1. Sekeres, Mikkael A. MD, MS

Article Content

What if you had the chance to create the perfect process for conducting clinical trials? What would you do?

MIKKAEL A. SEKERES, ... - Click to enlarge in new windowMIKKAEL A. SEKERES, MD, MS,

First step, maybe, focus on a defined disease, and an accepted set of clinical problems-questions that need answers in a patient population with few options, and results that have the potential for making a huge impact in people's lives.


Next, identify productive centers and investigators who have already devoted prime years of their lives-years during which many of my high school classmates at our recent 25th reunion reported to me that they had spent carousing, finding themselves, and creating mature families-already dedicated to the disease in question and to honing their clinical investigation skills, and get them to agree to collaborate for the next five to 10 years, for the good of our patients.


Arguably the toughest step-create streamlined processes to develop and open clinical trials quickly-ones that have not already been gerrymandered by a variety of stakeholders at a number of levels. To what extent is this a problem in the National Cancer Institute-funded cooperative groups? David Dilts and colleagues at Vanderbilt have devoted a lot of time to describing this in the Journal of Clinical Oncology, accompanied by thoughtful commentaries from David Steensma.


In their analyses from the first half of this past decade, they found that within the Cancer and Leukemia Group B (CALGB-now the Alliance), opening a trial took a median of 784 days, and that the preactivation sequence involved 370 distinct processes. To put it in terms even I can understand, that's over two years, and represents the number of times I have to answer, "Are we there yet" from my kids on any road trip cresting two hours.


The Eastern Cooperative Oncology Group (ECOG) fared no better-481 preactivation processes that consumed 54 percent of the time to conduct a Phase 3 study. In a dramatic physical display of what this entailed, the Vanderbilt team printed these steps on four-foot high sheets of paper, in small font, and posted them on a wall at an annual ECOG meeting. This "poster" stretched for 20 feet, prompting David Steensma to liken it to installation art created by Christo and Jean-Claude. Similarly, the NCI's Cancer Therapy Evaluation Program required a median of almost 300 processes, and no clinical trial was approved on the first submission. None. Nadda.


In my Utopian ideal for clinical research, centers would share clinical data and merge them into marvelous databases, allowing us to conduct exciting analyses for identifying disease risk factors, associations, and for developing accurate, validated prognostic algorithms. They would also share tissue samples linked to clinical databases, enabling clinically relevant, and accurate, translational science, the results from which would enhance our prognostic algorithms and inform our treatment decisions.


Oh, and while we're at it, this would all be gloriously funded, with monies going to support the people who make clinical research happen-data coordinators, program managers, research nurses, lab technicians, database managers, and fellows-fellows, because my wife has reminded me that at some point in my life I do need to consider actually retiring, and we need to find innovative ways to motivate the person taking over for me, to hopefully become committed to studying the same diseases as me, to advance the care of our patients where I'll leave off.


Well, we have the chance to do all of this.


The Aplastic Anemia & Myelodys-plastic Syndromes (MDS) International Foundation, a patient education, research, and advocacy group, has received a five-year grant from the Edward P. Evans Foundation to create the Myelodysplastic Syndromes Clinical Research Consortium (MDS CRC). Within this Consortium, Cleveland Clinic, MD Anderson Cancer Center, Dana-Farber Cancer Institute, Cornell/New York Hospital, H. Lee Moffitt Cancer Center, and Johns Hopkins-all centers with track records for conducting clinical research in MDS, with established MDS clinical databases, and with success in translational MDS research-will now have the infrastructure to collaborate in conducting MDS-specific research.


First of Its Kind

Hasn't this been done before? Well actually, no. This is the first time such a Consortium dedicated to a rare disease like MDS has ever been established in the United States. It will allow us to link clinical data about past MDS patients we've treated (which should total more than 4,000 people) to conduct epidemiologic studies, and conduct clinical trials for which the major costs of doing business-data and nursing time-are covered by the grant.


This should enable us to perform studies that focus on, for example, quality of life, often the first aspect of clinical trials cut due to high personnel costs, or molecularly focused drugs, in which rare subtypes of a rare disease can be targeted, because each of these centers has the infrastructure to identify unusual patients.


"One of the greatest challenges in research of rare diseases like MDS is having enough patients to conduct meaningful clinical trials. No single center can do it alone. This uniquely collaborative effort overcomes that barrier," said John Huber, Executive Director of the Aplastic Anemia & MDS International Foundation.


And what of those processes that make it so challenging to open clinical trials through the cooperative group mechanism? We will standardize our approach to writing trials and developing informed consent documents to accelerate the process, and because so much of the costs of conducting clinical trials are supported by the grant, we can bring the budget of doing research down, which should make contract negotiations more efficient.


Because let's face it-most centers participate in NCI-supported cooperative group research out of a sense of duty, but actually lose money in doing so. The MDS CRC will be cost-neutral, making center administrators happy, and removing the finance obstacle from important research.


Is this "pie in the sky" thinking, or can we actually accomplish these goals? We'll let you know in five years, but I can tell you this: we would be fools not to try. If current processes cover 20 feet of wall space, representing two years of start-up time, it's time to strip that wallpaper and repaint with a fresh color. We owe that much to our patients.


iPad Exclusive!!

PODCAST: Speaking on the iPad edition of this article, Dr. Sekeres, the MDS Clinical Research Consortium's Co-Chair, elaborates on the initiative's research agenda, the six institutions involved, and the research roadblocks it will overcome. The five-year, $16 million grant will fund the consortium's research efforts-including personnel, a sample tissue repository, and clinical databases-as well as the Edward P. Evans Fellowship (one individual is selected annually at each institution). "We like to think of this as funding the next generation of MDS doctors and researchers," he says.


The consortium's centralized clinical operations will be housed at Taussig Cancer Institute, and administered by the Aplastic Anemia & MDS International Foundation. Guillermo Garcia-Manero, MD, Chief of the Section of Myelodysplastic Syndromes and Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, is the Consortium's other Co-Director.


To receive our iPad issues, download the free Oncology Times app from the App Store today!! Visit follow the link on

Image... - Click to enlarge in new windowImage

More 'Second Thoughts'!!

Check out all the previous articles in Mikkael Sekeres' award-winning column in this collection on the OT website: