Medical Misinformation Causes Underuse of Statins

July 2, 2019 – The DCRI’s Ann Marie Navar, MD, PhD, writes that medical misinformation surrounding statins is causing patients to stop or avoid statins, missing out on a major opportunity to prevent heart attacks and strokes.

Ann Marie NavarIn a recent Viewpoint piece published in JAMA Cardiology, the DCRI’s Ann Marie Navar said that the proliferation of medical misinformation around statins is causing often misguided fears about statins, leading patients to refuse or stop treatment.

“While there are true risks and side effects associated with statins, the popular media is abuzz with false reports about statin side effects,” Navar said. “The reality is that statins are one of the best studied, safest, and most effective medications we have to prevent heart disease.”

Navar likens the incorrect information about statins to the false perceptions that led to an anti-vaccination movement.

“Measles outbreaks are highly visible: a rash appears, public health agencies respond, headlines are made, and the medical community responds vocally,” she writes. “In contrast, when a patient who has refused a statin because of concerns stoked by false information has a myocardial infarction, the result is less visible. Nevertheless, cardiologists and primary care physicians observe the smoldering outbreak of statin refusal daily.”

In the piece, Navar advocates for clear and transparent communication so medical providers can establish trust with patients and fight against medical misinformation.

The DCRI Welcomes Three Former Fellows As New Faculty

July 1, 2019 – The new faculty represent the pediatrics, nephrology, and musculoskeletal therapeutic areas.

The DCRI has hired three recent graduates of its fellowship program to continue working at the DCRI as full-time faculty. The new faculty represent three different therapeutic areas.

“We are proud to welcome these outstanding fellows from our most recent graduating class as new DCRI faculty colleagues,” said Matthew T. Roe, MD, MHS, faculty director for the DCRI Fellowship program. “The fact that they have chosen to continue their academic careers here showcases the DCRI’s mission of training the next generation of clinical researchers and highlights the future potential of the respective therapeutic areas within which each of these new faculty members will collaborate on research endeavors.”

Meet the new faculty members below.

Welcome to Karan Kumar, MD

Karan Kumar, MD

Karan Kumar, MD, joined the DCRI as an assistant professor of pediatrics in the Duke University Medical Center Division of Pediatric Critical Care Medicine on July 1.

Kumar received his MD degree from Johns Hopkins University and his MS degree in Biostatistics from Duke University. Most recently, he served as both a fellow in pediatric critical care medicine at Duke University Medical Center and a clinical research fellow at the DCRI. Before coming to Duke, he completed his residency at Stanford, where he also worked as a clinical instructor in pediatrics.

As a new pediatrics faculty member, Kumar will help advance research that helps improve the care of the youngest and most vulnerable patients. In addition to pediatric critical care, his research interests include biostatistics, clinical research informatics, and machine learning. He has contributed to work published in journals including Immunity, The Journal of Pediatrics, and Pediatric Nephrology.

“Dr. Kumar’s addition to the pediatrics therapeutic area will continue to grow our faculty’s footprint at the DCRI and broaden the scope of our services and skills,” said the DCRI’s Christoph Hornik, MD, PhD, MPH, associate professor of pediatrics. “Specifically, Dr. Kumar will bring immediate expertise in biostatistics and real world data analysis. His interest in machine learning and data management will be essential to the expansion of our group into the realm of real world evidence generation in support of pediatric drug and device development.”

During his time so far at Duke, Kumar has served as a mentor and statistician for the Duke STAR program, been recognized as a Duke Pediatric Research Scholar, and most recently received the Michael M. Frank teaching award given to the fellow most influential in the training of pediatric residents.

Welcome to Daniel Edmonston, MD

Daniel Edmonston, MDDaniel Edmonston, MD, joined the DCRI as a medical instructor in the Duke University Division of Nephrology on July 1.

Edmonston received his MD degree from the Mercer University School of Medicine. Most recently, he served as both a fellow in nephrology at Duke University Medical Center and a clinical research fellow at the DCRI. He completed his residency at New York Presbyterian Hospital-Weill Cornell Medical College.

Edmonston’s research interests include cardiovascular disease in persons with kidney disease including pulmonary hypertension, heart failure, and atherosclerotic disease. He will conduct research across the nephrology and cardiovascular therapeutic areas and support bidirectional enrichment of kidney and cardiovascular trials. His work has been published in journals including Kidney International, American Journal of Kidney Diseases, Clinical Journal of American Society of Nephrology, and the American Heart Journal. He has also collaborated on work published in Clinical Cardiology and Journal of American College of Cardiology: Heart Failure.

“We are pleased to welcome Dr. Edmonston, who has already made impressive contributions to the Division of Nephrology through his work as a DCRI clinical research fellow,” said Myles Wolf, MD, interim director of DCRI Nephrology. “Because his research interests lie in the intersection of nephrology and cardiovascular disease, we look forward to not only his help in advancing research on kidney disease, but also his support of continued collaborations between the nephrology and cardiovascular therapeutic areas.”

During his time at Duke so far, Edmonston has served as a post-doctoral research fellow with Duke’s American Heart Association Strategically Focused Research Network grant. He was also recently awarded second place in the 2019 National Kidney Foundation Young Investigators’ Forum.

Welcome to Trevor Lentz, PT, PhD, MPH

Trevor Lentz, PT, PhD, MPHTrevor Lentz, PT, PhD, MPH, joined the DCRI as an assistant professor in the Department of Orthopaedic Surgery on July 1.

Lentz received both his MPH degree in health policy and management and his PhD degree in rehabilitation science from the University of Florida in Gainesville. Most recently, he completed a postdoctoral fellowship in musculoskeletal research at the DCRI.

During his time as a DCRI fellow, Lentz acted as both co-chief fellow and as the lead fellow at a DCRI think tank on “Emerging Techniques for Monitoring and Analyzing Data in Pragmatic Streamlined Trials.” He also gave a presentation to Duke’s Doctor of Physical Therapy students on “Using Data Analytics to Drive Value-Based Care.”

Lentz’s research focuses on identifying individual and health care system-level factors that influence patient-reported outcomes, health care utilization, and costs related to the treatment of musculoskeletal pain.

“The musculoskeletal therapeutic area (aka Duke MSK) is excited to welcome Dr. Lentz as DCRI faculty,” said Steven George, PhD, PT, director of musculoskeletal research at the DCRI. “He joins our research team that is working toward discoveries to reduce the impact of musculoskeletal pain on health, physical function, and quality of life. Dr. Lentz will add to our existing team in several key areas: working in health services research and conducting pragmatic trials; building interdisciplinary collaborations to facilitate use of real-world data for improving clinical outcomes; and working with health policy experts to inform policy guidance that facilitates value-based management of surgical and non-surgical musculoskeletal conditions.”

Lentz’s published work includes appearances in the Journal of Pain and American Journal of Sports Medicine. He serves on the international editorial review board for the Journal of Orthopaedics and Sports Physical Therapy and as an associate editor for the British Journal of Sports Medicine.

ADAPTABLE Team Finishes Enrollment, Reflects on Lessons Learned

June 27, 2019 – ADAPTABLE is a large pragmatic clinical trial that leverages PCORnet to draw data from electronic health records.

The team behind ADAPTABLE, the first large, pragmatic clinical trial to be coordinated at the DCRI, recently celebrated a milestone as the trial reached its goal of enrolling 15,000 patients.

Many individuals living with heart disease are instructed to take aspirin to prevent heart attacks and strokes. However, aspirin can cause bleeding in some individuals, and there is no data available that can help physicians decide on the optimal dose to prescribe. ADAPTABLE will compare two different doses—a high dose of 325 mg and a low dose of 81 mg—to determine which is more safe and effective.

Using Real World Data from EHRs

ADAPTABLE, which is funded by the Patient-Centered Outcomes Research Institute (PCORI), is a pragmatic clinical trial, meaning that research is integrated in patient care and leverages technology to alleviate burden on patients and site staff. ADAPTABLE is a demonstration project of PCORnet, the National Patient-Centered Clinical Research network. Forty healthcare systems and three health plans are participating in ADAPTABLE.

ADAPTABLE draws data from electronic health records (EHRs), patient-reported outcomes, and insurance claims data to capture primary endpoints.

“ADAPTABLE is a ground-breaking clinical trial for several reasons, including primarily remote recruitment of patients outside of traditional research clinic settings, direct-to-patient follow-up, and surveillance of EHRs to identify patients for potential enrollment and to ascertain potential endpoints during follow-up,” said Matthew T. Roe, MD, MHS, co-principal investigator for ADAPTABLE. “Via a web-based platform, we conduct outreach to potentially eligible patients to ask them if they’re willing to provide informed consent via an electronic, web-based consent module, which then allows patients to self-randomize into the study. These approaches have never been used before for a large-scale clinical trial the size of ADAPTABLE.”

Viewing Patients as Partners

ADAPTABLE provides a new model of engaging with patients. Patient partners also known Adaptors represent the patient voice at every stage of the study by providing input on study recruitment, contributing to participant newsletters, participating in working groups, and presenting on ADAPTABLE at scientific meetings.

Incorporating a group like the Adaptors is reflective of DCRI’s mission to engage all stakeholders with the goal of improving the study participant experience in clinical research. Get to know and learn more about the Adaptors.

“Patients themselves may be the most important and yet underutilized voice in research,” said Adaptor Greg Merritt, of Ann Arbor, Michigan. “The ADAPTABLE Study is a wonderful example of how patients can assist researchers in prioritizing and studying what matters most to a patient who lives with an illness or disease every day. Their insight and perspective can help to uncover new ways to look at old problems.”

Learning Logistics through a Pragmatic Approach

The ADAPTABLE team—researchers, clinicians, and patients alike—has learned many lessons through the enrollment period of the first large pragmatic clinical trial conducted at the DCRI.

First and foremost, the researchers learned that collaboration between diverse organizations is critical in reaching a goal as large as 15,000 participants.

“Using novel tools and techniques, we are transforming how patients are identified and recruited for clinical trials,” Holly Robertson, PhD, project leader for ADAPTABLE, said. “We also developed strategies for clinician and patient engagement which are important in supporting recruitment and retention for virtual trials.”

The study team also shared that when recruiting patients, it is beneficial to contact potential participants through multiple modes of communication: online, by phone, through the mail, and in person.

“The ADAPTABLE study has encouraged increased collaboration and inspired us to work together to solve new interesting research challenges using a pragmatic approach,” said Schuyler Jones, MD, co-investigator for ADAPTABLE.

The study team also shared that when using electronic health records, it is essential to have processes in place for protecting patient privacy.

Patient partners learned that a good facilitator is helpful in liaising between patient advisors and researchers and assisting in incorporating patients’ thoughts and ideas into the study.

Answering an Important Health Question

Now that 15,000 patients have enrolled in ADAPTABLE, study researchers will continue following these participants, collecting data that will be essential in determining which dose of aspirin is most effective. Identifying the dose that works the best could change practice guidelines and prevent as many as 88,000 deaths per year worldwide.

Results from the study are expected in 2020.

DCRI Patient Preference Research Contributes to FDA Decision

June 26, 2019 – The DCRI surveyed patients to quantify the benefits and harms of esketamine, a drug recently approved to treat individuals with treatment-resistant depression.

A patient preference survey designed and conducted by the DCRI’s Preference Evaluation Research (PrefER) group was presented to the FDA prior to its recent approval of a treatment for patients with treatment-resistant depression.

Shelby ReedThe survey, which was conducted by the DCRI’s Shelby Reed, PhD (pictured); Juan Marcos Gonzalez, PhD; F. Reed Johnson, PhD; and Angela Fairchild, assessed patient preferences related to potential benefits and harms associated with esketamine. Esketamine had been shown in early clinical studies to rapidly improve depressive symptoms, but there were potential risks like permanent cystitis and cognitive impairment that had been observed in individuals abusing ketamine, a molecule similar to esketamine.

The survey was administered to two patient cohorts: 161 patients enrolled in clinical trials of esketamine and 301 respondents from an online panel who were identified as having a medical history consistent with treatment-resistant depression.

The DCRI team used the survey results to determine that in exchange for varying levels of improvement in depression symptoms, patients were willing to accept certain levels of risk of permanent and severe bladder problems, as well as a risk of permanent cognitive impairment. Results showed that respondents placed the greatest value on mood improvement and reduced chance of cognitive and memory problems.

The results of the DCRI survey were included in a presentation to the FDA advisory committee. During the meeting, two of the panelists noted that the survey results influenced their voting decision on the benefit-risk of esketamine.

“The impact of this survey and its results prove the importance of taking patient preferences into account,” Reed said. “Studies such as these can be helpful to reviewers who are charged with making value judgements about benefit-risk tradeoffs on behalf of patients.”

ARLG Study Employs Innovative Model to Test Diagnostics for Extragenital Gonorrhea

June 23, 2019 – The study’s design, which researchers hope to use for other conditions, enabled testing of multiple diagnostic assays simultaneously and resulted in cost savings.

Molecular diagnostic assays have transformed the field of infectious diseases, allowing for swift and sensitive detection of organisms previously challenging to diagnose, but it can be difficult to study how these new tests perform. Members of the Antibacterial Resistance Leadership Group (ARLG), which is facilitated by the DCRI, recently conducted a study of several assays used to detect extragenital gonorrhea and Chlamydia trachomatis. They say their latest research will help to quell the transmission of these infections and could change the landscape for how diagnostic tests are studied.

Prior to this study, there were no diagnostic tests approved by the U.S. Food and Drug Administration (FDA) for determining the presence of extragenital gonorrhea, despite recommendations from the U.S. Centers for Disease Control and Prevention for screening in certain populations, said the DCRI’s Vance Fowler, MD, MHS, (pictured), co-principal investigator for the ARLG.  As a result, few laboratories offered testing and clinicians lacked an FDA cleared diagnostic test. Lack of testing can result in the continued spread of the bacteria that causes gonorrhea, including drug-resistant strains.

Vance FowlerAccurate diagnostics that are more readily available will result in better detection and timely treatment, which could help to slow the rise of antibiotic resistance, Fowler said.

“Diagnosis is a major problem in antibacterial resistance, and gonorrhea has been identified by the U.S. Centers for Disease Control and the World Health Organization as a concerning bacterium with rapidly emerging resistance,” he said.

ARLG investigators collaborated with the National Institute of Allergy and Infectious Diseases (NIAID), the FDA, Cepheid, and Hologic on this unique study design that incorporated simultaneous testing of samples from a single patient’s pharynx and rectum on multiple diagnostic platforms. Results from this simultaneous testing were incorporated into a reference, or “gold,” standard that could then be used to assess whether each of the diagnostic platforms correctly diagnosed extragenital gonorrhea and chlamydia.

After establishing the reference standard, the study team conducted a clinical trial that enrolled more than 2,500 patients. The study tested a new design that allowed evaluation of multiple diagnostics from different companies simultaneously.

“This idea came from the work I do in my investigative lab, where we often reuse the same clinical samples to answer multiple questions,” Fowler said. “I began to realize that the same idea could be applied to evaluating new diagnostics — if we could test multiple diagnostics on the same patient enrolled into a single trial, we could potentially reduce costs associated with enrolling multiple patient cohorts. This is about enhancing pragmatism in the diagnostic space.”

In 2014, Fowler presented the concept of “one patient, more than one diagnostic” at a meeting sponsored by the National Institutes of Health.  Evaluating diagnostics for extragenital gonorrhea was a way to test this strategy. Fowler relied on the sexually transmitted infection expertise of his ARLG colleague and primary investigator of the project, Jeffrey Klausner, MD, MPH, from the University of California-Los Angeles. On May 23, 2019, two of the devices evaluated in this study received FDA clearance for use to detect pharyngeal and rectal gonorrhea and C. trachomatis, the first two devices approved for this indication.

Fowler sees wide applications for the design and believes the same technique of testing multiple diagnostics simultaneously could be used in many other conditions, such as urinary tract infections, bloodstream infections, and pneumonia.

This process could also benefit companies developing diagnostics in several ways.  First, the cost of enrolling patients into a Master diagnostic trial would be only a fraction of the conventional approach. Next, each company would ultimately receive the trial data relevant to their platform along with the reference standard for submission to the FDA for clearance of their diagnostic platform.

“Employing a platform such as this could enhance and facilitate the ability to develop and ultimately commercialize new diagnostic platforms, providing clinicians with more informed decision making in managing patients with infections caused by multidrug resistant bacteria,” Fowler said.

The ARLG develops, designs, implements, and manages a clinical research agenda to increase knowledge of antibacterial resistance. It aims to advance research by building transformational trials that will change clinical practice and reduce the impact of antibacterial resistance. The ARLG is facilitated by the DCRI and works under the centralized leadership of an executive committee and two principal investigators: Fowler and Henry ‘Chip’ Chambers, MD, of the University of California, San Francisco.

Other authors that collaborated on this study include Sarah Doernberg, MD,MAS, of the University of California-San Francisco.

Research reported in this article was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

DCRI Contributes to AHA Statement on HIV and Cardiovascular Disease

June 12, 2019 – The statement suggests that when treating people living with HIV who exhibit certain characteristics, clinicians should multiply conventional risk calculator scores by 1.5 to 2.

Gerald Bloomfield

The DCRI’s Gerald Bloomfield, MD (pictured), contributed to a statement from the American Heart Association recently published in Circulation that provides a thorough review of current knowledge on HIV-associated cardiovascular disease, as well as a gap analysis that details where more data are needed.

This statement was needed because currently no guidelines exist on how to address cardiovascular disease in people living with HIV, Bloomfield said. Because HIV used to be fatal, little is known about how people living with the virus experience cardiovascular disease. However, a number of observational studies have shown that as treatment for HIV has improved, people living with HIV are living longer and experiencing more age-related comorbidities, including cardiovascular disease.

“This population deserves special attention when assessing and treating for cardiovascular disease,” Bloomfield said. “We know that chronic exposure to HIV increases heart disease risk, so in treating people with HIV, we need to be aware that the underlying contributors to the disease may extend beyond traditional factors.”

For example, he explained, HIV affects heart muscle contraction in unique ways, increasing risk of heart failure. More data are needed to further understand the long-term impacts of these increased risks, as well as to address treatment and prevention. In addition to heart failure, the statement also addresses increased risk for heart attack and stroke which may be driven by the body’s chronic inflammatory response to the HIV virus.

Another important component of the paper, which distinguishes it from many statements made by the AHA, is that it examines how suggested guidelines could be applied outside the U.S.

“Because 70 percent people living with HIV live in Africa, our writing group thought it was important to discuss unique characteristics of HIV and cardiovascular disease in sub-Saharan Africa,” Bloomfield said. “If we had not addressed this, I think we would have been remiss.”

The paper also suggests that conventional risk calculators may under-predict risk for patients in this population and, for HIV+ patients with certain characteristics, recommends that clinicians multiply risk scores by 1.5 to 2.

“This is novel because there is no solid clinical trial data that supports this suggestion,” Bloomfield said. “However, because there are a large number of people living with HIV who are aging and clinicians are wondering what to do and how to treat them, we felt it was important to offer guidance now based on the best available evidence.”

Bloomfield added that studies are currently underway that will shed more light on this topic in a few years, such as the REPRIEVE trial, which the DCRI’s Pamela Douglas, MD, is working on.

Data Suggest Results From FDA-Mandated Testing Often Not Implemented in Clinical Practice

June 6, 2019 – Investigators were unsure how they would use genetic information to choose treatment choices, then often failed to follow through on their pre-stipulated plan to use this information.

Since 2010, the FDA has recommended that patients treated with clopidogrel undergo genetic testing to determine whether they have reduced metabolizer status. In these patients, certain enzymes that are important in metabolizing clopidogrel are less active, which makes it difficult to activate the drug and increases risk of cardiovascular events. However, findings from the DCRI recently published in JAMA Cardiology suggest that physicians are evenly split on how to incorporate results from this testing into decisions they make in clinical practice.

Thomas J. PovsicThe DCRI’s Thomas J. Povsic, MD, PhD (pictured), led a secondary analysis of a clinical trial that tested the safety of low dose rivaroxaban versus aspirin in addition to one of two P2Y12 inhibitors, clopidogrel or ticagrelor. For many clinical trials that involve clopidogrel, the FDA mandates that patients undergo the recommended genetic testing, with results reported to the investigators.

Investigators involved in the trial were asked whether they would use the test results to inform their decision to switch a patient’s P2Y12 inhibitor. The field of investigators was evenly split on their responses.

The results also showed inconsistencies between the investigators’ responses to this question and the actual treatment paths pursued. Of patients who were treated with ticagrelor, only one patient was switched to clopidogrel—despite the fact that investigators had said they would switch 93 patients based on their test results. Investigators had said they would make the decision to switch 27 of the patients who were treated with clopidogrel and who tested for reduced metabolizer status, but in the end, less than half (13) patients’ treatments were switched.

“We wanted to understand how the information provided by the testing affects physician behavior,” Povsic said. “What we found is that it really did not have an impact. Not only were investigators unsure at the beginning of a trial whether they would use the information to inform decisions, but they also were inconsistent with what they had originally said before they got the information. Even when investigators have the data, they are using the information less than a third of the time in reduced metabolizers on clopidogrel.”

Of the 3,037 patients enrolled in the trial overall, 24 had their P2Y12 inhibitor switched based on the provided genetic information.

“Although the FDA requires testing around this issue, our results show that only a small number of patients are actually impacted by the test results,” Povsic said. “Until we have clinical trial data that tells investigators the right approach to take or that genetic testing leads to improved patient outcomes, the evidence suggests that physicians will be hesitant to let this information influence their treatment decisions.”

Other DCRI contributors to this study include E. Magnus Ohman, MBBS; Matthew T. Roe, MD, MHS; Jennifer White, MS; and Frank W. Rockhold, PhD.

DCRI Co-Hosts Youth Tobacco Cessation Workshop at FDA

June 7, 2019 – The event drew nearly 900 registrants and discussed tobacco-cessation therapies that have been successful in youth populations, as well as gaps in knowledge surrounding e-cigarettes.

The DCRI and Institute for Advanced Clinical Trials for Children (I-ACT) co-hosted the Youth Tobacco Cessation: Strategies and Treatments Workshop on May 15 at the U.S. Food and Drug Administration (FDA) Headquarters in Silver Spring, Maryland.

Nearly 900 people registered to learn about existing experience with tobacco-cessation therapies in youth, the gaps in knowledge surrounding e-cigarettes, and expert recommendations for how to fill those gaps. The workshop speakers represented government agencies, research groups, youth advocacy groups, and the pharmaceutical industry. The FDA Acting Commissioner, Norman “Ned” Sharpless, MD, addressed the workshop participants.

“There is no dispute that years of progress to combat youth use of tobacco to prevent a lifetime of addiction to nicotine is now threatened by an epidemic of e-cigarette use among children,” Sharpless said. “These products are exposing a whole new generation of kids to nicotine and the possibility of addiction.”

The FDA, I-ACT and the DCRI will publish a meeting summary in the coming months. Workshop participants will use lessons learned during the workshop to help guide future use of resources to address youth tobacco cessation.

The topics addressed at the meeting included (slides can be found at the links below):

E-Cigarette Prevention in Youth: New Challenges, New Strategies

  • Brian King, PhD, MPH, Office on Smoking and Health, US Centers for Disease Control and Prevention – click to view slides
  • Kathleen Crosby, MPH, Center for Tobacco Products, FDA – click to view slides

The Science of Addiction in Adolescents

What Can We Learn from the Blueprint for Action?

Experience with Cessation Therapies in Adolescents

Addressing the Gaps: Where Should Treatment Efforts Be Focused?

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.