Over the past decade, artificial intelligence (AI) methods in pathology have advanced substantially. However, integration into routine clinical practice has been slow due to numerous challenges, including technical and regulatory hurdles in translating research results into clinical diagnostic products and the lack of standardized interfaces. The open and vendor-neutral EMPAIA initiative addresses these challenges. Here, we provide an overview of EMPAIA's achievements and lessons learned. EMPAIA integrates various stakeholders of the pathology AI ecosystem, i.e., pathologists, computer scientists, and industry. In close collaboration, we developed technical interoperability standards, recommendations for AI testing and product development, and explainability methods. We implemented the modular and open-source EMPAIA platform and successfully integrated 11 AI-based image analysis apps from 6 different vendors, demonstrating how different apps can use a single standardized interface. We prioritized requirements and evaluated the use of AI in real clinical settings with 14 different pathology laboratories in Europe and Asia. In addition to technical developments, we created a forum for all stakeholders to share information and experiences on digital pathology and AI. Commercial, clinical, and academic stakeholders can now adopt EMPAIA's common open-source interfaces, providing a unique opportunity for large-scale standardization and streamlining of processes. Further efforts are needed to effectively and broadly establish AI assistance in routine laboratory use. To this end, a sustainable infrastructure, the non-profit association EMPAIA International, has been established to continue standardization and support broad implementation and advocacy for an AI-assisted digital pathology future.

The goal of Machine Learning to automatically learn from data, extract knowledge and to make decisions without any human intervention. Such automatic (aML) approaches show impressive success. Recent results even demonstrate intriguingly that deep learning applied for automatic classification of skin lesions is on par with the performance of dermatologists, yet outperforms the average. As human perception is inherently limited, such approaches can discover patterns, e.g. that two objects are similar, in arbitrarily high-dimensional spaces what no human is able to do. Humans can deal only with limited amounts of data, whilst big data is beneficial for aML; however, in health informatics, we are often confronted with a small number of data sets, where aML suffer of insufficient training samples and many problems are computationally hard. Here, interactive machine learning (iML) may be of help, where a human-in-the-loop contributes to reduce the complexity of NP-hard problems. A further motivation for iML is that standard black-box approaches lack transparency, hence do not foster trust and acceptance of ML among end-users. Rising legal and privacy aspects, e.g. with the new European General Data Protection Regulations, make black-box approaches difficult to use, because they often are not able to explain why a decision has been made. In this paper, we present some experiments to demonstrate the effectiveness of the human-in-the-loop approach, particularly in opening the black-box to a glass-box and thus enabling a human directly to interact with an learning algorithm. We selected the Ant Colony Optimization framework, and applied it on the Traveling Salesman Problem, which is a good example, due to its relevance for health informatics, e.g. for the study of protein folding. From studies of how humans extract so much from so little data, fundamental ML-research also may benefit.