Jennifer B. McCormick

Improving understanding in the research informed consent process: A systematic review of 54 interventions tested in randomized control trials

BackgroundObtaining informed consent is a cornerstone of biomedical research, yet participants comprehension of presented information is often low. The most effective interventions to improve understanding rates have not been identified.PurposeTo systematically analyze the random controlled trials testing interventions to research informed consent process. The primary outcome of interest was quantitative rates of participant understanding; secondary outcomes were rates of information retention, satisfaction, and accrual. Interventional categories included multimedia, enhanced consent documents, extended discussions, test/feedback quizzes, and miscellaneous methods.MethodsThe search spanned from database inception through September 2010. It was run on Ovid MEDLINE, Ovid EMBASE, Ovid CINAHL, Ovid PsycInfo and Cochrane CENTRAL, ISI Web of Science and Scopus. Five reviewers working independently and in duplicate screened full abstract text to determine eligibility. We included only RCTs. 39 out of 1523 articles fulfilled review criteria (2.6%), with a total of 54 interventions. A data extraction form was created in Distiller, an online reference management system, through an iterative process. One author collected data on study design, population, demographics, intervention, and analytical technique.ResultsMeta-analysis was possible on 22 interventions: multimedia, enhanced form, and extended discussion categories; all 54 interventions were assessed by review. Meta-analysis of multimedia approaches was associated with a non-significant increase in understanding scores (SMD 0.30, 95% CI, -0.23 to 0.84); enhanced consent form, with significant increase (SMD 1.73, 95% CI, 0.99 to 2.47); and extended discussion, with significant increase (SMD 0.53, 95% CI, 0.21 to 0.84). By review, 31% of multimedia interventions showed significant improvement in understanding; 41% for enhanced consent form; 50% for extended discussion; 33% for test/feedback; and 29% for miscellaneous.Multiple sources of variation existed between included studies: control processes, the presence of a human proctor, real vs. simulated protocol, and assessment formats.ConclusionsEnhanced consent forms and extended discussions were most effective in improving participant understanding. Interventions of all categories had no negative impact on participant satisfaction or study accrual. Identification of best practices for studies of informed consent interventions would aid future systematic comparisons.

Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol.

OBJECTIVE To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR). PATIENTS AND METHODS We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. RESULTS The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. CONCLUSION This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.

Neurotalk: improving the communication of neuroscience research

There is increasing pressure for neuroscientists to communicate their research and the societal implications of their findings to the public. Communicating science is challenging, and the transformation of communication by digital and interactive media increases the complexity of the challenge. To facilitate dialogue with the public in this new media landscape, we suggest three courses of action for the neuroscience community: a cultural shift that explicitly recognizes and rewards public outreach, the identification and development of neuroscience communication experts, and ongoing empirical research on the public communication of neuroscience.

Strangers at the benchside: research ethics consultation.

Institutional ethics consultation services for biomedical scientists have begun to proliferate, especially for clinical researchers. We discuss several models of ethics consultation and describe a team-based approach used at Stanford University in the context of these models. As research ethics consultation services expand, there are many unresolved questions that need to be addressed, including what the scope, composition, and purpose of such services should be, whether core competencies for consultants can and should be defined, and how conflicts of interest should be mitigated. We make preliminary recommendations for the structure and process of research ethics consultation, based on our initial experiences in a pilot program.

Evaluating the Process of Online Health Information Searching: A Qualitative Approach to Exploring Consumer Perspectives

Background The Internet is a common resource that patients and consumers use to access health-related information. Multiple practical, cultural, and socioeconomic factors influence why, when, and how people utilize this tool. Improving the delivery of health-related information necessitates a thorough understanding of users’ searching-related needs, preferences, and experiences. Although a wide body of quantitative research examining search behavior exists, qualitative approaches have been under-utilized and provide unique perspectives that may prove useful in improving the delivery of health information over the Internet. Objective We conducted this study to gain a deeper understanding of online health-searching behavior in order to inform future developments of personalizing information searching and content delivery. Methods We completed three focus groups with adult residents of Olmsted County, Minnesota, which explored perceptions of online health information searching. Participants were recruited through flyers and classifieds advertisements posted throughout the community. We audio-recorded and transcribed all focus groups, and analyzed data using standard qualitative methods. Results Almost all participants reported using the Internet to gather health information. They described a common experience of searching, filtering, and comparing results in order to obtain information relevant to their intended search target. Information saturation and fatigue were cited as main reasons for terminating searching. This information was often used as a resource to enhance their interactions with health care providers. Conclusions Many participants viewed the Internet as a valuable tool for finding health information in order to support their existing health care resources. Although the Internet is a preferred source of health information, challenges persist in streamlining the search process. Content providers should continue to develop new strategies and technologies aimed at accommodating diverse populations, vocabularies, and health information needs.

Implementing individualized medicine into the medical practice

There is increasing recognition that genomic medicine as part of individualized medicine has a defined role in patient care. Rapid advances in technology and decreasing cost combine to bring genomic medicine closer to the clinical practice. There is also growing evidence that genomic‐based medicine can advance patient outcomes, tailor therapy and decrease side effects. However the challenges to integrate genomics into the workflow involved in patient care remain vast, stalling assimilation of genomic medicine into mainstream medical practice. In this review we describe the approach taken by one institution to further individualize medicine by offering, executing and interpreting whole exome sequencing on a clinical basis through an enterprise‐wide, standalone individualized medicine clinic. We present our experience designing and executing such an individualized medicine clinic, sharing lessons learned and describing early implementation outcomes.

Outcome of Whole Exome Sequencing for Diagnostic Odyssey Cases of an Individualized Medicine Clinic: The Mayo Clinic Experience

OBJECTIVE To describe the experience and outcome of performing whole-exome sequencing (WES) for resolution of patients on a diagnostic odyssey in the first 18 months of an individualized medicine clinic (IMC). PATIENTS AND METHODS The IMC offered WES to physicians of Mayo Clinic practice for patients with suspected genetic disease. DNA specimens of the proband and relatives were submitted to WES laboratories. We developed the Genomic Odyssey Board with multidisciplinary expertise to determine the appropriateness for IMC services, review WES reports, and make the final decision about whether the exome findings explain the disease. This study took place from September 30, 2012, to March 30, 2014. RESULTS In the first 18 consecutive months, the IMC received 82 consultation requests for patients on a diagnostic odyssey. The Genomic Odyssey Board deferred 7 cases and approved 75 cases to proceed with WES. Seventy-one patients met with an IMC genomic counselor. Fifty-one patients submitted specimens for WES testing, and the results have been received for all. There were 15 cases in which a diagnosis was made on the basis of WES findings; thus, the positive diagnostic yield of this practice was 29%. The mean cost per patient for this service was approximately

And then there were two: use of hESC lines.

8000. Medicaid supported 27% of the patients, and 38% of patients received complete or partial insurance coverage. CONCLUSION The significant diagnostic yield, moderate cost, and notable health marketplace acceptance for WES compared with conventional genetic testing make the former method a rational diagnostic approach for patients on a diagnostic odyssey.

Stakeholder engagement: a key component of integrating genomic information into electronic health records

volume 27 number 8 AuGuST 2009 nature biotechnology Using data on cell line shipments obtained from HSCI and WiCell—which curates the NSCB—we see that lines have been neither uniformly available nor uniformly used, indicating far less diversity of materials than most believe8. Our most recent data set tracks WiCell’s distribution of five of its own lines (derived by James Thomson) beginning in 1999, those available from the NSCB after its inception in 2005 and those distributed by HSCI since April 2004. No more than 18 approved cell lines have ever been available through the NSCB and that number is only accurate for the first months of 2009. Importantly, we find that just two NSCB lines—H1 and H9—are commonly used. The story is slightly better for HSCI, where all 28 bench has as much to do with past policies and the field’s history as it does with the variety of lines available in the banks. We enter this discussion with systematic data on the patterns of use of cell lines from the largest US repositories, the NSCB and the Harvard Stem Cell Institute (HSCI; Cambridge, MA, USA). In prior work, we examined the geographical patterns of distribution of hESC lines from these two sources. We showed that despite federal funding restrictions, hESC research is vigorous and growing in the United States. We see that states with high levels of research activity can blunt local laws and policies that would seek to restrict or chill hESC research7. To the Editor: Last month, the US National Institutes of Health (NIH) issued its final guidelines defining the types of human embryonic cell (hESC) lines that would be eligible for public funding. The number of NIHapproved hESC lines available for federal funding was a bellwether issue for scientists during the Bush era prohibition. Originally, the agency announced 78 lines could be used. This was later revised downward to 64, then downward again to 21, the number most often cited in the literature1,2. Among the criticisms of the remaining lines in the National Stem Cell Bank (NSCB) is that they have a limited range of genetic diversity3. Now that the NIH has announced its intention to set up a national registry of hESC lines, the biggest issue facing the agency will be how to rebuild the bank into a robust and valuable research resource. Getting many different stem cell lines— the fundamental tool of regenerative medicine—into numerous laboratories with varied scientific and clinical foci is a worthy goal. We caution, however, that social and institutional factors such as intellectual property rights, access fees, use restrictions and competition shape the choices scientists make about research materials4,5. Federal policies and institutional guidelines, established and well-understood protocols, assays, reagents and the prominence of some lines in the published literature also have an impact. State-level policies can be even more restrictive than federal rules, and the possibility of legal challenges makes transfer of materials to some locales more difficult than others. Indeed, initial social differences (in accessibility, ease of use or availability of technical complements such as known reagents and laboratory procedures) can lead to increasing returns for the selection of particular materials and eventually to lock-in on a dominant but often sub-par technological standard for a field6. In short, the diversity of lines actually in use at the And then there were two: use of hESC lines

Addiction: Current Criticism of the Brain Disease Paradigm

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.Genet Med 15 10, 792–801.Genetics in Medicine (2013); 15 10, 792–801. doi:10.1038/gim.2013.127