Privacy-Enhancing Technologies for Medical and Genomic Data: From Theory to Practice

The impressive technological advances in genomic analysis and the significant drop in the cost of genome sequencing are paving the way to a variety of revolutionary applications in modern healthcare. In particular, the increasing understanding of the human genome, and of its relation to diseases, health and to responses to treatments brings promise of improvements in better preventive and personalized medicine. Unfortunately, the impact on privacy and security is unprecedented. The genome is our ultimate identifier and, if leaked, it can unveil sensitive and personal information such as our genetic diseases, our propensity to develop certain conditions (e.g., cancer or Alzheimer's) or the health issues of our family. Even though legislation, such as the EU General Data Protection Regulation (GDPR) or the US Health Insurance Portability and Accountability Act (HIPAA), aims at mitigating abuses based on genomic and medical data, it is clear that this information also needs to be protected by technical means. In this thesis, we investigate the problem of developing new and practical privacy-enhancing technologies (PETs) for the protection of medical and genomic data. Our goal is to accelerate the adoption of PETs in the medical field in order to address the privacy and security concerns that prevent personalized medicine from reaching its full potential. We focus on two main areas of personalized medicine: clinical care and medical research. For clinical care, we first propose a system for securely storing and selectively retrieving raw genomic data that is indispensable for in-depth diagnoses and treatments of complex genetic diseases such as cancer. Then, we focus on genetic variants and devise a new model based on additively-homomorphic encryption for privacy-preserving genetic testing in clinics. Our model, implemented in the context of HIV treatment, is the first to be tested and evaluated by practitioners in a real operational setting. For medical research, we first propose a method that combines somewhat-homomorphic encryption with differential privacy to enable secure feasibility studies on genetic data stored at an untrusted central repository. Second, we address the problem of sharing genomic and medical data when the data is distributed across multiple mistrustful institutions. We begin by analyzing the risks that threaten patientsâ privacy in systems for the discovery of genetic variants, and we propose practical mitigations to the re-identification risk. Then, for clinical sites to be able to share the data without worrying about the risk of data breaches, we develop a new system based on collective homomorphic encryption: it achieves trust decentralization and enables researchers to securely find eligible patients for clinical studies. Finally, we design a new framework, complementary to the previous ones, for quantifying the risk of unintended disclosure caused by potential inference attacks that are jointly combined by a malicious adversary, when exact genomic data is shared. In summary, in this thesis we demonstrate that PETs, still believed unpractical and immature, can be made practical and can become real enablers for overcoming the privacy and security concerns blocking the advancement of personalized medicine. Addressing privacy issues in healthcare remains a great challenge that will increasingly require long-term collaboration among geneticists, healthcare providers, ethicists, lawmakers, and computer scientists

Audit of Antenatal Testing of Sexually Transmissible Infections and Blood Borne Viruses at Western Australian Hospitals

In August 2007, the Western Australian Department of Health (DOH) released updated recommendations for testing of sexually transmissible infections (STI) and blood-borne viruses (BBV) in antenates. Prior to this, the Royal Australian & New Zealand College of Obstetricians & Gynaecologists (RANZCOG) antenatal testing recommendations had been accepted practice in most antenatal settings. The RANZCOG recommends that testing for HIV, syphilis, hepatitis B and C be offered at the first antenatal visit. The DOH recommends that in addition, chlamydia testing be offered. We conducted a baseline audit of antenatal STI/BBV testing in women who delivered at selected public hospitals before the DOH recommendations. We examined the medical records of 200 women who had delivered before 1st July 2007 from each of the sevenWAhospitals included in the audit. STI and BBV testing information and demographic data were collected. Of the 1,409 women included, 1,205 (86%) were non-Aboriginal and 200 (14%) were Aboriginal. High proportions of women had been tested for HIV (76%), syphilis (86%), hepatitis C (87%) and hepatitis B (88%). Overall, 72% of women had undergone STI/BBV testing in accordance with RANZCOG recommendations. However, chlamydia testing was evident in only 18% of records. STI/BBV prevalence ranged from 3.9% (CI 1.5– 6.3%) for chlamydia, to 1.7% (CI 1–2.4%) for hepatitis C, 0.7% (CI 0.3–1.2) for hepatitis B and 0.6% (CI 0.2–1) for syphilis. Prior to the DOH recommendations, nearly three-quarters of antenates had undergone STI/BBV testing in accordance with RANZCOG recommendations, but less than one fifth had been tested for chlamydia. The DOH recommendations will be further promoted with the assistance of hospitals and other stakeholders. A future audit will be conducted to determine the proportion of women tested according to the DOH recommendations. The hand book from this conference is available for download Published in 2008 by the Australasian Society for HIV Medicine Inc © Australasian Society for HIV Medicine Inc 2008 ISBN: 978-1-920773-59-

The implementation of pharmacogenetics: evidence and preferences

Pharmacogenetics has huge potential to transform the field of medicine and deliver personalised treatments to patients. However, its wider use is limited by many factors, particularly a lack of suitable evidence of efficacy or safety for regulatory approval and clinical use. The evidence required can be difficult to ascertain, presenting three main problems. The first issue is that regulatory guidance for the evidence required is complex and varies greatly between different authorities and contexts. Guidance from the UK Medicines and Healthcare products Regulatory Authority (MHRA) and the US Food and Drug Administration (FDA) was reviewed along with criteria formulated by other industry and academic groups. It was found that there is a clear need for a unified set of standards for evidence gathering in pharmacogenetics. This was strengthened by an analysis of the evidence used by five different randomised controlled trials to justify the inclusion of their pharmacogenetic biomarker. Large variation in the quality and type of this evidence was found. These findings were used to make recommendations for future evidence gathering for trials, regulators, and journals. Additionally, the evidence required for clinical implementation has traditionally been the prospective randomised controlled trial. Gathering information from two novel systematic reviews and meta-analyses of carbamazepine-induced Stevens-Johnson syndrome, it was shown how these sources of observational evidence can produce effect estimates and measures of clinical validity of greater precision than that of a prospective trial. Finally, the level of evidence for a pharmacogenetic test that would be acceptable to the general public is not known. A discrete choice experiment (DCE) was designed to quantify these views. The first step was a systematic review of existing DCEs in this area, to extract useful information from these to inform the work. An extensive programme of qualitative work with healthcare professionals, patients, and the general public then further informed the design of this novel DCE. Participants were randomised to complete one of eight DCEs in different disease areas, with either a ‘high’ evidence scenario or a ‘low’ evidence scenario described. Launched in May 2021, over 2,000 responses were collected and the results were analysed in preference-weighted utility models. Although there was no difference in utility between ‘high’ and ‘low’ evidence tests, several important insights were generated (particularly in regard to data sharing and privacy) that will potentially have large impacts on policy in this area

Front-Line Physicians' Satisfaction with Information Systems in Hospitals

Day-to-day operations management in hospital units is difficult due to continuously varying situations, several actors involved and a vast number of information systems in use. The aim of this study was to describe front-line physicians' satisfaction with existing information systems needed to support the day-to-day operations management in hospitals. A cross-sectional survey was used and data chosen with stratified random sampling were collected in nine hospitals. Data were analyzed with descriptive and inferential statistical methods. The response rate was 65 % (n = 111). The physicians reported that information systems support their decision making to some extent, but they do not improve access to information nor are they tailored for physicians. The respondents also reported that they need to use several information systems to support decision making and that they would prefer one information system to access important information. Improved information access would better support physicians' decision making and has the potential to improve the quality of decisions and speed up the decision making process.Peer reviewe

Current Perspectives on Viral Disease Outbreaks

The COVID-19 pandemic has reminded the world that infectious diseases are still important. The last 40 years have experienced the emergence of new or resurging viral diseases such as AIDS, ebola, MERS, SARS, Zika, and others. These diseases display diverse epidemiologies ranging from sexual transmission to vector-borne transmission (or both, in the case of Zika). This book provides an overview of recent developments in the detection, monitoring, treatment, and control of several viral diseases that have caused recent epidemics or pandemics

The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues

The interface between assisted reproductive technologies (ART) and genetics comprises several sensitive and important issues that affect infertile couples, families with severe genetic diseases, potential children, professionals in ART and genetics, health care, researchers and the society in general. Genetic causes have a considerable involvement in infertility. Genetic conditions may also be transmitted to the offspring and hence create transgenerational infertility or other serious health problems. Several studies also suggest a slightly elevated risk of birth defects in children born following ART. Preimplantation genetic diagnosis (PGD) has become widely practiced throughout the world for various medical indications, but its limits are being debated. The attitudes towards ART and PGD vary substantially within Europe. The purpose of the present paper was to outline a framework for development of guidelines to be issued jointly by European Society of Human Genetics and European Society of Human Reproduction and Embryology for the interface between genetics and ART. Technical, social, ethical and legal issues of ART and genetics will be reviewed.JRC.J.5-Agriculture and Life Sciences in the Econom

Exploring the integration of traditional and molecular epidemiological methods for infectious disease outbreaks

BACKGROUND: Understanding the transmission dynamics of infectious pathogens is critical to developing effective public health strategies. Traditionally, time consuming epidemiological methods were used, often limited by incomplete or inaccurate datasets. Novel phylogenetic techniques can determine transmission events, but have rarely been used in real-time outbreak settings to inform interventions and limit the impact of outbreaks. METHODS: I undertook a series of novel studies to explore the utility of combining phylogenetics with traditional epidemiological analysis to enhance the understanding of transmission dynamics. I investigated HIV in an endemic South African setting and Ebola in an acute outbreak in Sierra Leone. The strengths and limitations of this combined approach are explored, ethical issues investigated and recommendations made regarding the implications of this work for public health. RESULTS: Phylogenetics provides an exciting and synergistic tool to epidemiological analysis in outbreak investigation and control. These combined methods enable a more detailed understanding than is possible through either discipline alone. My key findings include: • Identification of infection source: Phylogenetics gives new insight into the role of external introductions (e.g. migrators) in driving and sustaining the high incidence of HIV. • Earlier identification of new emerging clusters: I identified a new cluster of HIV from around a mining community. This is one of the first examples of molecular methods detecting a previously unknown outbreak. • Identification of novel mechanisms of transmission: This work suggests that children may have been infected by playing in puddles contaminated with Ebola, a previously unrecognised route of transmission. CONCLUSION: The integration of these two methods facilitate sophisticated real-time techniques to maximise understanding of transmission dynamics, allowing faster and more effectively targeted interventions. Moving forwards, sequence data should be incorporated into standard outbreak investigation. This is critical at a time when infectious disease outbreaks have led to the some of the most significant global health threats of the recent past