Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation.

Background Cold coagulation is an ablative method for treatment of cervical intraepithelial neoplasia (CIN). Despite reports of efficacy against all grades of CIN (CIN1-3), cold coagulation has been infrequently used since the 1980s, and was absent from the recent Cochrane review on CIN treatment.Objectives To provide a systematic review of cold coagulation efficacy and acceptability for CIN treatment through meta-analysis of clinical reports and a randomised control trial.Search strategy A literature search in PubMed, Web of Science, EMBASE, and regional databases yielded 388 papers. Title, abstract and/or reference list review identified 22 papers describing cold coagulation treatment of CIN, with 13 providing adequate data for inclusion in the meta-analysis.Selection criteria Publications or conference abstracts describing original data (number of women treated, followed up and cured, provider type, cure definition) were retained. No language or publication date limitations were imposed.Data collection and analysis Data extracted from 13 studies were pooled, and statistical analyses of proportion cured were conducted with data stratified by lesion grade and study region.Main results Among 4569 CIN patients treated with cold coagulation, summary proportion cured of 96% [95% confidence interval (CI) 92-99%] and 95% (92-98%) were obtained for CIN1 and CIN2-3 disease, respectively. Side-effects and adverse effects were infrequent, and fertility was not impaired.Conclusions Cold coagulation CIN cure rates were comparable to those of other excisional and ablative methods. Cold coagulation is indicated for all grades of CIN, is safe, quick and acceptable, and may be of particular relevance for use in resource-limited settings.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project’s outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases—Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)—as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

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