Differences in Patient Beliefs May Play Role in Women’s Underuse of Statins

September 18, 2019 – Recently published results explore reasons behind the well-documented phenomenon of gendered differences in statin use.

Women are less likely than men to receive statins, and those who do receive statins are more likely to receive a prescription below recommended guidelines.

DCRI fellow Michael Nanna, MD (pictured), examined patient data from the PALM (Patient and Provider Assessment of Lipid Management) Registry in an effort to ascertain reasons for these differences. He and his team found that women are offered statins at lower rates but refuse or discontinue statins at higher rates than men.

A paper discussing the findings was recently published in Circulation: Cardiovascular Quality and Outcomes. Nanna and his colleagues also presented findings at the 2018 American Heart Association Scientific Sessions.

“We were able to identify some key differences in terms of patient beliefs and perceptions around statins, as well as willingness to try statins,” Nanna said. “Female patients were less likely to believe statins were safe and less likely to believe they were effective. In addition, female patients who had previously been on a statin were less willing to try another statin compared to male patients. These differences in beliefs suggest that providers can do more to educate their patients on the safety and efficacy of statins.”

Other DCRI contributors to this study include Tracy Wang, MD, MHS, MSc; Eric Peterson, MD; Ann Marie Navar, MD, PhD; Zhoukai Li and Qun Xiang (formerly of DCRI).

Implantable Cardioverter Defibrillators Still Important in Clinical Practice

September 10, 2019 – Evidence supports that implantable cardioverter defibrillators still provide life-saving benefits, but more research is needed to improve the selection of patients for this treatment.

Although it is incorrect to discount the potential benefit of implantable cardioverter defibrillators, it is also critical to improve selection criteria for patients who would derive the most benefit, writes the DCRI’s Sana Al-Khatib, MD, (pictured), in two recent pieces on the topic.

For many patients with heart failure with a reduced ejection fraction (HFrEF), implantable cardioverter defibrillators (ICDs) can prevent sudden cardiac death and save lives. However, some clinicians argue that evidence supporting the benefit of ICDs is more than 15 years old and perhaps not still applicable. In a paper co-authored by Al-Khatib, which was recently published in Circulation, she counters that newer evidence exists that links ICDs with a survival benefit and lists several examples of recent studies and their findings.

The paper also points out that the original randomized clinical trials that supported the use of ICDs did not include good numbers of traditionally underrepresented patient populations, such as women, racial minorities, and older patients. Newer studies have shown that ICDs are associated with survival benefit in these populations.

However, Al-Khatib also writes, in a recent editorial in The Lancet, that patient selection for ICDs needs to be improved because of high costs and potential for complications associated with the device. Attempts to improve selection criteria to determine which patients would live longer with an ICD have so far been unsuccessful.

Al-Khatib also provides analysis of the results of an observational sub-study published in The Lancet, which found that high repolarization dynamics were associated with the greatest reduction in mortality in patients treated with ICDs. Although these results are potentially important, Al-Khatib writes, they need to be verified with further study and randomized clinical trials before being implemented in clinical practice.

DCRI Study Applies ACC/AHA Guidelines on Cholesterol Management

September 3, 2019 – A study led by a DCRI faculty member provides additional clarification on which patients may benefit the most from additional lipid-lowering therapies, if their cholesterol levels remain elevated despite optimal statin therapy.

A new DCRI-led study applied recently published guidelines on cholesterol management from the American College of Cardiology (ACC) and the American Heart Association (AHA) and confirmed that patients at the highest risk may benefit from lipid-lowering treatments in addition to statins.

The ACC/AHA Guidelines on the Management of Blood Cholesterol, published in December 2018, updates the 2013 guidelines and provides more guidance on newer lipid-lowering therapies that can lower cholesterol levels beyond what can be achieved with statins. By recommending the use of these classes of lipid-lowering drugs, which include ezetimibe and PCSK9 inhibitors, for patients with established atherosclerotic cardiovascular disease (ASCVD) and at high risk, the new guidelines promote more personalized treatments for individual ASCVD patients.

Matthew Roe

The study, which was recently published in Circulation, applied the updated guidelines to patients included in the ODYSSEY OUTCOMES trial, for which the DCRI served as the academic coordinating center from 2012-2018. Results of this trial, which were presented at the ACC 2018 Scientific Sessions, showed that alirocumab, a PCSK9 inhibitor, reduced cardiovascular events when compared with placebo in ASCVD patients with a recent acute coronary syndrome (ACS) and residual dyslipidemia, meaning they had not reached target cholesterol levels with optimized statin therapy.

The study was led by Matthew T. Roe, MD, MHS, (pictured), who was the DCRI faculty leader for the ODYSSEY OUTCOMES trial. Because the updated cholesterol management guidelines were published after the trial results were released, Roe and colleagues were interested in conducting an exploratory analysis to apply the guidelines risk stratification recommendations and determine which patients received the most benefit from the randomized study drug (alirocumab).

The study included 18,924 patients, with 11,935 (63 percent) classified as very high risk based upon the updated guidelines’ risk categorizations. The frequency of cardiovascular events was highest in those patients classified as very high risk and these patients had a greater absolute reduction in the frequency of cardiovascular events from treatment with alirocumab compared with patients classified as not very high risk.

“Through these analyses, we have provided some key messages that will help clinicians decide how to apply the updated cholesterol management guidelines in clinical practice,” Roe said. “Namely, we should target the use of additional lipid-lowering therapies, such as PCSK9 inhibitors, for very-high risk ASCVD patients with residual elevated cholesterol levels despite statin therapy because this population was found to benefit the most.”

Other DCRI contributors to this study include Renato Lopes, MD, PhD.

Hyperlipidemia Not Associated With Cardiovascular Risk in Older Adults

August 20, 2019 – Recent findings suggest that elevations in low-density lipoprotein cholesterol levels may not confer additional risk in populations 75 or older.

Although hyperlipidemia is a well-established factor that indicates risk for cardiovascular events in younger adults, findings from a recent DCRI study show that this measure may not be an accurate predictor in adults 75 or older.

The study, led by DCRI fellow Michael Nanna, MD, (pictured), examined 2,667 older adults with no known cardiovascular disease to determine the association between hyperlipidemia, or elevated low-density lipoprotein cholesterol (LDL) levels, and cardiovascular events. The study team assessed events over a 5-year period in patients with and without hyperlipidemia and recently published results in the Journal of the American Geriatrics Society.

“We wanted to look at this population because although there is a robust body of evidence for the association in younger adults, there is not as much evidence for the older population,” Nanna said. “We are caring for more and more older adults in the clinical setting, so it is increasingly important for us to understand how to assess and stratify their risk.”

The study team split its participants into three groups: no other risk factors—which was defined as free of smoking, diabetes, and hypertension; one non-hyperlipidemia risk factor; and two or more non-hyperlipidemia risk factors. In the group with no other risk factors, cardiovascular event rates were similar between those with and without hyperlipidemia. In the other two groups, there was also no association between hyperlipidemia and cardiovascular events.

“These findings show that in older adults, we should be looking more at cardiovascular risk factors such as hypertension and diabetes rather than LDL levels to identify people for aggressive risk reduction strategies,” Nanna said.

Although the investigators did not find an association between hyperlipidemia and increased risk, Nanna emphasized that these findings should not be misinterpreted to imply that statins are ineffective. “In younger adults, statins have been shown to lower cardiovascular risk across a large range of LDL levels, and randomized trials of statins in older adults are on the horizon,” he said.

“These data highlight the importance of conducting well-done randomized clinical trials to investigate the safety and efficacy of statin therapy for both primary and secondary prevention in older adults,” said the DCRI’s Eric Peterson, one of the co-authors of the study.

Other DCRI contributors to this study include Ann Marie Navar, MD, PhD.


DCRI and Responsum Health Announce Collaboration to Connect Uterine Fibroids Patients

August 13, 2019 – Responsum Health, a company that creates patient platforms for chronic diseases, will create a patient-centered information portal and community hub that will synchronize with the DCRI’s COMPARE-UF patient registry.

The DCRI is partnering with Responsum Health, an innovative creator of personalized patient newsfeeds and support platforms, to improve the quality of life for patients with uterine fibroids. They are joined in this effort by The White Dress Project and CARE About Fibroids, two of the nation’s top uterine fibroids patient advocacy organizations. The announcement follows Fibroids Awareness Month, recognized in July.

Through the partnership, Responsum will commit to developing and promoting a unique, uterine fibroids patient-centered information portal, similar to its work in other therapeutic areas. This new platform will serve the dual goals of providing comprehensive, understandable, and trustworthy information while helping to connect a nationwide community of patients. The new web-based tool and app, Responsum for UF, will synchronize with the DCRI’s unique patient registry, COMPARE-UF (Comparing Options for Management: Patient-centered Results for Uterine Fibroids).

The COMPARE-UF registry is funded by the Agency for Healthcare Research and Quality (AHRQ), in collaboration with the Patient-Centered Outcomes Research Institute (PCORI). DCRI serves as the Data and Statistical Coordinating Center.

The registry has enrolled more than 3,000 women from nine medical centers. By sharing their experiences with uterine fibroids treatments, these women are helping doctors understand symptom relief patterns, impact on pregnancy, and the need for additional treatment. The goal of COMPARE-UF is to help patients and their doctors make informed decisions about treatment options.

COMPARE-UF will follow the patients in its registry, who are women between the ages of 18 and 54 who have been diagnosed with uterine fibroids and who are not in the transition to menopause.

“We are very excited to be working with Responsum, CARE About Fibroids, and The White Dress Project to develop innovative ways for women to share their experiences with uterine fibroids, as well as to get the best possible information about their choices for treatment,” said Dr. Evan Myers, principal investigator of COMPARE-UF at DCRI.

“We look forward to collaborating with the Duke Clinical Research Institute to help collect valuable insights from women with uterine fibroids,” said Andrew Rosenberg, founder of Responsum Health. “By bringing the patient experience to bear through our partnerships with The White Dress Project and CARE About Fibroids, we will create an online tool, newsfeed, and support platform that fills a vital information gap while simultaneously convening an authentic, welcoming online community for women with uterine fibroids.”

“We are thrilled to partner with the Duke Clinical Research Institute and Responsum Health as we continue to fulfill our mission of heightening public awareness and creating a greater sense of urgency around the toll and challenge of uterine fibroids,” said Jenny Rosenberg, executive director of CARE About Fibroids. “Combined with The White Dress Project’s incredible patient advocate network, we look forward to bringing the strategic communications capabilities along with the scientific and policy expertise of CARE About Fibroids to join this extraordinary opportunity to provide women with a trustworthy, online information platform to replace Dr. Google.”

“The White Dress Project is committed to growing, educating, and enriching a community of women who feel confident knowing they no longer have to suffer in silence with uterine fibroids,” said Tanika Gray Valbrun, executive director of The White Dress Project. “Our partnership with the Duke Clinical Research Institute and Responsum Health is a groundbreaking way to make sure women are better informed and equipped to be their own best advocates.”

DCRI Study Finds New Predictor of Health Care Costs

August 6, 2019 – New findings from the DCRI suggest that how military service members interpret their pain may be able to predict pain-related costs and total medical costs.

New data from a DCRI study suggest that pain catastrophizing, a measure determined by the results of a 13-item questionnaire that indicates how patients interpret their pain, could be important in predicting future health care utilization and costs in patients with musculoskeletal pain.

Trevor Lentz, PT, PhD, MPHA recently published study in the Journal of Pain, led by the DCRI’s Trevor Lentz, PT, PhD, MPH, (pictured), examined a cohort of 283 military service members returning from Afghanistan who reported musculoskeletal pain during a medical screening process in August or September 2011. These service members were asked to complete both the pain catastrophizing scale (PCS) and a body diagram that details the location of their pain. Scores on the PCS indicate how patients interpret their pain by measuring three components: rumination, or how often they think about their pain; magnification, or how much they emphasize their pain, and helplessness in managing their pain.

The study team examined the results of both to determine processes that influence the following outcomes at 12 months: incident use of opioids over a short term, chronic use of opioids, condition-specific medical visits, condition-specific medical costs, and total medical costs.

The team also looked at how pain intensity at intake, as well as disability, influenced these outcomes. However, prior to this study, not much was known about the role that pain catastrophizing or distribution of symptoms on a body diagram played in predicting outcomes.

“The influence of certain psychological factors, like pain catastrophizing, for predicting pain related clinical outcomes is well-established in the literature, but less is known about how these same factors influence healthcare utilization and costs,”  said the DCRI’s Steven George, PT, PhD, FAPTA, one of the study co-authors.

“We wanted to understand the processes that result in these outcomes by asking, ‘What are the underlying characteristics we need to attend to while developing outcomes prediction models and treatment pathways?’” Lentz said.

The data showed that pain catastrophizing informs both condition-specific costs and total costs. This means that patients with higher pain catastrophizing scores were more likely to experience higher healthcare costs, even after considering the level of pain intensity at intake. The score also acted as a partial indicator for how many condition-specific visits a person would have.

“As we move toward value-based care, it will be important for us to determine where and with whom costs will be concentrated, enabling us to intervene earlier to improve the cost effectiveness of pain-related care,” Lentz said.

The results suggest that certain outcomes, such as healthcare costs and utilization, could be more accurately predicted by weighing factors like pain catastrophizing in addition to pain intensity or disability. In contrast, neither pain catastrophizing nor body diagram score improved prediction of future opioid use beyond baseline pain intensity and disability.

The findings also indicate that different approaches may be needed for building predictive models for costs versus healthcare utilization. But the primary takeaway, Lentz said, is the new information about how pain catastrophizing can be used.

“Although we’ve found that pain catastrophizing is important in predicting clinical outcomes, it is rarely screened for or evaluated in clinical practice,” he said. “We need to raise awareness of this measure’s utility in prediction—especially because pain catastrophizing is modifiable and can be addressed through treatment.”

The DCRI’s Steven George, PT, PhD, FAPTA and Duke adjunct faculty Daniel Rhon, DSc, also contributed to the study.

DCRI, Cerner Partner on New Study Using Real-World Data

August 6, 2019 – The pilot project and study, called the Learning Registry, will use electronic health records from the Cerner Learning Health Network to evaluate the use and potential impact of proven therapies for chronic cardiovascular disease.

Cerner Corporation (Nasdaq: CERN), a global health platform and innovation company, has announced the development of the Cerner Learning Health NetworkSM to help clinicians more easily and efficiently gain health insights and guide care. Cerner aims to automate data collection from multiple sources, including the electronic health record (EHR), to rapidly give medical researchers access to important information that has the potential to transform patient care. Through combined technology and expertise, Cerner and the Duke Clinical Research Institute (DCRI) have joined together to pilot the Cerner Learning Health Network and innovate clinical research registries in the process.

Ann Marie NavarThe pilot project and study, named the Learning Registry by the DCRI, will use the Cerner Learning Health Network to evaluate the use and potential impact of proven therapies for chronic cardiovascular disease. Cerner and the DCRI aim to bring together data and intelligence to deliver clinicians insights on chronic cardiovascular disease, which if not treated properly can lead to heart disease and stroke. In the pilot project, the DCRI will use Cerner technology to analyze de-identified patient data from the University of Missouri Health Care and Ascension Seton, in partnership with Dell Medical School at The University of Texas at Austin, with the goal of finding the most effective treatment options.

“Collaborating with the DCRI on the Learning Registry to pilot the Cerner Learning Health Network is an exciting step forward in improving the health of those living with chronic cardiovascular disease,” said Art Glasgow, senior vice president, Strategic Growth, Cerner. “At Cerner, we’re committed to taking four decades of digitized data and transforming it into insights that can help clinicians make more informed treatment decisions. We have an opportunity to use clinical research and data-driven insights to develop an intelligent network of health systems that can truly improve health experiences and outcomes for patients.”

After the pilot project and study are complete, the Cerner Learning Health Network is expected to have wide-reaching applications in life sciences, pharmaceuticals and health care at large. The automation and streamlining of health data for clinical research has the potential to speed innovation and life-saving insights. More research on populations’ health gives clinicians additional tools to identify and treat a myriad of diseases and health concerns.

Clients will be able to leverage HealtheDataLabTM with the Cerner Learning Health Network to aggregate de-identified patient data from both Cerner and non-Cerner EHRs. HealtheDataLab is a ground-breaking tool that leverages the capabilities of HealtheIntent®, Cerner’s big data and insights platform for population health management. Researchers can use HealtheDataLab to take de-identified patient data, transform the data sets into research-ready formats and build complex models and algorithms to give providers more information to make more informed care decisions. By using predictive modeling and intelligence, the platform supports early identification of individuals who may be at risk for costly episodes of care and can help pinpoint the most effective and cost-efficient treatment options.

“Current models for clinical research and registries that rely on mostly manual chart abstraction are too expensive, too slow and too small to continue. We have to figure out better ways to leverage existing electronic resources to transform how we do clinical research,” said Dr. Ann Marie Navar (pictured), principal investigator and cardiovascular prevention researcher, DCRI. “The EHR is an obvious starting point and HealtheIntent has all the right ingredients. It incorporates data from multiple EHRs, can link to national mortality and claims databases and helps us to harness the power and information security of cloud computing.”

The DCRI plans to publish the research results from the pilot project in a study sponsored by Janssen Pharmaceuticals, Inc., a pharmaceutical company of Johnson & Johnson, with several products used to treat and prevent cardiovascular disease.

DCRI Welcomes New Faculty

July 31, 2019 – A pediatric rheumatologist and a urologist have joined the DCRI.

Welcome to Mara Becker, MD, MSCE

Mara Becker, MD, MSCE, joined the DCRI on July 15 as an associate professor of pediatrics in the School of Medicine’s Division of Pediatric Rheumatology.Mara Becker, MD, MSCE

Becker comes to Duke from Children’s Mercy Kansas City, where she served as the associate chair of the department of pediatrics and division director for children’s rheumatology.

She received her MD degree from Jefferson Medical College in Philadelphia and her master’s degree in clinical epidemiology from University of Pennsylvania. She completed her residency in pediatrics and a fellowship in pediatric rheumatology at Thomas Jefferson University Hospital/duPont Hospital for Children in Wilmington, Delaware. She also completed an additional fellowship in pediatric clinical pharmacology at Children’s Mercy.

Her research interests have focused on identifying factors that enhance therapeutic response and minimize toxicity to drugs used for the treatment of rheumatic diseases in children.  Her current NIH-funded research is investigating methotrexate in Juvenile Idiopathic Arthritis, utilizing cellular biomarkers and genetic differences to predict drug response.

She has contributed to work published in journals such as the Journal of Pharmacology and Experimental Therapeutics, Arthritis & Rheumatology, and Arthritis Care & Research. She is actively serving in national organizations such as the FDA Arthritis Advisory Committee, the American Board of Pediatrics, the American College of Rheumatology, and the Childhood Arthritis Rheumatology Research Alliance.

Becker will also serve as vice chair for faculty development for the Department of Pediatrics at the Duke University School of Medicine, where she will focus on mentoring faculty at all levels and targeting opportunities for leadership development and career growth for faculty within the department.

“Dr. Becker’s expertise as a clinical pharmacology-trained pediatric investigator will make her a great fit with the DCRI pediatric group,” said the DCRI’s Rachel Greenberg, MD, assistant professor of pediatrics. “In addition, she brings a new depth to the program with her subspecialty training in pediatric rheumatology, extensive foundation in translational research, and experience in faculty career development.”

Welcome to Deborah Kaye, MD, MS

Deborah Kaye, MD, MS, will join the DCRI as an assistant professor in the School of Medicine’s Department of Surgery, Division of Urology on Aug. 19.Deborah Kaye, MD, MS

Prior to arriving at Duke, Kaye worked at the University of Michigan, where she was a clinical lecturer in the department of urology. Her research interests include developing and evaluating health care systems, tools, and processes, as well as exploring how to improve health care delivery systems. She is also interested in health care payment models and health outcomes in urologic oncology.

Kaye received her MD degree from the Medical College of Wisconsin and her master’s degree in health and health care research from the University of Michigan. She completed a residency at Johns Hopkins University, a Clinical Scholars Training Program at the NIH, and a combined urologic oncology and health services research fellowship at the University of Michigan.

Her work has appeared in journals such as New England Journal of Medicine, the Journal of Urology, and Cancer.

“Dr. Kaye will add meaningful insight to DCRI Urology,” said the DCRI’s Chuck Scales, MD, associate professor of surgery and population health sciences. “There are so many patients in need of treatment for urologic cancers, and her interest in improving health care delivery systems will ultimately help us to deliver on our mission of translating knowledge to better patient care.”

Open Data Critical to Clinical Research

July 30, 2019 – In a recent Perspective piece, the DCRI’s Frank Rockhold, PhD, outlines why data sharing is so important to the future of clinical research and shares suggestions for making the process more efficient.

Data sharing, especially at the individual patient level, is an integral component of enabling future research and improving patient care, according to a Perspective piece from the DCRI’s Frank Rockhold, PhD, (pictured)recently published in Clinical Trials.

The paper, which contains input from three contributors in addition to Rockhold, gives an overview of the current state of open data and data sharing and features strengths and weakness of current data access platforms. It also reviews successful examples of data sharing and makes suggestions about how to improve and streamline data sharing moving forward.

Data sharing has many benefits, including avoiding redundancy and duplicated efforts and encouraging collaboration. However, constraints also exist, such as confidentiality concerns and lack of time and resources.

“There are hurdles to clear, but the question at the center of the open discussion should not be whether data should be shared, but rather how and when responsible methods for doing so can be ushered in,” the writers note.

The future of data sharing lies in the hands of those involved in clinical research, Rockhold writes after laying out five suggested guidelines for data sharing and encouraging patient involvement and protection of patient rights.

“We believe the clinical research enterprise needs to come together to build on what exists and create a simpler model for truly open and responsible clinical trial data sharing,” he writes.

Duke Symposium Showcases Diverse Obesity Research, Patient Experiences

July 23, 2019 – The symposium convened multiple Duke obesity experts, community members, and patients to discuss current knowledge, challenges, and future opportunities.

Over 100 researchers, clinicians, community members, and patients came together to spotlight obesity-related research during the Transforming Obesity Research at Duke Symposium, which was co-hosted by the DCRI on June 21.

Attendees gathered at the DCRI to foster new collaborations and bolster opportunities for meaningful research, as well as to address causes of obesity, barriers in patient care, and treatment methods for the disease.

“It is interesting to see how many people at Duke are studyingPanelists speak at the Transdisciplinary Obesity Consortium Symposium. obesity, looking at it through their own perspective, but unaware of the other experts both at the university and within the community,” said the DCRI’s Sarah Armstrong, MD, associate professor of pediatrics, who co-hosted the symposium along with Matthew Roe, MD. “Each of them is examining [obesity], but through very different lenses.”

The day-long program included presentations, panel discussions, a debate, and breakout sessions. The DCRI’s Joseph Rogers, MD, chief medical officer of the Duke University Hospital System, provided the morning keynote highlighting the complex nature of obesity, rates across the U.S., and the shift in thinking that needs to occur to result in meaningful change.

Rogers’ call-to-action was an overarching theme of the symposium that carried into the patient perspectives panel, which introduced the attendees to six patients with the lived experience of obesity. Each person represented a different journey with weight loss, weight maintenance, and their accompanying health challenges. The panel asked the clinicians and researchers to listen, have compassion, and consider their patients’ quality of life. They also stressed that they are eager to be involved in research and invited the audience to continue advocating for patient engagement in their studies.

A solution-oriented panel then introduced tools and resources that attendees could utilize to close old knowledge gaps. They were followed by four Duke experts, who debated which obesity treatment approach is the most effective. Symposium organizers then divided participants into nine breakout groups to brainstorm critical questions in obesity research.

Following the group collaborations, Lesley Curtis, PhD, interim director of the DCRI and chair of the Department of Population Health Sciences, gave the afternoon keynote. Curtis focused on the opportunities and challenges inherent in applying big data to complex health problems like obesity, providing an overview of a learning health system model, available datasets and registries, and resources at Duke.

The symposium was made possible through the Duke University School of Medicine (SOM) Interdisciplinary Colloquia Fund, which provides support for colloquiums that bring together basic, translational, clinical, and data science faculty members with common interests in a biomedical problem or area. The event was a joint effort of the DCRI, SOM, CTSI, and the Transdisciplinary Obesity Consortium (TOC), directed by Armstrong and Roe. The TOC is a Duke organization dedicated to uniting and connecting obesity researchers and clinicians across Duke as they craft a strategic, campus-wide initiative.

The TOC meets monthly. Members may attend meetings, engage with sub-groups, contribute to the development of the patient panel, work with community stakeholders, and/or share data and other resources. To learn more about the TOC, contact Chris Clark at chris.clark@duke.edu or 919-668-7845.