Director’s Update – Applying for a New Collaborative Innovation Award

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors. This month, Martin Zand, M.D., Ph.D. discusses a new funding opportunity that encourages investigators to streamline the process of translating initial discoveries into patient care in collaboration with other CTSA institutions.MartinZandNEW

What is the new Collaborative Innovation Award?

This award was announced by the National Center for Advancing Translational Science (NCATS) last spring. Part of the mission of NCATS is to accelerate clinical and translational research. That means figuring out ways to move research from initial discoveries into patient care. This new award is designed to fund research that removes a barrier to advancing research from one phase to another. For example, a researcher discovers a new potential therapy for cancer. The researcher has tested it in the lab and wants to move it to a preclinical trial. There are many barriers to making that leap. These awards encourage investigators to find innovative ways to minimize those barriers and streamline that process.

What sorts of projects are they hoping to fund?

NCATS is interested in a broad range of research topics. These awards might fund projects aimed at educating people to become research coordinators to combat the current labor shortage in clinical and translational research.  Aiding research volunteer enrollment is also an area of interest. Some examples are: improving clinical trial enrollment by using informatics to help identify people with rare diseases and ensure that the study participants reflect the makeup of the whole community, or using internet-based research consent forms to enroll volunteers in clinical trials.

How do these awards foster collaboration?

There is a very large move at NCATS to encourage scientific team formation and center collaboration across clinical research in this country. Part of the reason is that we are stronger together as research centers than we are individually in terms of being able to enroll large numbers of individuals for research studies. However, one barrier addressed by these awards is that we are sometimes weaker together because we don’t have standardized methods and processes.

That is why NCATS is changing the way it funds research.  There are a number of funding opportunities now that require collaboration between three or more Clinical and Translational Science Award (CTSA) hubs and at least one outside collaborator. The goal is for the CTSA network to really function like an integrated network – not as a bunch of institutions doing their own thing.

 Have we had any success obtaining any of these grants?

These grants were just created last year. The first round of full applications will be reviewed in the fall, and we will know if any were funded in December. So far, we have written letters of collaboration and support for 12 pre-applications and 3 full applications ranging from establishing an education program for regulatory science to assessing the effectiveness of KL2 Mentored Career Development Awards and creating a new individual development program for those awards. These are in partnerships with institutions that span the country. We’re really excited about these applications – they give us a formal way of collaborating with other centers.

Who can apply?

These grants can be submitted by any investigator at an institution that currently has a funded CTSA, like the University of Rochester.  All that an investigator needs is a letter of support from their CTSA.

How can investigators apply?

Applications for Collaborative Innovation Awards can be submitted three times a year and involve a two-step process. The six-page pre-application, called X02, is reviewed like a normal grant. Based on the reviews, the program officer either encourages or discourages you from submitting a full application, or U01.

The U01 is a standard twelve page NIH grant application that includes a budget, a list of personnel, and all of the usual paperwork that goes with a grant. These grants can be $500,000 – $1 million per year for up to 5 year grant period – so, pretty big awards!

What advice do you have for investigators who are interested in applying?

We encourage investigators who are thinking about putting in applications to talk to us early.  The CTSI can help them find partners at other CTSA institutions and help them take full advantage of the available resources for their studies.

Anyone who would like more information about these awards should contact Carrie Dykes, Ph.D., CTSI Research Engagement Specialist, carrie_dykes@urmc.rochester.edu, (585) 275-0736.

 

 

Director’s Update – September 2015

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors. This month, Martin Zand takes a break from the upcoming CTSA grant application to discuss the efforts that the CTSI is taking to expand research subject engagement.MartinZandNEW

People within the CTSI are well aware of what’s been going on here because it’s all we’ve been doing for the past two months – but for the benefit of readers elsewhere, can you give us a quick update on how the renewal grant application is going?

I can say, with much relief, that it’s been submitted to the NIH. More than 50 people have contributed to the grant-writing process, and it came together beautifully.

And… I’m sure you’d love to talk about something other than the grant this month.

Yes, please! I’d actually like to highlight what we’ve been working on in regards to expanding our research subjects engagement program. We’re part of an academic medical center, and so one of our goals is to integrate research into the clinical mission in a substantial and meaningful way. What I mean by that is: We want the people coming to the Medical Center for their care to also be aware of research opportunities, and we are trying to work on different ways of making people aware of research and helping them understand what kind of research opportunities are available. We want to make it easy for them to express interest, be contacted by researchers, enroll in consent to participate.

It’s my understanding that following up after research is also very important. 

Yes, that’s the second part. We want to make sure that people get a real sense of what their contribution has been. So one of the missions of the CTSI is to try and create mechanisms by which investigators inform the people who participated in our research know what their participation has helped to build. People are very interested in that: “Well, what did you find when you took my blood? And did those findings lead to changes?” The other aspect of this would be if their participation also led to new research opportunities, like grants or new projects. When people give their time, it’s important for us to recognize that, and we have a responsibility to let them know what we did with whatever they contributed.

So how are you going about this?

We’re looking at several different routes. In terms of making people aware of research opportunities, we already have a research notification website where people can go and say “I’m interested in being contacted by researchers at URMC.” But we want to make this available on eRecord on MyChart. So one thing we’re exploring  is the ability for a patient to click on a separate tab in MyChart that says “Research studies,” and if an investigator enters a set of criteria, then a research opportunity for that patient might pop up. And if the person checks the box to stay they’re interested, then that notifies the researcher.

Other studies might allow for different types of enrollment. Tim Dye and Karl Kieburtz have both had projects where they used an Amazon service called the Mechanical Turk to do survey research, and that allows you to do survey work across the entire world for very cheap. Ray Dorsey’s mPower app allows people to enroll and consent to research studies with their phone. So it opens up huge doors to what we might do in terms of expanding access to research in nontraditional ways.

We want people to be engaged, interested, and excited about the research happening at UR. It’s what distinguishes us a medical center, and hopefully improves healthcare in our community. Translating that research into medical care is what we do here at the CTSI.


Previous Director’s Updates:
July 2015 – Karl Kieburtz seeks feedback in the wake of the CTSI Town Hall meeting.
June 2015 – Martin Zand gives an overview of what will likely be different about the next CTSA renewal application.
May 2015 – Nana Bennett discusses the enhanced role of the Strategic Leadership Group.
April 2015 – Karl Kieburtz talks about how the leadership is preparing for the Clinical and Translational Science Award renewals.
March 2015 – Martin Zand introduces himself and discusses his interest in informatics and population-based research.
February 2015 – Nana Bennett discusses the CTSI’s Seminar Series on population health.
January 2015 – Harriet Kitzman reflects on her time as a CTSI co-director.
More…

Director’s Update – June 2015

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors.

Below, Martin Zand talks about how the Clinical and Translational Science Awards are changing and how the CTSI is working towards the renewal.MartinZandNEW

Hello Martin. We’ve heard that the CTSA awards are going to be a bit different than they were in the past.

First, a bit of background. The Clinical and Translational Science Institute at the UR was one of the first in the country to be funded 9 years ago, and the grant was renewed 4 years ago. Every 5 years we have to compete with other current centers, and new center proposals, to renew our NIH funding through the National Center for Advancing Translational Sciences (NCATS). Our grant is coming up for its third competitive renewal this year.

What can you tell us about the changes, and why are they happening?

In the past, the awards were basically individual center awards, where a center puts out a plan for what it was going to do locally that was within the description and requirements of the grant requirements from NIH. Those activities included growing and providing services to support translational research, workforce training, pilot programs to help young investigators, and so on. In the past, there wasn’t much emphasis on collaborations and networking between the 62 centers funded across the country. But over the last two years, there’s been a dramatic shift. The expectation over the next funding period will be that all the CTSAs across the country will collaborate with each other, and create a cohesive nationwide research network. The goal of this is to accelerate clinical and translational research across the country.

One of the things that has motivated the National Center for Advancing Translational Science (NCATS) is that somewhere close to 30 percent of all NIH sponsored clinical trials are never completed. It’s not that they finished and weren’t published, they were just never even finished. So that’s a startling and very worrisome figure. We’re talking about hundreds of millions, if not a few billion dollars, that went into funding studies where, in the end, no usable results come out. Why does this happen?  A small portion of the answer turns out to be scientific: the problem was different than people thought, or they had to close down a trial because of early findings.

But that doesn’t account for all of them.

Unfortunately, no. Many studies never finish for structural reasons. And by that, I mean there are vast differences in how each research center handles the trial. All the centers currently have separate institutional review boards, contracting policies, cost structures. Some centers would negotiate for more funding because expenses were higher there than elsewhere. So if you’ve got a dozen institutions that agree conduct a clinical trial, you have to negotiate a dozen modifications to the consent form, which the other centers all then have to agree to. Then, you might need a dozen different contracts to pay for the trial, one with each center. Then you have the usual operational issues of enrollment, standardization of record keeping, and so on.  So, you can imagine that this process can take years. So, many studies didn’t even get started until the second or third year, and then funding finishes in year five.

What about the studies that actually finish?

Of the studies that actually finished, only about a 60-70 percent of them are published. The reasons for that are a little harder to ferret out. Negative studies often do not get published, and some end up having design flaws that become apparent in the statistical analysis after they were finished. But whatever the reason, if you’ve got scientific ideas you’re trying to take from the bench to the bedside, and in a large percentage of cases it doesn’t happen, then you should fix it. So Congress has been putting pressure on the National Institutes of Health, as they should. And NIH has tasked NCATS with creating a viable clinical trials network based on the CTSA centers. Overall, this is a really positive direction, and we all hope it leads to better, faster, and more scientifically insightful clinical trials.

What else has changed?

The other big change in the CTSA renewal is an increasing emphasis on team science. Scientific investigation has gotten very complex, with all the genomics, proteomics and other -omics technologies. Our ability to generate very, very large amounts of data has far outstripped our ability to analyze it. It’s really hard for any one investigator to do it all. The days when you could run your lab independently, without collaborators, and do all the statistics on an Excel spreadsheet or small statistical program are gone. Now you really need informatics databases, more sophisticated statistical collaborators, technical experts in RNA sequencing, and many other experts in complex methods and data analysis techniques that didn’t exist two decades ago..

Isaac Newton said “If I have seen further than others, it is by standing on the shoulders of giants.” Today, there continues to be an increasing recognition that no person can be doing discovery in isolation. So the nature of how we train people to be clinical researchers and scientists also has to change. Recognizing this, the coming CTSI renewal has a much greater emphasis on educating collaborative teams and fostering collaboration. These skills help Ph.D. researchers and clinicians collaborate and benefit from each other’s expertise, insights, and skills to take something from the bench to the bedside. So NCATS is placing less of an emphasis on funding individual projects and more of an emphasis on training scientists to work in teams.

If there’s less emphasis on individual projects, what will happen to the pilot program?

The pilot programs are an integral part of what the CTSI does, and will continue to be supported. You’re right that less of the funding will come from NCATS than in the past. But we are very fortunate that the Medical Center and the School for Medicine and Dentistry have recognized the importance of these programs, and provide other funds to help us keep them alive. In addition, the co-directors of the CTSI, Karl and Nana and I, are actively exploring ways of invigorating the funding program, so you might see more funding initiatives that ask for matching funds from divisions or departments, industry, and University wide partnerships.

I think one message for investigators is that we are all going to need to be more entrepreneurial. The more creative you can be in terms of finding matching funding and partnering with others, the greater your chances of success. A second message is to collaborate. Fortunately, the UR is a very collaborative institution, and it’s easy to find research partners. That’s also one of the roles of the CTSI – connecting people with common research interests.

Anything else you wanted to mention?

Well, writing the renewal itself is a team effort!  We have an incredible staff here at the CTSI, and there are individuals throughout the institution that are very dedicated to working on the renewal. We have over 40 authors right now for the renewal project. So it’s an industrial-sized undertaking. I think that all of us in leadership know that while it’s going to be a lot of work, I have no doubt that it’ll be done to an extraordinarily high level.


Previous Director’s Updates:

May 2015 – Nana Bennett discusses the enhanced role of the Strategic Leadership Group.
April 2015 – Karl Kieburtz talks about how the leadership is preparing for the Clinical and Translational Science Award renewals.
March 2015 – Martin Zand introduces himself and discusses his interest in informatics and population-based research.
February 2015 – Nana Bennett discusses the CTSI’s Seminar Series on population health.
January 2015 – Harriet Kitzman reflects on her time as a CTSI co-director.
December 2014  – Karl Kieburtz offers his takeaways from the CTSI all-hands retreat.
November 2014 – Nana Bennett speaks to the expansion of the role of the CTSI’s Community Advisory Council.
October 2014 – Harriet Kitzman discusses the science of team science.
September 2014 – Karl Kieburtz talks about why the CTSI is beefing up its informatics team.
August 2014 – Nana Bennett discusses the new Population Health pillar.
July 2014 – Harriet Kitzman offers her takeaways from the Mini Summer Research Institute.
June 2014 – Karl Kieburtz gives an overview of the CTSI’s six pillars.

Director’s Update – March 2015

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors.

Below, newly appointed co-director Martin Zand introduces himself and discusses his interest in informatics and population-based research methods.MartinZand

Martin, you’re not totally new to the CTSI, but I’m sure some people are more familiar with you than others. Could you tell us a little about your background?

Certainly. I started out as a transplant nephrologist — a medical kidney doctor who takes care of people with kidney transplants — and my clinical practice has been taking care of folks who have complicated immune issues for kidney transplantation. My laboratory, meanwhile, studies B cells — which make the antibodies that respond to vaccines and can cause kidney rejection. We are interested in learning more about how that biology works, how the cells differentiate, how many you need to create a rejection episode, what the molecular signals are for vaccine responses, and so on.

The tools we use in the laboratory involve many of the same mathematical methods used in data mining, which is the process of looking at complex data sets to reveal relationships between elements. We then go back to the bench and try to figure how these relationships work to create an immune response. And the mathematics used for that are, at their root, some of the same mathematics used in social network analysis. I realized that about two and a half years ago after reading a humorous article about finding terrorists in a network — the example was Paul Revere as the central revolutionary in his network — and I became very interested in clinical problems and population health problems that could be studied with the same methods.

Very interesting. So that system approach is what appeals to you most now?

Well, I’ve had, for a very long time, an interest in what people call computational biology — mathematical and computer analysis of data, and creating models of biological systems. I’ve always been fascinated by these models, because they give us a way of understanding how nature works, and, sometimes, how naïve we can be as scientists in terms of our theories.

So let me explain that. When you model a biological system — whether it’s vaccine response or kidney transplant rejection or development of B cells or the healthcare outcomes of a population of people — you begin with an idea of how the world that you’re studying works.  The model you build forces you to create an image of that world. If your models are quantitative and predictive, they provide a reality test for your ideas. What is really interesting is that the models are most useful when they’re wrong, because it tells you that the way you thought the world works is not the way that it really does. It tells you that you’re missing something. And then you can go look for that something. If you’re lucky, you find something really interesting.

Can you give a real-world example of this type of system-wide work?

One of our projects is looking at patients who go to the ICU, then get better and recover and are discharged to a medical floor, but then come back to the ICU because they’ve gotten sicker again. People who have that kind of pattern have a rather high chance of dying during their hospitalization. So we took some of the same methods used to look at patterns of gene expression and applied to the hospital admission and transfer data, and lo and behold, two things popped out.

The first was that we could graphically identify the patterns of who was returning to the ICU. They were a small fraction of those admissions, but accounted for a very large portion of our cost per patient. We are now using informatics to ask what medical conditions they had, what was going on right before they went back to the ICU. We want to put together a risk profile, an early warning system, that would tell us “This person has a high probability of ending up back in the ICU.” Then we can try to change the outcome.  That’s exciting, because we may have a chance to use data to save lives.

The second, really amazing thing, was that we were able to create a map — a flux diagram — of all the transfers within the hospital between the different floors and units. That kind of diagram is used in basic science to look at how organisms metabolize things by looking at all the nutrients and chemicals that go into a system, and how they’re shunted to various chemical reactions and come out as products. It’s also the same mathematics that FedEx uses to figure out how many planes they need and how much they need to load in each one, and so on. So with this map of the hospital, one project we’re working on now is to say “OK, we’ve got flu season here, and we’re going to overload this part of the hospital. What other parts are going to get stressed, and how could we creatively move patients around to provide better care, shorter ER stay times, and better outcomes?” The beauty of these approaches is they look at things as systems. It’s not just one part. Everything is connected to everything else.

This type of science, systems analysis, is very exciting right now, and we have a chance to see the world as a connected network using these tools.  My health informatics group, the Rochester Center for Health Informatics, is collaborating with the Institute for Data Science at the University of Rochester and Tim Dye’s CTSI Informatics group on these types of projects. Rochester is exactly the place where we can do this work.

—–

Previous director’s updates:
February 2015 – Nana Bennett discusses the CTSI’s Seminar Series on population health.
January 2015 – Harriet Kitzman reflects on her time as a CTSI co-director.
December 2014  – Karl Kieburtz offers his takeaways from the CTSI all-hands retreat.
November 2014 – Nana Bennett speaks to the expansion of the role of the CTSI’s Community Advisory Council.
October 2014 – Harriet Kitzman discusses the science of team science.
September 2014 – Karl Kieburtz talks about why the CTSI is beefing up its informatics team.
August 2014 – Nana Bennett discusses the new Population Health pillar.
July 2014 – Harriet Kitzman offers her takeaways from the Mini Summer Research Institute.
June 2014 – Karl Kieburtz gives an overview of the CTSI’s six pillars.

CTSI revamps leadership structure

The Clinical and Translational Science Institute has reorganized itself to broaden the range of expertise among the institute’s top leadership.

Karl Kieburtz, M.D., M.P.H., senior associate dean for clinical research at the School of Medicine and Dentistry, who has served as director of the CTSI since October 2013, has been joined by Nancy M. Bennett, M.D, M.S,., and Martin S. Zand, M.D., Ph.D., and the trio are serving as the Institute’s co-directors.

MartinZand

Martin S. Zand

KarlKieburtz

Karl Kieburtz

NanaBennett

Nancy M. Bennett

The leadership change became effective on January 1.

“Karl has enormous experience in clinical trials, Nana brings her community perspective and population health expertise, and Martin brings informatics and data science, as well as a basic science background,” said Stephen Dewhurst, Ph.D., vice dean for research at the School of Medicine and Dentistry. “So they have different clinical interests, research interests and expertise, and put together, they make an extraordinarily broad and effective leadership group.”

This team approach is becoming increasingly common within the Clinical and Translational Science Award network. In Rochester, the diverse skill sets of the three co-directors allows for CTSI leadership to encompass the research spectrum, starting with basic science discovery and continuing through clinical trials and implementation on the population level.

“It really does bridge the molecules to populations theme that we’re trying to express. And the truth is, no single person can bridge all that — it has to be a transdisciplinary, multidisciplinary effort,” said Kieburtz. “So we’re doing it the leadership level, and showing that you can lead an institute effectively with a team.”

For the past year, Bennett served as a CTSI co-director alongside Kieburtz and Harriet Kitzman, Ph.D., but in a more limited capacity. Now her role comes with increasing importance, as the CTSI recently placed a renewed emphasis on improving the health of the population as a whole.

“As we try to accentuate the theme of population health in the CTSI, the new leadership structure will make it much easier for me to contribute in a meaningful way,” said Bennett.

Zand, meanwhile, brings informatics expertise, paramount when it comes to analyzing the big data needed for impactful research into population health.

“We want to use data science to identify questions that we’re not asking and identify data we don’t yet have. This will allow us to be in that space of discovery,” said Zand. “That way, we can translate data into real clinical and community interventions that improve the health of a population as a whole.”

The new structure also fosters an environment that will allow the CTSI to more easily integrate with several other centers within the university. Kieburtz also has strong ties to the Center for Human Experimental Therapeutics, Bennett heads the Center for Community Health, and Zand is the director of the Rochester Center for Health Informatics and co-director of the Center for Biodefense Immune Modeling.

In terms of operations, Kieburtz will remain the CTSI’s liaison to university leadership and to the National Center for Advancing Translational Sciences (NCATS), while Bennett will be the main interface with the community through the Center for Community Health, and focus on overall CTSI strategy and developing the population health science theme for the CTSI.

Zand will take on integrating informatics activities throughout the Medical Center and the newly created Institute for Data Science, have responsibility for the CTSI’s day-to-day operations, and will lead the grant-writing process when NCATS releases its call for renewal applications.