From Bench to Bedside—and Beyond

In building bridges between research and patients, the Tufts Clinical and Translational Science Institute often provides a fresh take on health care

illustration of microscope

Because nearly a quarter of all kidney dialysis patients die each year, these terminally ill patients and their families face some tough decisions: Should they continue treatment? Draw up a health-care proxy? What about hospice care?

“Once we know who is likely to die, we should be putting our most rigorous efforts into end-of-life care for them,” says Lewis Cohen, a palliative care specialist who helped develop a diagnostic tool that predicts which dialysis patients are most likely to die within six months of beginning treatment.

That may sound grim, but Cohen, a professor of psychiatry at Tufts School of Medicine and a clinician-researcher based at the Tufts-affiliated Baystate Medical Center in Springfield, Mass., says it “opens up an opportunity” to help patients and their families negotiate a difficult time.

Cohen and biostatistics expert John L. Griffith, an associate professor at the medical school, developed a series of interventions to help doctors and nurses ease dialysis patients’ anxieties and fears and get them the information they need to make their end-of-life decisions. They encouraged collaborations between hospital staff in the dialysis unit and community hospice workers, who assisted patients and their families in working though end-of-life issues.

When Cohen needed to assess the effectiveness of such interventions, he turned to the Tufts Clinical and Translational Science Institute (CTSI), an NIH-funded enterprise to encourage experts from different fields—such as a psychiatrist and a kidney specialist—to work together to examine health-care issues from fresh perspectives.

One of 60 such centers across the country, the Tufts CTSI provides research teams such as Cohen’s with the education, research expertise and pilot grant awards they may need to turn their good ideas into new practices or policies. That’s both the mission and definition of translational science: quickly getting high-impact, often cost-effective approaches to health care out of the lab and to the patient—an approach commonly known as “bench-to-bedside”—as well as supporting interventions such as Cohen’s that improve medical practice.

Cohen and his colleagues received a CTSI Catalyst Pilot Grant in September 2012 to roll out small studies at several dialysis centers in western Massachusetts affiliated with Baystate Medical Center and Berkshire Medical Center.

Testing their protocol in the real world gave the scientists the chance to iron out unforeseen logistical problems. Now, in collaboration with kidney specialists from the University of Pittsburgh and Stanford Medical Center, Cohen and Griffith will apply in June for a $4.5 million, five-year grant from the National Institute of Diabetes and Digestive and Kidney Disorders to run large-scale trials of the interventions.

Data from the CTSI-sponsored study strengthens the group’s NIH application, Cohen says, improving their chances of obtaining federal funding. “Because of this catalyst grant, we are in an excellent position that I know we would not have been without Tufts CTSI,” he says. “It was absolutely essential.”

Team Science

With the goal of making headway on complex medical problems such as cancer, diabetes and heart disease, the National Institutes of Health in 2006 announced a plan to create a nationwide consortium of clinical and translational research centers. NIH funding for such centers, including the one at Tufts, encourages not only a wide range of cross-disciplinary research, but also community-engaged research. That is, it supports research done in concert with leaders in industry and government as well as with community programs and religious, ethnic and other interested groups.

Tufts received its grant to create a CTSI in 2008, but the university already had a well-established tradition of translational research, says Harry P. Selker, dean of Tufts CTSI and a professor of medicine.

The Sackler School of Graduate Biomedical Sciences has stressed interdisciplinary research since its founding in 1980. Under its first dean, Louis Lasagna, often called the founding father of clinical pharmacology, Sackler became the first graduate school of biomedical sciences to offer a degree in clinical research.

Out of this tradition came projects such as Shape Up Somerville, a collaboration of researchers at the Friedman School of Nutrition Science and Policy and city officials and residents in Somerville, Mass., that has become a national model in the campaign to combat childhood obesity. While Shape Up Somerville pre-dates Tufts CTSI, it’s the perfect example of the type of community-based, cross-disciplinary, collaborative work CTSI wants to foster.

“We don’t just focus on bench-to-bedside,” says Selker. “We go all the way from bench to bedside, bedside to practice, practice to public policy and public benefit. That’s the focus of Tufts CTSI: finding the best medicine or treatment or strategy for health.”

In addition to 10 Tufts schools and centers, the Tufts CTSI encompasses 10 affiliated hospitals, nine community organizations, three academic partners and three industry partners. That’s a total of 35 institutions, ranging from Maine Medical Center in Portland to the Boston Chinatown Neighborhood Association to the pharmaceutical company Pfizer. “That’s probably the most for any CTSI [in the country],” says Selker. “We are known by some as the extrovert CTSI. That’s in keeping very much with the Tufts personality.”

Laurel K. Leslie, director of CTSI’s Center for Aligning Researchers and Communities, helps scientists build relationships with community members, and vice versa. Collaborating with the community from the very beginning of a project can help focus the research or shape it in unexpected ways. “Pulling people together from different perspectives is really important these days, because NIH reviews [for research funding] are based on significance, innovation and impact, as well as methods,” says Leslie. “Tufts CTSI helps generate that kind of creative, cutting-edge research that’s going to get funded in this time of scarcity.”

Getting the Word Out

When a researcher had trouble recruiting volunteers for a study on parenting interventions in health centers, Leslie’s office helped him engage clinic staff to identify families who would be willing to participate. Likewise, when a community group expressed its concerns about asthma in urban day-care centers, Tufts CTSI matched individual centers with researchers in the appropriate fields.

“The critical importance of having the community’s voice involved is so that research is addressing real, felt needs,” says Leslie. “Community groups, patients and end-users of research, such as employers and health plans, they all have an important role making sure the research asks the right questions.”

A pediatrician at Tufts Medical Center and an associate professor at the medical school, Leslie cites her own experience as an example. In investigating aggressive behavior in children with autism, Leslie came at her study from a classic mental health perspective.

That approach assumed that these children—who often suffer significant speech delays—are venting their unspoken frustrations through aggression. But the parents she was working with offered another perspective: Could their kids be acting out because of the severe gastrointestinal issues commonly seen in autism? Leslie was aware of the stomach problems, “but it somehow wasn’t in my framing when I was thinking about how we would approach aggression,” she says. “To make a research project work, I needed to talk to the patients and families to find out what issues they needed addressed.”

For research to really make a mark, the dialogue between scientists and the community needs to continue after a study ends. “One of the problems we have is that researchers do the research, then it [gets published in the professional] journal, and you never see it getting implemented in the real world,” says Leslie.

In a recent collaboration with a multidisciplinary team of researchers, Leslie and her colleagues made their findings available to those who could put them into action. In 2008, a federal law requiring state child welfare agencies to oversee the use of psychotropic medications by children in foster care left many states scrambling to set up systems capable of keeping track of their wards. To find out which states already had oversight guidelines in place, Leslie and her team surveyed all of them, promising them access to the data in return for their participation. That promise resulted in 47 of the 50 states and the District of Columbia participating.

Some results were published in academic and professional journals, but Leslie and her colleagues prioritized creating a user-friendly document that was sent to all the study participants. The 24-page report is written for non-scientists: legislators, child welfare agency administrators, foster parents and even foster children themselves. In clear, jargon-free language, the report reveals that 26 of the responding states already had guidelines to monitor use of psychotropic drugs, while 13 states were in the process of implementing such programs.

The report also identifies the challenges states encountered, as well as their solutions. It includes questions that state child welfare administrators may use to devise their own systems, such as what state characteristics—rural vs. urban, for example—are important to consider.

“It’s a very practical document. States are looking for guidance so they don’t have to reinvent the wheel,” says Leslie, who adds her research team is now consulting on the federal level as well as continuing its work for the Massachusetts Office of Child Advocates. “It has been a really unique opportunity for researchers to partner with policymakers and make sure that data actually gets used and makes a difference.”

New Look at Autism

The CTSI-funded work of Roula Choueiri, a neurodevelopmental pediatrician at the Floating Hospital for Children at Tufts Medical Center, could make a difference for children with autism. An estimated 1 in 88 American children has a neurodevelopmental brain disorder that is on the autism spectrum—a 600 percent increase over the past two decades, according to the Centers for Disease Control.

Though researchers don’t fully understand the causes of autism, most agree that early intervention can allay the communication, behavioral and social challenges that are its hallmarks. The earlier in a child’s life these interventions begin, the better the outcome.

Most autism screenings involve parents filling out questionnaires about their child’s behavior. However, the disorder is best identified by triggering the “abnormal” behaviors—things that can go unnoticed by first-time parents, culturally diverse families where perception of social and communication milestones may vary and cases in which the symptoms are more subtle. But the lone interactive screening test takes a long time to administer, making it impractical to use widely.

Choueiri, an assistant professor at the School of Medicine, is developing an interactive autism screening tool for toddlers that is quick, accurate and fun. She and her colleague, Sheldon Wagner, an autism specialist who is director of Behavior, Development and Educational Services Inc., use a series of play-based activities to elicit the social and communication responses that are delayed in children with autism.

While they play with the kids, the researchers look for age-appropriate social and communication milestones, such as making eye contact and recognizing emotions in others and responding accordingly. Because the test is short, just five to 10 minutes, it can give clinicians a quick but illuminating glimpse into the minds of even very young children.

The assessment tool is now being tested in the Zero to Three Clinic at the Floating Hospital’s Center for Children with Special Needs. Choueiri notes that it was more than CTSI pilot funding that enabled her project. She participated in a CTSI summer research course taught by Griffith. The sessions helped Choueiri, a physician, think more like a clinical researcher, taking into account the study design and statistical analyses that can best answer the question at hand.

Whether they are investigating the cost-effectiveness of tai chi as a treatment for fibromyalgia or designing a study to prevent heart disease in a specific population, Tufts researchers are taking advantage of what Tufts CTSI can offer them. While the collaborative nature of this kind of work may be a shock to the system at some institutions, translational science is “in keeping with the strengths of Tufts University, our extroversion, our interest in policy and impact on health policy,” says Harry Selker. “That’s kind of our special niche.”

Jacqueline Mitchell can be reached at

A note regarding the above references to the Sackler School: In December 2019, Tufts University announced that it would remove the Sackler name from all programs and facilities—including the Sackler School of Graduate Biomedical Sciences. At that time, the school was renamed the Graduate School of Biomedical Sciences.

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