Setting clinical performance specifications to develop and evaluate biomarkers for clinical use

Background: Biomarker discovery studies often claim ‘promising’ findings, motivating further studies and marketing as medical tests. Unfortunately, the patient benefits promised are often inadequately explained to guide further evaluation, and few biomarkers have translated to improved patient care. We present a practical guide for setting minimum clinical performance specifications to strengthen clinical performance study design and interpretation. Methods: We developed a step-by-step approach using test evaluation and decision-analytic frameworks and present with illustrative examples. Results: We define clinical performance specifications as a set of criteria that quantify the clinical performance a new test must attain to allow better health outcomes than current practice. We classify the proposed patient benefits of a new test into three broad groups and describe how to set minimum clinical performance at the level where the potential harm of false-positive and false-negative results does not outweigh the benefits. (1) For add-on tests proposed to improve disease outcomes by improving detection, define an acceptable trade-off for false-positive versus true-positive results; (2) for triage tests proposed to reduce unnecessary tests and treatment by ruling out disease, define an acceptable risk of false-negatives as a safety threshold; (3) for replacement tests proposed to provide other benefits, or reduce costs, without compromising accuracy, use existing tests to benchmark minimum accuracy levels. Conclusions: Researchers can follow these guidelines to focus their study objectives and to define statistical hypotheses and sample size requirements. This way, clinical performance studies will allow conclusions about whether test performance is sufficient for intended use

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Strategische Ausrichtung bedeutender Anbieter von Internetplattformen

Google, Apple, Facebook und Amazon (kurz: GAFA) stehen bereits seit einiger Zeit im Fokus der öffentlichen Debatte. Gemeinsam ist diesen vier Konzernen, dass sie global agieren und ihre Geschäftstätigkeit weit über ihre ursprünglichen Geschäftsfelder hinaus ausgedehnt haben. Die strategische Weiterentwicklung erfolgte jeweils ausgehend von einem zentralen profitablen Kerngeschäft und nicht als planlose Diversifikation. Weiterhin zeichnen sich die erfolgreichen Internetkonzerne dadurch aus, dass sie die Möglichkeiten für Economies of Scale und Scope, die die Datenökonomie eröffnet, zu nutzen verstehen. Der vorliegende Diskussionsbeitrag untersucht diese strategische Diversifikation und die Integration verschiedener Schritte der Wertschöpfung innerhalb der Datenökonomie am Beispiel der vier Konzerne und richtet den Blick dabei auch auf wahrscheinliche zukünftige Entwicklungen. Die Analyse der bisherigen Strategien der GAFA-Unternehmen anhand des Data Value Circle(DVC), der datengetriebene Wertschöpfung als zirkulare und nicht klassisch linerare Schritte beschreibt, hat gezeigt, dass sich alle vier Unternehmen über alle Schritte hinweg diversifiziert haben. Nach wie vor steuert bei allen das ehemalige Kerngeschäft, das einen engen Kontakt zum Endkunden aufweist, den größten Anteil des Umsatzes bei. Deshalb ist es strategisch für diese Unternehmen wichtig, die Kundenschnittstelle sowohl mit Endgeräten als auch mit Dienstleistungen nachhaltig zu besetzen. Die daraus entstehende Gatekeeper-Position ermöglicht es den Unternehmen darüber hinaus, andere Nutzerrollen innerhalb ihrer Plattformdienste zu monetisieren. Das dritte Kapitel analysiert vor diesem Hintergrund die Patente der GAFA-Unternehmen in Bezug auf die Weiterentwicklung der direkten Kundeninteraktion. Es konnten 283.978 relevante Patente im Zeitraum von der jeweiligen Unternehmensgründung bis heute extrahiert werden. Des Weiteren wurden 513 Unternehmenszusammenschlüsse bzw. -übernahmen der vier Konzerne ebenfalls einer näheren Betrachtung unterzogen. Es konnte gezeigt werden, dass alle vier hier betrachteten Unternehmen ihre Akquisitions- und Innovationsaktivitäten in den Bereichen Sprachassistenten sowie AR und VR in den letzten Jahren merklich aufgestockt haben. Im Anschluss daran wurden die Entwicklungen im Bereich Sprachassistenz sowie Virtual und Augmented Reality anhand konkreter Beispiele von Endgeräten und Diensten in den genannten Technologiebereichen betrachtet. Es wurden die verschiedenen Geschäftsstrategien der GAFA-Unternehmen, die vermutlich dazu dienen, langfristig das Kerngeschäft, also den direkten Kundenkontakt und damit auch entscheidende Gatekeeperpositionen zu besetzen, aufgezeigt und diskutiert. Die Analyse wurde durch den Einbezug von Konkurrenzprodukten und -diensten ergänzt. Abschließend wurden die Erkenntnisse in potentielle wettbewerbliche und regulatorische Fragestellungen bzw. Handlungsfelder eingeordnet.Google, Apple, Facebook and Amazon (GAFA) have been the focus of public debate for some time. What these four companies have in common is that they operate globally and have expanded their business activities far beyond their original fields of business. Their strategic development has always been based on a profitable core business and not on random diversification. The successful internet companies are also distinguished by their ability to exploit the opportunities for economies of scale and scope that the data economy opens up. This discussion paper examines this strategic diversification and the integration of different steps of value creation within the data economy using the example of the four companies and also looks at probable future developments. The analysis of the previous strategies of the GAFA companies using the Data Value Circle(DVC), which describes data-driven value creation as circular and not classically linear steps, has shown that all four companies have diversified across all steps. The former core business, which has close contact to the end customer, continues to account for the largest share of sales. It is therefore strategically important for these companies to sustainably occupy the customer interface with both end devices and services. The resulting gatekeeper position also enables the companies to monetize other user roles within their platform services. Against this background, the third chapter analysed the patents of the GAFA companies with regard to the further development of direct customer interaction. It was possible to extract 283,978 relevant patents in the period from the respective company's foundation until today. In addition, 513 mergers and acquisitions of the four groups were also examined more closely. It could be shown that all four companies considered here have significantly increased their acquisition and innovation activities in the fields of voice assistants as well as AR and VR in recent years. Subsequently, the developments in the field of voice assistance as well as virtual and augmented reality were examined on the basis of concrete examples of terminals and services in the mentioned technology areas. The different business strategies of the GAFA companies, which presumably serve to fill the core business in the long run, i.e. direct customer contact and thus also decisive customer positions, were shown and discussed. The analysis was supplemented by the inclusion of competing products and services. Finally, the findings were classified into potential competitive and regulatory issues and fields of action

Online Attention Bias Modification for Obsessive-Compulsive Disorder: A Randomized Controlled Trial

There is evidence that attention bias modification trainings (ABMT) based on the dot-probe task are a promising therapeutic approach for several anxiety disorders. However, little is known about the malleability of attention bias in obsessive-compulsive disorder (OCD) and its impact on OCD symptoms. The present study tested this hypothesis using an online ABMT designed to train attention away from OCD-related stimuli. We hypothesized that ABMT would reduce attention bias and OCD symptoms. Participants were randomized to receive the active ABMT (n = 58) or a placebo control training (PCT; n = 50) and completed a minimum of 8 training sessions over a period of 4 weeks. As predicted, participants receiving ABMT showed a significant reduction in attention bias. This effect was not present in the placebo condition. ABMT did however not significantly outperform the PCT with regard to symptom reduction. In both conditions self-reported OCD symptoms decreased and the reduction of symptoms remained stable at 1-month follow-up. The present findings suggest that online ABMT can effectively reduce attention bias in OCD, but question its effectiveness in reducing OCD symptoms. More research on the mechanisms of attention training is inevitably needed before online ABMT can be recommended for clinical application

Online Attention Bias Modification for Obsessive-Compulsive Disorder: A Randomized Controlled Trial

There is evidence that attention bias modification trainings (ABMT) based on the dot-probe task are a promising therapeutic approach for several anxiety disorders. However, little is known about the malleability of attention bias in obsessive-compulsive disorder (OCD) and its impact on OCD symptoms. The present study tested this hypothesis using an online ABMT designed to train attention away from OCD-related stimuli. We hypothesized that ABMT would reduce attention bias and OCD symptoms. Participants were randomized to receive the active ABMT (n = 58) or a placebo control training (PCT; n = 50) and completed a minimum of 8 training sessions over a period of 4 weeks. As predicted, participants receiving ABMT showed a significant reduction in attention bias. This effect was not present in the placebo condition. ABMT did however not significantly outperform the PCT with regard to symptom reduction. In both conditions self-reported OCD symptoms decreased and the reduction of symptoms remained stable at 1-month follow-up. The present findings suggest that online ABMT can effectively reduce attention bias in OCD, but question its effectiveness in reducing OCD symptoms. More research on the mechanisms of attention training is inevitably needed before online ABMT can be recommended for clinical application

Fish fauna in Iberian Mediterranean river basins: biodiversity, introduced species and damming impacts

1. A basin approximation was used to analyse distribution patterns of different components of biodiversity (taxonomic richness, endemicity, taxonomic singularity, rarity) and conservation status of freshwater fish fauna in 27 Mediterranean Iberian rivers. 2. Basin area alone explained more than 80% of variation in native species richness. Larger basins featured not only a higher number of native species, but also more endemic and rare species and fewer diversified genera than smaller basins. 3. In contrast, smaller basins scored higher community conservation values, owing to their lower degree of invasion by introduced species. 4. The presence of dams was the most important factor determining the conservation status of fish communities, and it was also positively associated with the number of introduced species. 5. While the most important components of Iberian freshwater fish biodiversity are located in large basins, small unregulated basins feature better conserved fish communities.Peer reviewe