Traditional multiplicity adjustment methods in clinical trials

Dmitrienko, Alex; D’Agostino, Ralph B.

doi:10.1002/sim.5990

Cited by 116 publications

(89 citation statements)

References 68 publications

(87 reference statements)

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“…Meningioma subtypes ( n = 175, subtypes with 1–2 cases were excluded from analysis) and tumor localization ( n = 185, one intraventricular tumor was excluded from analysis) were compared using the Kruskal–Wallis test. When the Kruskal-Wallis test was significant, pairwise comparisons between groups were performed using Dunn’s test and the Hommel adjustment (Dmitrienko & D’Agostino, 2013, page 5191) for multiple comparisons and to preserve the familywise error rate. Cox regression was used in both univariable and multivariable survival analyses based on continuous SI-values.…”

Section: Methodsmentioning

confidence: 99%

Expression and clinical value of EGFR in human meningiomas

Arnli

Backer-Grøndahl

Ytterhus

et al. 2017

PeerJ

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BackgroundMeningiomas are common intracranial tumors in humans that frequently recur despite having a predominantly benign nature. Even though these tumors have been shown to commonly express EGFR/c-erbB1 (epidermal growth factor receptor), results from previous studies are uncertain regarding the expression of either intracellular or extracellular domains, cellular localization, activation state, relations to malignancy grade, and prognosis.AimsThis study was designed to investigate the expression of the intracellular and extracellular domains of EGFR and of the activated receptor as well as its ligands EGF and TGFα in a large series of meningiomas with long follow-up data, and investigate if there exists an association between antibody expression and clinical and histological data.MethodsA series of 186 meningiomas consecutively operated within a 10-year period was included. Tissue microarrays were constructed and immunohistochemically analyzed with antibodies targeting intracellular and extracellular domains of EGFR, phosphorylated receptor, and EGF and TGFα. Expression levels were recorded as a staining index (SI).ResultsPositive immunoreactivity was observed for all antibodies in most cases. There was in general high SIs for the intracellular domain of EGFR, phosphorylated EGFR, EGF, and TGFα but lower for the extracellular domain. Normal meninges were negative for all antibodies. Higher SIs for the phosphorylated EGFR were observed in grade II tumors compared with grade I (p = 0.018). Survival or recurrence was significantly decreased in the time to recurrence analysis (TTR) with high SI-scores of the extracellular domain in a univariable survival analysis (HR 1.152, CI (1.036–1.280, p = 0.009)). This was not significant in a multivariable analysis. Expression of the other antigens did not affect survival.ConclusionEGFR is overexpressed and in an activated state in human meningiomas. High levels of ligands also support this growth factor receptor system to be involved in meningioma tumorigenesis. EGFR may be a potential candidate for targeted therapy.

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Section: Methodsmentioning

confidence: 99%

Expression and clinical value of EGFR in human meningiomas

Arnli

Backer-Grøndahl

Ytterhus

et al. 2017

PeerJ

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“…The randomization algorithm is implemented using statistical package SAS 9.2 and modified according to Dmitrienko et al [32]. …”

Section: Methods and Designmentioning

confidence: 99%

Evaluation of efficacy of a new hybrid fusion device: a randomized, two-centre controlled trial

Siewe

Bredow

Oppermann

et al. 2014

BMC Musculoskelet Disord

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BackgroundThe 360° fusion of lumbar segments is a common and well-researched therapy to treat various diseases of the spine. But it changes the biomechanics of the spine and may cause adjacent segment disease (ASD). Among the many techniques developed to avoid this complication, one appears promising. It combines a rigid fusion with a flexible pedicle screw system (hybrid instrumentation, “topping off”). However, its clinical significance is still uncertain due to the lack of conclusive data.Methods/DesignThe study is a randomized, therapy-controlled, two-centre trial conducted in a clinical setting at two university hospitals. If they meet the criteria, outpatients presenting with degenerative disc disease, facet joint arthrosis or spondylolisthesis will be included in the study and randomized into two groups: a control group undergoing conventional fusion surgery (PLIF - posterior lumbar intervertebral fusion), and an intervention group undergoing fusion surgery using a new flexible pedicle screw system (PLIF + “topping off”), which was brought on the market in 2013.Follow-up examination will take place immediately after surgery, after 6 weeks and after 6, 12, 24 and 36 months. An ongoing assessment will be performed every year.Outcome measurements will include quality of life and pain assessments using validated questionnaires (ODI - Ostwestry Disability Index, SF-36™ - Short Form Health Survey 36, COMI - Core Outcome Measure Index). In addition, clinical and radiologic ASD, sagittal balance parameters and duration of work disability will be assessed. Inpatient and 6-month mortality, surgery-related data (e.g., intraoperative complications, blood loss, length of incision, surgical duration), postoperative complications (e.g. implant failure), adverse events, and serious adverse events will be monitored and documented throughout the study.DiscussionNew hybrid “topping off” systems might improve the outcome of lumbar spine fusion. But to date, there is a serious lack of and a great need of convincing data on safety or efficacy, including benefits and harms to the patients, of these systems. Health care providers are particularly interested in such data as these implants are much more expensive than conventional implants. In such a case, randomized clinical trials are the best way to evaluate benefits and risks.Trial registrationNCT01852526

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“…Here the type 1 error rate is kept under α because this is an example of an intersection-union test (Dmitrienko and D'Agostino, 2013). Then, at the approximate confidence level of (1 − α), we can conclude that…”

Section: Approximate Linearized Inequalitiesmentioning

confidence: 99%