Columbia University Medical Center

The Importance of Study Design in Pediatrics Research

Rajasekhar Ramakrishnan

Rajasekhar Ramakrishnan

By Beth Hanson

When Rajasekhar Ramakrishnan, PhD, director of the biomathematics/biostatistics division in the Department of Pediatrics, completed his degree and began working at CUMC in 1973, biostatisticians’ workhorse for analyzing clinical trial data was the room-sized mainframe computer.

Four decades later, things have changed. Physician-researchers can now crunch data on their laptop computers; however, two fundamental aspects of clinical research remain unchanged: the importance of framing a cogent research question before embarking on a study and analyzing the resulting data properly. To provide new doctors an understanding of these skills, Dr. Ramakrishnan teaches a biomathematics rotation to residents. In addition, he and his colleague Steve Holleran, the division’s other member, collaborate with more senior physician-scientists on the design and analysis of complex studies requiring biostatistical expertise.

A few years ago, the Department of Pediatrics began offering residents the option of a biomathematics rotation, and with a renewed emphasis on research. The department now requires incoming residents to devise a research project and identify a mentor by the end of their first year. “If residents plan on a clinical research project, they are strongly encouraged to do this rotation,” Dr. Ramakrishnan says. During the two-week rotation, residents learn about clinical research design and how to analyze and manipulate data. At the completion of the course, “they are well-equipped for their project,” he adds.

The main focus of the rotation is helping residents determine whether their research project makes sense statistically. “Sometimes they come up with a question, and their mentor says, okay, here are some data. But answering the question definitively might require a much bigger database, or much larger study. Thus, we analyze this critically up front, giving residents the chance to say, ‘There’s no point in my spending three months on this, because this question cannot be answered with the data I have.’” At the end of the rotation, residents write their proposals and present them to their colleagues and mentors.

This past summer, 19 of 24 second-year residents participated in the elective rotation.

Dr. Ramakrishnan and Mr. Holleran are also available to advise established investigators in the Department of Pediatrics on how to do basic statistical analysis on their own; they also may be called in to work on more complicated studies. The pair frequently collaborates with Melissa Stockwell, MD, MPH, in the Division of Child and Adolescent Health, who is very interested in using new technologies to improve patient care, says Dr. Ramakrishnan. Recently, Dr. Ramakrishnan and Mr. Holleran worked with Dr. Stockwell to design a complex randomized crossover trial based in four community clinics during two periods in the fall and two in the spring, to discern any seasonal or month-to-month trends in vaccinations. “Melissa is very creative and is constantly looking to bring newer approaches to health-care delivery,” says Dr. Ramakrishnan.

Other collaborators in pediatrics include diabetes researcher Michael Rosenbaum, MD, whose project “ROAD” examined the effects of supervised exercise and education on type 2 diabetes and obesity risk factors among middle-school-age children. In addition, they have worked with neonatologist Sudha Kashyap, MD, to design clinical studies in newborns and with Peter Dayan, MD, who is currently participating in a multicenter emergency-medicine study to determine which aspects of seizures are predictive of abnormalities in a scan.

Dr. Ramakrishnan says: “It’s very easy to do a trial where you don’t design the study properly, and then you can end up with results that are not interpretable. You do need to design these studies with some care so that you can get the effect that you’re looking for without it being confounded by other factors.”

First published in Connections, the quarterly newsletter of Columbia Women’s and Children’s Health (Fall 2013)