Empirische Begleitung der einwilligungsfreien Teilnahme an medizinischer Forschung unter Einbeziehung des Begriffs der Datenspende

Technologisch induziert ist der Begriff „Big Data“ ins Zentrum der Diskussion datenreicher Forschung in der Medizin gerückt. An der Erhebung, Verarbeitung und Nutzung großer heterogener Datenmengen sind viele Akteure beteiligt, neben Forschungsinstitutionen Einrichtungen der Krankenversorgung und der öffentlichen Gesundheit.Die Verfügbarkeit reichhaltiger Daten ist nicht nur eine unabdingbare Voraussetzung für die Förderung von Translation und Personalisierung als wesentliche Ziele medizinischer Forschung, sie sorgt auch für die notwendige Evidenzbasis für Maßnahmen der öffentlichen Gesundheit (Public Health). Initiativen weltweit arbeiten an technischen und organisatorischen Lösungen zur Verfügbarkeit von Daten aus unterschiedlichen Versorgungskontexten. Dabei hat sich die breite Einwilligung in eine zeitlich und thematisch wenig eingegrenzte Datennutzung (Broad Consent) als Rechtsgrundlage durchgesetzt.Vor dem Hintergrund wachsender Bereitschaft von Patienten und großer Teile der Bevölkerung, durch eigene Gesundheitsdaten zur Forschung beizutragen, hat sich in Deutschland die Diskussion um die sogenannte „Datenspende“ entwickelt - verstanden als (einwilligungsfreie) gesetzliche Erlaubnis zur Datennutzung durch die Forschung, verbunden mit der Möglichkeit zum Widerspruch. Ziel war es, empirisch belegte Bedingungen und Gestaltungselemente herauszuarbeiten, die für die Akzeptanz der Datenspende von zentraler Bedeutung sind. Die Ergebnisse deuten darauf hin, dass die Datenspende für die medizinische Forschung, umgesetzt als Kombination aus einem Rechtsanspruch und einem einfach auszuübenden Recht auf ein Opt-out, von deutschen Patienten weitgehend unterstützt wird. Besonderes Augenmerk erfordert das beobachtete Mißtrauen gegenüber der Datennutzung zur Forschung durch kommerzielle Unternehmen

Consent to research participation: understanding and motivation among German pupils

Background The EU's 2006 Paediatric Regulation aims to support authorisation of medicine for children, thus effectively increasing paediatric research. It is ethically imperative to simultaneously establish procedures that protect children's rights. Method This study endeavours (a) to evaluate whether a template consent form designed by the Standing Working Group of the German-Research-Ethics-Committees (AKEK) adequately informs adolescents about research participation, and (b) to investigate associated phenomena like therapeutic misconception and motives for research participation. In March 2016 a questionnaire study was conducted among 279 pupils (mean age 13.1 years) of a secondary school in northern Germany. Results A majority of participants showed a general good understanding of foundational research ethics concepts as understood from the AKEK consent form. Nevertheless, our data also suggests possible susceptibility to therapeutic misconception. Own health concerns and pro-social considerations were found to be significant motivational factors for participating in research, while anticipation of pain lessens likelihood of participation. Advice from trusted others is an important decisional influence, too. Furthermore, data security was found to be a relevant aspect of adolescents' decision-making process. Conclusion Bearing in mind adolescents' generally good understanding, we infer the lack of knowledge about medical research in general to be one source of therapeutic misconception. To further improve the quality of consent we propose a multi-staged approach whereby general research education is completed before an individual becomes a patient or potential participant. To the best of our knowledge this is the first German questionnaire-study addressing issues of informed consent in a large under-age sample

Standard values and relationship-specific validity of the Bielefeld Relationship Expectations Questionnaire (BFPE)

<p>Abstract</p> <p>Background</p> <p>The Bielefeld Partnership Expectations Questionnaire (BFPE) is a tool to assess attachment in the romantic relationships of adults. The attachment styles are operationalized as configuration patterns of scale scores. While convergent validity has already been investigated, discriminant validity is still lacking confirmation.</p> <p>Methods</p> <p>The present sample (n = 1509) is representative for the German population aged 18 to 50. The mean age was 34.6 years. Most of the participants lived in a relationship (77.3 %). Discriminant validity was analyzed using a marital quality questionnaire (PFB), a social support questionnaire (F-Soz-U K-14), and a life satisfaction questionnaire (FLZ).</p> <p>Results</p> <p>All the BFPE scales have a satisfying internal consistency between r = .79 and .86. Those individuals who showed a secure pattern, i.e. increased "Readiness for Self-Disclosure" and "Conscious Need for Care" as well as reduced "Fear of Rejection" experienced their partner as socially supportive, reported higher marital quality in all of its facets, and were more satisfied within the life-domains "family/children" and "relationship/sexuality". Standard values for each scale are presented.</p> <p>Conclusions</p> <p>The BFPE has repeatedly been verified as a short, reliable, and valid instrument applicable to research practice with healthy individuals as well as within clinical contexts.</p

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

Internationale Klausurwoche: „Neue ethische Herausforderungen in der datenreichen Forschungsmedizin: ein Ländervergleich“

Ensemble-based uncertainty quantification and global sensitivity analysis of environmental models requires generating large ensembles of parameter-sets. This can already be difficult when analyzing moderately complex models based on partial differential equations because many parameter combinations cause an implausible model behavior even though the individual parameters are within plausible ranges. In this work, we apply Gaussian Process Emulators (GPE) as surrogate models in a sampling scheme. In an active-training phase of the surrogate model, we target the behavioral boundary of the parameter space before sampling this behavioral part of the parameter space more evenly by passive sampling. Active learning increases the subsequent sampling efficiency, but its additional costs pay off only for a sufficiently large sample size. We exemplify our idea with a catchment-scale subsurface flow model with uncertain material properties, boundary conditions, and geometric descriptors of the geological structure. We then perform a global-sensitivity analysis of the resulting behavioral dataset using the active-subspace method, which requires approximating the local sensitivities of the target quantity with respect to all parameters at all sampled locations in parameter space. The Gaussian Process Emulator implicitly provides an analytical expression for this gradient, thus improving the accuracy of the active-subspace construction. When applying the GPE-based preselection, 70–90% of the samples were confirmed to be behavioral by running the full model, whereas only 0.5% of the samples were behavioral in standard Monte-Carlo sampling without preselection. The GPE method also provided local sensitivities at minimal additional costs

Dead in the Water: The Vicious Cycle of Blanks During Natural Level 14 C Manipulation of Marine Algal Cultures

Authentic biomarker standards were obtained from algal cultures in an attempt to accurately determine blank C added during sample processing for compound-specific radiocarbon analysis. Emiliania huxleyi and Thalassiosira pseudonana were grown under manipulated Delta C- 14 dissolved inorganic carbon (DIC) levels and chlorophyll a and either alkenones (E. huxleyi) or low molecular weight (LMW) alkanoic acids (T pseudonana) were isolated from the respective biomass using preparative liquid chromatography (LC), wet chemical techniques or preparative gas chromatography, respectively. (DIC)-C- 14 in the seawater medium was determined pre- and post-growth. Biomarker Delta C- 14 values mostly agree within 1 sigma or 2 sigma analytical uncertainties. In those cases where biomarker Delta C- 14 values differ significantly, chlorophyll a is up to 104% more C-14-depleted than alkenones or LMW alkanoic acids, consistent with a larger LC blank compared to the other purification methods. However, in the majority of experimental setups pre- and post-growth DIC Delta C-14 values seem to be compromised by an unknown and variable blank C contribution. DIC Delta C-14 values deviate strongly from the anticipated Delta C- 14 values (by up to ca. 560 parts per thousand, pre- and post-growth Delta C- 14 values differ significantly (by up to ca. 460 parts per thousand, and changes are not unidirectional. Accordingly, since the substrate Delta C- 14 value cannot unequivocally be constrained, blank C contributions for the different biomarker purification methods cannot be accurately calculated. This study illustrates the challenges and problems of producing authentic standards that are not readily commercially available and exemplifies how a laborious and time-consuming culturing approach may enter a vicious cycle of blank C contamination hampering accurate blank C determination

Secondary use of health care data and left-over biosamples within the ‘Medical Informatics Initiative’ (MII): a quasi-randomized controlled evaluation of patient perceptions and preferences regarding the consent process

Background Data collected during routine health care and ensuing analytical results bear the potential to provide valuable information to improve the overall health care of patients. However, little is known about how patients prefer to be informed about the possible usage of their routine data and/or biosamples for research purposes before reaching a consent decision. Specifically, we investigated the setting, the timing and the responsible staff for the information and consent process. Methods We performed a quasi-randomized controlled trial and compared the method by which patients were informed either in the patient admission area following patient admission by the same staff member (Group A) or in a separate room by another staff member (Group B). The consent decision was hypothetical in nature. Additionally, we evaluated if there was the need for additional time after the information session and before taking the consent decision. Data were collected during a structured interview based on questionnaires where participants reflected on the information and consent process they went through. Results Questionnaire data were obtained from 157 participants in Group A and 106 participants in Group B. Overall, participants in both groups were satisfied with their experienced process and with the way information was provided. They reported that their (hypothetical) consent decision was freely made. Approximately half of the interested participants in Group B did not show up in the separate room, while all interested participants in Group A could be informed about the secondary use of their routine data and left-over samples. No participants, except for one in Group B, wanted to take extra time for their consent decision. The hypothetical consent rate for both routine data and left-over samples was very high in both groups. Conclusions The willingness to support medical research by allowing the use of routine data and left-over samples seems to be widespread among patients. Information concerning this secondary data use may be given by trained administrative staff immediately following patient admission. Patients mainly prefer making a consent decision directly after information is provided and discussed. Furthermore, less patients are informed when the process is organized in a separate room