Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi.

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health.

Payer reimbursement practices and incentives for improving interpretation of germline genetic testing.

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for private payers and Medicare illustrate opportunities and challenges for data sharing to close knowledge gaps and improve clinical utility. Policy options include making data sharing (i) a condition of payment, and (ii) a metric of laboratory quality in payment contracts, yielding preferred coverage or enhanced reimbursement. Mandating data sharing sufficient to verify interpretations and resolve discordance among labs under Medicare and federal health programs is an option for the US Congress. Such policies can reduce the current waste of valuable data needed for precision oncology and improved patient outcomes, enabling a learning health system.

Fresh takes on five health data sharing domains: Quality, privacy, equity, incentives, and sustainability.

As entities around the world invest in repositories and other infrastructure to facilitate health data sharing, scalable solutions to data sharing challenges are needed. We conducted semi-structured interviews with 24 experts to explore views on potential issues and policy options related to health data sharing. In this Perspective, we describe and contextualize unconventional insights shared by our interviewees relevant to issues in five domains: data quality, privacy, equity, incentives, and sustainability. These insights question a focus on granular quality metrics for gatekeeping; challenge enthusiasm for maximalist risk disclosure practices; call attention to power dynamics that potentially compromise the patient's voice; encourage faith in the sharing proclivities of new generations of scientists; and endorse accounting for personal disposition in the selection of long-term partners. We consider the merits of each insight with the broad goal of encouraging creative thinking to address data sharing challenges.

Description of COVID-19 outbreaks in childcare facilities in Alberta, March 2020 to December 31, 2021.

Background: Children attending childcare are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and mitigation measures such as masking, distancing, enhanced hygiene are not feasible for this population. Describing outbreak growth during the coronavirus disease 2019 (COVID-19) pandemic in childcare centres may provide insight into how to best mitigate the risks of COVID-19 and other infectious diseases in these settings. This article describes the childcare outbreaks and associated cases in Alberta at different time periods throughout the pandemic. Methods: Our observational analysis used data on outbreaks and associated cases tracked through the Alberta Health Services Communicable Disease Outbreak Management database. We included all COVID-19 outbreaks opened in childcare facilities (March 2020 to December 31, 2021). We compared the characteristics of outbreaks and cases during each wave of the pandemic. Results: There were a total of 841 childcare outbreaks, including 4,613 cases (70.2% in children and 29.8% adults). Many characteristics of outbreaks and cases varied across pandemic waves, including attack rates (12.1%-28.7% in adults and 5.8%-16.3% in children), percent of cases in children (56.4%-77.3%), and percent of outbreaks with a child index case (34.0%-70.1%). The overall average cases/outbreak was 5.5 (range: 1-68), and case examples of large outbreaks showed that delaying testing and attending daycare while symptomatic seemed to drive higher transmission. Conclusion: Waves had different outbreak and case characteristics, for both adults and children. Transmission may happen more readily among adults and among children than between those two groups. Measures shown to be effective to reduce transmission in other settings can be implemented here, such as vaccination, strictly enforcing the exclusion of those symptomatic, and facilitating rapid testing.

Balancing openness with Indigenous data sovereignty: An opportunity to leave no one behind in the journey to sequence all of life.

The field of genomics has benefited greatly from its "openness" approach to data sharing. However, with the increasing volume of sequence information being created and stored and the growing number of international genomics efforts, the equity of openness is under question. The United Nations Convention of Biodiversity aims to develop and adopt a standard policy on access and benefit-sharing for sequence information across signatory parties. This standardization will have profound implications on genomics research, requiring a new definition of open data sharing. The redefinition of openness is not unwarranted, as its limitations have unintentionally introduced barriers of engagement to some, including Indigenous Peoples. This commentary provides an insight into the key challenges of openness faced by the researchers who aspire to protect and conserve global biodiversity, including Indigenous flora and fauna, and presents immediate, practical solutions that, if implemented, will equip the genomics community with both the diversity and inclusivity required to respectfully protect global biodiversity.

Challenges to Building a Gene Variant Commons to Assess Hereditary Cancer Risk: Results of a Modified Policy Delphi Panel Deliberation.

Understanding the clinical significance of variants associated with hereditary cancer risk requires access to a pooled data resource or network of resources-a "cancer gene variant commons"-incorporating representative, well-characterized genetic data, metadata, and, for some purposes, pathways to case-level data. Several initiatives have invested significant resources into collecting and sharing cancer gene variant data, but further progress hinges on identifying and addressing unresolved policy issues. This commentary provides insights from a modified policy Delphi process involving experts from a range of stakeholder groups involved in the data-sharing ecosystem. In particular, we describe policy issues and options generated by Delphi participants in five domains critical to the development of an effective cancer gene variant commons: incentives, financial sustainability, privacy and security, equity, and data quality. Our intention is to stimulate wider discussion and lay a foundation for further work evaluating policy options more in-depth and mapping them to those who have the power to bring about change. Addressing issues in these five domains will contribute to a cancer gene variant commons that supports better care for at-risk and affected patients, empowers patient communities, and advances research on hereditary cancers.

Burden of disease from Helicobacter pylori infection in western Canadian Arctic communities.

BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.

DNA barcoding in the media: does coverage of cool science reflect its social context?

Paul Hebert and colleagues first described DNA barcoding in 2003, which led to international efforts to promote and coordinate its use. Since its inception, DNA barcoding has generated considerable media coverage. We analysed whether this coverage reflected both the scientific and social mandates of international barcoding organizations. We searched newspaper databases to identify 900 English-language articles from 2003 to 2013. Coverage of the science of DNA barcoding was highly positive but lacked context for key topics. Coverage omissions pose challenges for public understanding of the science and applications of DNA barcoding; these included coverage of governance structures and issues related to the sharing of genetic resources across national borders. Our analysis provided insight into how barcoding communication efforts have translated into media coverage; more targeted communication efforts may focus media attention on previously omitted, but important topics. Our analysis is timely as the DNA barcoding community works to establish the International Society for the Barcode of Life.

Complete Genome Sequences of Two Helicobacter pylori Strains from a Canadian Arctic Aboriginal Community.

We report here the complete genome sequences of two Amerind Helicobacter pylori strains from Aklavik, Northwest Territories, Canada. One strain contains extra iron-cofactored urease genes and ~140 rearrangements in its chromosome relative to other described strains (typically differing from one another by <10 rearrangements), suggesting that it represents a novel lineage of H. pylori.

Disease manifestations of Helicobacter pylori infection in Arctic Canada: using epidemiology to address community concerns.

OBJECTIVES: Helicobacter pylori infection, linked to gastric cancer, is responsible for a large worldwide disease burden. H pylori prevalence and gastric cancer rates are elevated among indigenous Arctic communities, but implementation of prevention strategies is hampered by insufficient information. Some communities in northern Canada have advocated for H pylori prevention research. As a first step, community-driven research was undertaken to describe the H pylori-associated disease burden in concerned communities. DESIGN: Participants in this cross-sectional study completed a clinical interview and gastroscopy with gastric biopsies taken for histopathological examination in February 2008. SETTING: Study procedures were carried out at the health centre in Aklavik, Northwest Territories, Canada (population ∼600). PARTICIPANTS: All residents of Aklavik were invited to complete a clinical interview and gastroscopy; 194 (58% female participants; 91% Aboriginal; age range 10-80 years) completed gastroscopy and had gastric biopsies taken. PRIMARY AND SECONDARY OUTCOME MEASURES: This analysis estimates the prevalence of gastric abnormalities detected by endoscopy and histopathology, and associations of demographic and clinical variables with H pylori prevalence. RESULTS: Among 194 participants with evaluable gastric biopsies, 66% were H pylori-positive on histology. Among H pylori-positive participants, prevalence was 94% for acute gastritis, 100% for chronic gastritis, 21% for gastric atrophy and 11% for intestinal metaplasia of the gastric mucosa, while chronic inflammation severity was mild in 9%, moderate in 47% and severe in 43%. In a multivariable model, H pylori prevalence was inversely associated with previous gastroscopy, previous H pylori therapy and aspirin use, and was positively associated with alcohol consumption. CONCLUSIONS: In this population, H pylori-associated gastric histopathology shows a pattern compatible with elevated risk of gastric cancer. These findings demonstrate that local concern about health risks from H pylori is warranted and provide an example of how epidemiological research can address health priorities identified by communities.

A randomized controlled trial comparing sequential with triple therapy for Helicobacter pylori in an Aboriginal community in the Canadian North.

BACKGROUND: Helicobacter pylori infection occurs more frequently in Arctic Aboriginal settings than elsewhere in North America and Europe. Research aimed at reducing health risks from H pylori infection has been conducted in the Aboriginal community of Aklavik, Northwest Territories. OBJECTIVE: To compare the effectiveness of the Canadian standard therapy with an alternative therapy for eliminating H pylori infection in Aklavik. METHODS: Treatment-naive H pylori-positive individuals were randomly assigned to a 10-day regimen (oral twice-daily doses) with rabeprazole (20 mg): standard triple therapy (proton pump inhibitor, added clarithromycin [500 mg] and amoxicillin [1 g] [PPI-CA]); sequential therapy (ST) added amoxicillin (1 g) on days 1 to 5, and metronidazole (500 mg) and clarithromycin (500 mg) on days 6 to 10. Participants with clarithromycin-resistant H pylori were randomly assigned to ST or quadruple therapy. Treatment effectiveness was estimated as per cent (95% CI) with a negative urea breath test at least 10 weeks after treatment. RESULTS: Of 104 (53 PPI-CA, 51 ST) randomized participants, 89 (49 PPI-CA, 40 ST) had post-treatment results. Per-protocol treatment effectiveness was 59% (95% CI 45% to 73%) for PPI-CA and 73% (95% CI 58% to 87%) for ST. Based on intention to treat, effectiveness was 55% (95% CI 41% to 69%) for PPI-CA and 57% (95% CI 43% to 71%) for ST. Of 77 participants (43 PPI-CA, 34 ST) with 100% adherence, effectiveness was 63% (95% CI 43% to 82%) for PPI-CA and 81% (95% CI 63% to 99%) for ST. CONCLUSIONS: While additional evidence is needed to confirm that ST is more effective for Arctic Aboriginal communities than the Canadian standard H pylori treatment, these results show standard PPI-CA treatment to be inadequate for communities such as Aklavik.

Access and benefits sharing of genetic resources and associated traditional knowledge in northern Canada: understanding the legal environment and creating effective research agreements.

BACKGROUND: Research in northern Canada focused on Aboriginal peoples has historically benefited academia with little consideration for the people being researched or their traditional knowledge (TK). Although this attitude is changing, the complexity of TK makes it difficult to develop mechanisms to preserve and protect it. Protecting TK becomes even more important when outside groups become interested in using TK or materials with associated TK. In the latter category are genetic resources, which may have commercial value and are the focus of this article. OBJECTIVE: This article addresses access to and use of genetic resources and associated TK in the context of the historical power-imbalances in research relationships in Canadian north. DESIGN: Review. RESULTS: Research involving genetic resources and TK is becoming increasingly relevant in northern Canada. The legal framework related to genetic resources and the cultural shift of universities towards commercial goals in research influence the environment for negotiating research agreements. Current guidelines for research agreements do not offer appropriate guidelines to achieve mutual benefit, reflect unequal bargaining power or take the relationship between parties into account. CONCLUSIONS: Relational contract theory may be a useful framework to address the social, cultural and legal hurdles inherent in creating research agreements.

Challenges in conducting community-driven research created by differing ways of talking and thinking about science: a researcher's perspective.

Increasingly, health scientists are becoming aware that research collaborations that include community partnerships can be an effective way to broaden the scope and enhance the impact of research aimed at improving public health. Such collaborations extend the reach of academic scientists by integrating a variety of perspectives and thus strengthening the applicability of the research. Communication challenges can arise, however, when attempting to address specific research questions in these collaborations. In particular, inconsistencies can exist between scientists and community members in the use and interpretation of words and other language features, particularly when conducting research with a biomedical component. Additional challenges arise from differing perceptions of the investigative process. There may be divergent perceptions about how research questions should and can be answered, and in expectations about requirements of research institutions and research timelines. From these differences, misunderstandings can occur about how the results will ultimately impact the community. These communication issues are particularly challenging when scientists and community members are from different ethnic and linguistic backgrounds that may widen the gap between ways of talking and thinking about science, further complicating the interactions and exchanges that are essential for effective joint research efforts. Community-driven research that aims to describe the burden of disease associated with Helicobacter pylori infection is currently underway in northern Aboriginal communities located in the Yukon and Northwest Territories, Canada, with the goal of identifying effective public health strategies for reducing health risks from this infection. This research links community representatives, faculty from various disciplines at the University of Alberta, as well as territorial health care practitioners and officials. This highly collaborative work will be used to illustrate, from a researcher's perspective, some of the challenges of conducting public health research in teams comprising members with varying backgrounds. The consequences of these challenges will be outlined, and potential solutions will be offered.

Challenges created by data dissemination and access restrictions when attempting to address community concerns: individual privacy versus public wellbeing.

BACKGROUND: Population health data are vital for the identification of public health problems and the development of public health strategies. Challenges arise when attempts are made to disseminate or access anonymised data that are deemed to be potentially identifiable. In these situations, there is debate about whether the protection of an individual's privacy outweighs potentially beneficial public health initiatives developed using potentially identifiable information. While these issues have an impact at planning and policy levels, they pose a particular dilemma when attempting to examine and address community concerns about a specific health problem. METHODS: Research currently underway in northern Canadian communities on the frequency of Helicobacter pylori infection and associated diseases, such as stomach cancer, is used in this article to illustrate the challenges that data controls create on the ability of researchers and health officials to address community concerns. RESULTS: Barriers are faced by public health professionals and researchers when endeavouring to address community concerns; specifically, provincial cancer surveillance departments and community-driven participatory research groups face challenges related to data release or access that inhibit their ability to effectively address community enquiries. The resulting consequences include a limited ability to address misinformation or to alleviate concerns when dealing with health problems in small communities. CONCLUSIONS: The development of communication tools and building of trusting relationships are essential components of a successful investigation into community health concerns. It may also be important to consider that public wellbeing may outweigh the value of individual privacy in these situations. As such, a re-evaluation of data disclosure policies that are applicable in these circumstances should be considered.