Unkel, Steffen

[["dc.bibliographiccitation.firstpage","351"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Metrika"],["dc.bibliographiccitation.lastpage","362"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Unkel, Steffen"],["dc.date.accessioned","2018-11-07T10:25:48Z"],["dc.date.available","2018-11-07T10:25:48Z"],["dc.date.issued","2017"],["dc.description.abstract","In shared frailty models for bivariate survival data the frailty is identifiable through the cross-ratio function (CRF), which provides a convenient measure of association for correlated survival variables. The CRF may be used to compare patterns of dependence across models and data sets. We explore the shape of the CRF for the families of one-sided truncated normal and folded normal frailty distributions."],["dc.identifier.doi","10.1007/s00184-016-0608-6"],["dc.identifier.isi","000397497100007"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42927"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1435-926X"],["dc.relation.issn","0026-1335"],["dc.title","On the shape of the cross-ratio function in bivariate survival models induced by truncated and folded normal frailty distributions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","11"],["dc.bibliographiccitation.journal","Radiation Oncology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Belka, Claus"],["dc.contributor.author","Lauber, Kirsten"],["dc.date.accessioned","2018-11-07T10:19:09Z"],["dc.date.available","2018-11-07T10:19:09Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: The most frequently used method to quantitatively describe the response to ionizing irradiation in terms of clonogenic survival is the linear-quadratic (LQ) model. In the LQ model, the logarithm of the surviving fraction is regressed linearly on the radiation dose by means of a second-degree polynomial. The ratio of the estimated parameters for the linear and quadratic term, respectively, represents the dose at which both terms have the same weight in the abrogation of clonogenic survival. This ratio is known as the alpha/beta ratio. However, there are plausible scenarios in which the alpha/beta ratio fails to sufficiently reflect differences between dose-response curves, for example when curves with similar alpha/beta ratio but different overall steepness are being compared. In such situations, the interpretation of the LQ model is severely limited. Methods: Colony formation assays were performed in order to measure the clonogenic survival of nine human pancreatic cancer cell lines and immortalized human pancreatic ductal epithelial cells upon irradiation at 0-10 Gy. The resulting dataset was subjected to LQ regression and non-linear log-logistic regression. Dimensionality reduction of the data was performed by cluster analysis and principal component analysis. Results: Both the LQ model and the non-linear log-logistic regression model resulted in accurate approximations of the observed dose-response relationships in the dataset of clonogenic survival. However, in contrast to the LQ model the non-linear regression model allowed the discrimination of curves with different overall steepness but similar alpha/beta ratio and revealed an improved goodness-of-fit. Additionally, the estimated parameters in the non-linear model exhibit a more direct interpretation than the alpha/beta ratio. Dimensionality reduction of clonogenic survival data by means of cluster analysis was shown to be a useful tool for classifying radioresistant and sensitive cell lines. More quantitatively, principal component analysis allowed the extraction of scores of radioresistance, which displayed significant correlations with the estimated parameters of the regression models. Conclusions: Undoubtedly, LQ regression is a robust method for the analysis of clonogenic survival data. Nevertheless, alternative approaches including non-linear regression and multivariate techniques such as cluster analysis and principal component analysis represent versatile tools for the extraction of parameters and/or scores of the cellular response towards ionizing irradiation with a more intuitive biological interpretation. The latter are highly informative for correlation analyses with other types of data, including functional genomics data that are increasingly being generated."],["dc.description.sponsorship","BMBF [02NUK024C]"],["dc.identifier.doi","10.1186/s13014-016-0584-z"],["dc.identifier.isi","000368886200001"],["dc.identifier.pmid","26822015"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13179"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41606"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1748-717X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","On the analysis of clonogenic survival data: Statistical alternatives to the linear-quadratic model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","16"],["dc.bibliographiccitation.journal","Orphanet Journal of Rare Diseases"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Roever, Christian"],["dc.contributor.author","Stallard, Nigel"],["dc.contributor.author","Benda, Norbert"],["dc.contributor.author","Posch, Martin"],["dc.contributor.author","Zohar, Sarah"],["dc.contributor.author","Friede, Tim"],["dc.date.accessioned","2018-11-07T10:18:07Z"],["dc.date.available","2018-11-07T10:18:07Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: Randomized controlled trials (RCTs) are the gold standard design of clinical research to assess interventions. However, RCTs cannot always be applied for practical or ethical reasons. To investigate the current practices in rare diseases, we review evaluations of therapeutic interventions in paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD). In particular, we shed light on the endpoints used, the study designs implemented and the statistical methodologies applied. Methods: We conducted literature searches to identify relevant primary studies. Data on study design, objectives, endpoints, patient characteristics, randomization and masking, type of intervention, control, withdrawals and statistical methodology were extracted from the selected studies. The risk of bias and the quality of the studies were assessed. Results: Twelve (seven) primary studies on paediatric MS (CJD) were included in the qualitative synthesis. No double-blind, randomized placebo-controlled trial for evaluating interventions in paediatric MS has been published yet. Evidence from one open-label RCT is available. The observational studies are before-after studies or controlled studies. Three of the seven selected studies on CJD are RCTs, of which two received the maximum mark on the Oxford Quality Scale. Four trials are controlled observational studies. Conclusions: Evidence from double-blind RCTs on the efficacy of treatments appears to be variable between rare diseases. With regard to paediatric conditions it remains to be seen what impact regulators will have through e.g., paediatric investigation plans. Overall, there is space for improvement by using innovative trial designs and data analysis techniques."],["dc.description.sponsorship","EU's 7th Framework Programme [FP HEALTH 2013 - 602144]"],["dc.identifier.doi","10.1186/s13023-016-0402-6"],["dc.identifier.isi","000370410500001"],["dc.identifier.pmid","26897367"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41364"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1750-1172"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Systematic reviews in paediatric multiple sclerosis and Creutzfeldt-Jakob disease exemplify shortcomings in methods used to evaluate therapies in rare conditions"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","166"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Pharmaceutical Statistics"],["dc.bibliographiccitation.lastpage","183"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Amiri, Marjan"],["dc.contributor.author","Benda, Norbert"],["dc.contributor.author","Beyersmann, Jan"],["dc.contributor.author","Knoerzer, Dietrich"],["dc.contributor.author","Kupas, Katrin"],["dc.contributor.author","Langer, Frank"],["dc.contributor.author","Leverkus, Friedhelm"],["dc.contributor.author","Loos, Anja"],["dc.contributor.author","Ose, Claudia"],["dc.contributor.author","Proctor, Tanja"],["dc.contributor.author","Schmoor, Claudia"],["dc.contributor.author","Schwenke, Carsten"],["dc.contributor.author","Skipka, Guido"],["dc.contributor.author","Unnebrink, Kristina"],["dc.contributor.author","Voss, Florian"],["dc.contributor.author","Friede, Tim"],["dc.date.accessioned","2019-07-09T11:50:52Z"],["dc.date.available","2019-07-09T11:50:52Z"],["dc.date.issued","2018"],["dc.description.abstract","The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The statistical analysis of AEs is complicated by the fact that the follow-up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow-up times within the benefit assessment of therapeutic interventions. Instead of approaching this issue directly and solely from an analysis point of view, we first discuss what should be estimated in the context of safety data, leading to the concept of estimands. Although the current discussion on estimands is mainly related to efficacy evaluation, the concept is applicable to safety endpoints as well. Within the framework of estimands, we present statistical methods for analysing AEs with the focus being on the time to the occurrence of the first AE of a specific type. We give recommendations which estimators should be used for the estimands described. Furthermore, we state practical implications of the analysis of AEs in clinical trials and give an overview of examples across different indications. We also provide a review of current practices of health technology assessment (HTA) agencies with respect to the evaluation of safety data. Finally, we describe problems with meta-analyses of AE data and sketch possible solutions."],["dc.identifier.doi","10.1002/pst.1915"],["dc.identifier.pmid","30458579"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16016"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59845"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","321"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Hospital Infection"],["dc.bibliographiccitation.lastpage","327"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Fehling, P."],["dc.contributor.author","Hasenkamp, J."],["dc.contributor.author","Unkel, S."],["dc.contributor.author","Thalmann, I."],["dc.contributor.author","Hornig, S."],["dc.contributor.author","Trümper, L."],["dc.contributor.author","Scheithauer, S."],["dc.date.accessioned","2020-12-10T14:25:09Z"],["dc.date.available","2020-12-10T14:25:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.jhin.2019.06.004"],["dc.identifier.issn","0195-6701"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72459"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Effect of gloved hand disinfection on hand hygiene before infection-prone procedures on a stem cell ward"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","186"],["dc.bibliographiccitation.journal","Orphanet Journal of Rare Diseases"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Posch, Martin"],["dc.contributor.author","Zohar, Sarah"],["dc.contributor.author","Alberti, Corinne"],["dc.contributor.author","Benda, Norbert"],["dc.contributor.author","Comets, Emmanuelle"],["dc.contributor.author","Day, Simon"],["dc.contributor.author","Dmitrienko, Alex"],["dc.contributor.author","Graf, Alexandra"],["dc.contributor.author","Günhan, Burak Kürsad"],["dc.contributor.author","Hee, Siew Wan"],["dc.contributor.author","Lentz, Frederike"],["dc.contributor.author","Madan, Jason"],["dc.contributor.author","Miller, Frank"],["dc.contributor.author","Ondra, Thomas"],["dc.contributor.author","Pearce, Michael"],["dc.contributor.author","Röver, Christian"],["dc.contributor.author","Toumazi, Artemis"],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Ursino, Moreno"],["dc.contributor.author","Wassmer, Gernot"],["dc.contributor.author","Stallard, Nigel"],["dc.date.accessioned","2019-07-09T11:46:02Z"],["dc.date.available","2019-07-09T11:46:02Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1186/s13023-018-0919-y"],["dc.identifier.pmid","30359266"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15384"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59368"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/602144/EU//INSPIRE"],["dc.relation.issn","1750-1172"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Recent advances in methodology for clinical trials in small populations: the InSPiRe project."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Journal of Statistical Planning and Inference"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","182"],["dc.contributor.author","Unkel, Steffen"],["dc.date.accessioned","2018-11-07T10:27:10Z"],["dc.date.available","2018-11-07T10:27:10Z"],["dc.date.issued","2017"],["dc.description.abstract","Shared frailty models are frequently used for inducing dependence between survival times. In this paper, we consider bivariate current status data that are reasonable to model by shared frailty models. A time-dependent association measure that has a conditional probability interpretation is revisited for its potential application to such data. We propose a method of estimation and derive asymptotic standard errors for this measure. Its small sample performance and its performance in assessing the temporal variation in the strength of association in realistic scenarios is investigated by means of experiments. We show that the measure based on the conditional probability can vary with time even in the absence of any time-dependent effects. Furthermore, we give evidence that it lacks interpretability in suggesting appropriate frailty models. We provide an illustration with multivariate current status data arising from a community-based study of cardiovascular diseases in Taiwan. We compare the observed patterns of association with the ones obtained by employing a fairly new time-varying association measure that is relevant for shared frailty models, owing to its connection to the cross-ratio function, and which serves as a diagnostic tool for suggesting classes of frailty distributions with constant, increasing or decreasing association over time. (C) 2016 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jspi.2016.09.009"],["dc.identifier.isi","000389173900001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43193"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1873-1171"],["dc.relation.issn","0378-3758"],["dc.title","On the conditional probability for assessing time dependence of association in shared frailty models with bivariate current status data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","859"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Drugs & Aging"],["dc.bibliographiccitation.lastpage","869"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Djukic, Marija"],["dc.contributor.author","Braun, Larissa Maria"],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2020-12-10T14:14:45Z"],["dc.date.available","2020-12-10T14:14:45Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1007/s40266-018-0571-1"],["dc.identifier.eissn","1179-1969"],["dc.identifier.issn","1170-229X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71474"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Introduction of Non-Vitamin K Antagonist Anticoagulants Strongly Increased the Rate of Anticoagulation in Hospitalized Geriatric Patients with Atrial Fibrillation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","68"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of the American Academy of Audiology"],["dc.bibliographiccitation.lastpage","79"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Kiessling, Juergen"],["dc.contributor.author","Leifholz, Melanie"],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Pons-Kuehnemann, Joern"],["dc.contributor.author","Jespersen, Charlotte Thunberg"],["dc.contributor.author","Pedersen, Jenny Nesgaard"],["dc.date.accessioned","2018-11-07T10:03:57Z"],["dc.date.available","2018-11-07T10:03:57Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: In-situ audiometry is a hearing aid feature that enables the measurement of hearing threshold levels through the hearing instrument using the built-in sound generator and the hearing aid receiver. This feature can be used in hearing aid fittings instead of conventional pure-tone audiometry (PTA), particularly in places where no standard audiometric equipment is available. Differences between conventional and in-situ thresholds are described and discussed for some particular hearing aids. No previous investigation has measured and compared these differences for a number of current hearing aid models by various manufacturers across a wide range of hearing losses. Purpose: The purpose of this study was to perform a model-based comparison of conventionally and insitu measured hearing thresholds. Data were collected for a range of hearing aid devices to study and generalize the effects that may occur under clinical conditions. Research Design: Research design was an experimental and regression study. Study Sample: A total of 30 adults with sensorineural hearing loss served as test persons. They were assigned to three subgroups of 10 subjects with mild (M), moderate to severe (MS), and severe (S) sensorineural hearing loss. Intervention: All 30 test persons underwent both conventional PTA and in-situ audiometry with four hearing aid models by various manufacturers. Data Collection and Analysis: The differences between conventionally and in-situ measured hearing threshold levels were calculated and evaluated by an exploratory data analysis followed by a sophisticated statistical modeling process. Results: At 500 and 1500 Hz, almost all threshold differences (conventional PTA minus in-situ data) were negative, i.e., in the low to mid frequencies, hearing loss was overestimated by most devices relative to PTA. At 4000 Hz, the majority of differences (7 of 12) were positive, i.e., in the frequency range above 1500 Hz, hearing loss was frequently underestimated. As hearing loss increased (M -> MS -> S), the effect of the underestimation decreased. At 500 and 1500 Hz, Resound devices showed the smallest threshold deviations, followed by Phonak, Starkey, and Oticon instruments. At 4000 Hz, this observed pattern partly disappeared and Starkey and Oticon devices showed a reversed effect with increasing hearing loss (M -> MS -> S). Because of high standard errors for the estimates, only a few explicit rankings of the devices could be established based on significant threshold differences (5% level). Conclusions: Differences between conventional PTA and in-situ threshold levels may be attributed to (1) frequency, (2) device/hearing loss, and (3) calibration/manufacturer effects. Frequency effects primarily resulting in an overestimation of hearing loss by in-situ audiometry in the low and mid frequencies are mainly due to sound drain-off through vents and leaks. Device/hearing loss effects may be due to leakage as well as boundary effects because in-situ audiometry is confined to a limited measurement range. Finally, different calibration approaches may result in different offset levels between PTA and in-situ audiometry calibration. In some cases, the observed threshold differences of up to 10-15 dB may translate to varied hearing aid fittings for the same user depending on how hearing threshold levels were measured."],["dc.description.sponsorship","GN ReSound"],["dc.identifier.doi","10.3766/jaaa.26.1.8"],["dc.identifier.isi","000347763800008"],["dc.identifier.pmid","25597462"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38589"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Acad Audiology"],["dc.relation.issn","2157-3107"],["dc.relation.issn","1050-0545"],["dc.title","A Comparison of Conventional and In-Situ Audiometry on Participants with Varying Levels of Sensorineural Hearing Loss"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Strahlentherapie und Onkologie"],["dc.bibliographiccitation.volume","191"],["dc.contributor.author","Schoetz, U."],["dc.contributor.author","Shnayien, S."],["dc.contributor.author","Kinzel, L."],["dc.contributor.author","Hess, J."],["dc.contributor.author","Zitzelsberger, H."],["dc.contributor.author","Klein, D."],["dc.contributor.author","Jendrossek, V."],["dc.contributor.author","Belka, C."],["dc.contributor.author","Unkel, Steffen"],["dc.contributor.author","Lauber, Kirsten"],["dc.date.accessioned","2018-11-07T09:56:06Z"],["dc.date.available","2018-11-07T09:56:06Z"],["dc.date.issued","2015"],["dc.format.extent","S121"],["dc.identifier.isi","000362544800269"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36897"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Urban & Vogel"],["dc.publisher.place","Munich"],["dc.relation.conference","21st Annual Meeting of the German-Society-for-Radiation-Oncology"],["dc.relation.eventlocation","Hamburg, GERMANY"],["dc.relation.issn","1439-099X"],["dc.relation.issn","0179-7158"],["dc.title","Inherent radioresistance of head and neck squamous cell carcinoma cells: principal component analysis identifies cellular senescence as a crucial driver"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]