DCRI Research Contributes to FDA Approval of First Drug for Rare Disease in Pediatric Patients

June 4, 2019 – The team used pharmacokinetic modeling to assess how the drug would behave in children, leading to FDA approval without conducting a pediatric clinical trial.

For the first time, pediatric patients with Lambert-Eaton myasthenic syndrome (LEMS) have a treatment that has been approved by the U.S. Food and Drug Administration (FDA).

A team that included researchers from the DCRI was involved in developing the supporting evidence that led to the FDA’s approval of Ruzurgi (amifampridine) tablets. In a relatively rare occurrence, the drug was approved for a patient population in which it was not tested in a clinical trial.

Jeff Guptill

Instead, the DCRI’s Jeffrey Guptill, MD, explained, the DCRI Pharmacometrics Center was able to embark on a project, led by Huali Wu, PhD, that used data from a trial in which the drug was given to adults. These data were used for pharmacokinetic modeling to predict how the drug would behave in patients aged 6 to less than 17.

“Mathematical models were developed to predict how amifampridine moves through the adult body,” Guptill (pictured) said. “We adapted these models to fit children with LEMS, which helps us draw conclusions about the drug and determine appropriate dosing in this population.”

LEMS is a rare autoimmune disorder that affects the communication between a patient’s nerves and muscles, causing weakness and other symptoms. Duke has one of the highest concentrations of LEMS patients in the U.S.

Ruzurgi also received Orphan Drug designation from the FDA, which offers incentives to encourage drug development for rare diseases.

Study Examines Predictors of Transplant or Death in IPF Patients

May 30, 2019 — Researchers examined clinical factors at the time of a patient’s enrollment in the IPF-PRO registry that might predict lung transplant or death.

Patients in a recent study on idiopathic pulmonary fibrosis (IPF) had about a 50 percent chance of dying or having a lung transplant over the course of the 30-month study, according to findings recently published in Respiratory Research.

The study, which is also highlighted in a recent blog and podcast, examined data from 662 patients with IPF, a progressive and fatal lung disease. These patients were the first of 1,000 to enroll in the IPF-PRO registry, a partnership between the DCRI and Boehringer-Ingelheim to learn more about the disease. All patients were enrolled between June 2014 and October 2017.

Laurie SnyderThe study, led by the DCRI’s Laurie Snyder, MD, MHS, (pictured), examined clinical factors at time of patient enrollment that might predict lung transplant or death. In order to be included in the study, patients had to have been diagnosed with IPF or newly confirmed at a site within the six months prior to the study’s beginning.

The clinical factor that most strongly predicted lung transplant or death was oxygen use at rest, which was associated with a three-and-a-half fold increase in either outcome over the follow-up period.“Interstitial lung diseases like IPF don’t allow oxygen to diffuse across lung tissue,” Snyder said. “Patients who need oxygen not only while walking, but also at rest, are likely more advanced in their disease state and have a higher risk of the outcomes we were examining.”

Patients who had worse lung function were also at greater risk. Lung function was measured at enrollment by forced vital capacity and diffusion capacity, or the capacity of the lungs to exchange oxygen. Patients who scored progressively lower on each of these measures were more likely to need a lung transplant or die before the study’s end.

The study also showed a relationship between age and outcomes. The data collected showed a J-shaped curve, with the youngest patients (around 50 years old) at the highest risk. Risk of lung transplant or death then declined until about age 62, and then escalated again as age increased.

Snyder hypothesizes this could be because the youngest patients have a familial form of IPF, which could be more devastating than non-familial IPF.

“Results like this are the power of the IPF-PRO Registry,” Snyder said. “This is one of the first times we’ve had multicenter data to examine that represents the real world, without limitations on age range or pulmonary function.”

Assistance for the study also came from the DCRI call center.

“Participation in a registry doesn’t mandate that patients come back to a participating center,” Snyder said. “The call center was able to provide a touchpoint to patients and help with data collection, which helped us figure out whether patients had been hospitalized or received lung transplants.”

Next steps for the registry and this research include a move toward longitudinal data. Snyder said the team plans to examine whether changes in clinical factors better predict mortality than singular data points collected at enrollment in the registry.

In addition to Snyder, other DCRI authors included Megan L. Neely, Anne S. Hellkamp, Emily O’Brien, and Scott Palmer.

DCRI study honored as practice-changing by New England Journal of Medicine

May 29, 2019 – The ARISTOTLE study found that apixaban was superior to warfarin in preventing stroke and decreasing risk of bleeding for patients with atrial fibrillation.

A DCRI-led study published in 2011 was recently honored by the New England Journal of Medicine’s editor-in-chief as one of 12 studies that has most changed clinical practice since 2000.

The ARISTOTLE study found that apixaban was superior to warfarin in treating patients with atrial fibrillation who have an increased risk of stroke. Apixaban was not only more effective than warfarin in preventing stroke, but also caused less bleeding. The trial included more than 18,000 patients from 39 countries.

Prior to his upcoming retirement, Jeffrey Drazen, the editor-in-chief of the New England Journal of Medicine, looked back at the science the journal published over the 19 years he spent in the role. From more than 80,000 submissions and nearly 4,000 published studies, he selected 12 to highlight as “Drazen’s Dozen” of “practice-changing and lifesaving papers.”

“This is really quite an honor, as there are plenty of trials that are equally important,” said the DCRI’s Christopher Granger, MD (pictured), who served as a primary investigator and co-chair on ARISTOTLE. “This is a tribute to a great collaboration—both among so many people at the DCRI and worldwide, especially my co-chair Lars Wallentin from Uppsala University in Sweden.”

The DCRI team also credits its industry partners, Bristol-Myers Squibb and Pfizer, with contributing to the success of ARISTOTLE. The DCRI’s John Alexander, MD, MHS, who worked on ARISTOTLE, started studying apixaban with colleagues from Bristol-Myers Squibb in 2005, but the drug had an unfavorable risk-benefit profile in patients with acute coronary syndrome. By contrast, ARISTOTLE, according to Alexander, was “a home run.”

“It has been a rare privilege to be so intimately involved in the development of a drug that has made, and is making, such a difference in patients’ lives,” Alexander said. “I’ve been involved with a lot of trials, but none have had as great an impact on patient care as ARISTOTLE.”

Apixaban is now the most commonly initiated drug for stroke prevention for patients with atrial fibrillation, Granger said. It is easier to use than warfarin because warfarin is associated with several food and drug interactions and requires monitoring.

“It is gratifying to be able to generate evidence that can be used to help improve patients’ lives,” Granger said. “This honor aligns nicely with the DCRI’s mission to share knowledge that improves patient care around the world—we have been able to publish and share knowledge gained from ARISTOTLE that we now use every day in our practice.”

The DCRI’s Renato Lopes, MD, PhD, started working on the trial as a DCRI fellow, and later became part of the core leadership team of the study as a DCRI faculty member.

“When you work on a trial for so long and put in so much effort, it becomes part of your life,” Lopes said. “We are pleased that ARISTOTLE is still generating knowledge and helping patients all over the world, and it’s extremely rewarding and gratifying to be recognized for the work done by so many to make the trial successful.”

In addition to the primary manuscript published in 2011, there have been over 60 publications from ARISTOTLE with over half published in high-impact journals.

Other DCRI faculty who contributed to ARISTOTLE include Hussein Al-Khalidi, PhD, who was the statistician, and Sana Al-Khatib, MD, MHS, who ran clinical events classification for the trial. Many operational staff also contributed to ARISTOTLE’s success.

Duke joins Baseline Health Consortium to get patients more involved in research

May 16, 2019 – The DCRI’s Adrian Hernandez, MD, MHS, and Manesh Patel, MD, will serve as Duke’s representatives to the consortium.

Verily, an Alphabet company, today announced a new Project Baseline initiative, the Baseline Health System Consortium, composed of Verily, Duke University Health System, Vanderbilt University Medical Center, University of Mississippi Medical Center, Mayo Clinic, Regional Health in South Dakota and University of Pittsburgh. The strategic collaboration will identify and develop solutions to significant challenges in clinical research, including making research more accessible and engaging for patients, clinicians, researchers and research sponsors alike.

Adrian Hernandez

United by a vision of transforming clinical research, the consortium partners will embark on a pilot in 2019 to analyze existing research programs, and use tools and technology developed through Project Baseline, including the Baseline Platform — an end-to-end evidence generation platform — to make it faster and easier to conduct studies, capture health information in a more efficient way and generate better evidence to support scientific discovery. The consortium partners sit at the nexus of clinical research and clinical care, and are uniquely positioned to help Verily iterate on its technology to bridge the gap between research and care and further precision medicine.

“The clinical research system fails to provide the evidence that patients and clinicians need to make good health and healthcare decisions,” said the DCRI’s Robert Califf, MD, former FDA commissioner and advisor, Verily. “By developing useful tools and approaches, this robust collaboration has the potential to drive more efficient and effective research as we link patients, advocacy groups, clinicians, health systems and researchers.”

Verily launched Project Baseline in 2017 with the Project Baseline Health Study to develop the technology and tools to help researchers create a more comprehensive map of human health. Duke University School of Medicine, a collaborator in the Health Study, will partner with Verily on this next phase. The DCRI’s Adrian Hernandez, MD, MHS, Vice Dean of Duke University School of Medicine and a principal investigator for the Health Study (pictured), is joined by leaders in health research Manesh Patel, MD, Duke University Health System; Russell Rothman, MD, MPP, Vanderbilt University Medical Center; Javed Butler, MD, MPH, MBA, University of Mississippi Medical Center; Veronique L. Roger, MD, MPH, Mayo Clinic; Drew Purdy, MD, Regional Health in South Dakota; and Kathleen McTigue, MD, MPH, MS, University of Pittsburgh, as representatives to the consortium. Robert Harrington, MD, professor and chair of the Department of Medicine at Stanford Medicine, will chair the Steering Committee, building on Stanford Medicine’s role as a partner in the Health Study.

“We’re proud to be part of this group of institutions committed to changing research and creating a more deeply connected community of patients, researchers and clinicians,” Hernandez said. Project Baseline logo“Part of improving research means that we have to collect better feedback from patients and capture health outside of the four walls of the clinic. The consortium builds on the foundation we’ve created with the Project Baseline Health Study and will help us develop and test tools that could aid our ambitious goal of improving human health.”

“This consortium has a unique opportunity to harness data from past and present research programs, analyze what works and doesn’t work, and use the insights to improve the methodology of clinical research more broadly,” said Harrington of Stanford. “By embracing tools and technology to take research into the modern age, we hope to provide greater value in research to both patients and researchers and maximize what we learn about human health from every clinical and research interaction.”

In founding the consortium and partnering with sophisticated health systems, Verily continues to build a robust research ecosystem, with the goal of delivering modern solutions for faster evidence generation and discovery. In February, Verily announced it was joining forces with the American Heart Association (AHA) on Research Goes Red, a new initiative to engage women in heart health research and discovery. Earlier this month, Verily launched the Project Baseline Heart Biomarker Study, expanding its research into risk factors for heart disease.

Verily launched Project Baseline in 2017 with the goal of transforming clinical research through improved real-world evidence generation and by involving more people and clinicians through accessible and engaging studies. Its first initiative was the Project Baseline Health Study, a longitudinal observational study in partnership with Duke University School of Medicine, Stanford Medicine, Google and the American Heart Association to collect, organize and analyze broad phenotypic health data from a diverse cohort of participants over several years. Verily’s interdisciplinary team has also developed the Baseline Platform, an evidence generation platform designed to engage patients and clinicians in research, make it easier and faster to run clinical studies and collect high quality, comprehensive data in the real world. For more information, please visit www.projectbaseline.com.

DCRI joins Digital Therapeutics Alliance

May 15, 2019 – The DCRI will bring its regulatory experience and clinical expertise to the conversation surrounding digital therapeutics.

The DCRI has joined a new alliance focused on bringing digital therapeutics solutions to patients.

The Digital Therapeutics Alliance (DTA), formed in 2017, works to improve access to digital therapeutics for patients, providers, and payers, in an effort to reduce costs and enhance individualized health care. The DTA currently has 25 members, and the DCRI is the first academic member.

“The DTA seeks to broaden the global digital therapeutics conversation within their organization, and the DCRI brings a different perspective,” said the DCRI’s Scott Kollins, PhD (pictured top), who helped lead the DCRI’s application process to join the alliance. “This is a good way for to us to continue and amplify our work in digital therapeutics and potentially become leaders in the space.”

Kollins, whose research focuses on neuroscience and behavioral science, said the focus on clinically validated, technology-based interventions sets the DTA apart from other digital health organizations.

“Digital health is a broad umbrella term that can refer to many things,” Kollins said. “The DTA distinguishes itself by focusing on evidence-based therapeutic interventions that can prevent, manage, or treat a medical disorder or disease.”

The DCRI, Kollins said, can help companies clinically evaluate these interventions in a quickly growing space that can be difficult to regulate.

“I think the value of the DCRI comes from being able to help manufacturers distinguish themselves from many other companies and apps that are out there claiming they can do certain things, such as improve attention or depression or obesity, without any evidence,” he said. “Both with our clinical research and our regulatory knowledge, we can be the ones who are helping digital therapeutics companies rise above the din.”

As Kollins explored the opportunity for the DCRI to join the DTA, it eventually became clear that he was not the only DCRI faculty member who was interested in the idea.

Ann Marie NavarCardiologist Ann Marie Navar, MD, PhD (pictured bottom), was also looking into the alliance, engaging in conversation with Bray Patrick-Lake, the DCRI’s director of stakeholder engagement who also serves as a founding strategic advisor to the DTA.

Patrick-Lake brings her expertise in patient engagement to the alliance and said she looks forward to the work the DCRI can do to help advance the work of framing and defining the digital therapeutics industry.

“It was important to ensure that the patient voice was front and center,” she said. “For example, accessibility is crucial for patients, but we can’t increase access without evidence that an intervention works. The DCRI can help with the evidence piece through clinical trials, which can in turn improve access issues, such as reimbursement mechanisms. Joining the Digital Therapeutics Alliance enables the DCRI to implement rigor in the development of a new field.”

Navar agreed, adding that although digital therapeutics is currently a hot topic in healthcare, more work needs to be done to effectively deliver solutions to patients. She hopes that the DCRI’s membership in the DTA is a step toward completing this work.

“The promise of digital therapeutics is great, but for now we’re seeing mostly hype and clinically have seen very little on the delivery side,” Navar said. “At the DCRI, we feel that this is an area where strong clinical research is needed to help define where these solutions can actually make a difference on health.”

As the DCRI’s chief of digital health and strategy, Satasuk Joy Bhosai, MD, MPH, spends much of her time thinking about these opportunities. Bhosai is part of the DCRI committee working on the alliance.

“There are a lot of new digital technologies popping up, but we need to help provide guidance around clinical evaluation,” she said. “We can partner with innovators shaping these technologies to help them ensure their innovations actually translate to meaning.”

Now that the DTA membership is official, Kollins said, one of the first steps is to bring together researchers within the DCRI who are pursuing work in this space.

“There are many people within the organization doing relevant work, but this is a good time to centralize that work and set some strategy around digital therapeutics,” Kollins said.

“To be recognized as a digital therapeutic requires that a product go through a series of rigorous clinical trials to substantiate its outcomes,” said Megan Coder, executive director of the DTA. “The DCRI has a deep reputation in inclusive clinical trial design and execution and we welcome them to membership at DTA as our first academic member.”

Use of supportive palliative care lags for heart patients

May 3, 2019 – Patients tend to be sicker and miss full benefits by the time palliative care is provided.

While heart disease is the leading cause of death in the United States, relatively few of these patients receive a referral to palliative care focusing on quality of life and value-based treatment decisions.

When heart patients are referred to palliative care, they are typically nearing death and therefore benefit from hospice services geared to end-of-life, according to a study lead by Duke Health researchers.

“Hospice care is a subset of palliative care that is generally provided when a patient has about six months left to live,” said Haider J. Warraich, MD (pictured), a former DCRI fellow and lead author of the study appearing online Friday in JAMA Network Open.

“Palliative care is much broader, focusing on improving quality of life, easing pain and suffering and assuring that the patients’ treatments going forward are in line with their values and goals,” Warraich said. “There’s a huge gap that patients with heart disease face that has resulted in them not receiving this type of care.”

Warraich and senior author, Arif Kamal, MD, a palliative care specialist at Duke Cancer Institute, reviewed referrals to palliative care from a large national database to determine when and how often patients with cardiovascular disease were referred to palliative care.

The study included more than 1,800 patients with heart disease who had been referred to palliative care from 2015-2017. Of those, about 29 percent were bed-bound, meaning they were in the late stages of disease. By comparison, only about 10 percent of cancer patients, who are the largest group referred to palliative care, are bed-bound.

General medicine physicians increased referrals of heart patients to palliative care, from 43.2 percent in 2015 to 52.9 percent in 2017. But the proportion of referrals from cardiologists declined, from 16.5 percent in 2015 to 10.5 percent in 2017.

“Our data highlight the enormous potential for increased partnerships between cardiologists and palliative care specialists in providing comprehensive, high-touch, supportive care to all affected by advanced heart disease,” Kamal said.

In addition to Kamal and Warraich, study authors include Steven P.Wolf, Robert Mentz, Joseph G. Rogers, and Greg Samsa.

New professional development program aims to advance women’s clinical research careers

May 2, 2019 – The program, offered by the American College of Cardiology, will see involvement from DCRI faculty in chairing, teaching, and participating.

Several DCRI faculty members are developing a new professional development program for early- to mid-career female clinical researchers offered by the American College of Cardiology.

The Clinical Trials Research Program is a training and networking program open to women cardiologists who have committed to a career in clinical research and have been nominated by their institution for further development in research leadership. The program, which will be held in May in Washington, D.C., is co-led by Pamela Douglas, MD, and Tracy Wang, MD, MHS, MSc, at the DCRI, as well as Mary Norine Walsh, MD, at St Vincent’s. Douglas brought the idea for a women-specific professional development program to the American College of Cardiology’s Diversity and Inclusion initiative, which she also chairs.

“Half of all medical students are women, and roughly 45 percent of internal medicine residents are women, but only 20 to 25 percent of cardiology fellows are women,” said Douglas (pictured left), who has served as director of the DCRI’s imaging program since 2006. “So among practicing cardiologists, it’s only about 10 to 12 percent women. This means we’re missing a huge amount of talent—we’re missing about 30 percent of the brainpower in our profession.”

Over the years, Douglas and Wang have had ongoing discussions about how to best provide career opportunities for women. It is an issue that is personal for Wang, who wanted to be an interventional cardiologist but ultimately ended up choosing a different path. Although this decision was influenced by many factors, she attributes it in part to the fact that there were few female interventional researcher mentors at Duke and elsewhere during her training.

Wang and Douglas hope to help solve the representation problem with women-specific offerings like the ACC Clinical Trials Research Program.

“We want to help women navigate some of the same challenges we saw when we were early-career faculty,” Wang said. “We want this program to act as a launching pad to help these promising researchers get to where they need to be — at the highest levels of research leadership.”

Wang (pictured right) said the program will do this in three ways: by building a solid foundation of knowledge, by creating peer networks that help women sponsor each other for opportunities and leadership roles, and by connecting women with study funders/leaders, role models and other resources.

Wang and Douglas hope there will be future iterations of the program. Approximately 50 women were accepted to this inaugural cohort, which is 10 percent underrepresented minorities and 15 percent international researchers.

The program’s primary goal is to elevate women’s careers, but promoting women will also have a positive impact on science and on patients, Douglas and Wang said. This is because women are more likely to conduct research that is relevant to female patients, more likely to attract female research participants, and therefore, more likely to return sex-specific results.

Two DCRI researchers will be attending the program — Melissa Daubert, MD, whose work focuses on women’s cardiac health, cardio-obstetrics, and cardiac imaging, and Chiara Melloni, MD, whose primary research interest is cardio-oncology.

Daubert, who has been at the DCRI since 2012, said she applied to the program because the agenda offered each participant the opportunity to create her own personal career action plan. She is looking forward to forecasting new opportunities and collaborations as her clinical research career continues to grow.

“It’s important to train women in a male-dominated field like cardiology so that we can take a balanced approach to care and ensure that gender disparities are adequately addressed,” she said.

Melloni, who has been at the DCRI since she arrived for a fellowship in 2005, said she is most excited about enhancing her skills in certain areas, such as engaging with stakeholders and forging relationships with sponsors. Although she has worked on many different trials, she said she has more to learn.

Both Daubert and Melloni also said they will find value in making connections with other female cardiologists and helping to create a network for professional advancement.

“I like clinical research because each trial is different and presents different challenges,” Melloni said. “But the road to becoming an expert is long.”

The DCRI’s Kevin Thomas, MD, and Kevin Anstrom, PhD, will also serve as faculty for the program.

DCRI receives CRO Leadership Awards for fourth year

April 30, 2019 – The DCRI was recognized in five categories, including Capabilities, Compatibility, Expertise, Phase IV, and Reliability.

The DCRI has again received several CRO Leadership Awards from Life Science Leader magazine and Industry Standard Research. The awards, presented annually by the magazine to contract and academic research organizations, were created to recognize excellence in several key categories. This year, the DCRI was recognized in the categories of Capabilities, Compatibility, Expertise, Phase IV, and Reliability. The organization also received Individual Attribute Awards for Data Quality, Project Timelines, Operational Excellence, and Responsiveness. The DCRI has received CRO Leadership Awards for four consecutive years.

The awards are based on surveys of biopharmaceutical and medical device companies conducted by Industry Standard Research. For this year’s awards, more than 70 research organizations were evaluated on more than 20 different performance metrics. Respondents only evaluated companies with which they have worked on an outsourced project in the last 18 months.

A complete list of winners was published in the May 2019 issue of Life Science Leader. A formal awards ceremony will be held June 24 in San Diego.

“These awards are evidence of the incredible work that our faculty, fellows, and staff do every day,” said DCRI Interim Executive Director Lesley Curtis, PhD. “The DCRI is honored to again be recognized for its efforts to improve patient health around the world.”

DCRI helps FDA map strategy to broaden use of real-world evidence

April 24, 2019 – Through projects such as ADAPTABLE, CTTI, and the NIH Collaboratory, the DCRI is defining how to use RWE in clinical research.

From electronic health records to insurance claims, patient registries, and mobile devices, modern technology has ushered in a wealth of real world data (RWD) that can complement traditional randomized clinical trials to help researchers understand more about a drug or treatment. Until recently, however, there was little agreement on how to transform this data into solid evidence that can guide patients to better decisions.

In late 2018, the U.S. Food and Drug Administration (FDA) released a new Framework for Real-World Evidence (RWE). The document, which establishes a definitive roadmap for FDA’s development of standards for the use of RWD and RWE, is a product of insights gleaned from some of the nation’s most respected trailblazers in advancing the generation and use of RWE, including the DCRI.

Specifically, the Framework outlines various areas in which FDA will evaluate the use of RWD and RWE; FDA’s plan for evaluating how RWD can be incorporated into study designs and the regulatory considerations for such use of RWD; and FDA’s plan for developing guidance in a number of key areas, including on data standards and additional sources of RWD to help address current gaps in the capture of key information.

DCRI researchers’ contributions to this Framework build on a strong tradition of leadership in advancing the use of RWE. For example, the DCRI’s Adrian Hernandez, MD, MHS, participated  in a 2016 Bipartisan Policy Center roundtable, which focused on advancing the use of RWE and served as an opportunity for the DCRI to share its perspective on how the right policy pathways are critical to shaping the future of real-world medicine.

Leading by example

The DCRI’s work to advance the use of RWE continues today. Through several innovative programs, the DCRI continues to spearhead new and better ways of bringing RWE to the fore of research that will inform future regulatory policy.

As highlighted in the FDA’s framework document as a case example, the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) Study is a patient-centered, pragmatic clinical trial assessing two different daily doses of aspirin to evaluate which dose is more effective for patients living with cardiovascular disease.

The DCRI is the Coordinating Center for ADAPTABLE, which is funded through a Patient-Centered Outcomes Research Institute (PCORI) award and is conducted through PCORnet– the National Patient-Centered Clinical Research Network.

Forty healthcare systems and three health plans use electronic health records (EHRs) and health insurance information to identify potential study participants. Effectively using EHRs as a recruitment strategy requires transparency and communication with clinicians.

“Finding ways to make research more practical is what ADAPTABLE and pragmatic clinical research is all about,” said ADAPTABLE principal investigator Schuyler Jones, MD. “ADAPTABLE integrates conversations about participation into the clinical work flow, helping both clinicians and patients become more aware of the research question, and better understand if participation is the right choice for that individual patient.”

It takes a team approach to establishing best practices for leveraging electronic health records, engaging patients as partners, and overcoming regulatory hurdles. The ADAPTABLE team consists of patient partners, clinicians, and researchers who regularly discuss study progress, challenges, and success. Team members frequently share lessons learned and insights within the ADAPTABLE community and beyond as they continue to set the bar and put in place measures to innovate clinical research.

The DCRI also serves as the Coordinating Center for the National Institutes of Health Health Care Systems Research Collaboratory (NIH Collaboratory), helping to realize the program’s mission to strengthen the national capacity to implement cost-effective large-scale research studies that engage healthcare delivery organizations as research partners. Led by DCRI’s Lesley Curtis, PhD, Adrian Hernandez, MD, MHS, and Kevin Weinfurt, PhD, the Coordinating Center supports and learns from innovative pragmatic trials to advance the field.

“Through the NIH Collaboratory program, we are discovering the best ways to embed research in everyday clinical care,” said DCRI’s Tammy Reece, MS, project director for the Coordinating Center. “Everything we learn is fed back to the research community to shape how the next generation of clinical trials will be conducted.”

One example is the Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo), led by the DCRI’s Myles Wolf, MD, MMSc. HiLo is testing the effects of different levels of phosphate control for patients with end-stage renal disease under real-world conditions. This clinically important question will be answered through partnership with dialysis organizations and their providers.

Another DCRI-affiliated project, the Clinical Trials Transformation Initiative (CTTI), is working on a collaborative project with the FDA, industry, patients, and other stakeholders to advance the use of RWD—which is also used and analyzed to create RWE—in planning for regulatory submission trials. As part of this work, CTTI is developing recommendations and supporting resources for using data from electronic health records (EHR) and insurance claims to evaluate trial eligibility criteria and recruit potential research participants. The work is based on in-depth interviews and meetings with representatives from academia, biopharmaceutical companies, health systems, and other organizations to identify challenges and opportunities for incorporating RWE in regulatory submission trials.

“RWD is a potentially powerful tool for enhancing the quality and efficiency of clinical trials,” said CTTI Executive Director Pamela Tenaerts, MD, MBA. “Clarifying the best approaches for incorporating RWD into clinical trials can accelerate recruitment and completion of these trials and lead to substantial benefits for all stakeholders in the clinical trials enterprise, including sponsors, sites, and participants.”

The next era of research

Each of these DCRI projects is laying the groundwork for something bigger: a new era of drug development that seamlessly employs RWD and RWE to bring patients meaningful insights at less cost and greater speed than ever before.

As entities like the FDA continue mapping the right ways to enhance modern drug development with real world insights, it will be looking to the outcome of these DCRI efforts to guide its trajectory.

Many heart attack patients may be needlessly treated in ICU

April 15, 2019 – A new study finds that more than 80 percent of stable STEMI patients are treated in the ICU.

Many patients who suffer a type of heart attack known as an ST-elevation myocardial infarction (STEMI) are treated in the intensive care unit (ICU), despite a relatively low risk of developing a complication requiring ICU care, according to a new study published in JACC: Cardiovascular Interventions.

A STEMI is caused by a blocked blood supply to the heart and is the most severe type of heart attack.

“In recent years, treatment for STEMI patients has improved so much that cardiologists have seen the risk of developing a complication requiring care has significantly decreased,” said Jay S. Shavadia, MD, a cardiologist and researcher from the DCRI and the study’s lead author. “We wanted to quantify the risk and see whether ICUs are being overutilized for STEMI patients.”

The researchers analyzed data from the Chest Pain-MI Registry, which includes patients admitted to participating hospitals with STEMI or non-STEMI (NSTEMI). They examined patterns of ICU use among STEMI patients ages 65 years and older treated with PCI who were stable when they were first seen in the hospital. This meant they were not in cardiac arrest, were not in shock or had had a procedural complication.

“We know those patients [with shock] need to be in an ICU, so we didn’t include them in the study,” he said.

Of 19,507 stable STEMI patients treated at 707 hospitals, 82.3 percent were treated in an ICU with a median one-day ICU stay. Overall, 16.2 percent of patients developed complications requiring ICU care while hospitalized. The study found 3.7 percent died, 3.7 percent experienced cardiac arrest, 8.7 percent experienced shock, 0.9 percent suffered a stroke, 4.1 percent had a blockage of electrical signals between the heart’s upper and lower chambers (atrioventricular block) and 5.7 percent experienced respiratory failure. These complications were not limited to those related to heart problems.

“As patients get older, their risk of non-cardiovascular complications requiring an ICU stay increases, such as other causes of shock or respiratory failure, sepsis for instance,” Shavadia said.

Patients who waited longer to receive treatment were more likely to develop at least one complication. Those who received treatment within an hour of being evaluated by emergency medical service (EMS) personnel or going directly to the hospital without being seen by EMS, had a complication rate of 13.4 percent, compared with 18.7 percent for those who were not treated for at least 90 minutes.

“Although 16 percent is not a small number of STEMI patients who should be in the ICU, we found the majority of patients don’t need to be there,” Shavadia said.

He said that patients age 65 years and older are more likely to develop complications than younger patients, so the overall risk for STEMI patients of all ages who need ICU care may be even lower than 16 percent.

The study did not address which stable STEMI patients will need ICU care.

“We’re now trying to identify which patients are at greatest risk of complications, so we can predict who needs to be treated in the ICU,” Shavadia said.

In an accompanying editorial, Suartcha Prueksaritanond, MD, and Ahmed Abdel-Latif, MD, PhD, of the Gill Heart and Vascular Institute and division of cardiovascular medicine at the University of Kentucky, and the Lexington VA Medical Center in Lexington, Kentucky, wrote, “The high ICU utilization pattern despite declining complications following PPCI [primary percutaneous coronary intervention] calls for a new approach. This is particularly important as the overall health care cost continues to grow and calls for optimal resource utilization prevail.”

They noted that until a more comprehensive, simple-to-follow algorithm for stratifying risk in STEMI patients is developed, “the ICU admission decision for STEMI patients will continue to be based on individual judgment and traditional protocols rather than robust and evidence-based risk prediction models.”