Julie Ann Sosa appointed editor-in-chief of World Journal of Surgery

October 18, 2017 – Sosa has been a member of the DCRI since 2013.

The DCRI’s Julie Ann Sosa, MA, MD, has been named the next editor-in-chief of the World Journal of Surgery, the official journal of the International Society of Surgery.

The announcement was made in an email to journal subscribers this week.

Sosa is a professor of surgery and medicine at Duke, where she serves as chief of Endocrine Surgery and director of the Surgical Center for Outcomes Research, as well as leader of the Endocrine Neoplasia Diseases Group and the Solid Tumor Therapeutics Program at the Duke Cancer Institute. Her clinical interest is in endocrine surgery, with a focus in thyroid cancer. She is an NIH-funded investigator and author of more than 270 peer-reviewed publications and 50 book chapters, largely focused on outcomes research, health care delivery, hyperparathyroidism, and thyroid cancer, with a focus on clinical trials.

Sosa is treasurer-elect of the American Thyroid Association (ATA) and serves on the Board of Directors/Executive Council of the ATA, International Thyroid Oncology Group, and Society for Surgical Oncology, as well as practice guidelines committees for the ATA and the National Comprehensive Cancer Network. She has mentored more than 50 students, residents, and fellows. She received her AB at Princeton, her MA at Oxford, and her MD at Johns Hopkins, where she completed her residency and a fellowship.

Sosa’s term as editor-in-chief will begin in 2018.

DCRI and partners awarded FDA grant to create Global Pediatric Clinical Trials Network

October 17, 2017 – The DCRI will serve as the coordinating center for the network, which will support pediatric clinical trials around the world.

The DCRI and its strategic partners have been awarded a grant from the U.S. Food and Drug Administration (FDA) to establish a coordinating center for a Global Pediatric Clinical Trials Network (G-PCTN). The G-PCTN will support efficient pediatric clinical trials worldwide by developing scientific and operational infrastructure, fostering collaborative networks, sharing knowledge, and engaging stakeholders. The principal investigators for this program will be Daniel Benjamin, Jr., MD, MPH, PhD (pictured left), and Michael (Micky) Cohen-Wolkowiez, MD, PhD (pictured right).

Daniel Benjamin

“Although we’ve made a lot of progress in recent years, pediatric trials are still hard to complete successfully. There are perennial challenges – enrolling patients, finding access to supporting infrastructure, navigating a complex regulatory environment – that affect everyone working to advance pediatric research, but they can be especially challenging for research sites that don’t have access to resources or experience,” said Benjamin. “We’ve had great success with the Exclusivity Program, and NICHD’s off-patent program; but we need to work through some of the challenges that folks have had in meeting the requirements outlined by the Pediatric Research Equity Act. It’s crucial to have success across new therapeutics for children.”

Although the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were both implemented to encourage research sponsors to conduct more pediatric clinical trials, many drugs used in children lack sufficient information to guide their safe and effective dosing. Further, 42 percent of pediatric trials done under BPCA have not successfully supported pediatric indications.

“Despite how vital it is for children’s health, proper dosing information is still sorely lacking for many important therapies used in children and infants,” Cohen-Wolkowiez said, noting that the relatively small numbers of patients eligible to enroll in pediatric trials of therapies for rare diseases adds an additional layer of difficulty. “This Network will provide a key opportunity to address inefficiencies and build capacity across the globe for conducting more effective pediatric clinical trials, which will help inform the decisions parents and healthcare providers make when caring for our youngest patients.”

Michael Cohen-Wolkowiez

The grant will be used to create a coordinating center comprising three cores for network operations, patient engagement, and scientific oversight and five clinical study groups devoted to study design, dosing, regulatory/pharmacy, network partnerships, and rare diseases. Benjamin, who also serves as Principal Investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pediatric Trials Network (PTN) envisions the programs working synergistically: “There are natural interactions, or lessons learned, across the trials conducted in the older, off-patent medicines and the trials conducted for newer therapeutics.”

The creation of the Network reflects consensus findings from a multi-stakeholder group that included regulators, industry, academia, patient advocacy groups, disease networks, and parents. The group noted that no one set of stakeholders can address these problems in isolation; instead, a global network involving all stakeholders could better ensure successful pediatric trials, especially those being conducted in patients with rare diseases.

The G-PCTN will leverage and extend the extensive infrastructure, networks, and experience already in place via the PTN, whose administrative coordinating center is also located at the DCRI.

Use of CPR, defibrillators improves after public health initiatives

October 4, 2017 – The use of CPR and defibrillators was associated with increased survival in patients who experienced out-of-hospital cardiac arrest.

After coordinated and comprehensive public health initiatives in North Carolina, more patients received bystander CPR and first-responder defibrillation at home and in public, which was associated with improved survival, according to a study by former and current DCRI researchers published in JAMA Cardiology.

Almost 400,000 Americans experience out-of-hospital cardiac arrest (OHCA) annually, but less than 10 percent of them survive to hospital discharge. Although up to 80 percent of all OHCAs occur at home, those who experience an at-home OHCA have a 4 to 5 times lower chance of survival vs those who experience an OHCA in public locations. Little is known about the influence of public health initiatives to improve bystander and first-responder resuscitation efforts in patients who experience at-home cardiac arrest.

Former DCRI Fellow Christopher B. Fordyce, MD, MHS, MSc, of the University of British Columbia, Vancouver, and colleagues conducted a study that included 8,269 patients with OHCAs (68 percent at home and 32 percent in public) for whom resuscitation was attempted. The authors used data from the Cardiac Arrest Registry to Enhance Survival from January 2010 through December 2014. The setting was 16 counties in North Carolina. In 2010, North Carolina implemented public health initiatives to improve bystander and first-responder interventions by training members of the general population in cardiopulmonary resuscitation (CPR) and in the use of automated external defibrillators (AEDs), teaching first responders about team-based CPR, and instructing dispatch centers on recognition of cardiac arrest.

The researchers found that after the comprehensive public health initiatives, the proportion of patients receiving bystander CPR increased at home (from 28 percent to 41 percent) and in public (from 61 percent to 71 percent), while first-responder defibrillation increased at home (from 42 percent to 51 percent) but not significantly in public (from 33 percent to 38 percent). Survival to discharge improved for arrests at home and in public.

“Adopting some of these public health initiatives may likely be helpful for communities aiming to improve outcomes of OHCA,” the authors write.

The study notes some limitations, including that this was an observational study for which unmeasured or unmeasurable confounders could explain improved temporal outcomes independent of public health initiatives.

In addition to Fordyce, DCRI authors included former fellows Carolina M. Hansen, MD, PhD, and Kristian Kragholm, MD, PhD; Matthew E. Dupre, PhD; Mayme L. Roettig, MSN, RN; Steen M. Hansen, MD; Tomoya T. Hinohara, MD; Lisa Monk, MSN, RN; Clark Tyson, MS, NREMT-P; Monique L. Anderson, MD; and Christopher B. Granger, MD.

DCRI participates in new Duke Health research initiative

October 3, 2017 – Translating Duke Health will identify areas where Duke can make significant contributions to patient care.

A version of this story first appeared on the Duke School of Medicine (SOM) blog.

Translating Duke Health (TDH), an initiative principally sponsored by the Duke University SOM and Duke Health in collaboration with other Duke entities, formally launched on September 13. The multi-year, multidisciplinary program will focus on areas where Duke Health can make the most significant contributions to health and healthcare. TDH is a direct outgrowth of Duke Health’s Advancing Health Together Strategic Planning Framework.

“The creation of the Translating Duke Health initiative began months ago, spurred by the recognition that Duke is uniquely positioned to address many of the world’s most significant scientific and healthcare challenges. It represents a firm commitment by Duke Health to fulfill a vision of making impactful discoveries and transforming health for millions,” said Mary E. Klotman, MD, Dean, Duke University SOM and Vice Chancellor, Health Affairs. “This ambitious initiative will amplify Duke as a leader among our peers, as a unique destination for care and promise for our patients, and as a place where the best minds participate in meaningful, impactful science.”

TDH will initially focus on five opportunities—areas where Duke Health can have the greatest impact on transformative treatments and prevention strategies—selected by the steering committee:

  • Preserving and restoring cardiovascular health
  • Enhancing brain resilience and repair
  • Ending disease where it begins
  • Controlling the immune system
  • Combating solid tumor brain metastases

DCRI faculty have been involved in TDH at a leadership level since the planning begun. The cardiovascular area’s steering committee includes DCRI’s Pamela Douglas, MD, Ursula Geller Professor for Research in Cardiovascular Diseases (pictured), who leads the cardiovascular initiative; Lesley Curtis, PhD, Professor, Medicine and Interim Chair, Department of Population Health Sciences; Kevin Hill, MD, Associate Professor, Pediatrics; and Manesh Patel, MD, Professor, Medicine and Chief, Division of Cardiology.

Additionally, during the summer the cardiovascular steering committee held a series of cross-disciplinary workshops, in which the following DCRI faculty served as speakers or moderators for the discussions:

  • Recovery from MI: Lesley Curtis, Pam Douglas, Dan Mark, Kristin Newby
  • Prevention of Vascular Disease: Neha Pagidipati, Manesh Patel
  • Recovery from Heart Failure: Adrian Hernandez, Joseph Rogers
  • Recovery from Surgery: John Alexander, Kevin Hill, Paul Wischmeyer

“The TDH initiative will span basic research to clinical research to population health, which obviously includes DCRI’s areas of expertise and activities,” said Douglas. “DCRI could be a partner with TDH in every one of the five opportunity areas.”

In addition to the workshops and a symposium for fall 2018, the TDH cardiovascular team currently is focused on recruitment of key translational faculty positions; creating a new mechanism for cross-cutting seed grants; and planning for a model “clinic of the future” for cardiovascular care, in which patients are engaged in research as part of receiving care at the clinic.​

Visit the Translating Duke Health website to learn more and watch the videos about each of the five opportunity areas.

Study shows minimally invasive valve replacements hold up well after five years

September 27, 2017 – The biological valves used in TAVR and surgical procedures maintain function over time.

A minimally invasive procedure used to replace heart valves without open heart surgery appears to provide a durable remedy for people with a life-threatening form of heart disease in which the aortic valve opening narrows, diminishing blood flow.

The procedure, called trans-catheter aortic valve replacement, or TAVR, has been safely used in older patients who are not good candidates for open heart surgery. But strong research establishing its durability over five to 10 years has been lacking. This has created questions about whether it should be used in younger and healthier people.

Now a study, published in JAMA Cardiology and led by a member of the DCRI, provides some answers. Using data and follow-up from the first and largest studies of TAVR safety, the research team found that the biologic valves used in a TAVR procedure, as well as those used in open heart surgery, continue to perform well up to five years after implantation.

“I think these findings are incredibly reassuring at least out to five years,” said lead author Pamela Douglas, MD, the Ursula Geller Professor for Research in Cardiovascular Diseases at Duke University School of medicine and director of the DCRI imaging program. “The valve is quite durable and safe.”

Douglas and colleagues analyzed data from more than 2,700 patients who had been part of a large trial called PARTNER, which established the safety of TAVR. The study patients received either a minimally invasive TAVR procedure – which uses a catheter that is routed through a blood vessel in the leg or chest to access the heart – or an open heart surgery to replace the valve.

All of the study patients received biological valves, developed from animal or donated human tissue. Biological valves are increasingly favored over mechanical valves, which must be surgically implanted and require long-term use of anti-coagulation drugs to protect against blood clots.

In their analysis, the study authors also included echocardiograms of about 475 patients five years after either their minimally invasive or surgical valve replacement. The average age of patients in the study group was 84.5 years, and many had additional serious health risks.

Among the 2,404 TAVR patients in the study, 34 percent survived five years. Similarly, 37 percent of the 313 patients whose valves were replaced in an open surgery also survived to five years.

Twenty TAVR patients (0.8 percent) required a second valve procedure, and only five of the revisions arose from structural deteriorations of the valve.

The researchers found evidence that 3.7 percent of the TAVR patients developed a condition in which the valve allowed blood to flow back into the heart, and this problem increased over time.

“This was seen in only a handful of patients, but it’s certainly something of concern and warrants further study,” Douglas said. “Overall, however, the findings from this carefully designed study demonstrate that there is little evidence of valve failure or deterioration for either TAVR or surgery using biological valves.”

She said the study provides a first step in understanding the long-term benefits of minimally invasive valve replacement, and suggests additional studies could be safely undertaken.

In addition to Douglas, study authors include Martin B. Leon, Michael J. Mack, Lars G. Svensson, John G. Webb, Rebecca T. Hahn, Pillippe Pibarot, Neil J. Weissman, D. Craig Miller, Samir Kapadia, Howard C. Hermann, Susheel K. Kodell, Raj R. Makkar, Vinod H. Thourani, Stamatios Lerakis, Ashley M. Lowry, Jeevanantham Rajeswaran, Matthew T. Finn, Maria C. Alu, Craig R. Smith and Eugene H. Blackstone for the PARTNER Trial investigators.

The study was funded by Edwards Lifesciences, which markets TAVR products. Author conflicts of interest are listed in the manuscript.

Costs, health insurers impede patients’ access to cholesterol-lowering drugs

September 27, 2017 – Fewer than one-third of patients prescribed a new medication actually received therapy.

Most prescriptions for a class of drugs heralded as game-changers for people with stubbornly high cholesterol are going unfilled because of high out-of-pocket costs and challenges by pharmacy benefit managers, according to a study from the DCRI.

Publishing online Sept. 27 in JAMA Cardiology, the researchers found that fewer than one-third of patients prescribed a PCSK9 inhibitor — injectable drugs designed to lower cholesterol levels — actually got the drug.

Two factors limited access: lack of insurance approval for the prescription and high copays. Fewer than half of patients prescribed a PCSK9 inhibitor ever received approval for the drug by their insurer.

Even after approval, one in three patients failed to fill their prescription. Sticker shock was a key factor. A quarter of patients had copays over $300 per month for therapies that cost about $14,000 a year.

The net result was that just 31 percent of patients who were initially prescribed a PCSK9 inhibitor ever actually received the therapy, the researchers found.

“This study basically reveals a system of rationing by roadblocks,” said lead author Ann Marie Navar, MD, PhD, assistant professor of medicine at the DCRI. “Access comes down to patients whose doctors are persistent enough to win payer approval through multiple appeals, and patients who can afford the out-of-pocket costs.”

In their study, which was funded by a manufacturer of one of the drugs, Navar and colleagues analyzed a large database of pharmacy claims that included more than 45,000 prescriptions for PCSK9 inhibitors. These drugs work by blocking a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9), setting off a chain of events that breaks down LDL cholesterol, the “bad cholesterol” that causes heart disease.

The drugs include evolocumab (brand name Repatha, manufactured by the study’s funder, Amgen, Inc.) and alirocumab (brand name Praluent). Both therapies were approved by the FDA in 2015 for people with familial hyperlipidemia (a form of very high cholesterol that runs in families) and those with established heart disease who have high cholesterol despite traditional statin therapy.

In the first year after the drugs’ approvals, the researchers found that nearly 80 percent of doctors’ prescriptions were rejected by pharmacy benefit managers that govern drug coverage for health insurance plans. Most of the requests (73.5 percent) were resubmitted, but only 47.2 percent eventually won approval.

The median time between initial submission and approval was about four days, but some patients waited nearly three months for therapy.

Among patients who received approval, about 35 percent never picked up the medication, which was almost entirely due to high out-of-pocket costs. For example, more than 90 percent of approved patients who had no copayment filled their prescription, but if the copayment was over $300, only about 20 percent filled the prescription.

“Copay alone was highly predictive of whether a patient would fill their prescription — even adjusting for patient demographics, pharmacy, payer and other factors,” said senior author Eric D. Peterson, MD, executive director of the DCRI. “This leads to rationing of these new medications, often in the absence of alternative therapies. Those who cannot afford these high co-pays are left untreated.”

Navar said the study had a limitation, in that it was not designed to assess what was driving pharmacy benefit managers to reject requests for prescriptions. Most patients in the study had Medicare coverage, but it was unclear whether and what clinical factors were taken into account by different pharmacy benefit managers.

“The current system we have is at best a very blunt instrument to restrict use of high-cost therapies to those who need it most,” Peterson said. “We need to figure out a better way to contain costs. We also need to better identify which patients are the best candidates for prescribed therapies, so we can apply the same approval criteria across the board.”

Navar and Peterson receive funding from Amgen and other pharmaceutical manufacturers; full disclosures are provided in the published study.

ACA Medicaid expansion cut disparities in cancer care for minorities, poor

September 26, 2017 – In non-expanded states, benefits were seen primarily in whites and higher-income patients.

States that fully expanded their Medicaid programs under the Affordable Care Act cut their rates of uninsured cancer patients by more than half between 2011 and 2014. Black patients and those living in the highest poverty areas saw the greatest benefit from Medicaid expansion, according to an analysis by DCRI and Duke Cancer Institute researchers.

Rates of uninsured cancer patients in states without Medicaid expansion also declined, but in these states, improvements appeared to primarily benefit white patients and residents of low-poverty areas, with a portion transitioning to non-Medicaid health insurance.

There were no improvements in uninsured rates for black patients and residents of high-poverty areas in states without Medicaid expansion. In fact, patients in these groups appeared to be losing insurance coverage, although this finding was not statistically significant, according to lead study author Fumiko Chino, MD, a radiation oncologist at Duke.

The data was presented Sept. 26 as part of the press program at an annual meeting of the American Society for Radiation Oncology (ASTRO) in San Diego. The analysis is based on the records of more than 197,000 people ages 18 to 64 in a National Cancer Institute database who received radiation for a cancer diagnosis between 2011 and 2014. The DCRI’s Yousuf Zafar, MD, was one of the study’s authors.

“The debate over health care reform is ongoing,” Chino said. “Our findings indicate that Medicaid expansion was effective at decreasing disparities and improving access to care for cancer patients receiving radiation, but some disparities still exist. In states without Medicaid expansion, the rates of uninsured patients went down, but those who benefited were white patients living in higher-income areas, for whom it might have been possible to purchase plans through the health care exchange.”

According to the study data, states with expanded Medicaid programs cut the rate of uninsured cancer patients receiving radiation from 4.4 percent to 2.1 percent. At the same time, the proportion of Medicaid recipients rose from 15.2 to 18 percent.

Inversely, in states without Medicaid expansion, Medicaid enrollment dropped from 15.9 to 14.9 percent for cancer patients receiving radiation, while the portion of these patients having non-Medicaid insurance coverage grew from 75.7 to 77.1 percent.

“This study is part of a developing body of research to quantify healthcare delivery changes under the ACA,” Chino said. “We now are assessing if these insurance changes translate to differences in patient survival.”

In addition to Chino and Zafar, study authors include Gita Suneja, Haley Moss, Laura Havrilesky and Junzo Chino.

DCRI researchers receive grant to study biomarkers linked to chronic low back pain

September 25, 2017 – The DCRI’s Adam Goode, DPT, PhD, and his team will collaborate with UNC-Chapel Hill on the project.

The National Institute of Arthritis, Musculoskeletal and Skin Diseases, part of the National Institutes of Health, has awarded a four-year, $2.4 million grant to a team of Duke researchers led by the DCRI’s Adam Goode, DPT, PhD. The grant will fund an analysis of biomarkers that could be used to better understand the nature of chronic low back pain.

Chronic low back pain affects more than 31 million Americans and costs the national healthcare system between $100 and $200 billion each year. The condition has several different causes, making it difficult for physicians to treat effectively.

Physicians often determine how to treat chronic lower back pain through diagnostic clinical imaging. With a limited understanding of the etiologies of low back pain, however, patients often receive interventions that are unnecessary or even dangerous.

“Not knowing the exact source of a patient’s back pain can really hamper clinical decision-making,” Goode said. “The hope is that we can reduce some of that confusion through the use of biochemical markers.”

Goode and his team, working in concert with the Thurston Arthritis Center and Department of Epidemiology at the University of North Carolina-Chapel Hill, will conduct longitudinal analyses of an ongoing population-based study investigating the incidence and progression of knee, hip and spine osteoarthritis to determine if biomarkers and other risk factors can predict the incidence and progression of intervertebral disc degeneration and facet joint osteoarthritis with and without low back symptoms.

The data will come from serum samples collected by the Johnston County Osteoarthritis Project, a community-based, longitudinal study of approximately 3,200 rural white and African American residents funded by the Centers for Disease Control and conducted by the University of North Carolina School of Medicine.  These samples will be validated against data collected from a second project, the Genetics of Generalized Osteoarthritis study. That study is cohort study designed to identify regions of the human genome associated with multi-joint osteoarthritis.

“We are very proud of Dr. Goode and his team for this important work,” said Benjamin A. Alman, MD, James Urbaniak Professor and Chair of the Department of Orthopaedic Surgery. “This research is directly applicable to healthcare and will not only strengthen and diversify our research portfolio, but also pave the way to improve the way we care for patients.”

Co-investigators on the study also include the DCRI’s Steven Z. George, PhD, and Duke’s Jun Chen, PhD.

DCRI’s Steven George receives funding for non-drug pain management research project

September 21, 2017 – The project, in addition to others announced this week, is intended to address the needs of current U.S. service members and veterans.

The U.S. Department of Health and Human Services, the U.S. Department of Defense (DoD), and the U.S. Department of Veterans Affairs (VA) announced this week a multi-component research project focusing on non-drug approaches for pain management addressing the needs of service members and veterans. Twelve research projects, totaling approximately $81 million over six years (pending available funds), will focus on developing, implementing, and testing cost-effective, large-scale, real-world research on nondrug approaches for pain management and related conditions in military and veteran health care delivery organizations. The National Institutes of Health (NIH) will be the lead HHS agency in this partnership.

One of these projects is led by the DCRI’s Steven George, PhD, along with co-PI Susan Nicole Hastings, MD; and Duke/DCRI faculty Chad Cook, PhD, MBA; Corey Simon, DPT, PhD; and Adam Goode, DPT, PhD. The goal of this planning and demonstration project is to improve access to recommended nondrug therapies for low-back pain in the Department of VA Health Care System and involves researchers from the DCRI, Department of Psychiatry and Behavioral Sciences, Durham VA Center for Health Services Research in Primary, and the UNC Thurston Arthritis Research Center.

“We are hoping to provide non-pharmacological, frontline options that provide optimal pain relief to veterans and prevent unnecessary surgery, injections or opioid prescriptions,” George said.

Benjamin A. Alman, MD, James Urbaniak Professor and Chair of the Department of Orthopaedic Surgery, said, “We are incredibly proud of the work Dr. George is doing for our veterans, as well as the broader implications his work could have on the way we treat patients with chronic low-back pain.”

“Finding solutions for chronic pain is of critical importance, especially for military personnel and veterans who are disproportionately affected,” said NIH Director Francis S. Collins, MD, PhD. “Bringing the science to bear through these real-world research projects will accelerate our search for pain management strategies for all Americans, especially as we work to address the nation’s opioid crisis.”

The National Center for Complementary and Integrative Health (NCCIH), part of NIH, is contributing more than half of the total funding, and it is the lead for this multi-agency initiative called the NIH-DoD-VA Pain Management Collaboratory, which is modeled on the successful NIH Health Care Systems Research Collaboratory. This initiative also addresses the need to focus on “advancing better practices for pain management,” which is outlined in HHS’ 5-point strategy to combat the opioid crisis.

Studies report nearly 45 percent of soldiers and 50 percent of veterans experience pain on a regular basis, and there is significant overlap among chronic pain, post-traumatic stress disorder (PTSD), and persistent post-concussive symptoms. Data from the National Health Interview Survey shows that American veterans experience a higher prevalence of pain and more severe pain than nonveterans. Although opioids are often prescribed to treat chronic pain, research has not shown them to be very effective, and there are many issues with long-term use. Thus, there is a need for nondrug approaches to complement current strategies for pain management and to reduce the need for, and hazards of, excessive reliance on opioids.

Seven of the 12 projects, including George’s, have been awarded by HHS/NIH. The remaining five will be announced by the DoD and VA in the coming months.

NIH Health Care Systems Research Collaboratory celebrates five years

September 19, 2017 – The NIH Collaboratory is celebrating five successful years of innovation in pragmatic clinical trials.

The Common Fund at the National Institutes of Health (NIH), which supports innovative endeavors with the potential for extraordinary impact, instituted the NIH Health Care Systems Research Collaboratory five years ago in 2012, with its coordinating center based at the DCRI. The goal of the program is to improve the way clinical trials are conducted by creating a new infrastructure for collaborative research with healthcare systems. At a time when reducing the cost of clinical trials and generating real-word knowledge is becoming progressively crucial, the NIH Collaboratory is leading the way in expanding the national capacity for pragmatic clinical research.

“The NIH Collaboratory embodies what makes clinical research exciting and simply fun,” said Adrian Hernandez, MD, one of three principal investigators of the NIH Collaboratory coordinating center at the DCRI. “We’ve learned together how to address challenges and then seeing how those solutions go forward to change how clinical trials should be done as opposed to how they are currently done.”

Providing national leadership and technical expertise in all aspects of research with healthcare systems, the DCRI has worked with the NIH and other coordinating centers at the Center for Medical Technology Policy, Harvard Pilgrim Health Care Institute, Group Health Research Institute, and Johns Hopkins Berman Institute of Bioethics over the last five years to produce, document, and disseminate standards for healthcare systems research. Together they have created an infrastructure to facilitate multi-center studies and the responsible use of electronic health data. They have also been able to establish a structure supporting research with healthcare systems as partners.

“The hallmark of the NIH Collaboratory over the last five years has been the spirit of collaboration and curiosity from all the investigators,” said DCRI’s Kevin Weinfurt, PhD, co-principal investigator (pictured left). “One of the most prominent accomplishments of the Collaboratory during this time is successfully planning 10 very complex pragmatic clinical trial Demonstration Projects spanning 12 NIH institutes and centers, 9 of which proceeded to full implementation.”

The NIH Collaboratory’s pragmatic clinical trial Demonstration Projects gather real-world evidence to answer clinical questions of major public health importance and engage healthcare delivery systems in research partnerships. Seven Core Working Groups of experts, each focused on a specific topic, support all of the Demonstration Projects and initiatives across the program, helping the research teams navigate issues of research embedded in clinical care, as well as collect knowledge gained throughout the process.

“All of us in the NIH Collaboratory have learned a tremendous amount about how to successfully embed pragmatic clinical trials in health care delivery systems,” said DCRI’s Lesley Curtis, PhD, co-principal investigator (pictured right). “What’s most exciting is the universal commitment to sharing successes, surprises, and missteps so that we build the evidence base about embedded research while the trials answer important questions.”

Knowledge sharing has been a key component of the NIH Collaboratory over the past half a decade. Weekly Grand Rounds, delivered in the form of webinars, have been highly successful and provide a forum for sharing the latest advances in pragmatic research. Attended by a large audience of researchers and others in the clinical research community, including representatives from NIH and the U.S. Food and Drug Administration, the Grand Rounds also serve as a platform to discuss how to successfully conduct pragmatic clinical trials within the current ethical and regulatory framework for research.

“Another noteworthy accomplishment of the Collaboratory in the last five years is the creation of the continuously evolving Living Textbook, which is an easily available online repository of the

Lesley Curtis

lessons learned from the Collaboratory,” said Weinfurt. “To support the wider conduct of pragmatic trials, the investigators put in a lot of effort to update the Living Textbook as experiences were accumulated.”

Together with the DCRI, the program built a Knowledge Repository, a publicly available archive of resources related to the conduct of pragmatic trials. In the same spirit, it also created the NIH Collaboratory Distributed Research Network, which facilitates multi-site research collaborations to allow researchers to query electronic health records of over 90 million individuals in a way that protects participant privacy. According to the investigators, this paves the way for standards in data sharing, data quality, and reuse of electronic health record data.

“It takes a village,” said Tammy Reece, Project Leader of the NIH Collaboratory at the DCRI. According to Reece, the success is in the numbers: with more than 500 resources achieved in the Knowledge Repository, more than 200 Grand Rounds held since inception along with over 70 conference presentations or symposia, more than 60 total publications, and more than 320 citations in peer-reviewed journals, and these numbers are still growing.

According to the investigators, the numbers from the last five years add up to success but there is still much to achieve for both the DCRI and the NIH Collaboratory.

“In the future, we would like to see the Collaboratory learn a bit more about how to implement pragmatic trials in less than optimal settings with a goal to empower all health systems to be able to conduct trials on a variety of different platforms,” said Weinfurt. “Empowering health systems is an important and unique feature of the Collaboratory as a network.”