Getting the ADAM study approved for planning in 1990 and funded two years later are among Frank Lederle’s proudest moments. Lederle, professor of Medicine, University of Minnesota School of Medicine, director, Minneapolis VA Center for Epidemiological and Clinical Research, who is also principal investigator of the OVER trial, spoke to Vascular News about his career, his interest in abdominal aortic aneurysm research and his passion for travelling, cross country ski skating and inline skating races.
When did you decide you wanted a career in medicine?
I dodged career questions in college by saying I was going to become an oceanographer. Then in my junior year I did a semester abroad in Australia, whose very practical inhabitants pointed out that there were only about eleven people in the world making a living that way.
Contemplating this new reality and my biology major, and the usual attraction of combining science and humanity, I decided that the 90% of my classmates who were pre-med could not all be wrong. By then it was too late to take the tests so I had to take a year off, during which I picked oysters in Willapa Bay and did construction work in Albuquerque. In 2004 I gave Grand Rounds in a hall I had helped build in 1975.
Why the vascular field?
I did an internal medicine residency at the University of Minnesota and joined the faculty at the Minneapolis VA Medical Center, where our general internal medicine group was interested in research methodology and preventive medicine. The American Cancer Society’s journal CA would arrive unbidden in our mailboxes, and when the January 1986 issue listed the top 15 causes of death in the US, I was surprised to find aortic aneurysm among them. All the other “top 15” had societies and campaigns dedicated to their eradication, whereas this one seemed to be just sitting there waiting for someone to take an interest. I found Jack Collin’s November 1985 editorial in the British Journal of Surgery on “Screening for Abdominal Aortic Aneurysms”, inspired by Twomey’s abstract from the year before, and it inspired me to do a screening study in our clinic. This was a start but did not really set my course, as I pursued a lot of different topics back then. A few years later I was giving a talk to the medical residents on abdominal aortic aneurysm, as I did on most topics I had investigated, and mentioned that repair of small abdominal aortic aneurysms was increasingly recommended. One of them asked how we knew that was worthwhile, and in my stumbling answer, the ADAM study was born. Proposing and initiating a VA Cooperative Study is a massive endeavour that soon takes over your research agenda, so from then on you could say I was in the vascular field.
Who have your greatest influences been?
My career development was different from the classic surgical model of being guided by giants. A few senior clinicians in my department helped liberate my inner sceptic by their example, and our young general medicine group read each other’s drafts and fuelled each other’s enthusiasm, but my main influences were the papers I read. There was an explosion of clinical research methodology in the medical literature in the 1980s, before which terms like “sample size”, “confidence intervals”, and “meta-analysis” were rarely seen. I came of age wanting to be a part of that, and to help bring this kind of scientific approach to the topics I was addressing, such as abdominal aortic aneurysms.
What have your proudest moments been?
Assuming you mean in the world of work, getting the ADAM study approved for planning in 1990 and funded in 1992 were certainly two of them, as I was an assistant professor in my 30s and ADAM was my first grant. Presenting the results on behalf of the study group a decade later to 6,000 people at the American Heart Association meeting in New Orleans and seeing them published in the New England Journal of Medicine were two more, as was presenting the two-year OVER results at a JAMA press conference. Another special moment was receiving our medical school’s faculty mentor award last year, because your mentees do the nominating.
What area of the vascular system fascinates you most and why?
My interest has been in abdominal aortic aneurysm. Here you have a common cause of death that lies in wait, easily detectable for many years, without metastases to worry about, but with a treatment that is itself risky and must be applied selectively. During the Wall Street Journal’s 2004 Pulitzer Prize-winning series on aortic aneurysm, one of the reporters asked my opinion of another physician’s comment that deciding whether to repair an abdominal aortic aneurysm was like deciding whether to repair a defective hose in an aeroplane engine before you took off. I thought the analogy should take account of a few differences: aneurysm repair itself offered a risk of “crashing”, and its result was not “as good as new”. I suggested a revised analogy of whether to repair the hose with your jacket sleeve after turning the engine off in mid-flight. The reporter decided to steer clear of aeroplane analogies, but you cannot help being fascinated by a clinical problem like this!
What has the OVER trial added to the other EVAR vs. open repair randomised trials?
There are several ways in which OVER adds to the other studies: first, OVER is only the second trial (after EVAR 1) designed and powered to assess all-cause mortality; second, OVER describes more recently randomised patients than EVAR 1 or DREAM (2002–2008 vs. 1999–2003) in this area of rapidly changing technology; third, OVER is the only North American trial, and abdominal aortic aneurysm repair mortalities have been lower in the US than in the UK or Europe, raising the potential for differences in trial results; and fourth, OVER recorded intended endovascular system at randomisation, enabling subgroup comparisons between EVAR systems.
What has your analysis shown in terms of costs associated with EVAR and open repair?
We recently published the cost-effectiveness of OVER to two years in the Journal of Vascular Surgery, and the results were surprising. The high cost of endovascular grafts led most previous studies to conclude that endovascular repair was not cost-effective. In our study, although graft costs were far higher in the endovascular group, mean length of stay was only half as long, resulting in a significantly lower mean cost of the aneurysm repair hospitalisation in the endovascular group. Afterwards, from hospital discharge to two years, costs were nearly identical in the two groups, but the overall statistical significance was lost due to dilution.
How do you balance your research and clinical activities?
I continue to see my own primary care patients in clinic, supervise resident clinics, and attend on the general medicine wards, but most of my time is protected for research due to grant funding.
Tell us about one of your most memorable clinical cases…
Due to my limited clinical responsibilities, most recent memorable cases are ones I either hear about in our morbidity and mortality conferences or have sent to me by lawyers seeking an opinion. These sources are of course biased in this direction, but I am continually struck by how often problems can be traced back to a medical intervention that probably should not have been done in the first place. An example pertinent to this article was a 4cm abdominal aortic aneurysm discovered during a metastatic cancer work-up, for which the patient was told he needed an endovascular repair. He had severe complications resulting in loss of both legs, and still had to deal with his cancer. It seems to me that, especially in the USA, financial incentives, industry influence, and patient expectations (partly fuelled by marketing) all favour overtreatment, and these cases serve as a reminder that the price for this is paid not only in money.
What is the most interesting paper you have come across recently?
I am always most interested in the results of large randomised trials, as I consider them the only reliable path forward for clinical practice, but I assume you are looking for something quirkier. My other personal favourites are articles that reveal and refute misconceptions, especially if the misconceptions serve special interests, and most especially if this service is “enforced” through guidelines. Along these lines, I would propose a recent paper by Hayward and Krumholz titled “Three reasons to abandon low-density lipoprotein (LDL) targets: an open letter to the Adult Treatment Panel IV of the National Institutes of Health” available free at http://circoutcomes.ahajournals.org/content/5/1/2.full.pdf. These distinguished authors argue convincingly, as they have before, that the common practice of treating to target LDL levels (as opposed to fixed dose treatment of selected populations), though enshrined in guidelines, is unsupported by evidence and is often employed to promote the use of expensive drugs of no proven value.
Outside of medicine, what other interests do you have?
My wife and I took a year-long trip around the world for our honeymoon some 30 years ago, and travel has continued to be a big part of life. Besides vascular meetings, recent trips have included the Camino Santiago in Spain, Meteora in Greece, the Galapagos, Istanbul, and visiting our daughter and son wherever they might be. I also compete in cross country ski skating and inline skating races, and try to get an hour of training in most days. Then there is reading, mostly audiobooks during the daily commute. I am currently working on Robert Caro’s latest volume on Lyndon Johnson.
Education and training
1970–1974 Pomona College, Claremont, USA. Degree: BA
1975–1979 University of New Mexico School of Medicine, Albuquerque, USA. Degree: MD
1979–1982 Internal Medicine residency, University of Minnesota Hospitals, Minneapolis, USA Board certification
1980 Diplomate, National Board of Medical Examiners
1982 Diplomate, American Board of Internal Medicine
1982–1985 Instructor, University of Minnesota School of Medicine
1985–1993 Assistant professor of Medicine, University of Minnesota School of Medicine
1993–2000 Associate professor of Medicine, University of Minnesota School of Medicine
2000–present Professor of Medicine, University of Minnesota School of Medicine
Academic, administrative and educational activities (selected)
1984–1987 Director, General Medicine Consult Service, Minneapolis VAMC
1998 Consultant, VA Technology Assessment Program Report No. 9 (1998). Endovascularly placed grafts for infrarenal abdominal aortic aneurysms: a systematic review of published studies of effectiveness
2004–present Director, Minneapolis VA Center for Epidemiological and Clinical Research (CECR)
2005–2008 Director, UMN AHC Office of Clinical Research Distinguished Visiting Professor Program
2010–present Member, Editorial Board, Journal of Vascular Surgery
2011–present Consultant, US Preventive Services Task Force re-evaluation of screening for AAA
2012 Member, Minneapolis VA Department of Medicine Special Committee on Research
2010 Co-director, International Meeting on Aortic Diseases, Liège, Belgium
Awards and honours (selected)
2004 Minneapolis VA Medicine Service Award for Excellence in Clinical Research
2006 Minneapolis VA Center for Chronic Disease Outcomes Research Award for Leadership
2009 Honored Guest Lecture, 33rd Annual Meeting of the Midwestern Vascular Surgical Society
2011 UMN Medical School Carole J Bland Outstanding Faculty Mentor Award
2011 Minneapolis VA Dept of Medicine Education Excellence Award