Colleen R. Kelly, MD, FACG on Starting a Research Career after Fellowship

By Jill Gaidos, MD, FACG

Dr. Kelly practices with the Center for Women’s Gastrointestinal Medicine at the Lifespan Women’s Medicine Collaborative in Providence, RI. Following her presentation at the ACG Annual Postgraduate Course this fall, we sit and talk in a tiny sandwich and Hawai’ian fare local hole-in-the-wall across the street from the Honolulu Convention Center. Sunday Night Football, playing in the background, is already underway, even though it’s only noon.

JG:       Your practice was initially focused on treating IBS and pelvic floor dysfunction. How did you get involved with FMT?

Jill Gaidos, MD, FACG
Jill Gaidos, MD, FACG

CK:      Two years into my clinical practice, I said, “OK, I know how to do colonoscopies now.”  I was looking for something more, and joined the voluntary clinical faculty at Brown.  Right before I gave birth to my third daughter, I saw a patient in her mid-20’s who had recurrent C. difficile colitis.  At that point, she only had two recurrences, so I put her on a vancomycin taper and went on maternity leave.  When I came back 10 weeks later, she still was struggling with recurrent C. diff. After a few more courses of vancomycin, I sent her to see the experts up in Boston who told her, “You need a fecal transplant, but nobody here in Boston is doing it.” She came back to my office with a couple of papers; there were only a few FMT case reports at the time and said, “I really want you to do this for me. My boyfriend will be my donor.  Can we please just do a fecal transplant.” I said, “Let me think about it” and I read the literature; it made sense. I called Larry Brandt who instructed me on how to do it over the phone.  I did the transplant for her, and it worked. After that, I started getting referrals for “fecal bacteriotherapy” from Boston.  That was kind of funny; people were afraid to do it.  I didn’t see it as anything particularly risky at the time.  I did fecal transplants for about a year, maybe ten of them, and thought, “Wow, this really works. This is really amazing. Why isn’t everyone doing it?” These were all really refractory C. diff patients and they were all getting better.

I conducted a survey with one of the fellows. We asked people waiting in line for coffee at DDW if they were doing FMT.  Would they do it? Why not? The consensus among those we polled was that there were no randomized, controlled trials and a sense that efficacy data were needed before they would feel comfortable doing it.  I was very naïve and thought, “Well then, I’m going to do a randomized, controlled trial.”

Colleen R. Kelly, MD, FACG
Colleen R. Kelly, MD, FACG

I knew I needed funding, so, I called the NIH and they were interested and encouraged me, but suggested that I should probably partner up with someone who was a little bit more experienced. So, I circled back to Larry Brandt and suggested, that we do the study together. We met in person at ACG in 2010 in San Antonio. I attended a lecture he gave and we chatted afterward.  I remember him looking at me and saying “you could make a career out of this.”  We designed the protocol and applied for the grant from NIH, and, after an initial revision, we got it. That was really exciting for me, but the biggest thing was it through the FDA so that we could actually do the study.

We started the trial in late 2012. Around that time, my reputation around FMT was growing really quickly. Rhode Island is a small place, so people were talking: “Go see her, she does stool transplants.” I started building a big fecal transplant referral practice. Patients were coming from all over the country and I was being called and emailed daily by people suffering from C diff who didn’t know where to turn. There were only a few of us doing FMT at the time, and I would try to direct them to somebody close to them. I kept a list of the doctors offering FMT, and it was pretty short.  Most of the new patients I was seeing had C. diff, but there were some who had other diagnoses, such as IBS and IBD and thought that FMT might help.  I wouldn’t do FMT for those indications, but many of the patients I met stayed with me.  I began to accrue a lot of IBD patients, for example.

I was able to carve out some research time in my contract. I initially had 40%, now it’s 30%, but it’s nice to have that day and a half a week set aside where I see research patients, mentor residents and fellows, and write papers. It was a big career flip. All of a sudden, I’m going around to meetings and I’m giving talks. It happened fast. I know women always say, “I was at the right place at the right time,” but I was at the right place at the right time with this. I recognized that fact and acted on it. Very few people were doing fecal transplants when I started. Nobody else was looking for NIH money to study FMT at that time, so it made it easier to get. I knew this was the right career move. It’s an area that’s interesting, I’m helping patients, I enjoy and believe in FMT, so I moved on it.

JG:       How far into your career were you when you made the switch to research?

CK:      I graduated from fellowship in 2006 and did my first FMT in October 2008. I decided to do the clinical trial in the fall of 2010 andmy first inquiry to the FDA was in September 2010. We submitted the first NIH grant in February 2011 which didn’t get funded. So, we resubmitted in it later that year, whatever that cycle was. It was at the same time, simultaneously with all that FDA work, and were awarded the NIH grant in June 2012. Then we enrolled the first patient in our clinical trial in November 2012.

JG:       You were one of the first to get an Investigational New Drug (IND) approval from the FDA for FMT. You shared a little of that experience in your July 2013 post on the website The Huffington Post (available at: http://www.huffingtonpost.com/colleen-r-kelly-md/), but what did you learn from that process?

CK:      I think the regulatory stuff is really interesting. How does the FDA operate? What are they thinking about? What are their concerns? How will they go on and regulate this stuff? The first time I called them it was because somebody at my hospital said, “You know if you want to do a clinical trial, you’re going to need an IND for that.” I said, “No I don’t. That’s crazy! It’s just stool, not a drug. Why would I need an IND?” I called, and the FDA said, “Wait, that sounds like a biologic.”  Watching their position on this evolve has been fascinating. They designated FMT as a drug, though it doesn’t fit neatly into that category. There’s been some talk as to whether there will be a new category for microbiota.

It took me a year to get that IND and I do sometimes wonder: if I had realized how much work it was going to be, would I have even started? It was one of those things that I had to just do one step at a time. I put in 100’s of hours and would frequently start to get really frustrated.  Then I’d think, “There’s no turning back now because I’ve already done all of this work, so I might as well keep going.” I was just really persistent, and so proud of myself at the end when I got the IND.  It was this really big accomplishment. Drug companies hire regulatory experts to deal with the INDs and I’m just this person with no experience and I did it.

JG:       And so now, you are helping people who are going through the IND process?

CK:      After they made the announcement that you needed an IND for FMT, people who wanted to do clinical trials or needed an IND to treat their patients started calling me and sending me emails and asking me to send them a copy of my IND or to guide them through the process. I wanted to be helpful, but I don’t have any time to be a regulatory consultant, so I decided to write a paper on how to obtain an IND. I put the paper together with Alex Khoruts who had also been working with the FDA and Sachin Kunde, who had done a pediatric FMT for IBD trial. (Clin Gastroenterol Hepatol 2014;12(2):283-8).

Now, when people email me or ask me questions about the IND process, I can say, “Oh, let me refer you to my paper and Appendix 3 has all those things you need.” The FDA couldn’t endorse it, but I suspect they were kind of happy because they were getting all these queries, every day having to answer all these same questions about INDs for FMT over and over.  So now it’s out there in the medical literature and people can reference it.  I felt as if I went through all that work getting an IND, at least I got a publication out of it!

JG:       So, for someone with an NIH funded randomized clinical trial, what is your research background?

CK:      None. That is what has been so weird about it. I had to learn as I went along, right from the beginning. I can’t totally blame my fellowship for the lack of research training. We did have research months that we were given, but it was never protected enough, if you ask me.  I had never done clinical research. I asked a lot of questions: How do you calculate a sample size?  How do you actually randomize? All these things, every step of the way, I had to figure them out.

FDA was helpful because they reviewed our trial design as part of the IND process, and they come back with comments such as, “you didn’t think of this or that, we need to see your case report forms, what about drop outs? Did you account for that?” So the FDA process definitely helped me make it better. With all of my questions, I was probably was really frustrating to people initially, like the office of research administration at my hospital. However, there were some really great people who saw that I was passionate about this and wanted to help me.  For example, we have a really fabulous biostatistician who sat down with me. I was initially thinking of it not being placebo-controlled and was just going to do vancomycin versus FMT and he said, “Why are you doing that? You want to do the best trial, right? It’s got to be placebo-controlled.”

I had never written a grant before.  Every section was arduous because I was taking everything from scratch. I think every fellow who is interested in research should write a small grant during fellowship because it is a good experience.  It is so much easier once you do it a couple of times.  There’s a style to it, an art to it. I enjoy mentoring fellows and helping them get better at this.

My involvement with ACG has been really important. Between Chris Surawicz and Larry Brandt, I owe a great deal to them. Chris is an amazing mentor. From the moment I met her, we clicked. She is one of those people who wants to make sure women get credit for what we’ve done.  She was asked to give an international talk and couldn’t go, so she said, “You need to ask Colleen Kelly.”  She was the head of the data and safety monitoring board for our clinical trial and was very helpful along the way.  We talk a lot and she gives great advice. She’s also a really kind person.  She cares about people.  Larry is like a father-figure and is very proud of the things that I do.  Working with Larry on this study was important because he has been doing FMT for a long time, and has the experience.  Anybody that has worked with Larry knows that he is an extremely talented writer and editor and I’ve learned a lot about how to put ideas together and become a better writer thanks to him.

One of the reasons that I became so passionate about FMT is because it was something that I was doing that was really effective. Early on, I had a patient who was going to come up to Rhode Island and bring her donor from South Carolina.  I offered, “Let me talk to your GI doc.”  But he said, “I don’t want to do it.”  She ended up having to fly up, with her donor, and stay in a hotel.  At the time, I thought, “This is just dumb. FMT works. How do I convince everybody that they need to be doing it?” So, there was a clear need to do this work.  We’ve really helped shift the treatment paradigm for patients with recurrent C. difficile who were treated over and over again with expensive antibiotics that usually didn’t work.  I really enjoy research.   I value the collaborations and feel I can make a difference for large numbers of patients.  I plan to stick with it.

JG:       How did you get involved with the Women’s Medicine Collaborative?

CK:      I had my twins during my 2nd year of fellowship, so they were about a year-and-a-half old when I graduated. My husband hadn’t completed pulmonology fellowship, so we were going to be in Providence for maybe just another year. I was really just looking for a way to spend that year. It wasn’t The Women’s Medicine Collaborative at the time, it was “Women’s GI Medicine” at another hospital, but the same people that I’m working with now. They had three people and were looking to add a fourth, so the director suggested that I come work for them during for that year and, since I had small children, she suggested that I work part-time. It was 3 days a week, and I signed a one year contract. Then, the following year, my husband found a job at the VA in Providence. “Maybe we should stay here? Let’s do that.” So I signed another one year contract for 3 days a week. Then, towards the end of that second year, three days were turning more into four days and my practice was getting busier; the kids were getting older. I became more interested in possibly doing research on fecal microbiota transplant (FMT), so I went to a full-time schedule.

Around that time, a competing hospital system actually wooed us away from hospital A to hospital B and started a whole new comprehensive multi-specialty center dedicated to caring for women. We have behavioral health, primary care, nutrition and wellness programs.  We have a number of resources and a more posh building. I am a full-time, Lifespan employee and staff gastroenterologist for the Women’s Medicine Collaborative (WMC). There have been advantages to it. I have a supportive chief, who is interested in helping me further my research goals with FMT and encouraged me to get that NIH grant. We have research support at WMC, including a research office with two full-time research coordinators, a research manager and a senior research assistant to help with any projects. They are not just mine; I share them with other doctors who are doing research here, but they have a little infrastructure that I like.

JG:       You were interviewed in February 2008 for the Gastroenterology and Endoscopy News as one of the younger generation of female gastroenterologists. At that time, you were working 3 days a week and you had a babysitter watching your twins while you were at work. That was over 7 years ago. So, now, as your children have gotten older and your career is getting even more demanding, how do you manage your duties as a mother balanced with your duties as a physician scientist?

CK:      My babysitter. I give her much of the credit. She is an amazing woman and she is the only reason I can do what I do. She is absolutely reliable, loves my children, she’s a kind person and she understands my limitations and she makes up for them. So, if there’s some form that I’m supposed to sign for school and I didn’t sign it, she signs it for me. She remembers, oh, it’s gym day, the kids need sneakers. She’s that person. She’s almost like a third parent in our house. She’s been my children’s care-giver since 2006…almost 10 years. We really truly love her. We also pay her as much as we can possibly afford to pay her. When it’s her birthday, I lay on stuff. When it’s Christmas, I lay on stuff. I can’t show her enough how much I appreciate her. She doesn’t give me a hard time when I travel. She is with my kids this weekend while my husband and I are in Hawaii at this meeting. She doesn’t make me feel bad about it. She’s a one-in-a-million. I think there are these people. Look outside. You don’t have to go to a nanny service. She just happened to be my next-door-neighbor. She was a stay at home mom of 5 kids, she loved being a mom, meanwhile her kids started to grow up and headed to college. Working for us would help her to put her kids through college. She was happy to do it. She said, “You are going to have to buy me car seats because they are going to be a part of my life. They are going to be at my house and they are going to go to the store with me. And if I have to drive Suzie to Worcester back to school, then they are going to go for a ride.” And, I was very cool with that. I was not at all, “You have to be at my house and you have to do it my way. You can’t feed them this or that.” That never would have worked. You have to accept this person. I don’t micromanage her. I think that’s one of the reasons that this relationship works so well. I think if you start to try to micromanage your nanny that creates conflict.

JG:       What do you do to stay healthy?

CK:      I stopped drinking caffeine a couple of years ago. I try to exercise almost every day, but it probably comes out to 5 days a week. I’m in a running club and that’s a lot of fun. So, we do regular workouts together, team workouts, twice a week. And then I go on a long run on Saturday morning with a friend; we chat and the time flies by.  I go to the gym on other days and do other things, like lift weights. I vacillate between eating healthy and eating potato chips. I don’t use anything processed. I make everything from scratch, not so much for health, but because I’m a foodie and like the taste of homemade food better.  We eat a lot of farmer’s market stuff, avoid chain restaurants and fast food. I am trying to not have my kids grow up on Pop-Tarts and cocoa like I did. I go to church, because I think a spiritual life is important. I pray about stuff, like when I’m stressed out. When I’m worried, I’ll say, “Please, help me with this.” Towards the end of the study, I didn’t think we were going to enroll the last couple of patients, we were really struggling. I went 6 months without enrolling a patient. I said, “God, you really got to help me finish this study; you got me this far. You made miracles happen before.” Within a week, I enrolled the final 3 patients. To me, that was proof of God in my life, an answered prayer, I really believe it.