Keeping Trials on Track

Nov. 20, 2023

Lily Waddell, a clinical research assistant at Brigham and Women’s Hospital, is working on the first clinical trial directed by the Arthritis Foundation. The PIKASO trial (Preventing Injured Knees from Osteoarthritis: Severity Outcomes) will investigate whether the drug metformin, commonly used to treat diabetes, might help prevent osteoarthritis from developing after a knee injury, such as a torn ACL.

Q: Tell us about your background.

My dad was in the Army during my childhood, so my family moved around a fair bit. My dad is a surgical oncologist and my mom is an anesthesiologist. My dad was deployed overseas multiple times, and so watching my mom (a superwoman if there ever was one) raise two girls on her own while working full-time as a physician was certainly my earliest inspiration to pursue medicine.

We moved to Maine in 2009, and this is where I consider home to be. I went to Dartmouth College in Hanover, NH, where I played on the women’s rugby team. (I’m very proud of the fact that our team won two NCAA Division I National Championships during my time at Dartmouth.)

I was a biology major, but also took a lot of courses in the linguistics department. At Dartmouth, I did research for several years with a professor at the Geisel School of Medicine, Dr. Ruth Craig, on historical causes of death in the Hanover area. We collaborated with the Rauner Special Collections Library at Dartmouth to transcribe and digitalize an 18^th century manuscript containing meticulous death records for Hanover and surrounding towns. Detailed death records were uncommon at this time, which made this even more interesting. By analyzing death records like these, Dr. Craig and other researchers like her can analyze how causes of death change over time.

I graduated from college in June of 2022, and have been living and working in Boston since then.

Q: What drew you to science and research, and arthritis research in particular? And what do you hope to accomplish professionally?

I was first drawn to science and research through oncology. I did bench research in high school for two and a half years at Cancer Care of Maine. I worked with breast cancer cell lines, testing out a combination treatment of two DNA repair inhibitors. I thoroughly enjoyed my work in the lab but found that I wanted more direct involvement in patient care. I next interned with the Maine Cancer Genomics Initiative (MCGI) during college. MCGI is an incredible collaboration between the Jackson Laboratory and Maine oncology providers, which works to bring free precision oncology to rural Maine cancer patients. I worked with a database of tumor genomic testing results from over 1,000 patients to investigate whether access to tumor testing had a significant impact on treatment course.

I’m currently applying to medical school with the goal of eventually becoming a practicing physician at an academic medical center. Choosing a specialty is a long way off, but rheumatology and orthopedics are both big contenders.

Arthritis research was an entirely new field to me when I started working as a clinical research assistant at the Orthopedic and Arthritis Center for Outcomes Research (OrACORe) at Brigham and Women’s Hospital. I was drawn to it because I have a pretty significant family history of arthritis.

My paternal grandmother was diagnosed with rheumatoid arthritis in her early 30s and battled it for about 50 years until she passed away in 2021. When she was first diagnosed in 1975, she was treated with injectable gold. In the 1980s, she was one of the first RA patients to be treated with methotrexate. Finally, in the 21st century she was able to find some relief through treatment with second generation DMARDs like rituximab, but still suffered a lot of pain and physical deformity in her hands and feet as her condition worsened. It’s hard not to wonder if she was my parents’ age and diagnosed 30 years later, how many more years of life with reduced pain and high quality of life she could have had. She’s a powerful testament to how much treatment for RA has improved in the last 50 years, and I miss her a lot.

Could you describe what you do, especially with PIKASO?

I work as a clinical research assistant for a multidisciplinary research group focused on treatment and prevention of arthritis and other musculoskeletal conditions. As a research assistant, my job involves helping clinical investigators — namely Drs. Morgan Jones, Cale Jacobs, Jeff Katz and Elena Losina — plan, execute and analyze their clinical trials. I help with a lot of the day-to-day tasks that are necessary to keep clinical trials running smoothly. Right now, I split my time between five different clinical trials, with PIKASO being my biggest commitment. All of the trials I work on are in different stages. PIKASO is still in planning for another couple months, so I coordinate with the Institutional Review Board (IRB) to ensure that we get regulatory approval, write protocols, and organize them into a Manual of Operating Procedures so that all study staff across the nine sites are working from a standardized set of procedures. When trials are actively enrolling patients (such as the CoMeT study, another Arthritis Foundation-funded trial I work on for Dr. Jones), I communicate with patients to enroll them into the study and coordinate whatever procedures the specific study calls for – organizing imaging appointments, conducting physical exams, administering questionnaires, and collecting blood and urine biosamples, to name a few. Finally, after a trial is over, I help get data ready for analysis. I sometimes also help the investigators put together manuscripts to submit to academic journals or prepare presentations to deliver at conferences/meetings.

Do you expect PIKASO to affect patients directly or indirectly? If so, how?

Absolutely! I think PIKASO has extraordinary potential to affect patients both directly, for those people participating in the trial, and indirectly, by hopefully improving standard of care treatment following ACL reconstruction. Metformin shows a lot of promise at being able to delay the onset of post-traumatic osteoarthritis. Though I’ll hopefully be deep into my medical training and won’t be directly working on PIKASO anymore by the time the results of the trial are published in the late 2020s, I am so excited to see what findings come out of this research – both from the primary outcomes of pain levels and structural damage on MRI, but also the many fascinating secondary outcomes we are looking at in PIKASO, such as biomechanical outcomes and biomarker analysis.

Q: What else would you like to share about your involvement with arthritis research?

Before starting work on ACL injury and secondary PTOA prevention research, I had no idea just how much more susceptible to ACL tears women are than men. Anecdotally I knew it to be true, having played sports throughout high school and college and seeing more of my female peers sidelined by ACL injury than men. But I had no idea that, as a young woman athlete, I was a full 3 to 8 times more likely to be injured than my male peers. In the mission to conquer arthritis, I hope future researchers consider dedicated research to not only understanding why this gender disparity exists, but actively working to close it.