the Genomics Research and Innovation NetworkPurpose: Clinicians and researchers must contextualize a patient's genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care.Methods: Three of the nation's leading children's hospitals launched the Genomic Research and Innovation Network (GRIN), with federated information technology infrastructure, harmonized biobanking protocols, and material transfer agreements. Pilot studies in epilepsy and short stature were completed to design and test the collaboration model. Results:Harmonized, broadly consented institutional review board (IRB) protocols were approved and used for biobank enrollment, creating ever-expanding, compatible biobanks. An open source federated query infrastructure was established over genotype-phenotype databases at the three hospitals. Investigators securely access the GRIN platform for prep to research queries, receiving aggregate counts of patients with particular phenotypes or genotypes in each biobank. With proper approvals, de-identified data is exported to a shared analytic workspace. Investigators at all sites enthusiastically collaborated on the pilot studies, resulting in multiple publications. Investigators have also begun to successfully utilize the infrastructure for grant applications. Conclusions:The GRIN collaboration establishes the technology, policy, and procedures for a scalable genomic research network.Genetics in Medicine (2020) 22:371-380; https://doi.

The oversight of research involving human participants is a complex process that requires institutional review board (IRB) review as well as multiple non-IRB institutional reviews. This multifaceted process is particularly challenging for multisite research when each site independently completes all required local reviews. The lack of inter-institutional standardization can result in different review outcomes for the same protocol, which can delay study operations from start-up to study completion. Hence, there have been strong calls to harmonize and thus streamline the research oversight process. Although the IRB is only one of the required reviews, it is often identified as the target for harmonization and streamlining. Data regarding variability in decision-making and interpretation of the regulations across IRBs have led to a perception that variability among IRBs is a primary contributor to the problems with review of multisite research. In response, many researchers and policymakers have proposed the use of a single IRB of record, also called a central IRB (CIRB), as an important remedy. While this proposal has merit, the use of a CIRB for multisite research does not address the larger problem of completing non-IRB institutional review in addition to IRB review—and coordinating the interdependence of these reviews. In this paper we describe the overall research oversight process, distinguish between IRB and institutional responsibilities, and identify challenges and opportunities for harmonization and streamlining. We focus on procedural and organizational issues and presume that the protection of human subjects remains the paramount concern. Suggested modifications of IRB processes that focus on time, efficiency, and consistency of review must also address what effect such changes have on the quality of review. We acknowledge that assessment of quality is difficult in that quality metrics for IRB review remain elusive. At best, we may be able to assess the time it takes to review protocols and the consistency across institutions.

Residual clinical samples represent a very appealing source of biomaterial for translational and clinical research. We describe the implementation of an opt-in biobank, with consent being obtained at the time of registration and the decision stored in our electronic health record, Epic. Information on that decision, along with laboratory data, is transferred to an application that signals to biobank staff whether a given sample can be kept for research. Investigators can search for samples using our i2b2 data warehouse. Patient participation has been overwhelmingly positive and much higher than anticipated. Over 86% of patients provided consent and almost 83% requested to be notified of any incidental research findings. In 6 months, we obtained decisions from over 18 000 patients and processed 8000 blood samples for storage in our research biobank. However, commercial electronic health records like Epic lack key functionality required by a registrar-based consent process, although workarounds exist.

With passage and implementation of the Affordable Health Care Act, more vulnerable segments of the U.S. population will now have access to regular health care and increased opportunities to participate in biomedical research. Yet, access to new groups brings with it new responsibilities for investigators, most importantly, reducing burdens for participants. Data collected through this small pilot study suggest several preliminary but potentially important findings when working with adults from low-income populations: First, while all participants read some parts of the consent forms (55%), only a minority reported reading the entire form (45%); second, 73% of participants reported understanding the study very well whereas only 27% reported understanding the study "a little"; third, there was a slight reported advantage of the simplified form over the regular form; however, this difference varied by section. Relatedly, other research has shown a high incidence of persons reading none of the consent form, but signing a statement that they have read and understood the study. Why does this occur? What are we teaching people when we request that they sign a consent form they have chosen not to read? What are the ethical and regulatory implications? Embedded ethics studies such as this one, although pilot and preliminary in nature, offer a number of advantages, such as stimulating additional scientific inquiry as well as challenging established institutional practices.