A new software tool developed at the University of Arkansas for Medical Sciences (UAMS) will help researchers quickly create consent documents in plain language for their prospective study volunteers.

Called the Informed Consent Navigator, the web-based tool breaks new ground with its ability to guide researchers through the creation of plain-language informed consent forms at an eighth-grade reading level or below. The Journal of Clinical and Translational Science published the Translational Research Institute team’s work in December, drawing immediate interest from several research institutions across the United States.

“This is a big win for health equity and a big achievement for UAMS,” said co-author Mathias Brochhausen, Ph.D., a professor in the College of Medicine Department of Biomedical Informatics.

Interdisciplinary Research
First-author Jonathan Bona, Ph.D., led creation of the computer-guided navigation as part of an interdisciplinary research team that includes biomedical informaticists, software developers, research ethicists, and experts in community engagement, health literacy, health education, plain-language writing, clinical trials and informed consent.

“What has been really novel and beneficial is working with folks from across UAMS to make this the best possible tool for researchers and the community,” said Bona, an assistant professor in the College of Medicine’s Department of Biomedical Informatics.

The team was assembled and supported by UAMS Translational Research Institute Director Laura James, M.D., a co-author.

“This project truly played to UAMS’ strengths and is a testament to multidisciplinary team science and the vital support of the Translational Research Institute,” said Brochhausen. “In addition to the institute’s financial support, Dr. James and her team have been with us in the trenches, attending our meetings and helping connect us to key resources.”

Ensuring Readability
Consent forms are often long, detailed, and introduce new concepts, said co-author Alison Caballero, MPH, CHES, director of the Center for Health Literacy. The forms can be a barrier to conducting research, especially with populations underrepresented in research and with limited health literacy.

“Using language that is readable, understandable and actionable is a challenge, but it is essential for truly informed consents and ensuring the greatest possible diversity in research,” said Caballero, an associate professor.

While other institutions across the U.S. have been working on similar automated consent processes, UAMS appears to be first with its automated plain-language consents.  

“We were able to get further than any other group with our tool’s added health equity benefits,” Brochhausen said.

The Informed Consent Navigator builds on years of work by a collaborative team including the UAMS Center for Health Literacy, which created a plain-language consent form template and made it available to all researchers. Plain-language experts at the center created a large bank of text that is approved by the UAMS Institutional Review Board and covers a broad range of research. Now part of the navigator, the text is automatically populated in the informed consent form based on the user’s answers to questions presented by the navigator.

Where researchers must write original text about their specific studies, the navigator provides instructional text, content examples and real-time feedback with readability scores and suggestions to improve readability.

The navigator also uses survey logic that helps tailor what researchers see as they are guided through the process, reducing the difficulty and eliminating errors often made when using print-based templates.

“The goal for this is not just to make it easier for researchers to build forms, but to do so in a way that checks and encourages — and in some cases enforces — that the forms are readable,” Bona said.

Next Steps
The team plans to pilot the Informed Consent Navigator with clinical research studies at UAMS and other institutions. Prior to that, the latest version of the navigator will be presented to a Community Review Board made up of community representatives recruited by the Translational Research Institute’s Community Engagement team.

“Having community reviewers tell us what is clear and what is not clear is very useful,” Bona said, noting that the community board has given its feedback twice before. “We’ve had great communication with the board and their input has already led to improvements in the navigator.”

Longer term, the team will establish an electronic consenting platform (e-consent). It will also work toward artificial intelligence-powered management of consents to expand the navigator’s functionality.

Bona said the team ultimately hopes to see the navigator deployed at research institutions across the U.S. and beyond with the ability to query the network’s data.

UAMS Principal Investigator: Kyle Kalkwarf, M.D., assistant professor, College of Medicine Department of Surgery, Division of Trauma and Acute Care Surgery

Summary: This multi-site clinical trial involving hospitalized traumatic brain injury patients will test the effectiveness of a non-invasive device (Infrascanner) for detecting the growth of intracranial hematomas.

Significance: The study of this FDA-approved device, which uses near-infrared light to detect bleeding, may lead to earlier diagnosis and improved treatments for traumatic brain injury patients, especially in areas with limited resources, such as rural America or on military deployments

TRI Services: Medicare coverage analysis, study budget development, regulatory and nurse/clinical coordinator support, administration of Clinical Trial Management System, and post-award financial management

Sponsor: University of Alabama at Birmingham

Funding: U.S. Department of Defense

A National Institutes of Health (NIH) grant will allow UAMS researcher Nirmala Parajuli, DVM, Ph.D., to study a novel way to improve the long-term outcomes of patients who receive kidneys from deceased donors.

Parajuli, an assistant professor in the College of Medicine Department of Pharmacology and Toxicology, will use the five-year $2.46 million grant to study a drug therapy that could reduce damage to donated kidneys during cold storage.

Transplants from deceased donors account for about 70% of all kidney transplants, and long-term outcomes are generally poor.

“There are about 100,000 patients waiting for kidney transplants, and many of them will die while they are waiting,” Parajuli said. “My goal is to reduce the kidney injury caused by cold storage and increase the pool of healthy kidneys available to the people who need them.”

In her preclinical research, she is testing drugs mixed in the solution used to store kidneys from rats and donated human kidneys that were rejected for transplantation.

The drugs, Parajuli hopes, will block the molecular pathways that play a role in kidney injury during storage, which ultimately will increase long-term kidney survival.

As a UAMS Research Academy Scholar, Parajuli received training and other support to develop her grant submission. The academy’s Mentored Grant-Writing program is supported by the UAMS Division of Research and Innovation, the Translational Research Institute, and the Winthrop P. Rockefeller Cancer Institute.

The Translational Research Institute is supported by a Clinical and Translational Science Award from the NIH National Center for Advancing Translational Sciences.

A National Institutes of Health (NIH) grant will allow UAMS researcher Isabelle Racine Miousse, Ph.D., to ramp up her study of a nutrient that may have a role in the effectiveness of immunotherapy for cancer patients.

Miousse will receive $220,000 per year for up to five years as one of four project leaders at the Arkansas Integrative Metabolic Research Center, a new NIH-funded Center of Biomedical Research Excellence (COBRE) at the University of Arkansas, Fayetteville. The university announced April 6 that the center will receive $10.8 million over five years.

The funding will support Miousse’s preclinical cancer studies involving methionine, an amino acid important for human growth and derived primarily from consuming meat.

Miousse, an assistant professor in the UAMS College of Medicine Department of Biochemistry and Molecular Biology, will test whether reducing dietary methionine can improve results of immunotherapy drugs used to treat melanoma patients.

“This has never been tried in combination with immunotherapy drugs,” Miousse said, noting that immunotherapy alone works remarkably well, but only for 50% of melanoma patients. “So far the results of this research are very encouraging, and I am hopeful that this next phase of study will take us into clinical trials.”

Unlike most cancer treatments, she notes, this one has beneficial side effects.

“Reducing methionine in the diet promotes the metabolism of fats and sugars in animal models,” Miousse said. “Methionine restriction could fight cancer and improve general health at the same time.”

Miousse’s work has been supported by the UAMS Translational Research Institute’s two-year KL2 Mentored Research Career Development Award for promising early career researchers. The KL2 provides salary support, research seed funding of $50,000 and translational research training. The institute is supported by a Clinical and Translational Science Award from the NIH National Center for Advancing Translational Sciences.

LITTLE ROCK – Early results from a University of Arkansas for Medical Sciences (UAMS)-led COVID-19 antibody study show that 3.5% of Arkansans have been infected with the novel coronavirus through August.

UAMS researcher Joshua Kennedy, M.D., revealed the initial findings of the Arkansas Coronavirus Antibodies Seroprevalence Survey during a presentation Oct. 21 with Laura James, M.D., director of the UAMS Translational Research Institute.

The Arkansas Research Alliance (ARA)-sponsored talk focusing on UAMS’ COVID-19 research efforts featured James, an ARA fellow, Kennedy and John Arthur, M.D., Ph.D., also a UAMS COVID-19 researcher. UAMS has eight other studies testing new therapies for COVID-19 either active or in startup.

Kennedy, associate professor in the College of Medicine Department of Pediatrics, along with Craig Forrest, Ph.D., and Karl Boehme, Ph.D., associate professors in the College of Medicine Department of Microbiology and Immunology, have spearheaded an effort to analyze blood samples from Arkansans.

One aspect of the study involved using remnant blood samples from patients who visit UAMS clinics, including three Regional Campus clinics, and have their blood drawn for health reasons other than COVID-19. The samples, which would be discarded otherwise, are being collected and shipped to UAMS from across the state for the antibody test, which was developed in the laboratories of Boehme and Forrest.

Of 1,220 adult blood samples tested so far, 43 were positive, or 3.5%. From this analysis, samples were collected in July and August, 2020. While low overall, Kennedy said, there are noteworthy differences across racial and ethnic groups:

• Hispanic (13 of 73 positive = 17.8%)
• Black/African American (21/501 = 4.19%)
• White/Caucasian (7/550 = 1.27%)

Kennedy said that, “based on the data and statistical analysis to date, Hispanics/Latinx and Blacks/African Americans have a higher percentage of positive COVID-19 antibody tests. This relationship will need to be studied further for other factors that might influence these numbers. We hope to work through some of these issues over the next two waves of the study.”

“These early results show the importance of our efforts to survey statewide,” said James, associate vice chancellor for Clinical and

Translational Research at UAMS. “We will continue to evaluate antibody rates over the next several months to monitor the impact of COVID-19 in Arkansas.”

Seroprevalence is the proportion of people in a population whose blood serum tests positive for a particular disease. Unlike diagnostic tests for COVID-19 the seroprevalence antibody testing looks back into the immune system’s history. A positive antibody test means the person was exposed to the virus and developed antibodies against the virus.

It will give state leaders a good estimate of how many Arkansans have been infected with the virus since it first came to the state, even if they did not become ill or have symptoms.

Kennedy praised the collaboration of UAMS Regional Campuses, whose family medical centers in Fayetteville, Fort Smith and Pine Bluff are all contributing remnant blood samples. The collaboration was also made possible by the new UAMS Rural Research Network and the Translational Research Institute, whose resources are helping make use of Regional Campuses’ infrastructure to include rural areas of Arkansas in health research.

The study began this summer after UAMS researchers developed high-accuracy antibody testing methods. As part of the research program, UAMS is collecting blood samples from nearly 7,500 Arkansas adults and children. Arkansas Children’s is leading the pediatric component of the study. The UAMS College of Public Health is leading the epidemiology component of the study, using the contact tracing call center to enroll study participants and collect health histories and blood samples from individuals who represent the entire state.

The study is supported by $3.3 million in federal coronavirus aid that was then allocated by the Arkansas Coronavirus Aid, Relief and

Economic Security Act Steering Committee created by Gov. Asa Hutchinson.

The Translational Research Institute is supported by grant TL1 TR003109 through the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH).