Jan. 27, 2016 | It was Christmas night and Yogesh Jethava, M.D., was worried.
Working the holiday at UAMS Medical Center, he had just diagnosed a leukemia patient’s rare, life-threatening liver disease. The only known treatment was a drug awaiting U.S. Food & Drug Administration approval and not available at most medical centers.
What he thought would be a straightforward emergency-use request to the pharmaceutical company that developed the drug, turned into a near impossible hurdle when he was told that UAMS would have to go through the complex process of opening a clinical trial to receive the drug.
That’s when an extraordinary effort by dedicated UAMS employees from multiple offices began to unfold.
Opening a clinical trial typically takes months, and UAMS’ research support offices were closed for the long holiday weekend. Although Jethava had alerted the appropriate people, he wasn’t expecting what happened next.
While most people were busy sampling leftover pie Christmas night, UAMS’ Sandy Annis and Jennifer Roberts were at their home computers catching up on work.
Annis, who leads the Clinical Trials Office for the Winthrop P. Rockefeller Cancer Institute, saw Jethava’s request in an email from Roberts, director of the Research Pharmacy.
“Jennifer and I have worked together for so long she knew who to contact,” Annis said. “Luckily Jennifer included several of the appropriate people on campus and had already talked to the company.”
The following day Annis completed work on about 30 documents for the drug company. She also drafted an emergency-use informed consent document for the patient to sign. Any hope of getting the clinical trial approved quickly would also require involvement and approval from other UAMS officials, including Suzanne Alstadt, director of the Office of Research and Sponsored Programs, Dori Wong-Scoggins, senior contracts attorney, and Jennifer Holland, director of the Institutional Review Board office.
“In my 12 years in this office, this is the first time we’ve ever attempted to get something like this accomplished on a holiday or a weekend,” Annis said. “Amazingly everybody was on email and they were responsive. The drug company was, too.”
They worked by email and text, often using their smart phones. Wong-Scoggins was traveling in California that Saturday after Christmas. She used a smartphone to negotiate and edit the agreement with the drug company.
“I was a passenger in the car going up to Napa with my family,” Wong-Scoggins said. “Editing on a smartphone app is doable, but it’s harder. I was getting car sick.”
Holland, who was driving home from Tennessee the same day, counted more than 60 emails and text messages. When her UAMS email inbox reached capacity on her phone, she switched to her gmail account.
“Talk to text was a lifesaver,” Holland said. “I processed the IRB acknowledgement letter at a gas station parking lot somewhere between Nashville and Memphis.”
The biggest challenge, Holland said, was working through the drug company’s requirements.
“I’ve worked on several of these types of emergency-use situations in the past 15 years, and this is the first time we’ve ever been asked to fully execute a clinical trial agreement,” she said. Despite the obstacles, the clinical trial agreement was approved and the drug, Defibrotide, was at UAMS three days later.
Jethava said he was amazed at the extraordinary efforts of so many research staff. “This is the most remarkable thing that can happen,” Jethava said. “It is unheard of.”
Annis attributed the accomplishment to the group’s many years of working together, dedication to UAMS, and trust in each other.
“I don’t think this would have worked if even one person wasn’t a player,” she said. “It took everybody.”
She said there was no consideration of waiting until the following Monday to work on the request.
“It never crossed our minds,” she said. “We knew this patient was in a bad situation and there wasn’t any other alternative medically. We would expect the same if it had been our own family.”
When the call went out in 2015 for innovative collaboration ideas involving the Clinical and Translational Science Award (CTSA) consortium, UAMS researchers joined their CTSA colleagues to offer six proposals.
Two of those proposals are moving to the next phase; full UO1 applications were recently invited by the NIH National Center for Advancing Translational Sciences (NCATS). The two are led locally by UAMS Translational Research Institute (TRI)-supported researchers Mary Aitken, M.D., M.P.H., and Mathias Brochhausen, Ph.D. “I am very proud of all the researchers who submitted proposals, and I am excited by the two selected to go forward,” said Laura James, M.D., TRI director. “This new NCATS initiative has provided a great opportunity to showcase our expertise in translational research and our ability to work effectively in a collaborative national network.”
Linking Biobank Data
Brochhausen, principal investigator for the UAMS site, views his U01 collaboration with four other CTSA institutions as an opportunity to achieve the nationally elusive dream of making biobank data from multiple institutions available to researchers across the United States.
“We think now we have the right group of people to actually address the issue,” said Brochhausen, an assistant professor in the Department of Biomedical Informatics.
Other collaborating sites are Duke University, Medical University of South Carolina, University of Michigan, and University of Pennsylvania.
Biobanks include collections of biospecimens and data from electronic health records . Access to multiple sources of biobank data is expected to be a strong driver of biomarker discovery, hypothesis generation and new therapeutics. The biggest hurdle has been the lack of standard terminology among biobanks, Brochhausen said. To address the challenge, the collaborative developed an “integrative semantic framework,” with a common language for biobank data. Its proposal also integrates local informed consent procedures for donor specimens.
“For translational research, that is really significant because our proposal will allow researchers to query multiple databases from multiple sites,” Brochhausen said. “With informed consent as part of this program, we’ll reduce delays by weeding out query results that researchers can’t use.”
Educating Translational Researchers
Aitken is the UAMS site principal investigator collaborating with researchers at six other institutions to develop and improve upon educational curricula and tools supporting the training of translational scientists. The collaborating sites are the University of Utah, Ohio State University, Tufts University, University of California, Irvine, University of New Mexico, and Vanderbilt University.
“Our preliminary proposal was well received,” said Aitken, co-director of TRI’s KL2 Mentored Research Career Development Scholar Award program. “The full proposal will allow more detail about the courses to be offered across the consortium.”
The proposal, which targets KL2, TL1 and other trainees, calls for further developing the best education programs at each institution. It includes TRI-supported implementation science, regulatory science and community engagement as areas of training that UAMS could offer to other institutions.
“The idea is to provide courses lasting up to fivedays that trainees could travel to,” said Aitken, a professor in the Department of Pediatrics. “Telemedicine and online options are also likely.”
The collaborative’s proposal also calls for the development of preconference short courses that could be offered in conjunction with the annual Association for Clinical and Translational Sciences (ACTS) meeting each April.
Aitken is working closely with other UAMS research and education leaders on the project, including Geoffrey Curran, Ph.D., Jay Gandy, Ph.D., Laura James, M.D., Robert E. McGehee, Ph.D., Nancy Rusch, Ph.D., and Kate Stewart, M.D., M.P.H.
If approved, each research program will receive up to $500,000 a year for five years.
The January TRIbune newsletter features two TRI-supported collaborations with multiple institutions across the country. The collaborations led at UAMS by Mary Aitken, M.D., M.P.H., and Mathias Brochhausen, Ph.D., were invited to submit full applications in February by the NIH National Center for Advancing Translational Sciences (NCATS).
Also in this issue, TRI Director Laura James, M.D., writes about ARresearch.org, a TRI-sponsored participant recruitment website. A key feature of the website is a registry for people to sign up as potential research participants. You’ll also read about a BioVentures startup with TRI connections, PinPoint Testing LLC; new KL2 Scholars Bryce Marquis, Ph.D., and Shona Ray-Griffith, M.D.; a TRI perspective from Jean McSweeney, Ph.D., R.N.; and recent publications of TRI-supported researchers. It’s all in The TRIbune.
The 1-hour hands-on trainings will be conducted Feb. 23, noon – 1 p.m. and 4 – 5 p.m.; March 2, 4 – 5 p.m.; and March 8, noon – 1 p.m.
All trainings will be held in EDII 8/105 A/B. Register in Training Tracker. Sign up now – each training is limited to 30 participants. Contact: Nia Indelicato, firstname.lastname@example.org.