The Mission & The Challenges
The PARQ mission is to implement this knowledge to develop prevention and treatment guidelines to reduce the differences in survival rates and the overall burden of SCA across Europe. The first step in achieving this challenging goal is to collect and share data across all European regions and learn from differences in prevention and treatment strategies. Hence, sufficiently large cohorts of SCA patients with detailed clinical and environmental data are required. Although efforts to collect clinical data and biological samples exist at the national and international level, co-ordination between these study networks is lacking. The harmonization of data collection and analysis should be improved to enforce collaboration and data sharing between cohorts. In addition, the different European countries and regions are not equally well represented in existing research efforts. Hence, there is a need for a pan-European network to connect all stakeholders in SCA and resuscitation science and develop standards for research activities.
The PARQ Action will be built on two pillars. Read more below.
Multiple risk factors are associated with SCA occurrence. In each individual, a unique interaction of inherited, acquired and environmental risk factors determines the risk of ventricular fibrillation leading to SCA. Inherited risk factors may arise from variation in genes that control cardiac electrophysiology. Also gender accounts for variation in SCA risk; men have a higher chance of suffering from SCA, but women are less likely to be resuscitated and have lower chances of survival. In addition, acquired risk factors, such as myocardial ischemia, type II diabetes as well as environmental factors (in particular, socio-economic factors that may be related to psychosocial stress) can contribute to SCA. Inclusion of inherited, acquired and environmental factors as integral components of SCA occurrence and outcome is critical to establish new guidelines and preventive actions with cross-border relevance. In summary, designing individualized prevention and treatment strategies requires elucidation of the complex interplay of risk factors. Ongoing initiatives including large European cohort studies aim to unravel the interactions of inherited, acquired, and environmental risk factors.
- Cohort integration: Although efforts to collect clinical data and biological samples exist at national and international levels, co-ordination and harmonization between such study networks is lacking. The PARQ Action will provide the network to discuss standards for harmonization of data collection and analysis to enforce collaboration and data sharing between cohorts. In addition, the Action will include European countries and regions that are not equally well represented in existing research efforts, with a strong focus on Eastern Europe.
- Data collection and analysis: Standards will be developed for collection, storage and analysis of genomic data, pharmacological data, electrocardiogram (ECG) measurements, socioeconomic data and resuscitation data using the Utstein-style guidelines. These guidelines refer to an established consensus process, endorsed by the international resuscitation community, to facilitate and structure resuscitation research and publication. The Action members offer expertise in state-of-the-art genetic analysis methods (genome-wide association studies, genetic imputation methods, whole genome sequencing analysis) and will select the optimal methods for data handling. To support the complex bioinformatics analyses of large-scale phenotype and genotype data across Europe, the Action has access to existing parallelization frameworks for SCA data analysis. Such frameworks will facilitate use of statistical tools and analyses in parallel in different environments, including computer cluster and cloud environments. In addition, the Action will include medical ethics experts to evaluate ethical issues related to use and exchange of information and personal data of SCA patients from different EU countries.
- Inclusion of general practitioner (GP) files: SCA strikes individuals who are often unaware of their health risk and who are not monitored by cardiologists. Importantly, the recognition of individuals at risk must be improved. Novel insights could be derived from clinical information present in personal health records and GP files. The PARQ Action has formulated the unique ambition to include clinical information from GP files, to strengthen research on identification of relevant but so far unsuspected SCA risk factors. These GP files will be fully exploited using data mining methods developed by consortium members, which utilize advanced machinelearning algorithms that do not require an up-front selection of variables, but identify useful variables themselves based on the data. Data mining has the power to improve prediction models, in part because temporal information, so far untapped, is utilized, e.g., the number of GP visits preceding the study endpoint and/or the evolution over time from nonspecific signs/symptoms towards ever more specific signs/symptoms. In addition, the data mining algorithms may reveal signs/symptoms at GP visits which are so far unsuspected to be associated with SCA. We will first apply the pipeline we have described before to extract potential predictors. Thereafter, we apply advanced machine learning algorithms to create risk scores for patients. Machine learning methods to be used include decision tree algorithms, and support vector machines, and random forests algorithms. A dedicated GP task-force will design a strategic plan for collection, harmonization, safe handling and storage of GP data per Action Member country.
Multiple factors influence the chances of survival after SCA. The first minutes after SCA critically impact patient prognosis, yet the first care often occurs in an out-of-hospital setting. The delay between SCA and first-response treatment is the most important determinant of survival. European Resuscitation Council guidelines for resuscitation have been established and include instructions for first-response treatment: early recognition and call for help; early cardiopulmonary resuscitation, early defibrillation and standardized post-resuscitation treatment. Still, large disparities between SCA survival rates across Europe exist. To understand how these differences arise, other determinants of survival, such as patient characteristics and regional differences in SCA management, should be considered.
- The resuscitation science community has implemented Utstein guidelines for uniform reporting of SCA. However, to better understand the variation in survival rates, first-response management and patient characteristics should be systematically reviewed. The challenge that will be addressed by PARQ is to establish the network to exchange new knowledge related to SCA management, including regional differences in financial resources. The network will focus on sharing of data related to the effectiveness of text-message and app-based deployment of lay rescuers to understand how new technologies and treatment deployment strategies can enhance effectiveness of bystander response. This requires that consensus is established on best practices for harmonization of application-derived data. In addition, health economics experts in the PARQ Action network will be involved in evaluation of the financial drivers behind the emergency response and treatment procedures established in European countries.
- Overall, improvement of both individual risk prediction and intervention methods are required to achieve the lowest incidence of SCA and the highest chance of survival from SCA. Ultimately, the Action members aim to develop first-response treatment strategies that are as much as possible tailored to an individual (e.g., based on comorbidity, drug use, or medical/genetic background and biomarkers). Traditionally, the research communities that focus on Pillar 1 (typically cardiologist and molecular biologists) do not sufficiently interact with the Pillar 2 research communities (typically emergency medicine and resuscitation scientists), and vice versa. A key challenge addressed by PARQ is to connect these researchers to create a critical mass of participants and to establish education programmes and workshops to foster interdisciplinary training.