DCRI holds inaugural research training camp

April 19, 2017 – The event focused on providing the tools needed to bring research ideas to fruition.

On April 8 and 9, clinical fellows and health professionals from across the United States convened in Durham for the inaugural DCRI Research Training Camp. Chaired by DCRI Executive Director Eric Peterson, MD, MPH, and DCRI Education Director Tracy Wang, MD, MHS, MSc, (pictured), the hands-on program focused on providing the tools needed to bring research ideas to reality. Topics ranged from cutting-edge sessions on big data and innovating research with technology, to group-based discussions on industry funding and writing a first K or R Award.

“I’m very pleased with the success of this program, which was filled with lively discussions and great enthusiasm. The meeting showcased DCRI’s thought leadership in clinical research,” Wang said.

Daniel Mark, MD, MPH, professor of medicine, vice chief for academic affairs in the Division of Cardiology and director, Outcomes Research, DCRI, kicked-off the program sharing the habits of successful clinician researchers. Robert Califf, MD, Donald F. Fortin, MD, professor of cardiology, closed day one with a keynote address discussing the future of clinical research and the key role these young clinicians will play in the future of healthcare.

Highlights of day two included a comprehensive discussion about writing a great abstract, led by Wang, and an in-depth look at statistical analysis plans with Karen Pieper, MS, associate director, DCRI clinical trials statistical operations. The program closed with an esteemed panel of DCRI members—Peterson, Daniel B. Mark, MD, MPH, and Laine Thomas, PhD—who offered journal editors’ perspectives on manuscript review.

“The DCRI is committed to training the next generation of clinical researchers. This training camp was a great step towards this goal,” Peterson said.

To learn more about the inaugural DCRI Research Training Camp, contact DCRI Education Partner Relations Manager Heather Crown at heather.crown@duke.edu.

Duke, Verily, and Stanford announce first initiative of Project Baseline

April 19, 2017 – The study will recruit thousands of participants in an effort to better characterize health and the transition to disease.

Verily Life Sciences LLC, an Alphabet company, in partnership with Duke University School of Medicine and Stanford Medicine, announced today the initiation of the Project Baseline study, a longitudinal study that will collect broad phenotypic health data from approximately 10,000 participants, who will each be followed over the course of at least four years. The study is the first initiative of Project Baseline, a broader effort designed to develop a well-defined reference, or “baseline,” of health as well as a rich data platform that may be used to better understand the transition from health to disease and identify additional risk factors for disease. Beyond this initial study, Project Baseline endeavors to test and develop new tools and technologies to access, organize and activate health information.

“With recent advances at the intersection of science and technology, we have the opportunity to characterize human health with unprecedented depth and precision,” said Jessica Mega, MD, MPH, chief medical officer of Verily. “The Project Baseline study is the first step on our journey to comprehensively map human health. Partnering with Duke, Stanford and our community of collaborators, we hope to create a dataset, tools and technologies that benefit the research ecosystem and humankind more broadly.”

The Project Baseline study will begin enrolling participants at the Stanford and Duke study sites within the next few months. The committed study sites at this time include Duke’s sites in Durham and Kannapolis, North Carolina; Stanford’s site in Stanford, California; and the California Health and Longevity Institute in Westlake Village, California. The scientific executive committee is also exploring additional study sites across the United States.

Each site will gather deep datasets on participants through repeat clinical visits; daily use of a wrist-worn investigational device and other sensors; and regular participation in interactive surveys and polls by using a smartphone, computer or call center. Data collected will include clinical, imaging, self-reported, physical, environmental, behavioral, sensor, molecular, genetic, and other health-related measurements. Biospecimens collected will include blood and saliva, among others.

Adrian Hernandez

One of the focus areas of the Project Baseline study is participant involvement, which includes development of a participant committee and the option to receive certain health data and test results, participate in conference calls with members of the study team and evaluate new tools and technologies.

“Through the Project Baseline study, we are aiming to engineer a true twenty-first century approach to health – in a preventive and personalized way,” said Adrian F. Hernandez, MD, MHS, professor of medicine at Duke and member of the DCRI (pictured). “Instead of having the annual physical exam that has not changed in decades, we’re hoping to develop new platforms that will discover changes in health as they happen in meaningful and actionable ways. To do this successfully, we will partner with participants to learn and deliver the best approaches for every aspect of the study.”

“Currently, most of what we see as treating physicians are short snapshots in time of an individual and primarily after they are already ill. We are effectively missing a lot of valuable information years prior to illness,” said Sanjiv Sam Gambhir, MD, PhD, chair of radiology at Stanford and director of the Canary Center for Cancer Early Detection. “We’re dealing with illness in the absence of a well-defined reference of healthy biochemistry, and this underscores the criticality of what we hope to achieve here. By focusing on the health of a broad population, we can eventually have a meaningful impact on the well-being of patients around the world.”

The Project Baseline data repository will be built on Google computing infrastructure and hosted on Google Cloud Platform, which meets rigorous compliance standards that test for data safety, privacy and security. De-identified Project Baseline study data will be available to qualified researchers for exploratory analysis in the future. Initial research goals include characterizing the variation in the observed physical and biochemical traits of the study population, or phenotypic diversity, and identifying biomarkers of disease-related transitions, including those related to cardiovascular disease and cancer.

The study’s scientific executive committee is composed of Mega; Hernandez; Gambhir; Andrew Conrad, PhD, chief executive officer of Verily; Eric Peterson, MD, MPH, director of the DCRI; and Kenneth Mahaffey, MD, vice chair of clinical research at Stanford. Beyond the scientific executive committee, the Project Baseline study will seek input from a diverse coalition of experts from across the life science and healthcare communities including academia, medicine, science, technology, data, design, engineering, and patient advocacy groups.

“We have seen huge strides in cardiovascular disease research by better understanding specific disease patterns, causes, and effects in defined populations over time,” said Nancy Brown, chief executive officer of the American Heart Association. “The Project Baseline study has the opportunity to significantly influence our current body of knowledge by better understanding the indicators of wellness. The outcome of this study could inspire a new generation of tools that are geared towards disease prevention versus just diagnosis and treatment.”

For more information about the study, visit www.projectbaseline.com.

Laying a foundation for a national learning healthcare system

April 18, 2017 – A recent article discusses how PCORnet and ADAPTABLE could point the way toward new trend in health care.

The DCRI’s Adrian Hernandez, MD, MHS, and Henry Cruz, a patient Adaptor from the ADAPTABLE Study, recently published an article in Circulation on the lessons of PCORnet and the need for a national learning healthcare system.

The two authors discuss the need for and benefits of a national learning health system and how PCORnet is conducting research with enhanced quality, speed, and efficiency in “real-world settings” to achieve such a system. The piece also mentions the ADAPTABLE study’s collaboration with ADAPTORS, a group of patient representatives who are shifting the role of patients in the research process from participant to partner, and how this collaboration creates an effective organizational vision that can be useful in addressing one of the nation’s most pressing public health problems: cardiovascular disease.

Read the complete article here.

Dueling statin guidelines put 9 million Americans at crossroads

April 18, 2017 – Two groups recommend the drugs, but diverge on who needs them and when.

Dueling guidelines for the use of statins to prevent cardiovascular disease have fed confusion, but this much is now known: If all doctors followed advice from the U.S. Preventive Services Task Force, 9 million fewer adults would be taking the drug than if they adhered to the American College of Cardiology/American Heart Association recommendations.

The analysis by the DCRI also finds that most of those who would be dropped from the USPSTF guidelines are younger adults.

“Having multiple guidelines out there for cholesterol-lowering drugs can be confusing to physicians and patients,” said the DCRI’s Neha J. Pagidipati, MD, lead author of a study published April 18 in the Journal of the American Medical Association. “Until we get more definitive answers about the optimal approach, the best we can do is understand the pros and cons of each set of guidelines. Our study adds some of that context.”

Pagidipati and colleagues — including senior author Michael J. Pencina, PhD, professor of biostatistics and bioinformatics at the DCRI — analyzed the most recent-available six-year data from the National Health and Nutrition Examination Survey, a representative sample of U.S. residents that provides key health statistics over time.

The researchers estimated that, if fully implemented, the USPSTF recommendations would result in a 15.8 percent rise in the use of statins among U.S. adults aged 40 through 75 with no prior cardiovascular disease. Those newly recommended for statins would be in addition to the 21.5 percent of U.S. adults already taking the lipid-lowering therapy.

By comparison, the ACC/AHA guidelines would result in an additional 24.3 percent of U.S. adults beginning on statins.

“We estimate there could be a 9 million fewer individuals recommended for statin therapy under the USPSTF recommendations compared with the ACC/AHA guidelines,” Pagidipati said.

The Duke researchers found that of those who are recommended to receive statins by the ACC/AHA but not the USPSTF, over half are younger adults aged 40 to 59 years, and over a quarter are people with diabetes.

“Even though younger people have a modest short-term risk of developing cardiovascular disease in 10 years, the risk escalates over 30 years,” Pencina said. “Half of all cardiovascular events in men and one-third in women occur before the age of 65 years, so reliance on 10-year risk could miss many younger people who could potentially benefit from long-term statin therapy.”

In addition to Pencina and Pagidipati, study authors include Ann Marie Navar, Hillary Mulder, Allan D. Sniderman, and Eric D. Peterson.

The study received support from the DCRI.

Study launched to better understand real-world impact and progression of COPD

April 7, 2017 – The DCRI, the MURDOCK Study, and Boehringer Ingelheim Pharmaceuticals are working together on a new observational study of the disease.

The DCRI, Duke University’s MURDOCK Study, and Boehringer Ingelheim Pharmaceuticals Inc. announced today the launch of a new collaborative research effort to closely follow 850 people living with chronic obstructive pulmonary disease (COPD). The study will measure changes to participants’ health to better understand how COPD progresses within a community and follow participants for five years.

The MURDOCK COPD Study is an observational study that could help researchers develop a better way for healthcare providers to assess COPD progression in their patients. It could also provide new insights into the correlation between lung function, exercise capacity or COPD symptoms and disease progression.

COPD is a term that includes chronic bronchitis and/or emphysema. This disease can make breathing harder because less air flows in and out of the lungs. Chronic lower respiratory diseases, which include COPD, are the third-leading cause of death in the United States, and approximately 15 million Americans have been told by a healthcare provider that they have COPD.

Much of the understanding of current COPD management comes from randomized clinical trials that use strict inclusion criteria and regimented patient follow-up, which may not mirror real-world practices.

“By contrast, this observational study will create a diverse group of participants with COPD who will be followed for years, allowing us to better understand the impact and progression of COPD in a community,” said Scott Palmer, MD, director for DCRI Respiratory Research and principal investigator for the MURDOCK COPD Study (pictured left). “We hope this study will ultimately contribute to our understanding of how to provide better patient care and more effective treatment for patients in the community setting.”

In the MURDOCK COPD Study, researchers will use results to compare disease development and progression in a real-world setting to the current system for classifying the stages of COPD. Results could also help study investigators understand patterns of COPD therapy within the study group and create better benchmarks for evaluating the clinical course of COPD.

“This disease can have a profound impact on someone’s quality of life. As healthcare providers caring for patients with COPD, we want to help our patients understand their risk for flare-ups of breathing problems, hospitalizations and other outcomes that can negatively affect their lives,” said Jamie Todd, MD, assistant professor of medicine in the DCRI and co-principal investigator of the study (pictured right). “Much of what we have learned about COPD to date has been gathered from research done in large academic medical centers. But for this study, we have the unique opportunity to work with the MURDOCK Study to better understand the progression and management of COPD in a community setting.”

The most common symptom of COPD is shortness of breath, especially with physical activities. Coughing, with or without mucus production, is also a common symptom of COPD. These symptoms can be misunderstood as signs of aging. COPD is usually associated with progressive airway damage and loss of lung function that cause breathing to become more difficult.

Adults who are at least 40 years old and have COPD as determined by a breathing test administered during a screening visit may qualify to join the MURDOCK COPD Study. Enrollment is open to all who qualify, and no geographic restrictions apply.

During the five years of COPD study follow-up, Duke’s MURDOCK Study team in Kannapolis will contact participants every six months to measure changes to their health.

“Boehringer Ingelheim is proud to be a part of this important study to explore COPD itself with the goal of ultimately improving the care for people living with this chronic respiratory disease,” said Danny McBryan, MD, head of Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. “For over 40 years, we have had an unwavering commitment to the COPD community, and we will continue to support important research efforts, such as the MURDOCK Study, that strive to provide new answers and new hope from people living with COPD.”

People who would like to learn whether they qualify can start the process by calling 704-250-5861 or visiting www.murdock-study.org/COPD. Participants will be offered compensation for each in-person visit. Everyone who completes a screening visit will receive a copy of their lung function test. People who qualify for the study and choose to enroll will receive additional feedback, including the distance they walked in six minutes compared to the distance expected for someone of an identical age, sex, height and weight without COPD.

Greater exposure to flame retardants might be associated with thyroid cancer

April 3, 2017 – Use of flame retardant chemicals coincides with increased incidence of thyroid cancer.

Higher exposure to chemicals used to reduce the flammability of furniture, carpets, electronics and other household items appears to be associated with papillary thyroid cancer, according to study conducted by the Duke and DCRI researchers.

Reporting April 1 at the ENDO 2017 meeting in Orlando, the Duke research team found a significant association between higher levels of certain flame retardants in household dust and being a patient with papillary thyroid cancer, which is increasing at the fastest rate of any cancer in the United States.

“The incidence of papillary thyroid cancer has risen an average of 7 percent a year in the United States for the last two decades,” said co-senior author Julie Ann Sosa, MD, chief of endocrine surgery at the Duke Cancer Institute and member of the DCRI (pictured). “At the same time, exposure to flame retardant chemicals has also increased.

“These chemicals are known as endocrine disruptors, and specifically they affect thyroid function,” Sosa said. “We know that some flame retardants share a similar chemical structure with thyroid hormones, and there has been quite a bit of interest around their impact on thyroid regulation and clinically significant thyroid disease. Our study was designed to explore whether there is an association between these chemicals and having thyroid cancer.”

Sosa and co-senior author Heather M. Stapleton, PhD, associate professor of Environmental Chemistry and Exposure Science at the Nicholas School of the Environment, led an interdisciplinary team that studied 140 patients with and without papillary thyroid cancer. The patients had lived in their homes for an average of 11 years, providing a population with long-term exposures in the home that could be characterized by analyzing home dust samples.

The researchers collected household dust to measure flame retardants in the home environment. They also analyzed the participants’ blood, focusing on biomarkers for one class of flame retardants, polybrominated diphenyl ethers (PBDE), which were once the most common chemicals used to inhibit flammability in furniture until they were phased out in the 2000s because of toxicity and human health concerns.

“Despite declining use, PBDE chemicals are still detected in indoor dust samples because many people still have treated products in their home — for example, things like sofas or TVs,” Stapleton said. “Flame retardants readily leach from the products over time. The Environmental Protection Agency estimates that 80 percent of the U.S. population’s exposure to PBDE flame retardants is from indoor dust.”

Accounting for other risk factors for papillary thyroid cancer, the researchers identified several important associations between long-term flame retardant exposures and the odds of having papillary thyroid cancer, particularly with respect to increased tumor aggressiveness.

Exposures to two particular chemicals — decabromodiphenyl ether (BDE-209) and tris(2-chloroethyl) phosphate (TCEP) in dust – were most strongly associated with higher odds of having papillary thyroid cancer incidence.

Study participants with elevated concentrations of BDE-209 in dust were 2.3 times as likely to have thyroid cancer than those with low concentrations. TCEP in dust was more strongly associated with larger, more aggressive tumors. In contrast, patients with the highest levels of BDE-209 in dust had less aggressive tumors.

“Taken together, these results suggest exposure to several flame retardants may be associated with the diagnosis and severity of papillary thyroid cancer, potentially explaining some of the observed ‘epidemic’ in the incidence of this disease,” Stapleton said. “Next efforts should include replicating these results in a different, larger cohort of patients and understanding what the underlying mechanisms are that support these observations.”

“With the incidence of thyroid cancer quickly increasing and little knowledge of what may be leading to this drastic increase, it is of critical importance to understand potential environmental factors that might be contributing,” Sosa added.

In addition to Sosa and Stapleton, study authors include Kate Hoffman, Amelia Lorenzo, Craig M. Butt, Stephanie C. Hammel, Brittany Bohinc Henderson, Sanziana A. Roman, and Randall P. Scheri.

The study received funding support from Fred & Alice Stanback, the Duke Cancer Institute, and the Nicholas School of the Environment.

Anticoagulant apixaban superior to warfarin for reducing brain bleeds in AF patients

March 29, 2017 – The DCRI-led study also shows that use of aspirin increases risk of intracranial hemorrhage.

In a new analysis, patients with atrial fibrillation showed a substantially reduced risk of dangerous bleeding in the brain, known as intracranial hemorrhage, when taking the newer anticoagulant apixaban compared to those taking warfarin.

The study, published online today in Blood, the journal of the American Society of Hematology (ASH), also showed that taking aspirin increased the risk of intracranial hemorrhage, especially in older patients.

“Intracranial hemorrhage has high morbidity and high mortality and is the most severe and most feared complication among physicians prescribing oral anticoagulants,” said the DCRI’s Renato D. Lopes, MD, PhD, the study’s lead author. “This study shows apixaban is a better option for oral anticoagulation than warfarin because it reduces stroke while substantially reducing intracranial hemorrhage.”

Atrial fibrillation is a type of irregular heartbeat that affects between 2.7 and 6.1 million Americans, according to estimates from the Centers for Disease Control and Prevention. An erratic heartbeat can allow blood to pool in the heart, which can lead to the formation of a blood clot that travels through the bloodstream and blocks a blood vessel in the brain, causing a stroke. Patients with atrial fibrillation are five times more likely to experience a stroke compared to the general population.

Medical guidelines recommend the use of oral anticoagulant medications in patients with atrial fibrillation who are at high risk for stroke. These medications reduce the blood’s clotting ability, which substantially lowers the risk of stroke, but also increases the risk of uncontrolled bleeding.

Intracranial hemorrhage is a rare, but serious complication of these medications, occurring in about 1 percent of patients prescribed anticoagulants for atrial fibrillation. This type of bleeding in the brain can occur spontaneously or after trauma (such as a fall); can cause a range of symptoms including headache, vomiting, seizures, and coma; and has been associated with a 30-day mortality rate of 50 percent.

Historically, warfarin, a vitamin-K antagonist, has been considered the standard of care for oral anticoagulation therapy, but warfarin requires careful management to ensure patients receive the proper dosing. Drugs in a class of newer anticoagulants known as non-vitamin K antagonist oral anticoagulants, or NOACs, are easier to manage and have been shown to be as effective as warfarin, leading to a surge in the use of NOACs in patients with atrial fibrillation and other conditions in recent years.

The new analysis is the first to compare apixaban, a NOAC, to traditional warfarin in terms of the risk for intracranial hemorrhage.

The trial enrolled more than 18,000 patients in North America, Latin America, Europe, and Asia. All patients had atrial fibrillation and at least one additional risk factor for stroke. Patients were randomized to each medicine; half received apixaban and half received warfarin. Outcomes were tracked for a median of 1.8 years.

Intracranial hemorrhage occurred at a rate of 0.80 percent per year in patients taking warfarin and 0.33 percent per year in patients taking apixaban, meaning that patients taking apixaban were 58 percent less likely to experience intracranial hemorrhage compared to those taking warfarin. The difference was even greater for patients experiencing trauma-related intracranial hemorrhage; patients taking apixaban were 75 percent less likely to experience trauma-related bleeding compared to those taking warfarin. The results were consistent across all types and locations of bleeding in the brain.

The vast majority of patients taking warfarin showed INR (International Normalized Ratio) values, a measure of clotting factors, in the target range or below the target range within about two weeks of experiencing intracranial hemorrhage, which suggests their warfarin dosage was properly or under-calibrated, respectively.

Among all patients, the highest risk for intracranial hemorrhage was seen in patients who were age 80 or older, were treated in Asia or Latin America, or had a previous stroke or mini-stroke. Taking concomitant aspirin at the start of the study was found to significantly increase the risk of intracranial hemorrhage. About 30 percent of patients with atrial fibrillation use aspirin. Aspirin is a blood thinner that prevents platelets from clumping together, but it is not an anticoagulant medication and is not considered to effectively prevent strokes in patients with atrial fibrillation.

“We know that aspirin has only a modest effect in preventing stroke in atrial fibrillation patients, yet it was one of the top predictors of intracranial hemorrhage,” Lopes said. “Our finding demonstrates that aspirin is not as safe as one might think.”

The increased risk of intracranial hemorrhage associated with aspirin use was particularly pronounced in older patients. Future studies could help elucidate how the development and availability of antidotes for NOACs may affect the treatment and associated outcomes of intracranial hemorrhage, Lopes said.

The study’s other authors included Patricia O. Guimarães, Bradley J. Kolls, Daniel M. Wojdyla, Cheryl D. Bushnell, Michael Hanna, J. Donald Easton, Laine Thomas, Lars Wallentin, Sana M. Al-Khatib, Claes Held, Pedro Gabriel Melo de Barros e Silva, John H. Alexander, Christopher B. Granger, and Hans-Christoph Diener.

This study is an analysis of data generated by the ARISTOTLE trial, a large multinational trial that found the NOAC apixaban to be superior to warfarin in terms of preventing strokes, reducing bleeding complications, and reducing mortality. The ARISTOTLE trial was funded by Bristol-Myers Squibb and Pfizer.

Digital Health in Neurosciences

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

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

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

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

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

Other key takeaways from DCRI presentations at the meeting included:

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

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

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

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

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

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

DCRI introduces novel app for patients with hypertrophic cardiomyopathy

March 21, 2017 – The app will provide patient information and educational materials about the genetic heart condition.

The DCRI has partnered with cardiology experts to find new ways to inform and engage patients with hypertrophic cardiomyopathy (HCM), a genetic heart condition with an estimated prevalence of 1 in 500 adults.

The new, patient-focused app, called HCM Care, is available for both mobile devices and as a web-based version.  The app features videos of leading HCM clinicians and engaging medical animation to answer common questions faced by HCM patients in key aspects of diagnosis, symptoms, risk assessment, and treatment. It also provides patient education about genetic testing and family screening, and other resources related to research and patient support. MyoKardia, Inc., a clinical stage biopharmaceutical company focusing on novel therapeutics for genetic cardiovascular disease, sponsored development of HCM Care.

Patients with HCM typically have abnormal thickening of the heart muscle. There is a wide spectrum of clinical symptoms, risk, and treatment considerations among HCM patients. Some patients may be asymptomatic, while others have severe symptoms such as shortness of breath, chest pain or fainting; a small percentage of patients have life threatening heart arrhythmias. Advancements in diagnosis and treatment have led to improved outcome for HCM patients.

“Many patients have important concerns and don’t know where to look for information about this condition,” said the DCRI’s Andrew Wang, MD, who led the app’s development team. “HCM Care is based on actual questions that are frequently asked by HCM patients. We hope that this will better inform patients and their families before and after they see a cardiologist about HCM.”

“MyoKardia is thrilled to support this fresh and innovative approach to patient education,” said Marc Semigran, MD, MyoKardia chief medical officer. “The clinicians at DCRI and leading HCM centers have created an exciting and empowering resource that is much needed in the HCM community.”

Patients can download the free app from the Apple or Android app stores or can use the web-based version at https://hcmcare.com.

ACC 2017: Surgically sealing heart pouch in AF patients appears to reduce strokes, death

March 19, 2017 – The procedure could help atrial fibrillation patients who cannot tolerate anticoagulants.

People with an irregular heart rhythm known as atrial fibrillation are prone to blood clots that form in the heart and travel to the brain, causing a stroke.

In about 90 percent of these thromboembolic strokes, clots originate in a small pouch on the heart wall called the left atrial appendage. Surgeons and cardiologists sometimes remove or close the appendage to eliminate this source of blood clots.

Although closure of the left atrial appendage has been shown to be safe, the procedure remains controversial and evidence of its effectiveness has been inconclusive.

Now a team led by DCRI researchers has found that surgically sealing the pouch at the time of other cardiovascular surgeries is associated with fewer strokes from blood clots in older patients with atrial fibrillation.

“While our study was not a randomized trial, it does demonstrate strong support for the benefits of closing the left atrial appendage at the time of cardiac surgery in patients with atrial fibrillation,” said Daniel J. Friedman, MD (pictured left), a cardiology research fellow at the DCRI and lead author of a study presented on March 19 at the American College of Cardiology 66th Annual Scientific Session meeting in Washington, D.C..

Atrial fibrillation affects between 3 million and 6 million U.S. adults. Anticoagulation drugs such as warfarin are effective in managing blood clots in these patients, but more than half of them do not take the drugs for a variety of reasons, including the risk of bleeding.

Low rates of oral anticoagulant use have driven interest in other ways to control clotting, including sealing off the left atrial appendage either with a catheter through a vein in the leg or surgically during a cardiac procedure.

In the Duke-led study, researchers focused on the surgical approach. They used the Society of Thoracic Surgeons National Database to identify more than 10,000 Medicare recipients with atrial fibrillation undergoing cardiac surgery. Patients were predominantly male (61 percent), had a median age of 76, and were at high risk for stroke.

In 37 percent of cases, patients underwent the additional surgery to close off the appendage in a procedure called left atrial appendage occlusion, or LAAO. This group of patients tended to be in better cardiovascular health than those who did not undergo the surgical LAAO.

After statistically adjusting for these differences, the research team found that the surgical LAAO procedure was associated with a 40-percent reduction in thromboembolism and a 15-percent reduction in all-cause death after one year. Additional analyses demonstrated that the lower risk of thromboembolism occurred predominantly among patients who were discharged from the hospital without blood thinners.

“Our study suggests that surgical left atrial appendage occlusion appears safe regardless of whether patients received anticoagulation therapy after discharge, and it could be particularly beneficial for patients who cannot take anticoagulation therapies for medical reasons,” Friedman said.

“Patients scheduled to undergo open heart surgery should talk with their surgical teams about closure of the left atrial appendage,” said principal investigator J. Matthew Brennan, MD, an interventional cardiologist in Duke’s Division of Cardiology and member of the DCRI (pictured right). “Particularly among patients with atrial fibrillation, this may be one of the most effective available treatments to prevent future strokes. Until randomized trials are available, this study will represent the strongest available data in this field.”

The authors note that the study was limited by its use of Medicare data, which included only older adults. It also had a non-randomized design, and was unable to identify the method used to seal the appendage or to gauge the success of the procedure. Randomized studies are needed to determine whether anticoagulation can be safely withheld in patients who have had successful surgical LAAO.

In addition to Friedman and Brennan, study authors include Jonathan P. Piccini, Tongrong Wang, S. Chris Malaisrie, David R. Holmes, Rakesh M. Suri, Michael J. Mack, Vinay Badhwar, Jeffrey P. Jacobs, Jeffrey G. Gaca, Shein-Chung Chow and Eric D. Peterson.

The study received funding support from the Food and Drug Administration (1U01FD004591-01), and an Innovation in Regulatory Science Award from Burroughs Welcome Fund (1014158). Friedman is funded by the National Institutes of Health T 32 training grant (HL069749).