Novel Methods and Technologies for 21st-Century Clinical Trials

“New technologies are rapidly reshaping health care. However, their effect on drug development to date 1459F243510565C0D9F22F2E131324C7generally has been limited.” A recent article in the Journal of the American Medical Association (JAMA) highlights a literature review completed by a  team of URMC researchers led by Dr. Earl Ray Dorsey. The objective of the review was “…to evaluate disease modeling and simulation, alternative study design, novel objective measures, virtual research visits, and enhanced participant engagement and to examine their potential effects as methods and tools on clinical trials.” The article entitled “Novel Methods and Technologies for 21st-Century Clinical Trials: A Review” appears in the May 2015 edition of JAMA Neurology. The team conducted a systematic search of relevant terms on PubMed, references of previous publications, and private files. The search encompassed articles published from January 1, 2000, through November 30, 2014, and produced 7976 articles, of which 22 were determined to be relevant and were included in this review.

The review uncovered that “Few of these new methods and technologies have been applied to neurology clinical trials. Clinical outcomes, including cognitive and stroke outcomes, increasingly are captured remotely. Other therapeutic areas have successfully implemented many of these tools and technologies, including web-enabled clinical trials.” The team concluded that “Increased use of new tools and approaches in future clinical trials can enhance the design, improve the assessment, and engage participants in the evaluation of novel therapies for neurologic disorders.” Click here to read the full article.

Director’s Update – July 2015

Director’s Update — July 2015

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

Below, Karl Kieburtz circles back to the May 7 CTSI Town Hall Meeting.KarlKieburtz

For the benefit of the people who weren’t able to attend, can you give a quick recap of what was discussed at the CTSI Town Hall Meeting in May?

At the CTSI Town Hall, we asked people “What we do well here?” “What would you like to see more of?” We also asked: “If we went away, what would you miss most about us?”

We hope that by asking that last question, it’ll make people consider the CTSI in a different way. When a good innovation happens, we accommodate to our new circumstances, and the novelty becomes the new normal. You’re recording our conversation on an iPhone. Of course, right? But when that first came out, that was really cool. And when I want to start a manuscript now, I just turn on my app, I dictate to myself, it comes out in text and I email it to myself and edit it. I expect that now. But when I first did that, it was really cool.

So that’s what makes a good innovation. It comes out, gets incorporated into our lives, and then you stop being blown away by the fact that it’s there.

How does this relate to the upcoming renewal?

For the people writing the renewal, part of the effort involves going back over the past 9 years and looking at what’s happened. But because we’re in the midst of it and we take advantage of it, we don’t really stop to think that it wasn’t so long ago that we didn’t have X, Y, or Z. Things that we have now that we’ve grown accustomed to — we want to explicitly call those out and to ask people what they’d miss.

Some of those things people might not realize come from the CTSI. There’s the Junior Faculty Academic Core Curriculum, there’s the Seminar Series, there’s SCORE, pilot funding and incubator funding, the i2b2 to REDCAP tool we developed here, the community advisory council that allows researchers to get input into the community, recruitment capabilities. So to put this question another way, what elements of your day would be different if you didn’t have some of these resources?

And to be clear, we’re not threatening to take anything away, but we just want to know what matters to folks in a way that we might not always see or might not always expect. We develop these programs and resources because we think they are relevant, but those assumptions have to be validated by the people using them. And for the renewal, it’s important that we capture a sense of what things matter to people.

So you tell us. It’s important for us to know what we are doing well and what we need to do better in the future. Please contact ResearchHelp@urmc.rochester.edu and let us know: What would miss most about the CTSI, if it wasn’t here?

[Readers may also provide feedback by visiting the CTSI Suggestion Box to respond to a very brief feedback survey.]


Previous Director’s Updates:
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…

CTSI and Public Health Sciences Announce New Certificate Program in Biomedical Data Science

The Clinical and Translational Science Institute and Department of Public Health Sciences are excited to announce that a new Certificate of Advanced Study in Biomedical Data Science (CAS-BDS) has received approval from the New York State Department of Education.

Enrollment is open and classes begin on Monday, June 29.

Tim Dye, Ph.D.

Tim Dye, Ph.D.

The program, centered around a two-semester analytic project, prepares researchers to conduct “big data” analytics for health services, clinical, and public health research. This program prepares researchers for careers in data analytics, data wrangling, and clinical and health services research using large complex datasets.

“We consulted with people from industry and in academia, and looked at the state-of-the-art in terms of what people were teaching,” said Tim Dye, Ph.D., director of biomedical informatics at the CTSI. “We created this Certificate specifically to fit with all that.”

The CAS-BDS is a stackable data analytic credential for researchers and analysts with biomedical, computer science, statistical, or health service backgrounds. The curriculum draws on a range of courses that cover the fundamentals of disease biology, health care systems, and big data management and analytics.

Coursework begins with an intensive summer session that will give researchers a solid background in data science, data management, human biology, and team science. About a half dozen courses are new, having been created specifically for CAS-BDS.

“It’s pretty intense — starting with a summer Boot Camp that begins next week,” said Dye, who worked with faculty in the Institute for Data Science and elsewhere to make sure the Certificate complements other university data science offerings. “But we thought all these topics were required to have a good foundation in data science applied to the biomedical area.”

Several possibilities exist for the two-semester mentored project, which can have a basis in basic science, clinical work, health services, population health, or other fields. Projects will include attention to specific aim formulation, background, analytic plan development, database creation, data analysis, and reporting.

For more information on the CAS-BDS, visit https://urmc.rochester.edu/biomedical-data-science.aspx or contact tim_dye@urmc.rochester.edu.

Developing Common Metrics for Clinical and Translational Awards

ann dozier

Dr. Ann Dozier, Lead Evaluator for the University of Rochester Clinical and Translational Science Institute (CTSI).

Dr. Ann Dozier, lead evaluator for the University of Rochester Clinical and Translational Science Institute, contributed to a recent publication in the Clinical and Translational Science Journal entitled “Developing Common Metrics for the Clinical and Translational Science Awards (CTSAs): Lessons Learned.” The paper describes an effort by the national CTSA Evaluation Key Function Committee to develop and test a methodology for identifying common metrics to assess the efficiency of clinical research processes and for pilot testing these processes for collecting and analyzing metrics.

Dr. Dozier offered this comment: “This project further reinforced the importance of engaging stakeholders (potential end users) in the process of common metric development and how different the CTSAs are in what and how their internal data are gathered and maintained.”

The project involved more than one-fourth of all CTSAs and resulted in useful information regarding the challenges in developing common metrics, the complexity and costs of acquiring data for the metrics, and limitations on the utility of the metrics in assessing clinical research performance. The results of this process led to the identification of lessons learned and recommendations for development and use of common metrics to evaluate the CTSA effort.

Click here to access a PDF of the article.

 

 

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.

Success Stories: Pilot Program furthers Thy1, diabetes research

The CTSI’s Pilot Program offers researchers the chance to compete for pilot grants up to $50,000. Sherry Spinelli, Ph.D., received one such award in 2014, and spoke with CTSI Stories about her research.

SherrySpinelli

Thanks for taking a minute to chat, Sherry. Tell us a little bit about yourself.

I’m a research associate professor in the Department of Pathology and Laboratory Medicine, working with Drs. Neil Blumberg in transfusion medicine and Richard Phipps in environmental medicine. My main research pursuit is the study of platelets and inflammation, and I have a keen interest in the role of platelets in pathological processes such as Type 2 Diabetes. And that research brought me to the CTSI. I wanted to develop a translational project looking at platelets and their role in type 2 diabetes and obesity, and the CTSI has provided the support and resources I needed to jumpstart this project.

What was the focus of the study?

I’m studying a protein called Thy1, which was originally identified as a surface marker of unknown function, but recently, Dr. Phipps and colleagues have shown that this protein plays an essential role in fat formation. So in layman’s terms, if Thy1 is lacking, you get fat, and if it’s present, you don’t get fat. An over simplification, but you get the idea.

Once that discovery was made, I wondered if this protein was found on platelets and further whether extracellular vesicles, small cellular fragments shed by platelets, contained Thy1 and could be taken up by other cells in the circulation to influence the recipient cell’s function. So if Thy1 is normally present on platelets and vesicles, what happens when it is not? We found that Thy1 levels are much lower in type 2 diabetic platelets and in the vesicles shed by these platelets.

So this was very exciting because we thought this might be a mechanism by which platelets could promote the chronic inflammation and obesity often associated with type 2 diabetes and cardiovascular problems.

Stepping back a little bit, what happens with Thy1 in a normal, healthy person?

In short, Thy1 expression is present in normal, healthy individuals, but we do not yet know what signals cells to lose Thy1. The funds from this CTSI pilot study have allowed us to begin to characterize the role of Thy1 in platelets and extracellular vesicles, and the consequences of the loss of Thy1 that lead to the disease state.

And from a clinical standpoint, the idea would be to alter the biology so that doesn’t happen?

Yes. Hopefully in the future, we’ll develop a therapeutic that would allow us to regulate or restore levels of Thy1, with the goal of reducing obesity. This is an important consideration as there are over 25 million diagnosed type 2 diabetics in the United States, and it’s an escalating problem.

We also feel Thy1 might be a good biomarker. We haven’t looked at this yet, but it might be the case that Thy1 expression is lost before you see other symptoms of diabetes. So perhaps it could be a flag we can use for early diagnosis.

What’s the next step?

So the pilot grant was wonderful in terms of allowing us to get that early data to go forward and get more funding. We’re also getting ready to publish a paper, which, of course, is key to getting a larger grant.

Winner of URMC’s “America’s Got Regulatory Science Talent” competition presents idea to FDA

In some patients, acute myeloid leukemia strikes hard and fast. And in one subset of these individuals, researchers now know why: a mutation in their DNA which results in a more aggressive path for the disease.

With this knowledge, providers can potentially screen for this mutation, allowing them to treat the patients more intensively. The discovery was another success in the world of genome sequencing, which is being studied more and more frequently as scientists and physicians learn more about how variations in a person’s DNA can affect how they respond to disease and medication.  This approach is often referred to as personalized or precision medicine.

From left to right: Scott Steele, Ph.D.; Corey Hoffman; Stephen Ostroff, M.D.; Joan Adamo, Ph.D.

From left to right: Scott Steele, Ph.D.; Corey Hoffman; Stephen Ostroff, M.D.; Joan Adamo, Ph.D.

To further advance personalized medicine, Corey Hoffman wants all of the genomic data from trials utilizing genome sequencing to be accessible in the same database. This will allow researchers and scientists to easily expand on previous work, identifying and using these genetic markers to speed drug development and aid in drug safety by targeting specific populations likely to respond to a given treatment.  Hoffman’s idea won URMC’s “America’s Got Regulatory Science Talent” competition in February, and earned him a trip to Maryland, where he presented his database idea at the FDA’s 2015 Office of Regulatory Science and Innovation Science Symposium.

“There are two potential outcomes that I could see,” said Hoffman, a predoctoral student at URMC, told CTSI Stories in March. “The first is that you could screen a patient’s genome so that when patients do respond well in a trial, maybe there’s a genetic element they share.

“Secondly, certain individuals don’t respond well to certain drugs because of how their body metabolizes the drugs… so you could screen people for mutations in their CYP gene to give indications for drug response, and who is and isn’t a good candidate for a certain drug.”

Hoffman, who was joined at the conference by University of Rochester’s Scott Steele, Ph.D., and Joan Adamo, Ph.D., presented his idea to the FDA’s Acting Commissioner, Stephen Ostroff, M.D. and other leaders and staff at the FDA.