best-Worst-Scaling (BWS) survey was conducted in Austria among 1) psychiatric patients (direct mental ill-health experience), 2) (mental) healthcare experts (indirect mental ill-health experience), and 3) primary care patients with no mental ill-health experience. Relative importance scores for each item of the German OxCAP-MH instrument were calculated using Hierarchical Bayes estimation. Rank analysis and multivariable linear regression analysis with robust standard errors were used to explore the relative importance of the OxCAP-MH items across the three cohorts. RESULTS: The study included 158 participants with complete cases and acceptable fit statistic. The relative importance scores for the full cohort ranged from 0.76 to 15.72. Findings of the BWS experiment indicated that the items Self-determination and Limitation in daily activities were regarded as the most important for all three cohorts. Freedom of expression was rated significantly less important by psychiatric patients than by the other two cohorts, while Having suitable accommodation appeared significantly less important by the expert cohort. There were no further significant differences in the relative preference weights of OxCAP-MH items between the cohorts or according to gender. CONCLUSIONS: Our study indicates significant between-item but limited mental ill-health related heterogeneity in the relative preference weights of the different capability items within the OxCAP-MH. The findings support the future development of preference-based value sets elicited from the general population for comparative economic evaluation purposes.


Subject(s)
Mental Health Services , Mental Health , Bayes Theorem , Humans , Quality of Life/psychology , Surveys and Questionnaires
20.
Eur Heart J ; 43(31): 2921-2930, 2022 08 14.
Article in English | MEDLINE | ID: mdl-35639667

ABSTRACT

The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.


Subject(s)
Artificial Intelligence , Cardiovascular Diseases , Health Personnel , Humans , Software
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