DCRI receives CRO Leadership Awards for third year

May 10, 2018 – The DCRI earned top marks in four categories, including Capabilities, Expertise, Quality, and Reliability.

For the third year, the DCRI has been recognized by the CRO Leadership Awards presented by Life Science Leader magazine. The organization was recognized in five out of six categoriesCapabilities, Compatibility, Expertise, Quality, and Reliabilityand listed as a Top Performer in Capabilities, Expertise, Quality, and Reliability. The DCRI also received Individual Attribute Awards for Data Quality, Meeting Overall Project Timelines, Operational Excellence, and Responsiveness.

The awards are based on online surveys conducted by Industry Standard Research. This year, 70 contract research organizations (CROs) were evaluated on more than 20 different performance metrics. The survey respondents came from biopharmaceutical companies and were asked to evaluate only those CROs with which they had worked on an outsourced project within the last 18 months.

A full list of award winners can be found in the May issue of Life Science Leader. A formal awards ceremony will be held June 25 in Boston at the 2018 DIA Global Annual Meeting.

“We are honored to again be recognized for the work we are doing to advance clinical science and improve patient health,” said DCRI Executive Director Eric Peterson, MD, MPH. “These awards are a reflection of the efforts of our faculty, fellows, and operational teams to make the DCRI the world’s leading academic research organization.”

CTTI releases 2017 Annual Report, celebrates 10 years of changing clinical research

May 3, 2018 – The report highlights the organization’s efforts to improve the quality and efficiency of clinical trials.

CTTI logoThe Clinical Trials Transformation Initiative (CTTI) has issued its 2017 Annual Report, celebrating a decade of CTTI impact and highlighting its activities and accomplishments over the past year. The report includes reflections from past and present CTTI leaders, case studies on the use of CTTI recommendations and resources, and a glimpse into what lies ahead for CTTI and the clinical trials enterprise.

CTTI, cofounded by Duke University and the U.S. Food and Drug Administration and hosted by Duke, develops recommendations, tools and resources to enable a high-quality, efficient clinical trial system. The organization studies current clinical trials processes, identifies impediments to beneficial change, and develops consensus-driven, evidence-based recommendations and solutions to improve clinical trials.

Since its founding in 2007, CTTI has completed more than 25 projects with the aim of increasing the quality and efficiency of clinical trials. The resulting recommendations were downloaded more than 26,000 times over the past year.

CTTI issued five new sets of recommendations in 2017, many of which draw on recent advances in technology and data sciences to bring about improvements for clinical trials. The report includes CTTI’s latest recommendations and resources, which offer:

  • Practical guidance for using mobile technology to develop viable novel endpoints for clinical trials.
  • Best practices for assessing and designing registries for use in clinical trials so that the data can meet expectations for FDA review of new products.
  • Actions that can be taken to strengthen the investigator site community and create an environment that sustains long-term investigator engagement.
  • Guidance on planning for and making decisions about pregnancy testing in potential trial participants.
  • Suggested ways to address the unique challenges of conducting pediatric antibacterial trials.

As described in the report, these recommendations and resources are being implemented by organizations across the clinical trial spectrum, including IQVIA, monARC Bionetworks, and the Pulmonary Fibrosis Foundation.

DCRI Imaging: World-class core labs and strategic thought leadership

May 1, 2018 – The DCRI’s Precision Imaging Program is building on its record of success by adding new technologies and capabilities.

Pamela S. Douglas, MD, MACC, FACC, is the Ursula Geller Professor of Research in Cardiovascular Diseases and Director of DCRI’s Precision Imaging Program, which is updating its offerings.

DCRI Imaging launched its Core Lab in 2007 and has worked on many different trials both big and small. What makes the team so successful?

From the time we launched, we set about differentiating ourselves by offering excellence along with continued innovation. We offer the very latest imaging capabilities across therapeutic areas and are rapidly developing even more. Our modalities and applications currently include echocardiography, angiography, ECGs, MRIs, computed tomography, x-rays, and ultrasound—all providing the best quality imaging data for the most accurate results and greatest value to the parent research studies.​

Moving forward, we’re building on our record of success. We are looking at harnessing new technologies, applications, and software within our program. For example, while we have an active 3D program, we are planning for the future by considering adding telemedicine, device imaging, remote imaging, image adjudication, and data capture to our offerings, while keeping all that is good and proven about our current program.

Pamela DouglasYour team does a lot of work for both industry and government sponsors. What should researchers know about the many services you offer?

As a problem-solving group, we’ve enjoyed the support of industry sponsors and extensive repeat business for more than a decade. We’d like to encourage all DCRI investigators to add us to the conversation whenever considering a new study for which imaging can add efficacy or safety information.

Our goal is to harness the capabilities of each of our modalities to provide a deeper understanding of study results, including mechanisms of action and detailed outcomes. The GUIDE-IT heart failure management strategy trial is a perfect example. In this study, clinical data alone failed to prove the primary hypothesis. Through imaging, we demonstrated a positive impact that had not been visible otherwise; specifically, the echocardiographic findings revealed critical differences between subjects in their response to treatment which was dramatically associated with the effectiveness of medical therapy.

Through our close participation with the ASE (American Society of Echocardiography), ACC (American College of Cardiology), and the U.S. FDA, we led the development of these Societies’ and agency’s best practice standards for echocardiograms (echoes) in clinical research and imaging informatics.

When we work on clinical research trials, we are contributing investigators sharing our expertise and services, active partners with sponsors and trial leadership, and a vital step toward the most comprehensive and accurate results.

What are some of the trials DCRI Imaging has worked on?

One of our earliest studies was the landmark PARTNER (Placement of Aortic Transcatheter Valves) trial, the first ever randomized trial of percutaneous aortic valve replacement for severe aortic stenosis. The study included nearly 3,300 patients and more than 17,000 echoes and has led to more than 30 publications (and counting!) for DCRI investigators.

More recently, we became the core echo lab for another innovative intervention for cardiac valve disease: percutaneous mitral valve replacements. The MITRAL trial results were presented as late breaking clinical trials at TCT and at the AHA Scientific Sessions in fall 2017 and have significantly extended the use of devices for structural heart diseases.

Today, we’re the Imaging Coordinating Center for the BASELINE study funded by Verily Life Sciences. This study aims to fundamentally redefine the molecular and other definitions of health and disease. The imaging modalities we are contributing include rest echo, stress echo, and rest ECG, all familiar to us, as well as introducing ophthalmologic and radiologic imaging. Adding these modalities has meant forging new, highly collaborative relationships with the Duke Eye Center and Duke Radiology. In total, we’re coordinating nine imaging modalities on this study, which is very exciting.

When is the best time for researchers to bring the Imaging team into a study?

As soon as possible, even during the early phase of concept discussions. We can consult with teams on the best imaging strategy even before writing their protocol—asking ‘what information can imaging provide to assist in addressing the scientific question?’—and then figuring out a plan to capture this, including the right modality at the right time and analyzed in the right way. Of course, we’re delighted to work on any study for which we can add value—we are adept at rescue studies, too.

Simple one-page tool improves patient satisfaction with doctor visit

April 19, 2018 – Including a short list of goals for the visit makes patients feel empowered, researchers say.

A simple, one-page form given to patients ahead of their doctor visit can significantly improve satisfaction with the care they receive, according to a study by Duke and DCRI researchers.

The low-tech tool, which asks for a list of the topics patients wants to discuss during their visit, helps patients focus on what’s important to them. It also asks if all their questions were addressed at the end of the visit and if they were satisfied, giving doctors real-time feedback on how well they’re addressing their patients’ concerns.

“National surveys show that up to half of all patients leave the clinic visit with an unvoiced need,” said Oren Gottfried, MD, clinical vice chair for quality in the Department of Neurosurgery at Duke University School of Medicine and lead author of a study published this week in the journal Neurosurgery.

Megan Neely“In a typical visit, patients might forget or not articulate all of their concerns, due to being intimidated by the doctor’s office or doctor, feeling anxious or rushed, or not knowing how to share or voice their questions,” Gottfried said. “These miscommunications and missed opportunities can affect care and patient safety.”

To tackle the problem, Gottfried and colleagues developed a short, three-question form that they provided to patients at Duke clinical specialty practices over a one-year period. More than 14,600 patients were involved, and the tool was successfully completed 96 percent of the time.

The DCRI’s Megan Neely, PhD, was among the study’s authors.

The form was developed to augment a national survey tool that is administered by the Agency for Healthcare Research and Quality. That survey, called the Group Consumer Assessment of Healthcare Providers and Systems Clinician (CG-CAHPS), is geared to assess patient experiences, but has several limitations, the Duke researchers said.

It does not provide timely, actionable feedback to doctors, is cumbersome for patients to fill out so many decline to participate, and is primarily designed for primary care, not specialties. In addition, doctors often find these surveys unreliable, biased, or irrelevant to their practice, capturing patient frustrations with things like scheduling and parking instead of care. Most importantly, any feedback from this national survey is de-identified from the patient and delayed months from the encounter, making the results less relevant.

The Duke survey was more direct, and it provided immediate feedback. It also became part of a broader analysis that gave physicians and their practices a way to track progress. The tool worked. Its success was validated by improved global rating scores for physicians on the government’s CG-CAHPS survey, and improved patient satisfaction.

“From a patient standpoint, this simple tool helps them feel and know their doctor is listening to them and addressing their concerns,” Gottfried said. “From a physician standpoint, it very clearly tells them their patients’ goals, which means everyone’s time is used effectively. And doctors, like anyone, appreciate real-time feedback, including positive comments from patients.”

“This is all about patient satisfaction, patient-doctor communication, and doctor satisfaction,” Gottfried said. “In the end it boils down to being more patient-centric, and that’s what health care should be about.”

In addition to Gottfried and Neely, study authors include Rasheedat T. Zakare-Fagbamila, Elizabeth Howell, Ashley Y. Choi, Tracy Z. Cheng, and Mary Clement.

DCRI, University of Oxford to collaborate on chronic kidney disease study

April 18, 2018 – EMPA-KIDNEY will study the effects of empagliflozin in CKD patients with and without diabetes.

The DCRI will partner with the University of Oxford to investigate the effects of empagliflozin (sold under the brand name Jardiance) on the progression of kidney disease and the occurrence of cardiovascular death in adults with established chronic kidney disease. EMPA-KIDNEY will be conducted by the Medical Research Council Population Health Research Unit at the University of Oxford, in partnership with the DCRI. Boehringer Ingelheim and Eli Lilly and Company will provide the funding for the study.

Jennifer Green, MDThe plan to conduct a dedicated outcomes study in adults with chronic kidney disease is based on insights previously obtained from the EMPA-REG OUTCOME trial. That landmark trial investigated the effect of empagliflozin, when added to the standard of care, on cardiovascular outcomes in adults with type 2 diabetes and established cardiovascular disease, compared with placebo. Approximately one-third of patients in the EMPA-REG OUTCOME trial also had established chronic kidney disease at baseline. A secondary exploratory endpoint of the study provided promising data relating to the reduction in the relative risk of new onset or worsening kidney disease. EMPA-KIDNEY is designed to further researchers’ understanding of these data.

Chronic kidney disease is defined as a progressive decline of kidney function over time. About two-thirds of chronic kidney disease cases are attributable to metabolic diseases such as diabetes, hypertension, and obesity. Notably, chronic kidney disease is associated with increased morbidity and mortality. The majority of deaths among people with chronic kidney disease occur as a result of cardiovascular complications, often before reaching end stage renal disease. Chronic kidney disease affects approximately 15 percent of adults in the United States and treatment costs are estimated to exceed $48 billion annually. Because there are currently only few treatment options, the overarching unmet medical need for new treatment options in chronic kidney disease is evident.

“We need to explore new treatment options that can help slow the progression of chronic kidney disease, given that 30 million adults in the United States are living with this condition,” said Jennifer Green, MD, endocrinologist and associate professor of medicine at the DCRI, which is responsible for U.S. trial operations. “The EMPA-REG OUTCOME trial findings prompted us to explore further the effects of empagliflozin on the risk of new or worsening kidney disease in adults with type 2 diabetes and established cardiovascular disease. Now, EMPA-KIDNEY will examine whether empagliflozin has the potential to be a new treatment option for people with chronic kidney disease.”

EMPA-KIDNEY will include approximately 5,000 adults with established chronic kidney disease, with and without diabetes. The primary outcome of the study is to assess the effect of empagliflozin on time to clinically relevant kidney disease progression or cardiovascular death. The study will be part of the empagliflozin clinical development program, the largest clinical development program of an SGLT2 inhibitor.

“Boehringer Ingelheim and Lilly are committed to exploring how Jardiance can potentially fill gaps where unmet treatment needs exist,” said Thomas Seck, MD, vice president of Clinical Development and Medical Affairs – Primary Care, Boehringer Ingelheim Pharmaceuticals, Inc. “Given the institution’s knowledge and history of prestigious research in chronic kidney disease, we are excited to collaborate with the University of Oxford on this initiative to help address a pressing need for people with chronic kidney disease.”

“The EMPA-KIDNEY study, which will build on results of the EMPA-REG OUTCOME trial, will continue to expand our understanding of how Jardiance can impact the lives of a broad range of people with and without diabetes,” said Jeff Emmick, MD, PhD, vice president, Product Development, Lilly Diabetes. “We look forward to this new partnership and the opportunity to follow the progress of the EMPA-KIDNEY study.”

Most prolapse surgeries regress over time, but symptoms remain improved

April 17, 2018 – Despite the procedure’s high failure rates, women say their quality of life is still better five years after surgery.

An estimated one in three women in the United States has a pelvic floor disorder, a condition that often develops after bearing children and getting older. These disorders can lead to incontinence, painful intercourse and even the bulging or prolapse of pelvic organs into the vaginal canal.

Surgeons have been performing procedures to improve these symptoms for decades, but few studies have tracked how patients fared beyond the first couple of years after surgery. A Duke-led study published today in the Journal of the American Medical Association followed women for five years after two common prolapse surgeries and found failure rates for both procedures were equally high, at over 60 percent.

Eric JelovsekHowever, surveys of the nearly 300 women in the study found that even for patients whose surgical adjustments regressed or caused new or worsening symptoms, more than half still reported that their quality of life five years later was much better than before surgery, and relatively few women sought retreatment.

“This was surprising to us,” said lead author J. Eric Jelovsek, MD, director of Data Science for Women’s Health in Obstetrics and Gynecology at Duke and a member of the DCRI. “That failure rate was higher than we expected. But that does not necessarily align with how patients feel, and we don’t know why that is. It is possible the definitions we set for failure in this case were too stringent. We need to do some more research to understand what is the most optimal way to define success or failure, and how that factors in women’s quality of life and desire to seek retreatment.”

The randomized clinical trial, known by the acronym OPTIMAL, began in 2010 as an initiative of the National Institute of Child Health and Human Development (NICHD) Pelvic Floor Disorders Network. The mission was to compare two common treatments for prolapse — sacrospinous ligament fixation (SSLF), resulting in a 70.3 percent failure at five years, and ligament vaginal vault suspension (ULS), resulting in a 61.5 percent failure at five years. Participants’ median age was 57 years.

For both operations, surgeons access the affected area through the vagina, bringing points of the tissue upward to connect with ligaments on the pelvis. The goal is to reattach the woman’s own tissue to support pelvic organs and reduce incontinence. No synthetic mesh is used in either procedure.

If after five years, the repaired tissue descended past the upper third of the vaginal canal, researchers considered the surgery a failure. The procedure was also considered failed if the patient felt a bothersome bulge or sensation of prolapse, or were treated again with surgery or a removable pessary to relieve their symptoms. About 12 percent of ULS patients and 8 percent of SSLF patients were treated again with one of these options.

The trial also evaluated whether several weeks of behavioral therapy and pelvic muscle floor training could improve success rates for either procedure, but there was no significant difference in outcomes.

The results suggest that neither procedure might work as well in the long-term as surgeons once thought, Jelovsek said.

“We may be at the point where we need to think of treating prolapse as treating a chronic disease that’s likely to return over time,” Jelovsek said. “It’s like getting a hip or knee replaced. Will your quality of life improve? Yes. Is it worth it? Absolutely, but down the road this will likely be something we’ll have to revisit.”

However, he said, “These are still very reasonable surgical options to regain quality of life. The surgical improvements to the anatomy might gradually regress, but the relief is significant enough that after five years, more than half of the women report their symptoms were still improved.”

In addition to Jelovsek, study authors included Matthew D. Barber, Linda Brubaker, Peggy Norton, Marie Gantz, Holly E. Richter, Alison Weidner, Shawn Menefee, Joseph Schaffer, Norma Pugh, and Susan Meikle.

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health (U01 HD041249, U10 HD041250, U10 499 HD041261, U10 HD041267, U10 HD054136, U10 HD054214, U10 HD054215, U01 HD069031, and 500 U10 HD054241).

Combining telehealth and physical activity improves physical function for veterans

April 16, 2018 – A pilot study testing the effects of a home-based telephone-supported physical activity program for chronic low back pain provides a foundation for a larger trial to study the effectiveness of these interventions in older veterans.

A pilot randomized clinical trial on older veterans with chronic low back pain was recently published by DCRI researchers in Physical Therapy Journal, the official journal of the American Physical Therapy Association, for their special issue on pain management.

“The prevalence of chronic pain in the American veteran population is very high and among those who have chronic pain, musculoskeletal pain such as chronic back pain is very common,” said the DCRI’s Adam Goode, DPT, PhD, first author of the study. “Considering that in the general population, about 50 percent of all older adults have chronic low back pain and up to 60 percent of all veterans complain of chronic pain, the condition is extremely common and understudied.”

Adam GoodeChronic low back pain is a persistent pain in the lower back region that lasts for at least three months. It represents the second leading cause of disability worldwide and is a major economic problem resulting in approximately 100 to 200 billion dollars per year in costs for the United States. The prevalence of chronic low back pain in adults has increased more than 100 per cent in the last decade and continues to increase dramatically in the aging population in the country affecting both men and women in all ethnic groups with a significant impact on functional capacity and occupational activities.

Set in the Durham Veterans Affairs Healthcare System and funded by the Veterans Health Administration, one of the largest integrated healthcare systems in the United States, the pilot study demonstrated that home-based telephone-supported physical activity interventions are feasible, acceptable and safe for older veterans.

“To improve physical function among older adults was our primary outcome,” said Goode. “Improving function is very important for the population with chronic low back pain, for low back pain in older adults leads to functional decline, which is associated with many deleterious effects such as changes in cognitive function and mortality.”

According to the study, despite current guidelines indicating that individuals with chronic low back pain should participate in regular exercise, less than 40 percent of veterans with chronic pain, including chronic low back pain, use exercise to treat their pain.

“As far as back pain in general is concerned, there are not a lot of interventions that have a large impact on improving outcomes,” said Goode. “One simple intervention is exercise or physical therapy that can considerably improve physical function among older adults and can be successfully delivered in the home setting.”

According to Goode, this study found that a single in-person visit with a physical therapist and a home-based exercise program with telephone support can produce meaningful improvements in multiple outcomes among older adult veterans with chronic low back pain.

“Studies that involve older adults that have greater sample sizes and are of longer duration are the next step, which could be generalizable to the population at large,” said Goode

In addition to Goode, other researchers included Shannon Stark Taylor, S. Nicole Hastings, Catherine Stanwyck, Cynthia Coffman, and Kelli D. Allen.

Video informed consent leads to faster and more diverse patient enrollment

April 9, 2018 – An analysis of data from the PALM study suggests there may be a better way to reach underrepresented populations.

To help boost patient participation in clinical trials, researchers have developed a video-based consent tool to help reach populations that might not otherwise enroll.

When potential participants in the PALM (Patient and Provider Assessment of Lipid Management) study used video consent rather than traditional text, participating sites experienced shorter times from site approach to first patient enrollment and had a more diverse group of patients.

“Traditional text informed consent can be challenging for study subjects, including some older adults, minorities, and those with limited literacy,” said the DCRI’s Alexander Fanaroff, MD. “Video puts a lengthy document into the spoken language, and features real people enthusiastically speaking about the study to the viewer. We wanted to see what effect this tool could have on enrollment.”

The study was published recently in Circulation: Cardiovascular Quality and Outcomes.

In 2015, the PALM study enrolled 7,904 patients at cardiology, endocrinology, and primary care clinics across the U.S. to evaluate cholesterol management practices. Sixty-seven of the 153 participating clinics secured institutional review board (IRB) approval to use the tablet-based video — the remaining clinics did not receive IRB approval because of various regulatory barriers.

A single video was used for all of the sites and featured six vignettes totaling eight minutes in length. Modules described research studies in general, the rationale for the PALM study, detailed study procedures, and other core information found in the text version. A prototype was pilot tested at Duke University Medical Center in 2014, and the PALM video consent was built on feedback from that pilot.

Sites that approved video consent were likely to have a central IRB, according to Fanaroff, and tended to be rural and have a smaller number of providers. This meant that video consent could reach patients not always represented in clinical research, and that multiple patients could be enrolled at once.

Fanaroff’s team compared enrollment patterns and participant diversity between sites that did and did not use the video consent tool. They found that sites with video consent capability enrolled the same number of patients as those without – about three per week – but began enrollment 29 days sooner after site approach. More African-American, elderly patients, and those without college degrees were also enrolled at sites with video consent capability.

“There is considerable literature that videos can help patients with understanding and decision-making, but, to our knowledge, this is the first broad-scale use of video consent in a clinical trial,” said Fanaroff. “Video can help patients feel more comfortable with the process, and making it faster and simpler is certainly a win for clinical research.”

Fanaroff said that although more research is needed, the study showed that video informed consent is a promising tool for both the speed of enrollment and making the patient population more representative. “This way, we may be bringing new sites and patients into the fold,” he said.

Study co-authors include the DCRI’s Eric Peterson, MD, MPH; Tracy Wang, MD, MHS, MSc; Shuang Li, MS; Ann Marie Navar, MD, PhD; Vincent Miller; and Laura E. Webb, CCRP.

Duke to begin clinical trials for Pompe Disease gene therapy this fall

April 5, 2018 – The therapy is based in part on earlier research conducted by Duke researchers.

After decades pioneering treatments for Pompe disease, Duke Health and DCRI researchers have developed a gene therapy they hope could enhance or even replace the only FDA-approved treatment currently available to people with the rare, muscle-crippling disorder.

The experimental therapy uses a modified virus to deliver a gene to the liver, where it produces GAA, an enzyme missing in people with Pompe disease. The method was tested in mice, as described in a study published in 2017 in the journal Molecular Therapy – Methods & Clinical Development.

Researchers are currently screening adults with late-onset Pompe disease as they prepare for a phase I clinical trial to test the safety of the treatment in 20 people with the condition. The trial will be funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with support from the National Center for Advancing Translational Sciences. Both agencies are part of the National institutes of Health. The team also received support from the Duke Clinical & Translational Science Institute.

Pompe disease is an inherited condition that affects approximately 1 in 20,000 babies and can also appear in adulthood. Without the enzyme GAA, bodies can’t metabolize the sugar glycogen. As a result, glycogen builds up in the muscles, leading to degradation of the tissue. If undiagnosed and untreated, it can lead to respiratory problems, heart failure and death.

“The outlook for Pompe disease is much improved since enzyme replacement has become available it can reverse involvement of the heart and prolong survival,” said Dwight Koeberl, MD, PhD, professor of pediatrics and a medical genetics specialist at Duke who developed the new therapy.

The enzyme replacement therapy (ERT), developed using foundational research from Duke, was heralded as a breakthrough for an orphan disease in 2006, and was dramatized in the major motion picture “Extraordinary Measures.”

“But not everyone responds to this treatment,” Koeberl said. “Many patients make some antibodies, and this can really interfere with treatment. Some infants still die from Pompe disease. Others have to add immune suppression to their treatment, which can lead to other complications. Gene therapy could help these patients.”

In the research published in 2017, the Duke-led research team found that a single small dose of gene therapy was as effective as ERT in clearing the buildup of glycogen from the muscles in mice. A larger dose offered superior results to ERT.

A single treatment spurred the liver to continuously produce GAA without additional treatment, the study authors said. Enzyme therapy requires infusions two to four times a month to lower glycogen levels in the muscles.

Unlike ERT, the gene therapy doesn’t trigger an immune response, a reaction that can limit successful treatment in about half of babies with Pompe. In fact, the gene therapy appeared to reverse immune responses in mice that had previously developed antibodies in response to enzyme replacement, Koeberl said.

The gene therapy uses an inactivated form of adeno-associated virus, which does not cause illness and has been used as a delivery system for hemophilia B and muscular dystrophy treatments, among others, Koeberl said.

The emerging gene therapy is just the latest development for a team of scientists at Duke that has been working for three decades to study the causes and potential treatments for glycogen-storage diseases and specifically Pompe.

“When we enter our careers in the field of genetics, we are faced with the many unmet needs for patients with rare diseases,” said the DCRI’s Priya Kishnani, MD, chief of the medical genetics division at the Duke University School of Medicine. “Before enzyme replacement became available for Pompe disease, we would continue to give parents bad news — take your beautiful baby home; he or she will die within their first year of life. I knew we had to do something about this.”

Kishnani has researched Pompe for 25 years, beginning under prominent geneticist Y.T. Chen, the previous chief of the medical genetics division at Duke. In the 1990s and 2000s, Chen and Kishnani worked with biotech firm Genzyme to develop ERT and lead clinical trials.

Since then, Kishnani and dozens of other Duke physicians have been national leaders in Pompe disease, continuing to research the condition, improve the delivery of ERT, manage immune responses to the drug and improve genetic counseling for families.

The Duke team has also helped develop a blood test to diagnose Pompe and a biomarker to monitor severity of the disease and patients’ response to treatment. For nearly 10 years, Kishnani has led a group of physicians to advocate nationally for universal newborn screening, which became a formal recommendation of the U.S. Department of Health and Human Services in 2015. The team’s next step is to develop small molecule or oral drugs that could suppress the buildup of glycogen in the muscles.

“There’s a rich heritage of expertise on glycogen storage disease at Duke, spanning about 40 years,” Kishnani said. “We have continued to grow from the era of cloning genes to developing animal models, to collaborating with pharma to conduct clinical trials here at Duke. I think we have come full circle, from bench to bedside and back to the bench in every aspect of the disease.”

Disclosures: Koeberl developed the technology that is being used in the clinical trial of gene therapy. If the technology is commercially successful in the future, the developers and Duke University may benefit financially. Koeberl has received research and grant support from Sanofi Genzyme Corporation in the past, and the rhGAA (enzyme replacement agent) used in the development of the experimental therapy was supplied by Sanofi Genzyme. Koeberl and Kishnani hold equity in a company that will manufacture the gene therapy.

NESTcc recognizes two DCRI projects

April 3, 2018 – RAPID and SAFE STEMI for Seniors were among 11 projects selected to provide proof of concept for new approaches to real-world evidence generation.

The National Evaluation System for health Technology Coordinating Center (NESTcc) selected two DCRI projects as Medical Device Real-World Evidence Demonstration Projects: Registry Assessment of Peripheral Interventional Devices (RAPID) and Study of Access Site for Enhancing PCI in STEMI (SAFE STEMI for Seniors).

A total of 11 demonstration projects were recognized for their potential to provide proof of concept for innovative and scalable approaches to real-world evidence generation across the medical device total product life cycle (TPLC).

NESTcc was established by the Medical Device Innovation Consortium (MDIC) to serve as a catalyst in establishing functional and efficient pathways for key stakeholders to generate quality, low-cost, near-time real-world evidence for regulatory, coverage, patient, and clinical decision-making.

The RAPID program, comprised of three phases, is focused on devices for peripheral arterial intervention as an archetype of the envisioned TPLC. In addition, it leverages collaborative leadership and methodologies to advance interoperable collection and exchange of electronic health information related to the care and treatment of patients with peripheral arterial disease. Throughout the phases, RAPID aims to:

  • Prioritize data elements
  • Extract registry or EHR data to develop objective performance goals for specific devices and optimize device identification protocols
  • Bring together interoperable datasets from multiple RAPID data partners to support a regulatory decision

SAFE STEMI for Seniors is an investigator-initiated, multicenter, randomized, open-label, unblinded, active, and historical controlled trial in which approximately 875 seniors undergoing urgent PCI from at least 70 centers in North America will be enrolled. All consented subjects will undergo attempted radial arterial access. SAFE STEMI for Seniors is currently enrolling patients and recruiting investigational sites.