Lillian Geza Rothenberger

Research across the disciplines: a road map for quality criteria in empirical ethics research

BackgroundResearch in the field of Empirical Ethics (EE) uses a broad variety of empirical methodologies, such as surveys, interviews and observation, developed in disciplines such as sociology, anthropology, and psychology. Whereas these empirical disciplines see themselves as purely descriptive, EE also aims at normative reflection. Currently there is literature about the quality of empirical research in ethics, but little or no reflection on specific methodological aspects that must be considered when conducting interdisciplinary empirical ethics. Furthermore, poor methodology in an EE study results in misleading ethical analyses, evaluations or recommendations. This not only deprives the study of scientific and social value, but also risks ethical misjudgement.DiscussionWhile empirical and normative-ethical research projects have quality criteria in their own right, we focus on the specific quality criteria for EE research. We develop a tentative list of quality criteria – a “road map” – tailored to interdisciplinary research in EE, to guide assessments of research quality. These quality criteria fall into the categories of primary research question, theoretical framework and methods, relevance, interdisciplinary research practice and research ethics and scientific ethos.SummaryEE research is an important and innovative development in bioethics. However, a lack of standards has led to concerns about and even rejection of EE by various scholars. Our suggested orientation list of criteria, presented in the form of reflective questions, cannot be considered definitive, but serves as a tool to provoke systematic reflection during the planning and composition of an EE research study. These criteria need to be tested in different EE research settings and further refined.

Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases

Due to the new European regulations for pediatric medications, future clinical trials will include an increasing number of minors. It is therefore important to reconsider and evaluate recent methodological and ethical aspects of clinical trials in minors.

Biomarkers in Child Mental Health: a bio-psycho-social perspective is needed.

© 2015 Rothenberger et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Rethinking the past There is still an increasing interest in biomarkers in (child) psychiatry although some disappointment took place within the last decades for those who expected simplistic solutions. For example, the Dexamethasone Suppression Test (DST) showed initial promise to diagnose endogeneous depression, drug response and clinical relapse, but finally it was of limited clinical value and abandoned [1]. The same holds true for former expectations to find a certain gene for a certain mental health disorder and treat it by genetic therapy. Fortunately, neurobiological research in psychiatry has overcome such simplistic models. Meanwhile our scientific knowledge has increased tremendously and we discuss the highly complex pathophysiological background of mental disorders on a broad empirical basis. Hence, to find biomarkers of clinical utility we should rethink our approach. Not only a fresh and critical look at the biological underpinnings of mental disorders is recommended, but also one should take into account aspects of their interaction with environment and translation into patient care. There are many papers just comparing people with typical development with a group of psychiatric patients to report an association between one parameter or several single biological parameters (e.g. genes, brain oscillations, cortisol, oxytocin, BDNF, event-related potentials, fMRI regions) and the disorder. They frequently conclude that the investigated parameter “may be a promising biomarker” [2, 3, 4]. This approach is more or less on the wrong track, if no further steps for testing the validity of the biomarkers are undertaken, as is rarely the case. Especially, things become more challenging when developmental aspects have to be added in studies with minors. In order to understand why earlier research paved such a simplistic way one should go back to the point where and how the idea of biomarkers in psychiatry was promoted. Since decades psychiatrists are trying to elucidate the biological underpinnings and neuroscientific dynamics of mental disorders in children (e.g. [5, 6]). This approach is still valid and should be followed further in parallel to the research on the objectives related to biomarkers. With the advent of new technologies like brain mapping, neuroimaging, genetics, epigenetics, proteomics, neurotransmitters, metabolic assessment, neuropsychology, brain-computer-interface, many researchers and clinicians expressed the hope to advance the field by developing a biologically guided psychiatric classification, diagnostic system and treatment recommendation [1, 7]. In other words, a paradigm shift in psychiatry with a promise of rescuing the validity of symptom based psychiatric diagnosis through its link to the pathophysiology of mental disorders. However, so far, the limited robust facts did not allow for implementing such an approach into DSM-V. Moreover, Peterson [8] stated that the NIMH promoted Research Domain Criteria (RDoC), i.e. a mechanistically and neurobiologically oriented new approach to psychiatric nosology, is still “premature, ... theoretically problematic and its measures psychometrically untested”. Thus “it seems unlikely that a single RDoC domain validly represents a single link in the causal pathway from genes to behavior.” Hence, it can hardly be expected that related biomarkers will be clinically more relevant than those related to DSM-V categories and the intrinsic dimensions.

Psychopharmacological treatment in children: always keeping an eye on adherence and ethics

Within the last few years, several psychopharmaca, formerly used off-label, received an on-label status for drug treatment in Child and Adolescent Psychiatry (CAP) (e.g., fluoxetine, fluvoxamine, risperidone), but beyond that new options were quite rare (e.g., aripiprazole and melatonin; [1–3]). Also, publications on child and adolescent psychopharmacology in ECAP usually included information on single studies and reviews concerning well-known substances such as haloperidol and other neuroleptics, stimulants, atomoxetine, fluoxetine, and other SSRIs [4]. In 2011, such kind of articles presented 8.5 % (excluding a supplement on an observational trial on a methylphenidate-ER preparation [5]) and in 2012, there appeared 7 % of the ECAP papers on that topic. The content of most of these 2011/2012 publications reflects special aspects of psychopharmacological treatment, where management of adverse effects plays the major role (e.g., [6, 7]) besides quality of life, satisfaction with treatment, and adherence (e.g., [8]). The off-label use of psychopharmaca in children and adolescents is still a matter of debate either with the focus on indication or age or both. Therefore, it is welcome that Dorks et al. [9] inform us about the antidepressant drug use and off-label prescribing in children and adolescents in Germany. They report retrospectively from a large-scale population based cohort study and analyzed cross-sectional data from four German statutory health insurances (comprising about 17 % of the population from all regions in Germany; making up 2,599,685 patients up to 17 years of age). Although the prescription of SSRIs increased slowly from the 2004 to the 2006 cohort, the prescription behavior of physicians seems to reflect good clinical practice, since the use of St. Johns Wort and tricyclic antidepressants decreased. Also, prescribing antidepressants seems to be similar all over Europe, which underlines the process of harmonization in European CAP. However, the authors stated, ‘‘that more than 50 % of children and adolescents received only a single prescription of antidepressants’’. Also, a British Study [10] reported ‘‘more than 50 % discontinued treatment after two months’’. Further, ‘‘around half of all antidepressant prescriptions were off-label with respect to age or indication’’ in the Dorks et al. [9] study, but the off-label use was mostly guided by a specialist and those SSRIs were used which were recommended by clinical guidelines and/or received official on-label qualification later on. The report of Dorks et al. [9] touches another highly important problem in childhood psychopharmacotherapy, namely, how can we improve adherence to guarantee adequate drug treatment? This topic was already reviewed and discussed in ECAP earlier [11]. The author states that ‘‘adherence is the single most modifiable factor associated with treatment outcome ... the best treatment is rendered useless if not adhered to’’. In order to explore this field further, Roedelof et al. [12] investigated the treatment engagement in adolescents with severe psychiatric problems. The authors tried to answer the question how to get the highest profit possible from an evidence-based treatment applied in clinical practice. Using the Treatment Engagement Rating Scale and longitudinal latent class A. Rothenberger (&) Child and Adolescent Psychiatry, University Medical Center Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany e-mail: arothen@gwdg.de