112 results on '"Peters, Bas"'
Search Results
2. Methotrexate Polyglutamate Concentrations as a Possible Predictive Marker for Effectiveness of Methotrexate Therapy in Patients with Sarcoidosis: A Pilot Study
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Janssen Bonás, Montse, Sundaresan, Janani, Keijsers, Ruth G. M., Struys, Eduard A., Peters, Bas J. M., Kahlmann, Vivienne, Wijsenbeek, Marlies S., de Rotte, Maurits C. F. J., Grutters, Jan C., and Veltkamp, Marcel
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- 2023
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3. Fully invertible hyperbolic neural networks for segmenting large-scale surface and sub-surface data
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Peters, Bas, Haber, Eldad, and Lensink, Keegan
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- 2024
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4. Pembrolizumab Plus Chemotherapy Per PD-L1 Stratum In Patients With Metastatic Non–Small Cell Lung Cancer: Real-World Effectiveness Versus Trial Efficacy
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Verschueren, Marjon V., Peters, Bas JM., Bloem, Lourens T., Kruik, Veerle R., Uitvlugt, Elien B., Bijsmans, Annette R., Egberts, Antoine CG., and van de Garde, Ewoudt MW.
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- 2024
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5. Fully hyperbolic convolutional neural networks
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Lensink, Keegan, Peters, Bas, and Haber, Eldad
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- 2022
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6. Impairment in work and activities of daily life in patients with psoriasis: results of the prospective BioCAPTURE registry.
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van Hal, Tamara W., van den Reek, Juul M. P. A., Wenink, Mark H., Otero, Marisol E., Ossenkoppele, Paul M., Njoo, Marcellus D., Oostveen, Annet, Peters, Bas, Tjioe, Milan, Kop, Else N., Körver, John E. M., Dodemont, Sharon R. P., Kleinpenning, Marloes M., Berends, Maartje A. M., Veldkamp, Wendelien R., van Doorn, Martijn B. A., Mommers, Johannes M., Lindhout, Robert-Jan, Kuijpers, Astrid L. A., and van Lümig, Paula P.
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GENERALIZED estimating equations ,PSORIASIS ,ACTIVITIES of daily living ,EVERYDAY life ,LABOR productivity - Abstract
Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors. Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations. Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p<0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p=0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12months, p=0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning. Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Trends in Drug Costs and Overall Survival in Patients with Metastatic Non-small Cell Lung Cancer in The Netherlands Diagnosed from 2008 Through 2014
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Cramer-van der Welle, Christine M., Peters, Bas J. M., Deenen, Maarten J., Schramel, Franz M. N. H., and van de Garde, Ewoudt M. W.
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- 2021
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8. Trends in prescribing systemic treatment and overall survival for non-small cell lung cancer stage IIIB/IV in the Netherlands: 2008–2012
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Peters, Bas J.M., Cramer-vd Welle, Christine M., Smit, Arthur A.J., Schramel, Franz M.N.H., and van de Garde, Ewoudt M.W.
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- 2017
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9. Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands
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Reesink, Daan J., van de Garde, Ewoudt M. W., Peters, Bas. J. M., van der Nat, Paul B., Los, Maartje, Horenblas, Simon, and van Melick, Harm H. E.
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- 2020
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10. The potential for deprescribing in a palliative oncology patient population: a cross-sectional study.
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van Merendonk, Lisanne N., Peters, Bas J. M., Möhlmann, Julia E., Hunting, Cornelis B., Kastelijn, Elisabeth A., and van den Broek, Marcel P. H.
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- 2024
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11. Treatment of oncogene-driven non-small cell lung cancer
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Kastelijn, Elisabeth A., de Langen, Adrianus J., and Peters, Bas J.M.
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- 2019
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12. Quantitative and qualitative assessment of real world data comparative effectiveness research of systemic therapies in lung oncology: A systematic review
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Peters, Bas J.M., Janssen, Vivi E.M.T., Schramel, Franz M., and van de Garde, Ewoudt M.W.
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- 2016
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13. CQnet: convex-geometric interpretation and constraining neural-network trajectories
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Peters, Bas
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FOS: Computer and information sciences ,Computer Science - Machine Learning ,68T07 ,Artificial Intelligence (cs.AI) ,Optimization and Control (math.OC) ,Computer Science - Artificial Intelligence ,I.2.6 ,G.1.6 ,FOS: Mathematics ,Mathematics - Optimization and Control ,Machine Learning (cs.LG) - Abstract
We introduce CQnet, a neural network with origins in the CQ algorithm for solving convex split-feasibility problems and forward-backward splitting. CQnet's trajectories are interpretable as particles that are tracking a changing constraint set via its point-to-set distance function while being elements of another constraint set at every layer. More than just a convex-geometric interpretation, CQnet accommodates learned and deterministic constraints that may be sample or data-specific and are satisfied by every layer and the output. Furthermore, the states in CQnet progress toward another constraint set at every layer. We provide proof of stability/nonexpansiveness with minimal assumptions. The combination of constraint handling and stability put forward CQnet as a candidate for various tasks where prior knowledge exists on the network states or output., 12 pages, 7 figures
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- 2023
14. The effect of the CYP2D6 genotype on the maintenance dose of metoprolol in a chronic Dutch patient population
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Poulussen, Fenna C.P., Peters, Bas J., Hua, Ken Ho, Houthuizen, Patrick, Grouls, Rene J., and Deenen, Maarten J.
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- 2019
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15. Durvalumab after chemoradiotherapy in patients with stage III non-small-cell lung cancer: real-world outcomes versus clinical trial results.
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Verschueren, Marjon V, Dijs, Talitha, Gulikers, Judith L, Veelen, Ard van, Croes, Sander, Hendriks, Lizza EL, Smit, Adrianus AJ, Bloem, Lourens T, Egberts, Antoine CG, van de Garde, Ewoudt MW, and Peters, Bas JM
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- 2023
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16. Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in extensive disease small cell lung cancer
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Cramer-van der Welle, Christine M, Schramel, Franz M N H, Peters, Bas J M, van Putten, John W G, Klungel, Olaf H, Groen, Harry J M, van de Garde, Ewoudt M W, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology
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medicine.medical_specialty ,real-world ,Lung Neoplasms ,Epidemiology ,world ,efficacy ,CISPLATIN PLUS ETOPOSIDE ,MULTICENTER ,effectiveness ,PLACEBO-CONTROLLED TRIAL ,030226 pharmacology & pharmacy ,Systemic therapy ,survival ,03 medical and health sciences ,DOUBLE-BLIND ,pharmacotherapy ,0302 clinical medicine ,Pharmacotherapy ,ETOPOSIDE/CISPLATIN ,Internal medicine ,RANDOMIZED-PHASE-III ,CYCLOPHOSPHAMIDE ,Taverne ,medicine ,Humans ,In patient ,Poor performance status ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,Retrospective Studies ,CARBOPLATIN ,Performance status ,Extensive Disease ,business.industry ,real‐ ,OPEN-LABEL ,Small Cell Lung Carcinoma ,Clinical trial ,1ST-LINE TREATMENT ,Non small cell ,small cell lung cancer ,business - Abstract
Purpose The aim of this study is to assess how clinical outcomes in real-world (effectiveness) correspond to the outcomes in clinical trials (efficacy) of systemic treatments for extensive disease small cell lung cancer (ED SCLC).Methods All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. For every patient, an efficacy-effectiveness factor (EE factor) was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment.Results From 792 diagnosed patients, 568 (72%) started with first-line treatment. Overall, the median EE factor was 0.79 (P = 2) and a higher age at diagnosis (age >= 65 years) were independent predictors for a lower EE factor. The EE gap was 43% in patients with both age >= 65 years and ECOG >= 2 (EE factor 0.57). The mean age and the proportion of patients with ECOG >= 2 in real-world were different from those in clinical trials (mean age of 66 versus 62 years, and ECOG >= 2 25% versus 17%; both P Conclusion OS of patients with ED SCLC treated with systemic therapy in real-world practice is 21% shorter than for patients included in trials. Age at diagnosis and performance status partly explain this gap.
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- 2021
17. POINT-TO-SET DISTANCE FUNCTIONS FOR OUTPUT-CONSTRAINED NEURAL NETWORKS.
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PETERS, BAS
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NEURAL circuitry ,COMPUTER vision ,OPTIMALITY theory (Linguistics) ,BACK propagation ,MACHINE learning - Abstract
Training a neural network for semantic segmentation with many images and pixel-level segmentations is a well-established computer-vision technique. When pixel-level segmentations are unavailable, weak supervision or prior information like bounding boxes and the size/shape of objects still enables training a network. Directly including prior knowledge on the segmentations means constraining the network output. This complicates the possible optimization strategies because the regularization then acts on the non-linear neural-network function output and not on the optimization variables. We present a new algorithm to include prior information via constraints on the network output, implemented via projection-based point-to-set distance functions, that are differentiable and always have the same functional form for the derivative. Thus, there is no need to adapt penalty functions or algorithms to various constraints. The distance function's differentiability also avoids issues related to constraining properties typically associated with non-differentiable penalties. We show that by explicitly taking a general neural network structure into account, the Lagrangian for the problem 'naturally' decouples the constraints and neural network, which allows for a gradient computation via backpropagation/adjoint-state as is common in deep learning. We present a suite of constraint sets suitable for segmentation problems. The numerical experiments show that learning from constraint sets applies to the broader imaging sciences, including visual and non-visual imagery, even when training a network for a single example. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in extensive disease small cell lung cancer
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Cramer, Christine, Schramel, Franz, Peters, Bas, van Putten, John, Klungel, Olaf, Groen, Harry, and van de Garde, Ewoudt
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- 2020
19. Point-to-set distance functions for weakly supervised segmentation
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Peters, Bas
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FOS: Computer and information sciences ,Computer Vision and Pattern Recognition (cs.CV) ,Image and Video Processing (eess.IV) ,FOS: Electrical engineering, electronic engineering, information engineering ,Computer Science - Computer Vision and Pattern Recognition ,Electrical Engineering and Systems Science - Image and Video Processing ,68T45 - Abstract
When pixel-level masks or partial annotations are not available for training neural networks for semantic segmentation, it is possible to use higher-level information in the form of bounding boxes, or image tags. In the imaging sciences, many applications do not have an object-background structure and bounding boxes are not available. Any available annotation typically comes from ground truth or domain experts. A direct way to train without masks is using prior knowledge on the size of objects/classes in the segmentation. We present a new algorithm to include such information via constraints on the network output, implemented via projection-based point-to-set distance functions. This type of distance functions always has the same functional form of the derivative, and avoids the need to adapt penalty functions to different constraints, as well as issues related to constraining properties typically associated with non-differentiable functions. Whereas object size information is known to enable object segmentation from bounding boxes from datasets with many general and medical images, we show that the applications extend to the imaging sciences where data represents indirect measurements, even in the case of single examples. We illustrate the capabilities in case of a) one or more classes do not have any annotation; b) there is no annotation at all; c) there are bounding boxes. We use data for hyperspectral time-lapse imaging, object segmentation in corrupted images, and sub-surface aquifer mapping from airborne-geophysical remote-sensing data. The examples verify that the developed methodology alleviates difficulties with annotating non-visual imagery for a range of experimental settings.
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- 2020
20. Deep connections between learning from limited labels & physical parameter estimation -- inspiration for regularization
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Peters, Bas
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Physics - Geophysics ,I.2.10 ,I.4.6 ,Computer Science - Computer Vision and Pattern Recognition ,Electrical Engineering and Systems Science - Image and Video Processing ,68T45 - Abstract
Recently established equivalences between differential equations and the structure of neural networks enabled some interpretation of training of a neural network as partial-differential-equation (PDE) constrained optimization. We add to the previously established connections, explicit regularization that is particularly beneficial in the case of single large-scale examples with partial annotation. We show that explicit regularization of model parameters in PDE constrained optimization translates to regularization of the network output. Examination of the structure of the corresponding Lagrangian and backpropagation algorithm do not reveal additional computational challenges. A hyperspectral imaging example shows that minimum prior information together with cross-validation for optimal regularization parameters boosts the segmentation accuracy.
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- 2020
21. Fully reversible neural networks for large-scale surface and sub-surface characterization via remote sensing
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Peters, Bas, Haber, Eldad, and Lensink, Keegan
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FOS: Computer and information sciences ,Physics - Geophysics ,Computer Vision and Pattern Recognition (cs.CV) ,Image and Video Processing (eess.IV) ,I.4.6 ,FOS: Electrical engineering, electronic engineering, information engineering ,Computer Science - Computer Vision and Pattern Recognition ,FOS: Physical sciences ,Electrical Engineering and Systems Science - Image and Video Processing ,68T45 ,Geophysics (physics.geo-ph) - Abstract
The large spatial/frequency scale of hyperspectral and airborne magnetic and gravitational data causes memory issues when using convolutional neural networks for (sub-) surface characterization. Recently developed fully reversible networks can mostly avoid memory limitations by virtue of having a low and fixed memory requirement for storing network states, as opposed to the typical linear memory growth with depth. Fully reversible networks enable the training of deep neural networks that take in entire data volumes, and create semantic segmentations in one go. This approach avoids the need to work in small patches or map a data patch to the class of just the central pixel. The cross-entropy loss function requires small modifications to work in conjunction with a fully reversible network and learn from sparsely sampled labels without ever seeing fully labeled ground truth. We show examples from land-use change detection from hyperspectral time-lapse data, and regional aquifer mapping from airborne geophysical and geological data.
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- 2020
22. Validation of an automated method for compounding monoclonal antibody patient doses: Case studies of Avastin® (bevacizumab), Remicade® (infliximab) and Herceptin® (trastuzumab)
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Peters, Bas J.M., Capelle, Martinus A.H., Arvinte, Tudor, and van de Garde, Ewoudt M.W.
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- 2013
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23. CYP2C19 and ABCB1 genes and individualized treatment with clopidogrel
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Peters, Bas JM, Harmsze, Ankie M, ten Berg, Jurriën M, Maitland-van der Zee, Anke-Hilse, Tjoeng, Mathieu M, de Boer, Anthonius, and Deneer, Vera HM
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- 2011
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24. Pharmacogenetic interactions between ABCB1 and SLCO1B1 tagging SNPs and the effectiveness of statins in the prevention of myocardial infarction
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Peters, Bas JM, Rodin, Andrei S, Klungel, Olaf H, van Duijn, Cornelia M, Stricker, Bruno H Ch, van’t Slot, Ruben, de Boer, Anthonius, and Maitland-van der Zee, Anke-Hilse
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- 2010
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25. Genetic determinants of response to statins
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Peters, Bas JM, Klungel, Olaf H, de Boer, Anthonius, and Maitland-van der Zee, Anke-Hilse
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- 2009
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26. Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.
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VAN MUIJEN, Marloes E., THOMAS, Sarah E., GROENEWOUD, Hans M. M., OTERO, Marisol E., OSSENKOPPELE, Paul M., NJOO, Marcellus D., DODEMONT, Sharon R. P., KOP, Else N., BERENDS, Maartje A. M., KOETSIER, Marjolein I. A., MOMMERS, Johannes M., KÖRVER, John E. M., TUPKER, Ron A., DE BRUIN-WELLER, Marjolein S., WEPPNERPARREN, Lizelotte J. M. T., PETERS, Bas, KLEINPENNING, Marloes M., KUIJPERS, Astrid L. A., ARNOLD, W. Peter, and VAN LÜMIG, Paula P. M.
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PSORIASIS ,BIOLOGICALS ,RANDOMIZED controlled trials ,BIOTHERAPY ,LOGISTIC regression analysis - Abstract
Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-a)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study. [ABSTRACT FROM AUTHOR]
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- 2022
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27. Generalized Minkowski sets for the regularization of inverse problems
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Peters, Bas and Herrmann, Felix J.
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Optimization and Control (math.OC) ,68U10, 86A22 ,Image and Video Processing (eess.IV) ,FOS: Electrical engineering, electronic engineering, information engineering ,FOS: Mathematics ,Computer Science - Numerical Analysis ,Numerical Analysis (math.NA) ,Electrical Engineering and Systems Science - Image and Video Processing ,Mathematics - Optimization and Control - Abstract
Many works on inverse problems in the imaging sciences consider regularization via one or more penalty functions or constraint sets. When the models/images are not easily described using one or a few penalty functions/constraints, additive model descriptions for regularization lead to better imaging results. These include cartoon-texture decomposition, morphological component analysis, and robust principal component analysis; methods that typically rely on penalty functions. We propose a regularization framework, based on the Minkowski set, that merges the strengths of additive models and constrained formulations. We generalize the Minkowski set, such that the model parameters are the sum of two components, each of which is constrained to an intersection of sets. Furthermore, the sum of the components is also an element of another intersection of sets. These generalizations allow us to include multiple pieces of prior knowledge on each of the components, as well as on the sum of components, which is necessary to ensure physical feasibility of partial-differential-equation based parameters estimation problems. We derive the projection operation onto the generalized Minkowski sets and construct an algorithm based on the alternating direction method of multipliers. We illustrate how we benefit from using more prior knowledge in the form of the generalized Minkowski set using seismic waveform inversion and video background-anomaly separation., 18 pages, 3 figures
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- 2019
28. Intersections and sums of sets for the regularization of inverse problems
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Peters, Bas
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Inverse problems in the imaging sciences encompass a variety of applications. The primary problem of interest is the identification of physical parameters from observed data that come from experiments governed by partial-differential-equations. The secondary type of imaging problems attempts to reconstruct images and video that are corrupted by, for example, noise, subsampling, blur, or saturation. The quality of the solution of an inverse problem is sensitive to issues such as noise and missing entries in the data. The non-convex seismic full-waveform inversion problem suffers from parasitic local minima that lead to wrong solutions that may look realistic even for noiseless data. To meet some of these challenges, I propose solution strategies that constrain the model parameters at every iteration to help guide the inversion. To arrive at this goal, I present new practical workflows, algorithms, and software, that avoid manual tuning-parameters and that allow us to incorporate multiple pieces of prior knowledge. Opposed to penalty methods, I avoid balancing the influence of multiple pieces of prior knowledge by working with intersections of constraint sets. I explore and present advantages of constraints for imaging. Because the resulting problems are often non-trivial to solve, especially on large 3D grids, I introduce faster algorithms, dedicated to computing projections onto intersections of multiple sets. To connect prior knowledge more directly to problem formulations, I also combine ideas from additive models, such as cartoon-texture decomposition and robust principal component analysis, with intersections of multiple constraint sets for the regularization of inverse problems. The result is an extension of the concept of a Minkowski set. Examples from non-unique physical parameter estimation problems show that constraints in combination with projection methods provide control over the model properties at every iteration. This can lead to improved results when the constraints are carefully relaxed.
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- 2019
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29. Multi-resolution neural networks for tracking seismic horizons from few training images
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Peters, Bas, Granek, Justin, and Haber, Eldad
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FOS: Computer and information sciences ,Physics - Geophysics ,Computer Science - Machine Learning ,68T45 (Primary) ,Statistics - Machine Learning ,Computer Vision and Pattern Recognition (cs.CV) ,Computer Science - Computer Vision and Pattern Recognition ,FOS: Physical sciences ,Machine Learning (stat.ML) ,Geophysics (physics.geo-ph) ,Machine Learning (cs.LG) - Abstract
Detecting a specific horizon in seismic images is a valuable tool for geological interpretation. Because hand-picking the locations of the horizon is a time-consuming process, automated computational methods were developed starting three decades ago. Older techniques for such picking include interpolation of control points however, in recent years neural networks have been used for this task. Until now, most networks trained on small patches from larger images. This limits the networks ability to learn from large-scale geologic structures. Moreover, currently available networks and training strategies require label patches that have full and continuous annotations, which are also time-consuming to generate. We propose a projected loss-function for training convolutional networks with a multi-resolution structure, including variants of the U-net. Our networks learn from a small number of large seismic images without creating patches. The projected loss-function enables training on labels with just a few annotated pixels and has no issue with the other unknown label pixels. Training uses all data without reserving some for validation. Only the labels are split into training/testing. Contrary to other work on horizon tracking, we train the network to perform non-linear regression, and not classification. As such, we propose labels as the convolution of a Gaussian kernel and the known horizon locations that indicate uncertainty in the labels. The network output is the probability of the horizon location. We demonstrate the proposed computational ingredients on two different datasets, for horizon extrapolation and interpolation. We show that the predictions of our methodology are accurate even in areas far from known horizon locations because our learning strategy exploits all data in large seismic images., 24 pages, 13 figures
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- 2018
30. Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in metastatic nonsmall cell lung cancer
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Cramer-van der Welle, Christine M., Peters, Bas J. M., Schramel, Franz M. N. H., Klungel, Olaf H., Groen, Harry J. M., van de Garde, Ewoudt M. W., Polman, A. J., van den Borne, B. E. E. M., van Putten, J. W. G., Smit, A. A. J., Termeer, A., Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
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Pulmonary and Respiratory Medicine ,Oncology ,Male ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,MAINTENANCE BEVACIZUMAB ,Multicenter trial ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,PERFORMANCE STATUS ,Carcinoma ,medicine ,Humans ,GEMCITABINE PLUS CARBOPLATIN ,030212 general & internal medicine ,Registries ,Neoplasm Metastasis ,Aged ,Netherlands ,MULTICENTER TRIAL ,Chemotherapy ,Clinical Trials as Topic ,Performance status ,business.industry ,Lung Cancer ,Cancer ,PHASE-III TRIAL ,Original Articles ,Middle Aged ,CISPLATIN VS. GEMCITABINE ,medicine.disease ,OPEN-LABEL ,STAGE IIIB ,Discontinuation ,Clinical trial ,1ST-LINE TREATMENT ,Treatment Outcome ,COOPERATIVE-ONCOLOGY-GROUP ,030220 oncology & carcinogenesis ,Female ,business - Abstract
The divergence between clinical trial results and real-world outcomes is largely unknown for many cancer types. The present study aims overall to assess the efficacy–effectiveness gap (difference between outcomes in clinical trials and the real world) in systemic treatment for metastatic nonsmall cell lung cancer (NSCLC). All patients diagnosed with stage IV NSCLC between 2008 and 2014 within a network of seven Dutch large teaching hospitals (Santeon) were studied. For every patient, an efficacy–effectiveness (EE) factor was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment. From 2989 diagnosed patients, 1214 (41%) started with first-line treatment. For all studied regimens, real-world OS was shorter than OS reported in clinical trials. Overall, the EE factor was 0.77 (95% CI 0.70–0.85; p, Survival of patients with metastatic NSCLC treated with chemotherapy or targeted therapy in real-world practice is nearly one quarter shorter than for patients included in clinical trials. These real-world data provide useful information for clinicians. http://ow.ly/Khd230minFF
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- 2018
31. How soil-borne pathogens may affect plant competition
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Van Der Putten, Wim H. and Peters, Bas A.M.
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Vegetation dynamics -- Research ,Plant-pathogen relationships -- Research ,Competition (Biology) -- Research ,Biological sciences ,Environmental issues ,Research - Abstract
A role for pathogens in plant competition has often been suggested, but examples are rare and, in the case of soil pathogens, virtually absent. In this paper we examine if and how soil-borne pathogens may play a role in plant competition. As a model, two successional plant species from coastal sand dunes were used: Ammophila arenaria (marram grass) and Festuca rubra ssp. arenaria (sand fescue). The root zone of A. arenaria contains pathogens that contribute to the degeneration of their host when dunes become stabilized. These pathogens (plant parasitic nematodes and pathogenic fungi) are relatively harmless to the immediate successor F. rubra. We tested the hypothesis that F. rubra, when grown in a mixed culture with A. arenaria, will be favored when A. arenaria is exposed to soil-borne pathogens from its own root zone. In a greenhouse, seedlings of both species were grown in replacement series in sterilized (pathogen-free) and unsterilized (pathogen-containing) soils originating from the root zone of natural A. arenaria. Nutrient additions, soil moisture, and the length of the experiment were based on two pilot studies. When exposed to its soil-borne pathogens, A. arenaria was outcompeted, especially when it constituted Key words: allocation; Ammophila arenaria; apparent competition; clonal plants; coastal sand dunes; Festuca rubra ssp. arenaria; fungi; host specificity; nematodes; The Netherlands; plasticity; succession., INTRODUCTION Competition is generally regarded as an important ecological factor structuring the composition and diversity of natural communities in space and time (Grace and Tilman 1990). In many cases, direct [...]
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- 1997
32. Trends in prescribing systemic treatment and overall survival for non-small cell lung cancer stage IIIB/IV in the Netherlands: 2008-2012
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Peters, Bas J M, Cramer-Vd Welle, Christine M, Smit, Arthur A J, Schramel, Franz M N H, van de Garde, Ewoudt M W, Santeon NSCLC Study Group, Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology
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Cohort Studies ,Male ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung ,Humans ,Female ,History, 21st Century ,Survival Analysis ,Aged ,Neoplasm Staging ,Netherlands ,Retrospective Studies - Abstract
BACKGROUND: The present study aims to give a detailed overview of day-to-day practice in the systemic treatment of NSCLC stage IIIB/IV and its clinical outcomes in six large teaching hospitals in the Netherlands in the period 2008-2012. METHODS: A retrospective observational cohort study was conducted in the Care for Outcome registry. Patients diagnosed with stage IIIB/IV NSCLC were included and drug data were collected. Outcomes included percentage of patients treated with systemic treatment, percentage of different first line treatment options, survival, and number and percentage of switches, dose reductions (
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- 2017
33. Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands.
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Cramer-van der Welle, Christine M., Verschueren, Marjon V., Tonn, Merel, Peters, Bas J. M., Schramel, Franz M. N. H., Klungel, Olaf H., Groen, Harry J. M., van de Garde, Ewoudt M. W., The Santeon NSCLC Study Group, Kastelijn, E. A., Vermeer, L. C., van den Borne, B. E. E. M., van Putten, J. W. G., Schouwink, J. H., and Smit, A. A. J.
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NON-small-cell lung carcinoma ,CANCER immunotherapy ,PEMBROLIZUMAB ,FOLLOW-up studies (Medicine) - Abstract
This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015–2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75–1.55), and HR 0.91 (95% CI 0.74–1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07–2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this. [ABSTRACT FROM AUTHOR]
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- 2021
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34. Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias
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Clarke, Robert, Bennett, Derrick A., Parish, Sarah, Verhoef, Petra, Dotsch-Klerk, Mariska, Lathrop, Mark, Xu, Peng, Nordestgaard, Borge G., Holm, Hilma, Hopewell, Jemma C., Saleheen, Danish, Tanaka, Toshihiro, Anand, Sonia S., Chambers, John C., Kleber, Marcus E., Ouwehand, Willem H., Yamada, Yoshiji, Elbers, Clara, Peters, Bas, Stewart, Alexandre F.R., Reilly, Muredach M., Thorand, Barbara, Yusuf, Salim, Engert, James C., Assimes, Themistocles L., Kooner, Jaspal, Danesh, John, Watkins, Hugh, Samani, Nilesh J., Collins, Rory, and Peto, Richard
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Meta-analysis -- Research ,Coronary heart disease -- Physiological aspects -- Development and progression ,Homocysteine -- Physiological aspects -- Health aspects ,Biological sciences - Abstract
Background: Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so 'Mendelian randomization' studies using this variant as an instrumental variable could help test causality. Methods and Findings: Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98-1.07;p = 0.28) overall, and 1.01 (0.95-1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09-1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04-1.21) in the 14 larger studies (those with variance of log OR < 0.05; total 13,119 cases) and 1.18 (1.09-1.28) in the 72 smaller ones (total 15,498 cases). Conclusions: The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems. Please see later in the article for the Editors' Summary., Introduction Rare genetic defects that cause extremely high plasma homocysteine levels also cause coronary heart disease (CHD) [1-3]. It was therefore hypothesised that, even within the normal range of plasma [...]
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- 2012
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35. Recurrent Episodes of Nivolumab-Induced Pneumonitis after Nivolumab Discontinuation and the Time Course of Carcinoembryonic Antigen Levels: A Case of a 58-Year-Old Woman with Non-Small Cell Lung Cancer.
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de Jong, Corine, Peters, Bas J.M., and Schramel, Franz M.N.H.
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NON-small-cell lung carcinoma , *CARCINOEMBRYONIC antigen , *PNEUMONIA , *IMMUNOTHERAPY , *DRUG side effects , *DISEASE relapse - Abstract
Introduction: The introduction of immune checkpoint inhibitors heralded a new era in the treatment of non-small cell lung cancer. However, nivolumab, an anti-PD-1 antibody, can cause serious adverse events that are mostly autoimmune related. Case Presentation: A 58-year-old woman was treated with nivolumab as second-line therapy for stage IV adenocarcinoma. The patient developed a nivolumab-induced recurrent pneumonitis preceding durable clinical remission after seven cycles of nivolumab. Although high-dose glucocorticosteroids were tapered to conform to contemporary guidelines, recurring episodes of pneumonitis occurred without nivolumab rechallenge. In addition, carcinoembryonic antigen (CEA) serum levels were associated with treatment response, since CEA decline correlated with a near complete radiological response and, conversely, elevated CEA serum levels were associated with progressive disease. Conclusions: In this case, we described recurrence of nivolumab-induced pneumonitis as a serious adverse event in immune checkpoint inhibitors. Our case illustrates that immune-related adverse events may correlate with antitumour activity, even after treatment discontinuation. In addition, this case suggests the possible clinical utility of CEA serum levels for the assessment of (durable) effects of immunotherapy. [ABSTRACT FROM AUTHOR]
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- 2018
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36. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height (vol 88, pg 6, 2010)
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Lanktree, Matthew B., Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T., Bailey, Swneke D., Onland-Moret, N. Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P., Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S., Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J., Maloney, Cliona M., Lobmeyer, Maximilian T., Stanton, Alice, Zafarmand, M. Hadi, Romaine, Simon P. R., Mehta, Amar, van Iperen, Erik P. A., Gong, Yan, Price, Tom S., Smith, Erin N., Kim, Cecilia E., Li, Yun R., Asselbergs, Folkert W., Atwood, Larry D., Bailey, Kristian M., Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R., Bhangale, Tushar, Boer, Jolanda M. A., Boehm, Bernhard O., Bradfield, Jonathan P., Brown, Morris, Braund, Peter S., Chen, Wei, Hofker, Marten H., Wijmenga, Cisca, Kumari, Meena, Center for Liver, Digestive and Metabolic Diseases (CLDM), Vascular Ageing Programme (VAP), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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- 2012
37. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
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Johnson, Toby, Mehta, Amar, Pankratz, Nathan, Zafarmand, M. Hadi, Lobmeyer, Maximilian T., Price, Tom S., Kim, Cecilia E., Rajagopalan, Ramakrishnan, Pankow, James S., Smith, Erin N., Gong, Yan, Bailey, Swneke D., Guo, Yiran, Nelson, Christopher P., Shen, Haiqing, Padmanabhan, Sandosh, Stanton, Alice, Ongen, Halit, Baumert, Jens, Romaine, Simon P.R., Taylor, Kira, Lettre, Guillaume, Peters, Bas J., Barnard, John, Murtaza, Muhammed, Glessner, Joseph T., M. Maloney, Cliona, Lanktree, Matthew B., van Iperen, Erik P.A., Onland-Moret, N. Charlotte, Klopp, Norman, and Shah, Sonia
- Abstract
Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
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- 2011
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38. Pharmacogenetics of cardiovascular drug therapy
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Peters, Bas J.M., Klungel, Olaf H., de Boer, Anthonius, Ch. Stricker, Bruno H., and Maitland-van der Zee, Anke-Hilse
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Mini-Review - Abstract
In developed countries cardiovascular disease is one of the leading causes of death. Cardiovascular drugs such as platelet aggregation inhibitors, oral anticoagulants, antihypertensives and cholesterol lowering drugs are abundantly prescribed to reduce risk of cardiovascular disease. Notable interindividual variation exists in the response to these pharmacotherapeutic interventions, which can be partially explained by factors such as gender, age, diet, concomitant drug use and environmental factors. Notwithstanding, a great part of this variability remains unknown. To a smaller or larger extent, genetic variability may contribute to the variability in response to these cardiovascular drugs. This review gives an overview of pharmacogenetic studies of genes that were reported to be associated with four commonly prescribed drugs/drug classes (platelet aggregation inhibitors, coumarins, antihypertensives and statins) and were studied at least 2 times with a similar outcome measure. In the field of cardiovascular drug therapy, polymorphisms in candidate genes such as the cycloxygenase-1, vitamin K reductase complex subunit 1, CYP2C9, alpha adducin and 3-hydroxy-3-methylglutaryl-CoA reductase have received a great amount of interest in the pharmacogenetics of aspirin, coumarins, antihypertensives and statins respectively. However, only variations in VKORC1 and CYP2C9 have consistently been associated with drug response (coumarins) and have clinical implications. Clinical trials should provide evidence for the effectiveness of genotyping before this procedure will be a part of every day anticoagulant therapy. In spite of the tremendous amount of publications in this field, there is no reason to advocate for genetic testing for any other drugs cardiovascular drug therapy yet. Current approaches in pharmacogenetic research do not seem to lead to results that meet our expectations of individualized medicine. Therefore, new approaches are needed addressing issues and challenges such as the number of SNPs studied, study power, study design and application of new statistical methods in (pharmaco-)genetic analysis.
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- 2009
39. Methane emission reduction from storage of manure and digestate-slurry.
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Oonk, Hans, Koopmans, Jan, Geck, Christoph, Peters, Bas, and van Bergen, Jan
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METHANE & the environment ,GAS storage ,GREENHOUSE gas mitigation ,METHANE ,OXIDATION ,METHANOTROPHS - Abstract
Manure storage is a source of methane. An option to mitigate methane emissions from manure storage is to collect the methane produced in the storage and feed it into a dispersion layer underground. In the soil above, the methane is subsequently oxidized by methanotrophic bacteria. A previous study indicated that the method seems technically and economically feasible with costs for emission reduction of methane of €1–4 per ton CO2‐eq. mitigated. The concept was demonstrated at a pilot facility next to a storage for manure digestate and proof of concept was achieved at field scale. It was technically simple to capture methane and feed it into a dispersion system at about 1 m below the surface. Indications exist, that part of the methane was oxidised in the soil. However actual methane oxidation could not be determined, because there are serious doubts whether all methane did enter the oxidation field. For actual applications, quantification of gas generation in manure and oxidation rate of the soil need to be improved, to design an oxidation field. [ABSTRACT FROM AUTHOR]
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- 2015
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40. The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study.
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De Keyser, Catherine E., Peters, Bas J.m., Becker, Matthijs L., Visser, Loes E., Uitterlinden, André G., Klungel, Olaf H., Verstuyft, Céline, Hofman, Albert, Maitland-Van Der Zee, Anke-Hilse, and Stricker, Bruno H.
- Abstract
The SLCO1B1 c.521T>C polymorphism is associated with statin plasma levels and simvastatin-induced adverse drug reactions. We studied whether the c.521T>C polymorphism is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy, because these events are indicators of adverse drug reactions.We identified 1939 incident simvastatin and atorvastatin users in the Rotterdam Study, a population-based cohort study. Associations were studied using Cox proportional hazards analysis. Meta-analysis was performed with data from the Utrecht Cardiovascular Pharmacogenetics study.Simvastatin users with the c.521 CC genotype had a significantly higher risk of a dose decrease or switch than users with the TT genotype [hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.05-2.88]. Female sex, age below 70 years, and low starting dose were risk factors. In atorvastatin users with starting dose of more than 20 mg, the risk of a dose decrease or switch was higher in users carrying a C allele than in users with the TT genotype (HR 3.26, 95% CI 1.47-7.25). In the meta-analysis the association in simvastatin users remained, with a significantly higher risk of a dose decrease or switch in simvastatin users with two minor alleles (HR 1.69, 95% CI 1.05-2.73). For atorvastatin users no significant association was found.In simvastatin users in the Rotterdam Study, we demonstrated an association between the c.521T>C polymorphism and dose decrease or switching, as indicators of adverse drug reactions, and provided risk factors for this association. For atorvastatin, an association was found in users with a starting dose of more than 20 mg. [ABSTRACT FROM AUTHOR]
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- 2014
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41. Genetic variability within the cholesterol lowering pathway and the effectiveness of statins in reducing the risk of MI
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Peters, Bas J.M., Pett, Helmi, Klungel, Olaf H., Stricker, Bruno H. Ch., Psaty, Bruce M., Glazer, Nicole L., Wiggins, Kerri L., Bis, Josh C., de Boer, Anthonius, and Maitland-van der Zee, Anke-Hilse
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HUMAN genetic variation , *CHOLESTEROL , *STATINS (Cardiovascular agents) , *DRUG efficacy , *MYOCARDIAL infarction , *PHARMACOGENOMICS , *HOSPITAL admission & discharge , *HYPERCHOLESTEREMIA - Abstract
Abstract: Genetic variability has been shown to affect statin responsiveness. Participants from the Utrecht Cardiovascular Pharmacogenetics (UCP) studies were enrolled from a population-based registry of pharmacy records linked to hospital discharge records (PHARMO) to investigate tagging SNPs within candidate genes involved in the cholesterol lowering pathway for modification of the effectiveness of statins in reducing the risk of myocardial infarction (MI). Patients who received a prescription for an antihypertensive drug and/or had hypercholesterolemia were selected from the PHARMO database. We designed a nested case-control study in which cases were hospitalized for MI and controls were not. Patients were contacted through their community pharmacies. For this study, only hypercholesterolemic participants were selected. Logistic regression analysis was used to investigate pharmacogenetic interactions. The Heart and Vascular Health Study (HVH) was used to replicate findings from UCP. The study population included 668 cases and 1217 controls. We selected 231 SNPs of which 209 SNPs in 27 genes passed quality control. Ten SNPs in eight genes were found to influence the effectiveness of statins in UCP, of which the most significant interaction was found with SCARB1 rs4765615. Other genes that reached statistical significance (p <0.05) included two SNPs in PCSK9 (rs10888896 and rs505151 (E670G)), two SNPs in ABCG5 (rs4245786 and rs1864815), LIPC rs16940379, ABCA1 rs4149264, PPARG rs2972164, LRP1 rs715948, and SOAT1 rs2493121. None of the total of 5 SNPs that were available for replication in HVH reached statistical significance. In conclusion, ten SNPs were found to modify the effectiveness of statins in reducing the risk of MI in the UCP study. Five were also tested in the HVH study, but no interactions reached statistical significance. [Copyright &y& Elsevier]
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- 2011
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42. Variants of ADAMTS1 modify the effectiveness of statins in reducing the risk of myocardial infarction.
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Peters, Bas J.m., Rodin, Andrei S., Klungel, Olaf H., Stricker, Bruno H.ch., De Boer, Anthonius, and Maitland-Van Der Zee, Anke-Hilse
- Abstract
To investigate the influence of tagging single-nucleotide polymorphisms (SNPs) within candidate genes involved in the putative anti-inflammatory effects of statins on the effectiveness of statins in reducing the risk of myocardial infarction (MI).We conducted a case-control study in a population-based registry of pharmacy records linked to hospital discharge records (PHARMO). Cases and controls were selected from within a hypercholesterolemic cohort. Cases were hospitalized for MI, whereas controls were not. Logistic regression analysis was used to investigate pharmacogenetic interactions.The study population comprised 668 cases and 1217 controls. We genotyped 84 SNPs in 24 genes. The effectiveness of statins was found to be modified by seven SNPs in three genes. Five out of six SNPs that were selected in the A disintegrin and metallopeptidase with thrombospondin motif type I (ADAMTS1) gene were associated with a modified response to statins, three of which were in strong linkage disequilibrium. The strongest interaction was found for ADAMTS1 rs402007. Homozygous carriers of the variant allele had the most benefit from statins [adjusted odds ratio (OR): 0.10, 95% confidence interval (CI): 0.03-0.35], compared with heterozygous (OR: 0.43, 95% CI: 0.24-0.51) and homozygous wildtype carriers (OR: 0.49, 95% CI: 0.32-0.57).Consistent with earlier findings, polymorphisms within the ADAMTS1 gene influenced the effectiveness of statins in reducing the risk of MI. Other pharmacogenetic interactions with SNPs in the TNFRSF1A and ITGB2 genes were established and the confirmation will be pursued in future studies. [ABSTRACT FROM AUTHOR]
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- 2010
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43. Methodological and statistical issues in pharmacogenomics.
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Peters, Bas J. M., Rodin, Andrei S., De Boer, Anthonius, and Maitland-van der Zee, Anke-Hilse
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PHARMACOGENOMICS , *BIOINFORMATICS , *HUMAN genetic variation , *ANTIRETROVIRAL agents , *ABACAVIR - Abstract
Pharmacogenomics strives to explain the interindividual variability in response to drugs due to genetic variation. Although technological advances have provided us with relatively easy and cheap methods for genotyping, promises about personalised medicine have not yet met our high expectations. Successful results that have been achieved within the field of pharmacogenomics so far are, to name a few, HLA-B*5701 screening to avoid hypersensitivity to the antiretroviral abacavir, thiopurine S-methyltransferase ( TPMT) genotyping to avoid thiopurine toxicity, and CYP2C9 and VKORC1 genotyping for better dosing of the anticoagulant warfarin. However, few pharmacogenetic examples have made it into clinical practice in the treatment of complex diseases. Unfortunately, lack of reproducibility of results from observational studies involving many genes and diseases seems to be a common pattern in pharmacogenomic studies. In this article we address some of the methodological and statistical issues within study design, gene and single nucleotide polymorphism (SNP) selection and data analysis that should be considered in future pharmacogenomic research. First, we discuss some of the issues related to the design of epidemiological studies, specific to pharmacogenomic research. Second, we describe some of the pros and cons of a candidate gene approach (including gene and SNP selection) and a genome-wide scan approach. Finally, conventional as well as several innovative approaches to the analysis of large pharmacogenomic datasets are proposed that deal with the issues of multiple testing and systems biology in different ways. [ABSTRACT FROM AUTHOR]
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- 2010
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44. The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13) on the effectiveness of statins: the GenHAT study.
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Maitland-Van Der Zee, Anke-Hilse, Peters, Bas J.m., Lynch, Amy I., Boerwinkle, Eric, Arnett, Donna K., Cheng, Suzanne, Davis, Barry R., Leiendecker-Foster, Catherine, Ford, Charles E., and Eckfeldt, John H.
- Abstract
Pharmacogenetic research has shown that genetic variation may influence statin responsiveness. Statins exert a variety of beneficial effects beyond lipid lowering, including antithrombotic effects, which contribute to the risk reduction of cardiovascular disease. Statins have been shown to influence the expression of coagulation factors II, V, VII, XII and XIII.Data from a large randomized clinical trial of pravastatin, designed to show efficacy relative to usual care, were used to investigate whether a pharmacogenetic effect of polymorphisms in genes coding for coagulation factors II, V, VII, XII and XIII is associated with reduced fatal coronary heart disease (CHD) and nonfatal myocardial infarction, combined CHD and all-cause mortality.The Genetics of Hypertension Associated Treatment is an ancillary study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The genotyped population in the lipid-lowering trial of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial included 9624 participants randomly assigned to pravastatin or to usual care. The efficacy of pravastatin in reducing risk of all-cause mortality, CHD and nonfatal myocardial infarction and combined CHD, was compared among genotype strata by examining an interaction term in a proportional hazards model.None of the polymorphisms were associated with the clinical outcomes. For the F7 (-323) ins/del polymorphism there was no interaction with pravastatin for either outcome. For both the F5 Arg506Gln G>A (rs6025) polymorphism and F7 Arg353Gln G>A (rs6046) polymorphism there were no interactions with pravastatin in relation to all-cause mortality, but there were significant interactions with combined CHD [interaction hazard ratio = 1.33, 95% confidence interval (1.01-1.76) and interaction hazard ratio = 1.92, 95% confidence interval (1.00-3.65), respectively]. There were no interactions between the polymorphisms in the other coagulation genes and pravastatin in relation to any outcome.Polymorphisms in anticoagulation genes (F5 and F7) seem to modify the efficacy of pravastatin in reducing risk of cardiovascular events. [ABSTRACT FROM AUTHOR]
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- 2009
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45. Pharmacogenomic importance of pravastatin.
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Peters, Bas and Maitland-van der Zee, Auke-Hilse
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PHARMACOGENOMICS ,PRAVASTATIN ,STATINS (Cardiovascular agents) ,ANTICHOLESTEREMIC agents ,CARDIOVASCULAR diseases - Abstract
In developed countries, cardiovascular disease is one of the leading causes of death. Among other statins, pravastatin is abundantly prescribed to reduce risk of coronary artery disease by lowering cholesterol. Genetic factors are thought to be partly responsible for the interindividual variation in the response to pravastatin. This article reviews the most important studies conducted on the pharmacogenetics of pravastatin. Currently there is no evidence to advocate pharmacogenetic testing before initiating therapy. [ABSTRACT FROM AUTHOR]
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- 2008
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46. Effectiveness of statins in the reduction of the risk of myocardial infarction is modified by the GNB3 C825T variant.
- Author
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Peters, Bas J.m., Maitland-Van Der Zee, Anke-Hilse, Stricker, Bruno H.ch., Van Wieren-De Wijer, Diane B.m.a., De Boer, Anthonius, Kroon, Abraham A., De Leeuw, Peter W., Schiffers, Paul, Janssen, Rob G.j.h., Van Duijn, Cornelia M., and Klungel, Olaf H.
- Abstract
The GNB3 C825T polymorphism has been shown to affect lipid parameters, atherosclerosis progression, and incidence of myocardial infarction (MI). Therefore, we assessed whether the effectiveness of statins in reducing the risk of MI was modified by the GNB3 C825T polymorphism.In a population-based registry of pharmacy records linked to hospital discharge records (PHARMO), we used a nested case-control design. We selected patients hospitalized for MI as cases if they used antihypertensive drugs and had a diagnosis of hypercholesterolemia before their first MI. Controls met the same eligibility criteria, but were not hospitalized for MI. Logistic regression analysis was used to calculate odds ratios (OR) and synergy index with corresponding 95% confidence intervals (CI), and to adjust for potential confounding factors.We included 459 cases and 1805 controls. The risk of MI was significantly lower among participants exposed to statins compared with participants not exposed to statins (adjusted OR: 0.37, 95% CI: 0.29-0.47). The GNB3T allele was associated with a reduced risk of MI (adjusted OR: 0.74, 95% CI: 0.60-0.92). Among homozygous wild-type (CC) individuals (n=1119), exposure to statins was associated with a lower risk of MI (OR: 0.48, 95% CI: 0.34-0.67). However, T allele carriers (CT and TT) who used statins had an even stronger reduced risk of MI (OR: 0.27, 95% CI: 0.19-0.39). Overall, the interaction between exposure to statins and the GNB3 C825T polymorphism was significantly increased on the multiplicative scale (synergy index: 1.67, 95% CI: 1.06-2.65).Our findings show that T allele carriers of the GNB3 C825T polymorphism have less risk of MI and are more likely to benefit from statin therapy in a hypercholesterolemic population of antihypertensive drug users. [ABSTRACT FROM AUTHOR]
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- 2008
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47. Switching to an Infliximab Biosimilar Was Safe and Effective in Dutch Sarcoidosis Patients.
- Author
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Peters, Bas J. M., Bhatoe, Anish, Vorselaars, Adriane D. M., Veltkamp, Marcel, and Calender, Alain
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SARCOIDOSIS , *INFLIXIMAB , *TERMINATION of treatment , *PHYSICAL mobility , *ADALIMUMAB - Abstract
The effect of switching from originator infliximab to biosimilar infliximab in patients with sarcoidosis is unknown. The objective of this study is to investigate the effect of switching from Remicade® or Inflectra® to Flixabi® in patients with severe refractory sarcoidosis. This single center retrospective cohort study was performed at St Antonius Hospital Nieuwegein, The Netherlands. All patients diagnosed with severe refractory sarcoidosis receiving Remicade® or Inflectra® switched to Flixabi®. The primary outcome was infliximab discontinuation within 6 months of switching. Secondary endpoints included adverse events and loss of clinical, functional, or inflammatory response. Out of 86 patients who switched to Flixabi®, 79 patients had complete data. None of the 79 patients discontinued infliximab during the first 6 months after switching. Five patients reported an adverse event related to Flixabi® treatment. We found no change from baseline in FVC, FEV1, DLCOc, 6MWT, and infliximab trough levels 26 weeks after switching. An improvement in physical functioning of 7.3 ± 13.4 points (p = 0.002) with RAND/SF36 and in biomarker sIL-2R (−475.58 ± 1452.39; p = 0.005) was observed. Switching from originator infliximab Remicade® or biosimilar infliximab Inflectra® to biosimilar infliximab Flixabi® did not result in treatment discontinuation or loss of clinical/functional/inflammatory remission. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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48. Trends in Drug Costs and Overall Survival in Patients with Metastatic Non-small Cell Lung Cancer in The Netherlands Diagnosed from 2008 Through 2014.
- Author
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Cramer-van der Welle, Christine M., Peters, Bas J. M., Deenen, Maarten J., Schramel, Franz M. N. H., and van de Garde, Ewoudt M. W.
- Abstract
The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). All patients diagnosed (in 2008–2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years ( p = 0.437 andp = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011–2014 compared with 2008–2010.This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years. [ABSTRACT FROM AUTHOR] - Published
- 2020
- Full Text
- View/download PDF
49. The potential for deprescribing in a palliative oncology patient population: a cross-sectional study.
- Author
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van Merendonk LN, Peters BJM, Möhlmann JE, Hunting CB, Kastelijn EA, and van den Broek MPH
- Subjects
- Humans, Aged, Inappropriate Prescribing prevention & control, Cross-Sectional Studies, Potentially Inappropriate Medication List, Deprescriptions, Neoplasms drug therapy, Neoplasms epidemiology
- Abstract
Objectives: The use of preventive medication in palliative oncology patients may be inappropriate due to limited life expectancy. Deprescribing tools are available but time-consuming and not always tailored to this specific population. Our primary goal was to identify potentially inappropriate medications (PIMs) in palliative oncology patients with a life expectancy of up to 2 years using an adapted deprescribing tool. Our secondary aim was to identify patient characteristics associated with the presence of PIMs., Methods: Oncology patients with a life expectancy of up to 2 years were included cross-sectionally. An adapted deprescribing tool was developed to identify PIMs. Logistic regression was used to identify factors associated with having PIMs., Results: A total of 218 patients were included in this study of which 56% had at least one PIM with a population mean of 1.1 PIM per patient. Most frequently defined PIMs were antihypertensive drugs and gastric acid inhibitors. Identification of PIMs by review took an estimated 5-10 min per patient. Polypharmacy, age >65 years and inpatient/outpatient status were found to be associated with having at least one PIM., Conclusions: Deprescribing is possible in more than half of palliative oncology patients with a life expectancy of up to 2 years. The adapted deprescribing tool used is non-time consuming and suitable for palliative oncology patients, regardless of age., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
50. Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in extensive disease small cell lung cancer.
- Author
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Cramer-van der Welle CM, Schramel FMNH, Peters BJM, van Putten JWG, Klungel OH, Groen HJM, and van de Garde EMW
- Subjects
- Aged, Humans, Retrospective Studies, Lung Neoplasms drug therapy, Small Cell Lung Carcinoma drug therapy
- Abstract
Purpose: The aim of this study is to assess how clinical outcomes in real-world (effectiveness) correspond to the outcomes in clinical trials (efficacy) of systemic treatments for extensive disease small cell lung cancer (ED SCLC)., Methods: All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. For every patient, an efficacy-effectiveness factor (EE factor) was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment., Results: From 792 diagnosed patients, 568 (72%) started with first-line treatment. Overall, the median EE factor was 0.79 (P < .001 from 1.00). Poor performance status (ECOG≥2) and a higher age at diagnosis (age ≥ 65 years) were independent predictors for a lower EE factor. The EE gap was 43% in patients with both age ≥ 65 years and ECOG ≥2 (EE factor 0.57). The mean age and the proportion of patients with ECOG≥2 in real-world were different from those in clinical trials (mean age of 66 versus 62 years, and ECOG≥2 25% versus 17%; both P < .001)., Conclusion: OS of patients with ED SCLC treated with systemic therapy in real-world practice is 21% shorter than for patients included in trials. Age at diagnosis and performance status partly explain this gap., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
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