The effect of estimating prevalences on the population-wise error rate.

The population-wise error rate is a type I error rate for clinical trials with multiple target populations. In such trials, a treatment is tested for its efficacy in each population. The population-wise error rate is defined as the probability that a randomly selected, future patient will be exposed to an inefficient treatment based on the study results.

Adaptive Multiple Comparisons With the Best.

Subset selection methods aim to choose a nonempty subset of populations including a best population with some prespecified probability. An example application involves location parameters that quantify yields in agriculture to select the best wheat variety. This is quite different from variable selection problems, for instance, in regression.

Effectiveness of a peer-supported crisis intervention to reduce the proportion of compulsory admissions in acute psychiatric crisis interventions in an outreach and outpatient setting: study protocol for an exploratory cluster randomised trial combined with qualitative methods.

Introduction: Compulsory admissions are associated with feelings of fear, humiliation and powerlessness. The number of compulsory admissions in Germany and other high-income countries has increased in recent years. Peer support has been shown to increase the self-efficacy of individuals with mental health conditions in acute crises and to reduce the use of coercive measures in clinical settings.

An exhaustive ADDIS principle for online FWER control.

In this paper, we consider online multiple testing with familywise error rate (FWER) control, where the probability of committing at least one type I error will remain under control while testing a possibly infinite sequence of hypotheses over time. Currently, adaptive-discard (ADDIS) procedures seem to be the most promising online procedures with FWER control in terms of power. Now, our main contribution is a uniform improvement of the ADDIS principle and thus of all ADDIS procedures.

Simultaneous confidence intervals for an extended Koch-Röhmel design in three-arm non-inferiority trials.

Three-arm 'gold-standard' non-inferiority trials are recommended for indications where only unstable reference treatments are available and the use of a placebo group can be justified ethically. For such trials, several study designs have been suggested that use the placebo group for testing 'assay sensitivity', that is, the ability of the trial to replicate efficacy. Should the reference fail in the given trial, then non-inferiority could also be shown with an ineffective experimental treatment and hence becomes useless.

Discussion on "Optimal test procedures for multiple hypotheses controlling the familywise expected loss" by Willi Maurer, Frank Bretz, and Xiaolei Xun.

This comment builds on the familywise expected loss (FWEL) framework suggested by Maurer, Bretz, and Xun in 2022. By representing the populationwise error rate (PWER) as FWEL, it is illustrated how the FWEL framework can be extended to clinical trials with multiple and overlapping populations and the PWER can be generalized to more general losses. The comment also addresses the question of how to deal with midtrial changes in the posttrial risks and related losses that are caused by data-driven decisions.

How to avoid concerns with the interpretation of two primary endpoints if significant superiority in one is sufficient for formal proof of efficacy.

Formal proof of efficacy of a drug requires that in a prospective experiment, superiority over placebo, or either superiority or at least non-inferiority to an established standard, is demonstrated. Traditionally one primary endpoint is specified, but various diseases exist where treatment success needs to be based on the assessment of two primary endpoints. With co-primary endpoints, both need to be "significant" as a prerequisite to claim study success.

Effectiveness and costs of a low-threshold hearing screening programme () for individuals with intellectual disabilities: protocol for a screening study.

Introduction: Individuals with intellectual disabilities (ID) often suffer from hearing loss, in most cases undiagnosed or inappropriately treated. The implementation of a programme of systematic hearing screening, diagnostics, therapy initiation or allocation and long-term monitoring within the living environments of individuals with ID (nurseries, schools, workshops, homes), therefore, seems beneficial.

Methods And Analysis: The study aims to assess the effectiveness and costs of a low-threshold screening programme for individuals with ID.

Smartphone-assisted training with education for patients with hip and/or knee osteoarthritis (SmArt-E): study protocol for a multicentre pragmatic randomized controlled trial.

Introduction: Hip and knee osteoarthritis are associated with functional limitations, pain and restrictions in quality of life and the ability to work. Furthermore, with growing prevalence, osteoarthritis is increasingly causing (in)direct costs. Guidelines recommend exercise therapy and education as primary treatment strategies.

COVID-19 in German Nursing Homes: The Impact of Facilities' Structures on the Morbidity and Mortality of Residents-An Analysis of Two Cross-Sectional Surveys.

The COVID-19 pandemic constitutes an exceptional risk to people living and working in nursing homes (NHs). There were numerous cases and deaths among NH residents, especially at the beginning of the pandemic when no vaccines had yet been developed. Besides regional differences, individual NHs showed vast differences in the number of cases and deaths: while in some, nobody was affected, in others, many people were infected or died.

The population-wise error rate for clinical trials with overlapping populations.

We introduce a new multiple type I error criterion for clinical trials with multiple, overlapping populations. Such trials are of interest in precision medicine where the goal is to develop treatments that are targeted to specific sub-populations defined by genetic and/or clinical biomarkers. The new criterion is based on the observation that not all type I errors are relevant to all patients in the overall population.

Single-stage, three-arm, adaptive test strategies for non-inferiority trials with an unstable reference.

For indications where only unstable reference treatments are available and use of placebo is ethically justified, three-arm "gold standard" designs with an experimental, reference and placebo arm are recommended for non-inferiority trials. In such designs, the demonstration of efficacy of the reference or experimental treatment is a requirement. They have the disadvantage that only little can be concluded from the trial if the reference fails to be efficacious.

Blinded sample size re-estimation in a comparative diagnostic accuracy study.

Background: The sample size calculation in a confirmatory diagnostic accuracy study is performed for co-primary endpoints because sensitivity and specificity are considered simultaneously. The initial sample size calculation in an unpaired and paired diagnostic study is based on assumptions about, among others, the prevalence of the disease and, in the paired design, the proportion of discordant test results between the experimental and the comparator test. The choice of the power for the individual endpoints impacts the sample size and overall power.

A multiple testing framework for diagnostic accuracy studies with co-primary endpoints.

Major advances have been made regarding the utilization of machine learning techniques for disease diagnosis and prognosis based on complex and high-dimensional data. Despite all justified enthusiasm, overoptimistic assessments of predictive performance are still common in this area. However, predictive models and medical devices based on such models should undergo a throughout evaluation before being implemented into clinical practice.

Sociodemographic aspects and health care-related outcomes: a latent class analysis of informal dementia care dyads.

Background: Studies revealed the importance to assess dementia care dyads, composed of persons with dementia and their primary informal caregivers, in a differentiated way and to tailor support services to particular living and care circumstances. Therefore, this study aims first to identify classes of dementia care dyads that differ according to sociodemographic, care-related and dementia-specific characteristics and second, to compare these classes with regard to healthcare-related outcomes.

Methods: We used data from the cross-sectional German DemNet-D study (n = 551) and conducted a latent class analysis to investigate different classes of dementia care dyads.

Efficient Adaptive Designs for Clinical Trials of Interventions for COVID-19.

The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible.

Assessing consistency in clinical trials with two subgroups and binary endpoints: A new test within the logistic regression model.

In late stage drug development, the experimental drug is tested in a diverse study population within the relevant indication. In order to receive marketing authorization, robust evidence for the therapeutic efficacy is crucial requiring investigation of treatment effects in well-defined subgroups. Conventionally, consistency analyses in subgroups have been performed by means of interaction tests.

[Older patients' involvement in research (INVOLVE-Clin): a study protocol].

Introduction: Patient involvement in health research is an integral part of health care in many countries. It promotes the relevance and quality of research and increases the meaningfulness of research results. Meanwhile, the value of patient involvement has also been recognised in Germany.

Parameter Optimization in High-Throughput Testing for Structural Materials.

High-throughput screenings are established evaluation methods in the development of functional materials and pharmaceutical active ingredients. The transfer of this approach to the development of structural materials requires extensive adaptations. In addition to the investigation of new test procedures for the determination of material properties and the treatment of metallic materials, the design of experiments is a research focus.

Simultaneous confidence intervals for ratios with application to the gold standard design with more than one experimental treatment.

Considering a study design with two experimental treatments, a reference treatment and a placebo, we extend a previous approach considering the ratios of effects to a procedure for analyzing multiple ratios. The technical framework for constructing tests and compatible simultaneous confidence intervals is set in a general manner. Besides a single step procedure and its extension to a stepdown procedure, also, an informative stepwise procedure in the spirit of our previous work is developed.

Testing multiple dose combinations in clinical trials.

Drug combination trials are often motivated by the fact that individual drugs target the same disease but via different routes. A combination of such drugs may then have an overall better effect than the individual treatments which has to be verified by clinical trials. Several statistical methods have been explored that discuss the problem of comparing a fixed-dose combination therapy to each of its components.

Evaluation of multiple prediction models: A novel view on model selection and performance assessment.

Model selection and performance assessment for prediction models are important tasks in machine learning, e.g. for the development of medical diagnosis or prognosis rules based on complex data.

New stains for anterior capsule surgery.

Purpose: To investigate whether new dyes and dye combinations can give equivalent or better staining in anterior capsule surgery than existing dyes with a low degree of toxicity on relevant cells.

Setting: University laboratory of Jacobs University Bremen, Germany.

Design: Laboratory experimental study.

Comparison of different approaches for dose response analysis.

Characterizing an appropriate dose-response relationship and identifying the right dose in a clinical trial are two main goals of early drug-development. MCP-Mod is one of the pioneer approaches developed within the last 10 years that combines the modeling techniques with multiple comparison procedures to address the above goals in clinical drug development. The MCP-Mod approach begins with a set of potential dose-response models, tests for a significant dose-response effect (proof of concept, PoC) using multiple linear contrasts tests and selects the "best" model among those with a significant contrast test.