The new European Medicines Agency guideline on antidepressants: a guide for researchers and drug developers.

According to the World Health Organization (WHO), depressive disorders are currently considered as one of the most disabling medical conditions in the world with one of the highest disability-adjusted life years [1] and this situation has apparently been further worsened during the COVID-19 pandemic [2]. Up to two thirds of patients with major depressive disorders (MDD) do not achieve full remission following an adequate first line standard of care and/or experience residual symptoms such as anxiety, impaired cognition, fatigue, sleep disturbance, or anhedonia [3]. Several attempts are often needed to find the most suitable treatment [4].

Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With and Polymorphisms.

Background: Dose requirements of vitamin K antagonists are associated with and , but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear.

Methods: Aim was to scrutinize phenprocoumon dose requirements, dose stability and anticoagulation quality in association to and in a natural cohort of elderly primary care patients.

Disentangling estimands and the intention-to-treat principle.

Randomized controlled trials (RCTs) aim at providing reliable estimates of treatment benefit. Missing data and nonadherence to treatment are distinct problems that can substantially impede this task. In practice, the fact that the handling of missing data due to nonadherence affects the question that is addressed is often ignored.

Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial.

Background: Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels.

Choosing Appropriate Estimands in Clinical Trials.

Lack of adherence to study protocol and missing data are often unavoidable in clinical trials, and both increase the need to differentiate between the ideal treatment effect if the medication is taken as directed and the treatment effect in presence of the actual adherence pattern. In this regard, estimands have become the focus of attention. An estimand is simply that which is being estimated.

Estimation of the treatment effect in the presence of non-compliance and missing data.

Treatment non-compliance and missing data are common problems in clinical trials. Non-compliance is a broad term including any kind of deviation from the assigned treatment protocol, such as dose modification, treatment discontinuation or switch, often resulting in missing values. Missing values and treatment non-compliance may bias study results.

A new location-scale test based on a combination of the ideas of Levene and Lepage.

Lepage's test combines the Wilcoxon rank-sum and the Ansari-Bradley statistics. We propose to replace the latter statistic by a Wilcoxon rank-sum calculated after Levene's transformation. We use the medians for this transformation, i.