Unkel, Steffen

[["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.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"]]