Datavant selects DCRI as founding academic partner to accelerate innovation in data-driven clinical research

January 5, 2018 – Datavant and the DCRI will work closely together in engaging biopharmaceutical partners and implementing innovative approaches to clinical trial design and interpretation, leveraging the power of their combined datasets. 

Datavant, a healthcare technology company that aggregates and structures healthcare data to generate actionable insights for clinical trials, has selected the DCRI as an analytical partner to accelerate data-driven approaches in drug development, the company announced today.

As Datavant’s Founding Academic Partner, the DCRI will bring deep insights and unique perspectives on data-driven clinical research and access to clinical trial and health system data to augment Datavant’s analytical tools and data assets. The DCRI will gain early access to Datavant’s data and technology. Together, the organizations will create further opportunities to facilitate rapid scaling of best practices in clinical research to improve patient outcomes.

Michael Pencina

“New clinical insights come from matching the right question with data that can actually inform its answer,” said Michael J. Pencina, PhD, the DCRI’s director of biostatistics and a professor of biostatistics and bioinformatics at Duke School of Medicine. “The promise of this partnership comes from the blend of the DCRI’s analytic innovations with Datavant’s unique datasets, creating unmatched capacity for discovery.”

“Too many drugs fail clinical trials due to deficiencies in trial design and interpretation, depriving patients of new treatment options they desperately need.  We believe that the combination of DCRI’s analytical expertise and rich datasets combined with Datavant’s products and data hold the potential to be transformative for the industry,” said Travis May, co-founder and CEO of Datavant.

Initial collaboration will be focused on focused on phase II design in cardiopulmonary space.

Heart patients help doctors determine best aspirin dose

January 4, 2018 – The ADAPTABLE study, coordinated by the DCRI, will enroll as many as 15,000 cardiac patients to determine the optimal aspirin dose.

Doctors have known for decades that taking aspirin can reduce the risk for future heart attacks and strokes in people with cardiovascular disease. What is less clear is which dose is best. Participants in a new kind of clinical trial are helping them find out.

Some doctors prescribe a “baby aspirin” (81mg) once a day, while others recommend a full-strength (325mg) aspirin tablet. The difference is important because taking aspirin daily can potentially increase your risk of bleeding. Until now, there hasn’t been enough good-quality data to guide doctors’ decisions.

That’s where the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness) study comes in. The DCRI is coordinating the study, one of the first to make patients key partners in an effort to gather vast amounts of data quickly and efficiently. People with heart disease and who are at high risk of having a heart attack or stroke are randomly assigned to take an 81mg or 325mg aspirin daily and are followed for up to 30 months. Eventually, as many as 15,000 people around the U.S. will participate.

Patients Appreciate Opportunity to Advance Medical Knowledge

Retiree John Turk started having shortness of breath and chest tightness while juggling the stresses of selling his Cleveland, OH, home and buying a new one in Raleigh to be near his daughter. He hadn’t had symptoms before.

“My general practitioner immediately referred me to Duke to get checked out,” Turk said. “Within a few weeks, I had bypass surgery.” Duke interventional cardiologist Schuyler Jones, MD, worked with Turk during his post-surgical recovery period and encouraged him to get involved in the ADAPTABLE study.

“If this helps, I’m glad to be part of it,” Turk said. “Makes me feel good to help with the research.”

For full story from Duke Health Blog:

Digital Health in Neurosciences

March 21, 2017 -The first Neurosciences Medicine Digital Health Clinical Trials Symposium was held last month in San Francisco.

The DCRI hosted the inaugural Neurosciences Medicine Digital Health Clinical Trials Symposium in San Francisco this February. The agenda included a wide-ranging discussion of the current state of clinical trials for games, apps, and electronic medical devices to diagnose or alleviate symptoms of psychiatric and neurological disorders.

“There are unique challenges in digital health applications for neurosciences medicine, and the genesis of this meeting was the concept of bringing together experts to identify and develop solutions to move the field forward,” said Andrew Krystal, MD, MS, (right) in opening remarks. Krystal is co-director of Neurosciences Medicine at the DCRI; adjunct professor of Psychiatry and Behavioral Sciences at Duke University School of Medicine; and Ray and Dagmar Dolby distinguished professor of psychiatry and vice chair for research in the Departments of Psychiatry and Neurology, University of California San Francisco.

“The DCRI is active in developing diagnostic and treatment interventions for neuropsychiatric conditions, including studies of digital health applications.” Krystal also gave a talk on designing appropriate control devices for trials.

Adam GazzaleyThe keynote presentation, “Neuroscience Meets Technology: A vision of the future of brain health,” was given by Adam Gazzaley, MD, PhD, (left) who is a professor in Neurology, Physiology and Psychiatry at UC San Francisco; founder and executive director of Neuroscape; co-founder and chief science advisor of Akili Interactive Labs; and co-founder and chief scientist of JAZZ Venture Partners. He noted that challenges include the need to better assess and enhance cognition – including elements such as attention, memory, mood, compassion, and empathy – in a meaningful and lasting way.

Other key takeaways from DCRI presentations at the meeting included:

  • There are currently no standard endpoints for psychiatry trials in digital health, and the endpoints used for drug trials may not be appropriate; academia, industry, the Food and Drug Administration, and the National Institute of Mental Health should all work together to address this.
  • There are unique challenges in designing control interventions for digital health apps such as games, since none have been definitively proven to be effective or ineffective. As a result, careful control design is essential to elucidate effects.
  • Many statistical challenges are unique to digital health, and these must be taken into account in innovative trial designs, since “there are no right answers to wrong questions.”
  • Computerized testing has potential in standardizing measurements of cognition. Today, these measurements are based on tests developed in the 1980s, often administered by testers with no psychometric experience, which poses a risk of inaccuracy and inconsistency. This can potentially be addressed via computerization.
  • Technology is moving forward rapidly, but medicine and research are still catching up, mainly due to regulatory issues and trial design limitations. Enhanced recruitment using the web will help reduce the effort required to collect data and the cost of trials, by allowing brick and mortar sites to be added where the patients are, instead of maintaining non-enrolling sites. The electronic medical record has potential as a viable tool for large-scale clinical research, though integration into clinical trial designs and validation of data flow remain issues. There are opportunities to provide standardization of protocol, decision support and automated data capture within the workflows of ongoing clinical care.

nsm crowd panelOther DCRI speakers on the agenda were: Scott H. Kollins, PhD, professor and vice chair for research strategy and development, and director of the Duke ADHD Program, Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, and global lead for ADHD and SUD, Neurosciences Medicine, DCRI, who examined standard and exploratory endpoints for psychiatry trials in digital health; Roseann White, MA, director, Pragmatic Clinical Trial Statistics, who described biostatistical trial design and the need to power studies properly; Richard Keefe, PhD, professor in Psychiatry and Behavioral Sciences, Duke Institute for Brain Sciences, and Global Cognition Sciences Lead, DCRI, who focused on where cognition fits into trial design; and Brad J. Kolls, MD, PhD, of the Department of Neurology, Duke University School of Medicine, and Clinical Informatics Global Trials Lead, DCRI Neurosciences Medicine, whose presentation focused on capturing data from systems and digital interfaces in clinical trials.

The business side of digital health was discussed by a panel including: Eddie Martucci, CEO, Akili Interactive Labs; Henry Mahnke, CEO, Posit Science; Zack Lynch, general partner, JAZZ Venture Partners; Craig Fischer, vice president of Medical Professional Markets, Pearson; Anand Iyer, chief strategy officer, Welldoc; and Carolyn Jasik, medical director, Omada Health.

A panel discussion addressed the question of “What do emerging digital health companies need to know about business decisions regarding clinical trials?” Key takeaways included:

  • There is no agreed blueprint for digital health clinical trials. A company must identify the most important question, then think two questions ahead and try to get preliminary answers to those, too.
  • Access to patients is a major issue. Many psychiatrists and psychologists are outside of the mainstream health care system.
  • Clinical outcomes open the door in discussions with payers, but the challenge is demonstrating what financial impact these outcomes have and what the intervention does from an efficacy standpoint.
  • The company must understand whom they are delivering the study results to: the needs may be different for the medical community vs. the psychology community. Potential customers should be asked what they need. It is vital to make sure that the study output includes tools and resources.
  • It is essential to understand the value of the product to your customer’s customer. The customer will need to “sell” the product to someone else – such as the government, employers, health care organizations, medical groups, health plans, or patients
  • From venture capital viewpoint, clinical trial results are table stakes. Investors are most concerned about reimbursement on a broad scale and how that will happen.

Participants also had a choice of two breakout sessions, on FDA Guidance on Digital Health, and Business Models 101: Direct-to-consumer, workplace wellness, and the payer model.

New editorial discusses the importance of ADAPTABLE

August 25, 2015 – Adrian Hernandez, MD, MHS, and his co-authors outline how the study has the potential to change how clinical trials are conducted.

An upcoming study comparing two doses of aspirin for secondary prevention of cardiovascular events in high-risk patients will answer an important clinical question while simultaneously testing a new approach to conducting pragmatic clinical trials. The authors of a commentary in Annals of Internal Medicine explain the significance of this effort.

The article was written by the DCRI’s Adrian Hernandez, MD, MHS; Rachael Fleurence, PhD, of the Patient-Centered Outcomes Research Institute (PCORI); and Russell Rothman, MD, MPP, of Vanderbilt University.

Known as ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness), the trial is the first to be facilitated by the National Patient-Centered Clinical Research Network (PCORnet). PCORnet is a “network of networks” created by PCORI to overcome the challenges that make medical research expensive, inefficient, and slow to provide results.

The mission of PCORnet is to support rapid and efficient randomized comparative effectiveness trials embedded in the delivery of usual care. In the ADAPTABLE trial, health record data collected during usual care will be used to identify, recruit, and follow up with research participants. Once the study is complete, researchers will have answers about aspirin and a better understanding of PCORnet’s capacity to accomplish its core mission.

“As ADAPTABLE progresses,” the authors write, “we believe it will illuminate PCORnet’s remarkable new approach to conducting pragmatic clinical trials and demonstrate how ‘big data’ can be leveraged to enhance the efficiency of clinical trials by facilitating the identification, recruitment, and follow-up of research participants.”

Medicare proposed rule clarifies merit-based physician payment, but leaves work to be done, experts say

May 23, 2016 – The DCRI’s Jeffrey Clough, MD, MBA, and Mark McClellan, MD, PhD, of the Duke-Margolis Center for Health Policy discuss the questions raised by the new rule in a JAMA editorial.

On April 27, the Centers for Medicare and Medicaid Services (CMS) proposed rules that will move physician payments away from fee for service and toward a model that aligns payments with better quality of care that avoids unnecessary costs.

These changes, outlined in a 962-page document proposed for implementing the Medicare Access and CHIP Reauthorization Act (MACRA), are expected to affect payments throughout the entire U.S. health care system.

Jeff CloughIn a Viewpoint commentary published Monday in the Journal of the American Medical Association, Jeffrey Clough, MD, MBA, of the DCRI (pictured), and Mark McClellan, MD, PhD, director of the Duke-Margolis Center for Health Policy, encourage physicians to take time to understand the key features of the rule and the opportunities it presents to shape the future of payment and medical practice.

“Our aim in this commentary is to provide physicians with an overview of the options for participation in payment reform and quality improvement under MACRA. Their leadership is essential to the future of high-value health care,” Clough said.

The proposed payment models aim to create greater accountability for efficiency and care improvement.  CMS expects the vast majority of clinicians to initially participate in the new Merit-based Incentive Payment System (MIPS). Under this model, which begins in 2019, payment will be adjusted based on factors that include specific patient outcome measures, efficiency, use of information technology and clinical practice improvement activities.

As outlined in the proposed rule, Alternative Payment Models (APMs) provide an option for physicians to be exempt from MIPS by taking on a higher level of accountability for quality and expenditure performance. Clough and McClellan say new APMs should be aggressively developed for a broad range of physician practices.

“We estimate that about 10 percent of physicians could qualify for extra payments associated with advanced Alternative Payment Models based on the Medicare payment options and pilots available now.  These would mainly include certain primary care doctors and clinicians practicing within large integrated systems that take on significant financial risk,” McClellan said.

Clough and McClellan note challenges with existing measures or for pay-for-performance in reducing overall costs.  They urge physicians to work through professional organizations to participate in improving the proposed rule and in developing better utilization and quality measures, as well as advanced APMs.

“Physicians have a real opportunity to shape the future of clinical practice, by developing models that enable a broader range of physicians to qualify for advanced APMs.  These include models affecting specialists involved in the care of patients with complex or advanced needs, and models with meaningful but manageable risk for physicians in small practices,” McClellan said.

CTTI releases new recommendations and tools for improving patient recruitment in clinical trials

May 20, 2016 – The tools were developed with input from clinical researchers, patient advocates, and representatives from academia, industry, and the FDA.

The Clinical Trials Transformation Initiative (CTTI) has released new recommendations and tools for enhancing the efficiency of clinical trial recruitment that are now available for download.

Patient recruitment is a leading challenge in the efficient completion of clinical trials, which can result in wasted resources and delays in bringing new therapies to market. The foundational principle for this new approach is that recruitment planning should be started earlier in the clinical trial development process and continue throughout the implementation.

Bray Patrick-Lake“The Recruitment Project recommendations are the result of an in-depth study evaluating why too often clinical trial recruitment efforts fail,” said Jonca Bull, MD, assistant commissioner for minority health at the U.S. Food and Drug Administration (FDA). Bull served as a team lead for the project.

“These recommendations have the potential to catalyze greater efficiencies in diverse patient recruitment – women, minorities and older adults– by focusing on the earliest stages in protocol development,” Bull said.

The recommendations and tools were developed with input from a diverse team of stakeholders, including clinical researchers, patient advocates, and representatives from academia, industry, and the FDA.

“What we found was that, to truly make a difference, we need a comprehensive solution that covers all areas of clinical research, from making sure the study is asking the right questions—questions that matter to patients and providers—to shaping study design and feasibility, to budget and implementation,” said Kelly McKee, a project team member from Eli Lilly and Company.

Among the released tools, a new framework outlines considerations for strategic recruitment planning throughout all stages of a clinical trial. According to the recommendations, recruitment planning should also be more inclusive of all relevant stakeholders.

“Too often important feedback from patients, study coordinators, and health care providers is not obtained when their insights can make or break a trial and prevent avoidable amendments,” said Bray Patrick-Lake, Director of Patient Engagement for the Duke Clinical and Translational Science Award (pictured). “CTTI’s evidence-based recommendations and toolkits provide practical guidance for successful clinical trial recruitment planning that will help ensure stakeholders are appropriately engaged and the right questions are asked during study design, feasibility, and recruitment planning activities.”

A thoughtful approach to recruitment planning before study activation is expected to alleviate downstream recruitment challenges and ensure trial viability. The work builds on CTTI’s previous advancements in the areas of engaging patient groups in clinical trials and a quality by design approach to improving clinical trials.

Established by Duke University and the FDA as a public-private partnership in 2007, CTTI comprises more than 70 member organizations working to identify and promote practices that will improve the quality and efficiency of clinical trials.

Women suffer more with atrial fibrillation, survive longer

May 18, 2016 – DCRI researchers evaluated 4,293 women and 5,842 men treated for atrial fibrillation at 176 practices throughout the country.

Despite having more symptoms, worse quality of life and greater risk of stroke, women with atrial fibrillation also have better overall survival than men with the same disease, researchers from the DCRI report.

This stroke-survival paradox for women with atrial fibrillation, while not fully understood, suggests key differences in how cardiovascular treatments affect outcomes in women compared to men. The findings,published May 18 in the journal JAMA Cardiology, should be taken into account when doctors guide care.

jonathan-piccini“For example, it’s important to determine whether atrial fibrillation is causing symptoms in women, because that could determine whether drugs are prescribed to control heart rhythm,” said lead author Jonathan D. Piccini, MD, an assistant professor of medicine and electrophysiology at Duke. “That’s an important distinction with clinical implications, because women are more likely to have worse quality of life and functional impairment, and this could be a consequence of drug therapies.”

The Duke researchers evaluated 4,293 women and 5,842 men who were treated for atrial fibrillation at 176 practices throughout the country, spanning a wide variety of settings from small community practices to large academic medical centers. The patients were enrolled between June 2010 and August, 2011, and were followed for a median 2.3 years.

This large group of patients in “real-world” situations gave researchers a unique insight into treatments and health status for atrial fibrillation, which is the most common form of abnormal heart rhythm. The condition afflicts more than 2 million people in the United States.

The researchers found key differences in how the condition manifests in women and men. Women experienced significantly more symptoms, including heart palpitations, light-headedness, fatigue and chest discomfort. Such symptoms, along with concerns about treatments and impaired ability to perform daily activities, contributed to a lower quality of life.

Women were also at higher risk for stroke and embolism than men, while the risks of heart failure, major bleeding and hospitalizations were similar between the sexes.

Yet despite having a more difficult disease presentation than men, women still had a lower risk for most severe outcomes, including death by any cause and cardiovascular death.

“It is a paradox that women seem to have worse disease and do better in the end,” Piccini said. “We don’t why that is – and this bears further study – but these differences between men and women are important and likely to inform us about the nature of atrial fibrillation. We need to treat both women and men in ways that take into account these differences, so that we eventually can eliminate them.”

In addition to Piccini, study authors include DaJuanicia N. Simon; Benjamin A. Steinberg; Laine Thomas; Larry A. Allen; Gregg C. Fonarow; Bernard Gersh; Elaine Hylek; Peter R. Kowey; James A. Reiffel; Gerald V. Naccarelli; Paul S. Chan; John A. Spertus; and Eric D. Peterson.

DCRI wins CRO Leadership Awards

May 12, 2016 – The DCRI received awards in the categories of capabilities, expertise, and quality.

The DCRI announced today it has been recognized for excellence in clinical research by Life Science Leader magazine’s 2016 CRO Leadership Awards.

The DCRI received awards in the categories of capabilities, expertise, and quality. The DCRI also received “individual attribute awards” for data quality, innovative solutions, and real-time access to data.

Now in their fourth year, the awards are based on research conducted by Industry Standard Research.  The research incorporates responses from biopharmaceutical industry leaders who work with contract research organizations (CROs) on clinical research projects. Each respondent evaluated the nominees on 27 different metrics. Respondents only evaluated companies with which they have worked on an outsourced project within the past 18 months.

The results appear in the May issue of Life Science Leader.

“We are pleased to be recognized for the work we do to advance knowledge that improves patient care,” said DCRI Executive Director Eric Peterson, MD, MPH. “These awards are evidence that the hard work of our faculty and staff is recognized throughout the clinical research community.”

Pediatric Trials Network study results in label change for hypertension drug

May 11, 2016 – The change could affect the hundreds of children who are prescribed lisinopril after kidney transplants each year.

A study conducted by the Pediatric Trials Network (PTN) has resulted in a labelling change for a widely used drug.

Lisinopril is an angiotensin converting enzyme inhibitor that is commonly prescribed to treat high blood pressure or heart failure in adults. It is also given to children who have hypertension, including children who have undergone kidney transplants. As with many other drugs, however, there has been little research to suggest the optimal dose for pediatric transplant patients. The PTN was established to answer these types of questions about drugs given to children and adolescents.

daniel-benjamin“There is a great medical need but a small market for these types of studies,” said Daniel Benjamin, Jr., MD, MPH, PhD, the PTN’s principal investigator (pictured). “This is why the PTN was formed—to conduct the studies that no one else will.”

A study led by DCRI researcher Uptal Patel, MD, and other researchers for the PTN recently resulted in a decision by the the U.S. Food and Drug Administration (FDA) to update the label for lisinopril. In addition to Patel, the study’s authors included Howard Trachtman, MD, of New York University; Adam Frymoyer, MD, of Stanford University; Laurence Greenbaum, MD, PhD, of Emory University; Daniel Feig, MD, PhD, of the University of Alabama at Birmingham; Debbie Gipson, MD, of the University of Michigan; Bradley Warady, MD, of Children’s Mercy Hospital of Kansas City; Jens Goebel, MD, of Cincinnati Children’s Hospital; and George Schartz, MD, of the University of Rochester.

The study was a multicenter, open-label pharmacokinetic study of daily oral lisinopril in 22 children, aged 7–17 years, with stable kidney function following transplant.

The researchers found that the pharmacokinetics of lisinopril in children who underwent kidney transplant were similar to hypertensive children who did not receive kidney transplants. Lisinopril was generally well tolerated by the patients and was accompanied by a lowering of blood pressure at approved pediatric doses in the study population.

The results of the study were published in the July 2015 issue of Clinical Pharmacology & Therapeutics.

Approximately 1,200 children in the United States develop end-stage renal disease (ESRD) each year. Because kidney transplantation has become the primary method of treating ESRD for children, many of these patients will be prescribed lisinopril. As a result of the FDA’s recent decision, Benjamin noted, doctors will now have a better understanding of the correct dose.

“This has been a problem for over 60 years, and we’re only now addressing it,” he said. “With the PTN, we now a have a vehicle to make those changes.”

Study seeks women’s insights on what works best for uterine fibroids

May 9, 2016 – COMPARE-UF will enroll more than 10,000 women across the country.

 A new registry that launches this month gives women who have uterine fibroids the opportunity to help determine which strategies are most effective in treating the common condition.The registry, called Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF), will enroll more than 10,000 women at clinics affiliated with nine medical centers across the country. Participating women will be asked at annual intervals specific questions about the treatments they’ve elected to receive, and how well the treatments seem to be working for them.

uterine_fibroidsApproximately three years after initial treatment, researchers at the DCRI will analyze the patients’ feedback to determine which procedures provide the greatest benefit to women – insights that have been lacking for both women and their physicians.

Specifically, studies will focus on symptom relief, reproductive effects, and effectiveness among different patient subgroups, including African-American women, who are disproportionately affected by uterine fibroids.

“This is a common condition – it affects up to 75 percent of women to varying degrees and is the leading cause of hysterectomies in the country – yet we don’t know which treatment works best for a given patient,” said the study’s principal investigator, Evan Myers, MD, professor in the Department of Obstetrics and Gynecology at Duke University School of Medicine.

“Patients have clearly stated that they wanted these questions answered, but preferred a registry to randomized trials, particularly because hysterectomy is one of the current options,” Myers said.

The registry was funded in 2013 with a $20 million funding award from the Patient-Centered Outcomes Research Institute (PCORI), in partnership with the Agency for Healthcare Research and Quality (AHRQ), which provides scientific oversight and administration.

The DCRI serves as the research and data coordinating center for the five-year project. Enrollments sites include Mayo Clinic Collaborative Network, University of California Fibroid Network, Henry Ford Health System, University of Mississippi Medical Center, University of North Carolina, Brigham and Women/Harvard Clinical Center, Inova Health Systems and the Department of Defense Clinical Consortium. The University of Michigan will become an enrollment site later this year.

Potential participants must have a documented diagnosis of uterine fibroids and be older than 18 and young enough to still have menstrual periods. Current treatments to be evaluated are hysterectomy (removal of the uterus), myomectomy (removal of the fibroids within the uterus), endometrial ablation (laser or heat treatments to destroy the uterine lining), radiofrequency ablation (using radio waves to destroy the fibroid), uterine artery embolization (blocking blood supply to the uterus), and magnetic resonance guided focused ultrasound (using ultrasound to destroy the fibroids). The study will add other treatments, including medications.

“Uterine fibroids have a big impact on women’s quality of life, affecting their ability to work and to participate in the things that they enjoy,” Myers said. “There are also high costs, both in treatments and in managing the pain and heavy bleeding that many women experience.

“One of the things that makes fibroids difficult to study is that they cause lots of different kinds of symptoms, and the symptoms can be complex, ranging from fairly minor discomfort to infertility,” Myers said. “This registry for the first time will help us collect strong, relevant information from the patients themselves that can then be analyzed to determine what treatments work best for which women.”

Patient advocacy groups, which had been integral in helping design the study, said the registry launch this month is a much-anticipated milestone.

“There are far too many women suffering with complications from uterine fibroids. This research effort initiated by AHRQ and PCORI is groundbreaking and crucial,” said Sateria Venable, founder and executive director of the Fibroid Foundation. “My hope is that COMPARE-UF will lead the way to more consistently and adequately funded fibroid research. If we focus our efforts, we will reap the rewards – health, fertility and quality of life.”