Kelly Edwards

From patients to partners: participant-centric initiatives in biomedical research

Advances in computing technology and bioinformatics mean that medical research is increasingly characterized by large international consortia of researchers that are reliant on large data sets and biobanks. These trends raise a number of challenges for obtaining consent, protecting participant privacy concerns and maintaining public trust. Participant-centred initiatives (PCIs) use social media technologies to address these immediate concerns, but they also provide the basis for long-term interactive partnerships. Here, we give an overview of this rapidly moving field by providing an analysis of the different PCI approaches, as well as the benefits and challenges of implementing PCIs.

From consent to institutions: Designing adaptive governance for genomic biobanks

Biobanks are increasingly hailed as powerful tools to advance health research. The social and ethical challenges associated with the implementation and operation of biobanks are equally well-documented. One of the proposed solutions to these challenges involves trading off a reduction in the specificity of informed consent protocols with an increased emphasis on governance. However, little work has gone into formulating what such governance might look like. In this paper, we suggest four general principles that should inform biobank governance and illustrate the enactment of these principles in a proposed governance model for a particular population-scale biobank, the British Columbia (BC) Generations Project. We begin by outlining four principles that we see as necessary for informing sustainable and effective governance of biobanks: (1) recognition of research participants and publics as a collective body, (2) trustworthiness, (3) adaptive management, and (4) fit between the nature of a particular biobank and the specific structural elements of governance adopted. Using the BC Generations Project as a case study, we then offer as a working model for further discussion the outlines of a proposed governance structure enacting these principles. Ultimately, our goal is to design an adaptive governance approach that can protect participant interests as well as promote effective translational health sciences.

A review of the key issues associated with the commercialization of biobanks

A review of the key issues associated with the commercialization of biobanks Timothy Caulfield∗, Sarah Burningham, Yann Joly, ZubinMaster, Mahsa Shabani, Pascal Borry, Allan Becker, Michael Burgess, Kathryn Calder, Christine Critchley, Kelly Edwards, Stephanie M. Fullerton, Herbert Gottweis, Robyn Hyde-Lay, Judy Illes, Rosario Isasi, Kazuto Kato, Jane Kaye, Bartha Knoppers, John Lynch, AmyMcGuire, Eric Meslin, Dianne Nicol, Kieran O’Doherty, Ubaka Ogbogu, Margaret Otlowski, Daryl Pullman, Nola Ries, Chris Scott, Malcolm Sears, HelenWallace andMa’n H. Zawati†

ELSI 2.0 for Genomics and Society

We need an international infrastructure for the ethical, legal, and social implications of genomic research. Anticipating and addressing the ethical, legal, and social implications (ELSI) of scientific developments has been a key feature of the genomic research agenda (1–4). Research in genomics is advancing by developing common infrastructures and research platforms, open-access and sharing policies, and new forms of international collaborations (5–12). In this paper, we outline a proposal to establish a “collaboratory” (13) for ELSI research to enable it to become more coordinated, responsive to societal needs, and better able to apply the research knowledge it generates at the global level. Current ELSI research is generally nationally focused, with investigator-initiated approaches that are not always aligned with the developments in international genomics research. This makes it difficult to efficiently leverage findings that impact global practice and policy. Moreover, as translational genomic research design challenges become more pressing (14), ELSI research will need to develop greater capacity to respond rapidly to new developments. The ELSI 2.0 Initiative is designed to catalyze international collaboration in ELSI genomics and to enable those in the field to better assess the impact and dynamics of global genome research.

A Simple Schema for Informed Decision Making About Prostate Cancer Screening

Screening for prostate cancer with prostate-specific antigen (PSA) testing is a problematic aspect of primary care. With the exception of the U.S. Preventive Services Task Force, which made an influential (1) but highly criticized (2) recommendation against any early detection efforts based on PSA testing, most organizations recommend that an informed decision be made by the patient after discussion with a physician. For example, the American College of Physicians is generally skeptical of the benefits of PSA testing (for most men, the harms will outweigh the benefits) but recommends that doctors and patients should discuss the potential benefits and harms of screening (3, 4). Similarly, the American Urological Association, although more favorably disposed to screening, strongly recommend[s] shared decision-making (5). Implementing shared decision making in primary care is not straightforward because it must account for the wide range of information and data that could be discussed, the complex tradeoff between immediate harms and long-term benefits, and the limited time primary care clinicians have for in-depth discussions about PSA testing in the context of the many other issues in a typical visit. Recent years have seen a considerable amount of literature develop on decision making for PSA screening, including specific advice to primary care providers about what they should tell patients. Our multidisciplinary group, which comprises a statistician specializing in localized prostate cancer, a bioethicist who has conducted empirical research about decision making in PSA screening, an academic urologic oncologist and epidemiologist, and an academic primary care physician, has followed this literature closely. We believe that recommendations specify either too little information to allow patients to make a decision or so much that it overwhelms their ability to decide rationally. Recommendations requiring extensive information also have low clinical feasibility (one suggests that physicians inform patients on 16 separate points and ask 12 questions about preferences [6]); include data that might be hard for patients to understand or assign a value to, such as the risk for deep venous thrombosis (7); or cite estimates that are conflicting and questionable, such as PSA screening leading to either 30 (8) or 110 (7) extra prostate cancer diagnoses per 1000 men screened. Given the inadequacies of current recommendations and attendant poor adherence, we propose an alternative approach to informed decision making about PSA testing in primary care. This approach is based on 3 primary principles. First, the information given to the patient must be based on best evidence and mustto the extent possible in such a controversial fieldbe beyond dispute. This would help to avoid the situation of many decision tools, such as the infographic provided by the National Cancer Institute (7), in which many of the key numbers cited, such as the risk for overdiagnosis, are subject to considerable controversy. Second, the patient should be presented with a clear framework for a decision, in contrast to complex decision aids that provide patients with a large number of estimates and then ask them to somehow integrate these into a discrete choice. Third, the schema should be appropriate for primary care. It should not assume that the provider has detailed knowledge of PSA testing and prostate cancer and should not require more than a few minutes to implement. As a starting point, we assume that primary care providers would correctly identify eligible patients: men in their mid-40s through mid-70s with minimal comorbidity. We also assume that providers would adopt the ask-tell-ask approach that has been previously advocated (9). Starting with the initial ask, the clinician would gain critical information on what the patient already knows about PSA screening or what the patients level of concern or interest may be. This would allow the clinician to then tailor the tell portion of the conversation more succinctly and directly to the patients particular needs and level of current understanding. This portion of the conversation would follow the simple schema outlined in the Table. The Supplement provides evidence supporting each point. Table. Decision Tool for Prostate Cancer Screening Supplement. Recommendations on Shared Decision Making for Prostate Cancer Screening: Review of the Literature The brief decision tool shown in the Table meets our criteria of being evidence-based, facilitating a discrete decision, and being appropriate for primary care in that it requires a relatively limited amount of time and only general knowledge about PSA screening. This sharing of information would be followed by a final ask (9), in which the clinician would confirm that what he or she has just explained makes sense and would ask for the patients preference regarding the decision. With this revised, streamlined approach, clinicians can follow the recommendation of having an informed, evidence-based discussion that provides a clear framework for decision making about PSA screening.

The Haystack Is Made of Needles

Developing genetic tests that have clinical utility and validated biomarkers presents many challenges. Much has been written about these challenges for the development of genetic test evidence (Khoury et al., 2010; Horn and Terry, 2012) and biomarker validation (Lesko and Atkinson, 2001; Surh, 2009). One consistent thread through these challenges is the lack of well-characterized cohorts. This is already generally true for common conditions (< 5% of patients with cancer participate in clinical trials [Michaels, 2012]), and it seems likely this problem will only worsen as cancers are stratified by genomic tests. Finding a robust cohort has always been difficult for rare diseases, simply by virtue of their rarity (Griggs et al., 2009; Gliklich and Leavy, 2011). Finding individuals to create these cohorts can feel like finding a needle in a haystack. And yet, this way of framing the problem unnecessarily boxes us in. As a solution, we are designing and pursuing research innovations that turn that framing on its head. Notice what happens to the possibilities when we consider that we have before us not a needle in a haystack but a haystack composed of needles! Instead of trying to enroll participants in a clinical trial by seeking only those few rare individuals with a particular variation or individuals affected by a rare disease (the needles in a haystack), we need to engage all individuals (because the haystack is made of needles). This simple concept has been discounted as too expensive, producing excessively noisy and dirty data, and being fundamentally impractical in an age when researchers are burdened by national and institutional regulations that make it difficult to engage anyone but a welldefined cohort formed around a hypothesis. As more people are becoming aware of this hidden potential, we are seeing a shift from hypothesis-constrained cohort identification toward the creation of hypothesis-generating registries and repositories (Ritchie et al., 2010; Manolio et al., 2012). Although this is a welcome shift, it generally originates in institutions seeking robust resources in the form of registries to support their own research, or those that are bravely encouraging open data sharing (Norman et al., 2011). As a result of this limited scope, each has limited value for creating meaningful cohorts for advancing widespread research objectives. We speculate that given the right tools, it is possible to create a novel type of registry that overcomes these limitations and identifies more robust cohorts for both common and rare diseases. This shift in capability requires looking at biomedical research from the perspective of the people who will benefit most: each of us. This work starts from the premise that a carefully maintained haystack made of needles will be of use to researchers and appealing to participants. Genetic Alliance has a long history of engaging the public with comprehensive and accessible health information and in building capacity in disease advocacy organizations to create platforms to better engage their respective populations. Two major results of these endeavors are Disease InfoSearch (www.diseaseinfosearch.org) and the Genetic Alliance Registry and BioBank (GARB; www.biobank.org). Since their creation, Genetic Alliance has experienced some of the challenges described earlier. As increasingly powerful and less costly technologies are developed for genomic testing, data analysis, and exchange, Genetic Alliance has also been mindful of the ethical issues inherent in data sharing; it led the coalition that moved the Genetic Information Nondiscrimination Act of 2008 (GINA) through the US Congress over 12 and a half years. GARB was created in 2003, the only layperson-owned and -managed cross-disease registry and biorepository platform in the world, but unfortunately it has not yet reached critical mass. The many registries created by disease advocacy organizations are highly trusted, but they lack the cross-disease features needed to support a systems approach to diseases; ease of discovering cohorts; and appropriate, individualized access to clinical trials for their participants. We observed a common characteristic in all these databases of personally identified information. In these registries— whether owned by disease advocacy organizations, universities, government agencies, or industry (and indeed, even in the case of GARB)—the individuals who elect to participate hand over control of their data and samples to a proxy. Although that proxy is often considered a trusted entity, the fact is that the individual who contributed data is no longer a participant in the registry. Data context is lost because the experience of the individual and the community in which she or he lives are not available. More often than not, the opportunity for engaging individuals in their own health, and moving translation forward toward effects on actual health outcomes, is neglected in favor of more conventional research goals.

Participant-Centric Initiatives: Tools to Facilitate Engagement In Research.

Clinical genomic research faces increasing challenges in establishing participant privacy and consent processes that facilitate meaningful choice and communication capacity for longitudinal and secondary research uses. There are an evolving range of participant-centric initiatives that combine web-based informatics tools with new models of engagement and research collaboration. These emerging initiatives may become valuable approaches to support large-scale and longitudinal research studies. We highlight and discuss four types of emerging initiatives for engaging and sustaining participation in research.

Values in Translation: How Asking the Right Questions Can Move Translational Science Toward Greater Health Impact

The speed and effectiveness of current approaches to research translation are widely viewed as disappointing given small gains in real population health outcomes despite huge investments in basic and translational science. We identify critical value questions—ethical, social, economic, and cultural—that arise at moments throughout the research pathway. By making these questions visible, and promoting discussion of them with diverse stakeholders, we can facilitate handoffs along the translational pathway and increase uptake of effective interventions. Who is involved with those discussions will determine which research projects, populations, and methods get prioritized. We argue that some upfront investment in community and interdisciplinary engagement, shaped by familiar questions in ethics, social justice, and cultural knowledge, can save time and resources in the long run because interventions and strategies will be aimed in the right direction, that is, toward health improvements for all. Clin Trans Sci 2012; Volume 5: 445–451

Ethics and communication

Ethics education aims to train physicians to identify and resolve ethical issues. To address ethical concerns, physicians may need to confront each other. We surveyed medical students to determine if their comfort challenging members of their ward teams about ethical issues varies by specialty and what attributes of students and their teams contributed to that comfort. Compared to other specialties, students felt significantly less comfortable challenging team members about ethical issues on surgery and obstetrics/gynecology. We suggest that ethics education must address the atmosphere on ward teams and give students skills to help them speak out despite their discomfort.

Building a chain of trust: using policy and practice to enhance trustworthy clinical data discovery and sharing

Advances and significant national infrastructure investment into clinical information systems are spurring a demand for secondary use and sharing of clinical and genetic data for translational research. In this paper, we describe the need for technically leveraged policy models and governance strategies to support data sharing between a range of disparate stakeholders where trust is not easily established or maintained.