Sharp, Richard R.

As genomic sequencing expands to screen larger numbers of individuals, offering genetic counseling to everyone may not be possible. One approach to managing this limitation is for a genetic counselor to communicate clinically actionable results in person or by telephone, but report other results by mail. We employed this approach in a large genomic implementation study. In this paper, we describe participants’ experiences receiving genomic screening results by mail. We conducted 50 semi-structured telephone interviews with individuals who received neutral genomic screening results by mail. Most participants were satisfied receiving neutral results by mail. Participants generally had a good understanding of results; however, a few participants had misunderstandings about their genomic screening results, including mistaken beliefs about their disease risk and the comprehensiveness of the test. No one reported plans to alter health behaviors, defer medical evaluations, or take other actions that might be considered medically problematic. Reporting neutral results by mail is unlikely to cause recipients distress or generate misunderstandings that may result in reduced vigilance in following recommended preventive health strategies. Nonetheless, some individuals may benefit from additional genetic counseling support to help situate their results in the context of personal concerns and illness experiences.

Introduction: Minority communities have had limited access to advances in genomic medicine. Mayo Clinic and Mountain Park Health Center, a Federally Qualified Health Center in Phoenix, Arizona, partnered to assess the feasibility of offering genomic screening to Latino patients receiving care at a community-based health center. We examined primary care provider (PCP) experiences reporting genomic screening results and integrating those results into patient care. Methods: We conducted open-ended, semi-structured interviews with PCPs and other members of the health care team charged with supporting patients who received positive genomic screening results. Interviews were recorded, transcribed, and analyzed thematically. Results: Of the 500 patients who pursued genomic screening, 10 received results indicating a genetic variant that warranted clinical management. PCPs felt genomic screening was valuable to patients and their families, and that genomic research should strive to include underrepresented minorities. Providers identified multiple challenges integrating genomic sequencing into patient care, including difficulties maintaining patient contact over time; arranging follow-up medical care; and managing results in an environment with limited genetics expertise. Providers also reflected on the ethics of offering genomic sequencing to patients who may not be able to pursue diagnostic testing or follow-up care due to financial constraints. Conclusions: Our results highlight the potential benefits and challenges of bringing advances in precision medicine to community-based health centers serving under-resourced populations. By proactively considering patient support needs, and identifying financial assistance programs and patient-referral mechanisms to support patients who may need specialized medical care, PCPs and other health care providers can help to ensure that precision medicine lives up to its full potential as a tool for improving patient care.

Given the dearth of established safe and effective interventions to respond to COVID-19, there is an urgent ethical imperative to conduct meaningful clinical research. The good news is that interventions to be tested are not in short supply. Unfortunately, the human and material resources needed to conduct these trials are finite. It is essential that trials be robust and meet enrollment targets and that lower-quality studies not be permitted to displace higher-quality studies, delaying answers to critical questions. Yet, with few exceptions, existing research review bodies and processes are not designed to ensure these conditions are satisfied. To meet this challenge, we offer guidance for research institutions about how to ethically consolidate and prioritize COVID-19 clinical trials, while recognizing that consolidation and prioritization should also take place upstream (among manufacturers and funders) and at a higher level (e.g. nationally). In our proposed three-stage process, trials must first meet threshold criteria. Those that do are evaluated in a second stage to determine whether the institution has sufficient capacity to support all proposed trials. If it does not, the third stage entails evaluating studies against two additional sets of comparative prioritization criteria: those specific to the study and those that aim to advance diversification of an institution’s research portfolio. To implement these criteria fairly, we propose that research institutions form COVID-19 research prioritization committees. We briefly discuss some important attributes of these committees, drawing on the authors’ experiences at our respective institutions. Although we focus on clinical trials of COVID-19 therapeutics, our guidance should prove useful for other kinds of COVID-19 research, as well as non-pandemic research, which can raise similar challenges due to the scarcity of research resources.

AbstractPopulation‐based genomic screening has the potential to improve health outcomes by identifying genetic causes of disease before they occur. While much attention has been paid to supporting the needs of the small percentage of patients who will receive a life‐altering positive genomic screening result that requires medical attention, little attention has been given to the communication of negative screening results. As there are currently no best practices for returning negative genomic screening results, we drew on experiences across the electronic medical records and genomics (eMERGE) III Network to highlight the diversity of reporting methods employed, challenges encountered in reporting negative test results, and “lessons learned” across institutions. A 60‐item survey that consisted of both multiple choice and open‐ended questions was created to gather data across institutions. Even though institutions independently developed procedures for reporting negative results, and had very different study populations, we identified several similarities of approach, including but not limited to: returning results by mail, placing results in the electronic health record via an automated process, reporting results to participants' primary care provider, and providing genetic counseling to interested patients at no cost. Differences in procedures for reporting negative results included: differences in terminology used to describe negative results, definitions of negative results, guidance regarding the meaning of negative results for participants and their family members, and recommendations for clinical follow up. Our findings highlight emerging practices for reporting negative genomic screening results and highlight the need to create patient education and clinical support tools for reporting negative screening results.

AbstractBackgroundData shared for research use must be de‐identified to protect participant confidentiality. A recent study has shown that face imagery from brain imaging studies could be used to re‐identify anonymous participants via automatic face recognition, linking them with all study‐collected protected health information. Here we measure how well existing software for removing MRI face imagery protects against this privacy threat.MethodWe recruited 153 participants with existing 3D FLAIR MRI and photographed their face from 5 varying angles. We used surf_ice to reconstruct each participant’s face from their MRI and tested whether free, publicly‐available face recognition software (Microsoft Azure) could match their photos to their correct MRI. We tested two existing programs for removing face voxels in MRI: mri_deface (FreeSurfer) and pydeface (python package), and one in‐house implementation. We observed that existing methods often left participants’ eyes intact while removing most of their nose/mouth/chin. This prevented Azure from detecting the reconstructions as faces, therefore preventing its attempt of face recognition. We hypothesized that the retained eye imagery alone could be sufficient for face recognition, if a face were detected. Therefore, we also reconstructed each de‐faced MRI after applying novel pre‐processing that replaced any removed/missing face voxels with those from our population‐average template, e.g. replacing missing noses/mouths/chins with population‐average noses/mouths/chins, before testing face recognition.ResultsWithout any MRI de‐facing, Microsoft Azure correctly matched 78% of participants’ photos to their MRI. After mri_deface and pydeface, 8% and 6% were still identified, respectively. After preprocessing the de‐faced MRI to replace missing areas with those from a population‐average template prior to face reconstruction, the face imagery remaining in the de‐faced images was enough to allow re‐identification of 23% and 20% of participants, respectively. With an in‐house face removal implementation that removes the whole face from every image, 0% of faces were re‐identified from the standard reconstructions, and 5% were identified from the “missing‐parts‐replacement” reconstructions.ConclusionsEven after applying popular MRI de‐facing software, Microsoft Azure face recognition automatically re‐identified up to 23% of participants. Better de‐facing software is needed to remove more of the face more reliably, without affecting brain measurements from de‐faced images.

As applications of genomic sequencing have expanded, offering genetic counseling support to all patients is arguably no longer practical. Additionally, whether individuals desire and value genetic counseling services for genomic screening is unclear. We offered elective genetic counseling to 5110 individuals prior to undergoing sequencing and 2310 participants who received neutral results to assess demand. A total of 0.2% of the study participants accessed genetic counseling services prior to sequencing, and 0.3% reached out after receiving neutral results. We later conducted 50 interviews with participants to understand why they did not access these services. Many interviewees did not recall the availability of genetic counseling and were unfamiliar with the profession. Interviewees described not needing counseling before sequencing because they understood the study and felt that they could cope with any result. Counseling was considered equally unnecessary after learning neutral results. Although the participants had questions about their results, they did not feel that speaking with a genetic counselor would be helpful. Genomic screening efforts that employ opt-in models of genetic counseling may need to clarify the potential value of genetic counseling support from the outset and feature genetic counseling services more prominently in program materials.