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2018 Director’s Messages

Select a 2018 message from the list below:

Jan. 2, 2018:  Innovations to Increase Participation in Clinical Research

Every person with an illness wants the best treatment available, and given the pace of biomedical research, that best treatment may be new or even still under study. And Americans are well-known for their attraction to the “new!”, believing that new likely means better. It is curious, therefore, that only a small number of people with any disease — generally less than 10 percent — participate in clinical trials of new treatments. This lack of participation greatly increases the time and cost of clinical testing of new interventions and regularly delays or prevents new treatments from being approved. One particular issue, given the increasing diversity of the U.S. population and the advent of precision medicine, is our inability to enroll enough diverse participants to adequately represent the U.S. population or the subpopulation for which an intervention is being developed. Too often, an investigator simply cannot find enough volunteers who meet the trial criteria and must either find additional resources to boost study recruitment efforts or cancel the study.

Put simply, our increasing recruitment failures threaten to choke off translational progress. As a result, NCATS has designated recruitment innovation as one of its top priorities.

A centerpiece of our efforts is the Clinical and Translational Science Awards (CTSA) Program’s Recruitment Innovation Center (RIC), a part of the CTSA Program Trial Innovation Network. Researchers at the RIC, which is based at Vanderbilt University with connections to all the CTSA Program hubs, are developing and disseminating best practices for engaging and recruiting participants, particularly from communities traditionally underrepresented in clinical research.

Through the CTSA Program’s Accrual to Clinical Trials (ACT) initiative, researchers are forming a national network of sites that will use electronic health record (EHR) data to identify potential participants. Since health care systems vary widely in how their EHR data are organized, searching across institutions for eligible patients has been a persistent challenge. ACT investigators are working with widely used open-source technologies to enable a qualified researcher to search for eligible participants while protecting patient privacy and meeting all legal and ethical requirements.

I also am excited about the Strengthening Translational Research in Diverse Enrollment (STRIDE) initiative, a collaboration among three CTSA Program hubs to develop and test innovations to increase participation of underrepresented groups, including African Americans and Latinos, in clinical trials and other research efforts. STRIDE tools will include culturally, linguistically and literacy-tailored recruitment and informed consent protocols. Once the innovations are shown to be effective, STRIDE investigators will disseminate the tools broadly so that anyone can use them to improve recruitment diversity for clinical trials and other translational research.

Through these and other efforts to increase participation in research, NCATS is both accelerating translation and ensuring that its benefits reach all who need them.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

Feb. 1, 2018:  Patients Are Key to Rare Disease Day at NIH 

There are about 7,000 diseases officially defined as “rare,” or affecting fewer than 200,000 people in the U.S.; only a few hundred of these diseases have any approved treatment. Added together, these disorders are anything but rare: They affect 25 million people in the U.S., and approximately 50 percent of these patients are children. Most clinicians go through their entire careers without seeing a patient with one of these rare diseases; thus, patients and their families struggle first to get an accurate diagnosis, and then to get proper care and treatment, all while coping with frequently debilitating and costly illnesses.

NCATS is deeply engaged in finding breakthrough approaches to all aspects of this urgent and oft-neglected problem. One of the approaches we feel has the most potential is to turn the usual paradigm of diagnostic and treatment development on its head, by putting the ultimate consumers of these products — patients and their families — at the head of the line of consideration in research projects, versus at the end. For many reasons, patients have traditionally been brought into the translational projects late in the process; not surprisingly, this has led to interventions that are not well-suited to the needs and realities of actual patients — and, ultimately, to translational failure. As one of my first directives as NCATS director, I therefore exhorted the Center’s scientists to involve patients in every project we do, to test the hypothesis that such involvement will make translation more relevant and effective.

I am glad to report that NCATS now partners with patients and their caregivers and advocates at every stage of the translational science spectrum, with the goal of not only improving research efficiency and effectiveness, but also developing “best practices” for patient involvement in translational research — that is, a translational science of patient engagement. Patients were principal drivers in the construction of the NCATS Toolkit for Patient-Focused Therapy Development. They also partner with the Rare Diseases Registry, or RaDaR, Program to build registries to increase understanding of the characteristics and progression of a disease, improve the design of clinical trials to study a disorder, and help select meaningful study endpoints to evaluate. To increase public and research community awareness of these disorders, we have promulgated the perspectives of individual patients, such as Alani Daniels and Marcela Ferrada.

Our “patients first” approach will be on display March 1 of this year during Rare Disease Day at NIH, which is co-sponsored by NCATS and the NIH Clinical Center. “Patients and Researchers — Partners for Life” is the guiding principle for NIH’s annual event that connects patients and their support groups with scientists, clinicians and policymakers to discuss collaborative research efforts that are making a difference. Based on feedback from last year’s participants, we are incorporating new formats that facilitate greater audience participation. If you are able to travel to the NIH campus in Bethesda, Maryland, for this event, please register here; if you are unable to join us in person, please join us via webcast.

Most important, know that every day is rare disease day at NCATS. For example, our support helped the Primary Immune Deficiency Treatment Consortium, part of our Rare Diseases Clinical Research Network, address the high incidence of a genetic condition in the Navajo Nation. In addition, through our Therapeutics for Rare and Neglected Diseases program, we collaborated to advance a new gene therapy for a muscle disorder.

Learn more about NCATS’ work in all aspects of rare diseases research by viewing our newly released video. See you on March 1!

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

March 5, 2018: A New Map to Guide and Improve Therapeutics Development  

Anyone embarking on an unfamiliar journey will want a map to help plan needs, anticipate problem spots and formulate contingency plans. This is all the more true if the journey being contemplated is known to take many years, be fraught with hazards and rarely be completed successfully. In this case, one would want a very good map indeed, one that could both guide new travelers and assist construction engineers in improving it.

The drug development process is such a journey, taking decades from idea to patient, during which hundreds of attempts fail and enormous costs are borne. The common moniker of a drug development “pipeline” is wildly and tragically misleading, implying as it does a simple and inevitably successful path from a laboratory observation to an available therapeutic. The pipeline misnomer engenders improbable expectations among patients, scientists, physicians, and policymakers and impedes efforts to improve the therapeutic development process.

NCATS took on the creation of a new and accurate map as central to our mission to develop solutions to translational roadblocks and disseminate them for use by the research community. I am glad to report that an exciting new map has now been produced and is publicly available on our website. In true NCATS fashion, we partnered with academics, pharmaceutical and biotech companies, regulators, foundations and patient groups to create the map under the auspices of a component of the National Academies of Sciences, Engineering, and Medicine. This Drug Discovery, Development and Deployment Map, or “4DM,” was described in two recent pieces in Nature Reviews Drug Discovery and Clinical and Translational Science.

Even the casual observer will note that the 4DM is complicated, with different phases, termed “neighborhoods,” and multiple steps within and between neighborhoods that may need to be attempted multiple times before success occurs. But a truly useful map not only indicates routes, it enables travelers to anticipate problem spots. So like the ubiquitous smartphone apps for road traffic we all use, the 4DM has a crowdsourced feature that indicates the steps in the process that previous drug developers have found particularly prone to failure, delays or high cost. Like road engineers, NCATS will use this “traffic” feature to focus our translational re-engineering efforts on the most problematic steps of the process.

In this initial version, the 4DM is static, but we have already begun developing additional features to make the map interactive. For example, future versions will enable users to locate their translational project on the map via a “GPS” feature based on answers to a series of questions, allowing them to identify next steps and options to best advance their efforts. We’ll also be adding connections to NCATS resources to help users through these steps. These resources include our Therapeutics for Rare and Neglected Diseases program for pre-clinical studies and our Clinical and Translational Science Awards Program in the clinical and implementation domains.

The 4DM is available under a Creative Commons license, so anyone in the world can download, adapt and display it for their own use. Please use the map and give us feedback on what features we should add next to make it even more useful. I hope you will find the 4DM to be as helpful as we have for education, planning, engineering and ultimately increasing successful outcomes in the translational journey.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

April 5, 2018: Practice Makes Perfect — “Good Clinical Practice” Makes Perfect Sense for Researchers

Given that translational science is such a young and growing field, NCATS places emphasis on training and workforce development. Until very recently, no one — myself included — trained to be a “translational scientist,” since the discipline did not exist. Translational science shares this characteristic with other new and exciting fields, such as data science. I have previously written about NCATS’ extramural and intramural trainee programs, our Assay Guidance Manual, Toolkit for Patient-Focused Drug Development, and international educational efforts, all of which aim to give those new to translational science the knowledge and skills they need to be contributors to the translational team.

As readers of this column will know, studies of diseases and treatments in people are the lynchpin of translation but present many scientific and logistical challenges that are currently limiting efficiency and effectiveness. One reason for the persistence of these challenges has been the heterogeneity in practices of investigators conducting studies in humans. To tackle this issue, NCATS Clinical and Translational Science Awards (CTSA) Program investigators, led by the University of Michigan, collaborated to enhance, streamline and standardize training in clinical research processes across the consortium. These research processes are termed “good clinical practice” (GCP) by analogy to established standardized processes for the research laboratory (“good laboratory practice,” or GLP) and manufacturing (“good manufacturing practice,” or GMP). GCP is an international ethical and scientific quality standard for the design, conduct, recording and reporting of clinical studies. These common standards can help ensure the integrity of the data collected, which in turn boosts confidence in research results.

The CTSA Program GCP team identified a need for training that addressed the unique aspects of clinical trials for behavioral interventions. Behavioral trials tend to pose lower risk to participants and are not regulated by the U.S. Food and Drug Administration. But they can be more complicated, taking place in a range of settings outside the clinic, such as in schools and homes or even online, where investigators have less control over the research environment. In addition, behavioral trials can be administered by personnel with a variety of backgrounds, from clinicians to social workers to community leaders. Some aspects of traditional GCP training were not relevant to behavioral research, while other unique issues were not covered at all.

To solve this systemic problem, the CTSA Program team developed an e-learning course that applies GCP principles to social and behavioral research. The course was initially disseminated throughout the CTSA Program consortium, and it is now available through the NIH Office of Behavioral and Social Sciences Research. It has been adopted by professional organizations such as the Society of Behavioral Medicine and by the NIH Common Fund’s Science of Behavior Change program. Moreover, the Collaborative Institutional Training Initiative, a leader in certifying researchers in GCP, has now integrated the training into its offerings. GCP certification is now required for every investigator and coordinator working on an NIH-funded study involving human participants.

The GCP project is a notable example of NCATS’ “3 Ds” in action. We supported development of the GCP training for behavioral intervention trials as well as testing to demonstrate its usefulness, and we have disseminated the training broadly to the social sciences and behavioral research community. I invite you to learn more about all our clinical research tools that are helping to improve health through smarter science.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

May 1, 2018: Advancing Chemical Testing for the 21st Century

“Chemicals” are sometimes thought of as being universally detrimental to health, with the possible exception of “natural” chemicals. In fact, the word “chemical” describes a vast universe of millions of molecules, both naturally occurring and man-made, that can have beneficial effects (like penicillin or vitamin C) or toxic ones (like carbon monoxide or dioxin). Further, most chemicals — even pure water — can be toxic if consumed in large enough quantities.

Our inability to predict whether a new chemical might cause adverse health effects at doses people are normally exposed to is one of the greatest causes of translational failure in drug development and uncertainty in environmental health. Remarkably, our methods for evaluating the safety (or its opposite, toxicity) of chemicals have changed little over the past 50 years due to technical barriers and appropriate caution about protecting public health. But beginning about 10 years ago, this began to change as NIH and several other federal agencies joined together in an unprecedented collaboration to drive toxicity testing into the 21st century. This ambitious vision required better methods to rapidly and efficiently evaluate the safety of environmental chemicals, pesticides, food additives and drugs.

Established in 2008, the Toxicology in the 21st Century (Tox21) program became part of NCATS when our Center was launched in fiscal year 2012. Through the program, scientists have developed and validated new high-throughput screening assays (tests) and generated and made public data on tens of thousands of chemicals; for many of them, there had been no information about potential toxic side effects. These data are now beginning to inform regulatory decisions about safety.

Tox21-supported advances are remarkable and have transformed how chemicals are evaluated for their potential effects on human health. But the work is just beginning, since these successes also have enabled a greater understanding of key obstacles that must be overcome to achieve our original vision. These roadblocks include technical and biological limitations of current methods, as well as barriers to efficiently translating screening results into regulatory decision making.

To address these challenges, Tox21 partners from NCATS, the National Toxicology Program at NIH’s National Institute of Environmental Health Sciences, the Environmental Protection Agency, and the Food and Drug Administration have released a new strategic and operational plan that expands the program’s research activities. The plan shifts Tox21’s primary focus from screening libraries of chemicals to follow-up studies that address specific focus areas, using a new type of cross-partner project.

There are many examples of how discoveries from Tox21 are informing new research directions. For instance, in a previous message I discussed how Tox21 scientists had screened cells from a group of genetically diverse people and demonstrated that individual responses to many chemicals varied much more than previously thought. One of the five new focus areas for Tox21 will address genetic variability between different groups of people by creating alternative test systems. This approach could further improve the predictive power of chemical evaluations and identify populations that are especially susceptible to certain substances.

Tox21 is just one example of NCATS’ success in developing entirely new paradigms that are making translation more efficient and effective through collaboration, new operational models and smarter science.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

June 6, 2018: Translating Translation

NCATS is unique at NIH in that the name in the Center’s mission — “translation” — has a firmly established meaning that is generally associated with languages, not biomedical research. By contrast, other NIH components are named for widely known medical problems, such as cancer, diabetes and stroke. NCATS’ outreach and education efforts are therefore especially complex. First, we must define what “translation” means as a biomedical research term. Second, we must convey why it matters. And third, we must explain what NCATS is doing to improve it.

To understand NCATS’ definitional challenge, imagine for a moment that neither you nor anyone you know, including your scientist and physician friends, had ever heard of cancer. But you knew it to be an enormous and deadly problem, and you were working hard to find a cure for it. You would have a difficult time garnering interest in your work until your colleagues understood what “cancer” was. Substitute “translation” for “cancer” and you can better understand NCATS’ challenge as well as its potential.

To help bridge this gap, I recently published a brief about three related terms — translation, translational research and translational science — in Nature Reviews Drug Discovery. I hope you will take a look at this freely available commentary and send me feedback.

“Translation” is firmly established as meaning the conversion of a message from one language into another. Biomedical translation, by analogy, is the process of converting a scientific or clinical observation into an intervention (e.g., drug, device, surgical procedure, behavioral change) that is shown to improve health.

Scientific translation is an exceedingly complicated process that involves dozens of steps. (See our Drug Discovery, Development and Deployment (4DM) Maps for a glimpse of just how complicated translation can be.) Imagine the child’s game of “telephone,” in which a message is translated into one person’s language, and then another, and so on a dozen or more times. The likelihood that the original meaning of the message would be successfully delivered in the final person’s language would be very small. Welcome to the world of biomedical translation!

The definitions of “translational research” and “translational science” follow from this understanding of the meaning of translation. Translational research attempts to move a particular project across one step of the translational process. In our telephone game analogy, translational research would correspond to the attempt to accurately convert a message from one language to another language (e.g., English to Chinese).

By contrast, translational science is the quest to understand how the translational process works, both at each step and as an integrated whole, so that we can improve the process to work faster and more successfully. In our telephone game, this would correspond to the study of what languages have in common, why individual translational steps fail, how to make those steps more reliable and whether it is possible to skip certain steps altogether. Why do so many drugs that are safe and effective in animals turn out to be toxic in humans? How could lab tests give better, more accurate answers about whether a new drug will work? How could clinical trials in humans be conducted more efficiently and safely? These are some of the translational science questions NCATS is trying to answer.

Understanding these definitions leads to rethinking the fundamental biomedical challenge of our era: how to deliver on the promise of science for patients in need. I will explore this reconceptualization, and its implications for NCATS, in upcoming messages. Stay tuned!

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

July 10, 2018: Bringing Translational Science to the Opioid Crisis

Every 13 minutes in the United States, a person dies from an opioid overdose. The number of these overdose deaths — more than 42,000 in 2016 — continues to rise dramatically, paralleling the rise in deaths from HIV/AIDS during the height of that epidemic. Opioid-induced death is a public health crisis of historic proportions, with devastating consequences for individuals, families, communities and the nation.

Opioid addiction is a complex problem that will require medical, social, legal and community solutions. But research also has an important role to play in understanding the underlying biology of addiction and pain, developing new interventions to treat them, and determining which interventions are most effective. This past April, NIH launched an innovative research agenda called the HEAL (Helping to End Addiction Long-term) initiative, focused on two critical areas: improving treatments for opioid misuse and addiction, and finding non-opioid approaches to pain management.

Over the last year, I have been working closely with my NIH colleagues to apply NCATS’ translational science approach to the HEAL initiative. The opioid crisis typifies the translational challenge at every step, from validation of new targets to development of innovative treatments and clinical trial end points to recruitment for clinical studies, which is particularly difficult since the population is stigmatized and may be in legal jeopardy. And even when new interventions demonstrate effectiveness in controlled clinical trials, their uptake in medical care settings is often low, limiting their dissemination to patients in need. This problem was the focus of a study published last month on medication-based treatment after opioid overdose. With support from NCATS’ Clinical and Translational Science Awards Program, investigators found that only a fraction of individuals who would likely benefit from medications to treat opioid use disorder receive them after surviving an overdose.

NCATS is bringing our unique approach to bear on these many challenges. Through the HEAL initiative, we are leading a trans-NIH effort to develop innovative, human cell-based screening platforms and novel drugs to treat opioid misuse, addiction and pain. Our efforts will tap into many of NCATS’ existing efforts, including induced pluripotent stem cells, 3-D Tissue Bioprinting and Tissue Chips for Drug Screening. We will use these innovative platforms to identify drugs that will undergo pre-clinical development via our NCATS Chemical Genomics Center and the Bridging Interventional Development Gaps and Therapeutics for Rare and Neglected Diseases programs. We are planning similarly ambitious and innovative efforts in the clinical development and implementation of new opioid misuse/addiction and pain interventions, and I look forward to sharing more with you in a future message.

Through the HEAL initiative, NCATS will demonstrate the breakthrough potential of translational science to address the public health challenge of our era.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences