Genebank: An Ambitious Project for Coronary Artery Disease Research at the Cleveland Clinic

It’s taking place at the Cleveland Clinic, and will enroll a total of 10,000 patients undergoing coronary procedures. The purpose of the study is to generate information about the genetic basis of coronary disease, then relate it to the cause of the disease. We will use the information to eventually formulate and design novel therapies and new treatments for CAD. Our two primary goals are: 1. Discover information about the origins of CAD, particularly in patients who may be predisposed or at increased risk for CAD. 2. Generate new, improved treatments for CAD. We’re collecting blood samples and vast amounts of clinical data from study patients. We’re collecting their general medical history, and we tap into our databases for results of different testing, such as EKGs or if a patient has had an echocardiogram, we are able to tap into those results. Basically, we utilize any of the relevant laboratory data that’s on record at the Clinic. We also hold the patient’s cath data for their procedure that day, so that we have their catheterization results available. The enrollment goal is 10,000 patients? Yes. We celebrated the 5,000 patient milestone a few months ago. How long do you think the project will take to complete? We’ve hit the 5,000 patient mark, and I’m guessing we have approximately 16 months left before reaching 10,000 patients. We originally thought we could finish the Genebank, from start to finish, within two years. However, along the way, we more fully realized the complexity of doing genetic research, and we want to take the time to make sure we are including everything necessary. When was Genebank first begun? We actually started planning in earnest around November of 2000. Genebank is the brainchild of Dr. Eric Topol, Chairman of the Department of Cardiovascular Medicine. Dr. Topol, Principal Investigator on the project, called on Dr. Stephen Ellis, Director of the Sones Cardiac Catheterization Laboratory, and Dr. Ramtin Agah, one of our talented interventional fellows, to serve as co-investigators. Dr. Topol then came to our clinical trials group and gave us the mission of making his idea a reality. We identified some personnel, started meeting, and discussed how we were going to approach the project and who within cardiology needed to be involved in order to get this project done. We first had 6-8 months of planning and then we enrolled our first patient in mid-July 2001. How many nurses and physicians are working on this project along with you? Actually, I would say this project has been the epitome of a team effort. It seems that the Genebank project has a majority of cardiology employees involved from the moment the patient hits our doors or from a patient’s outpatient appointment prior to a cardiac cath. Believe me, Genebank wouldn’t have been possible without such an expansive team approach. We wanted to design the project with a high enrollment goal and we wanted to do it as efficiently and as quickly as we could. What we tried to do is to add project enrollment into our normal routine; i.e., the normal flow of getting a patient into the clinic, seen by a physician, and into our cardiac cath lab. We involved appointment scheduling and desk receptionists, as well as staff physicians and fellows, who have been instrumental. On our clinical research team, we have three full-time research nurses on this project, as well as the rest of the team, who also enroll patients. Our cardiac cath lab nursing staff does all of the drawing; they draw the patient’s blood in the lab and make sure it gets placed for pickup. We have an interventional registry, and we’ve added to that staff. We have two full-time nurses on the project, and they interview the patient after enrollment and gather all of the clinical data that we need. We also have some research coordinators that help out with a lot of the incidental things that keep the project moving on a daily basis. Our application development people designed the database for the clinical data and to allow tracking of the samples as required. It’s a pretty sophisticated database, as are the applications. Laboratory staff does the processing of the samples and prepares serum samples and DNA for storage. Clearly, there are a lot of people involved, and in cardiology we have a lot of pride because this project is such a team effort. This is actually the largest research undertaking that cardiovascular medicine has ever undertaken. It’s such a large project and so many people are involved that in a nice way, it’s been a lot of work, but because of the scope of the project, we couldn’t really do it ourselves. We had to have each different area within cardiology take their piece of the puzzle to make sure Genebank happened. That aspect has been very rewarding and we’ve had a lot of positive feedback from everyone involved. Once the project is finished, how will researchers access the data? There is a scientific advisory board comprised of cardiologists from the various disciplines/sub-specialties within cardiology, geneticists, molecular biologists, and bio-statisticians, all from the Cleveland Clinic. The advisory board reviews all the proposals and requests that come in from researchers. They review proposals for scientific merit (in other words, it has to be a question that’s important to answer). There’s a lot of genetic research going on, and we want to make sure that the request is not only important, but also for a unique project. By this I mean that the project answers a new question or will make a new discovery so we’re not duplicating work already being done. Genetic discoveries are moving so quickly that when the advisory board receives a proposal, they need to check and make sure that the work hasn’t already been performed. There are so many questions to answer that we want to focus on the most important ones. How long will the project remain viable once the final patient has been entered? We expect to be tapping into this resource over the next 10 or 20 years. The Genebank is going to contain a wealth of information, and I think it will be a valuable resource for many years to come. Has any research already been initiated? We have a couple of proposals that we are getting ready to pull samples on, but no results thus far. It’s been a challenge to entertain requests at the same time that we’re enrolling, although that’s what we expected would happen. Almost as soon as we had a few patients enrolled, we started getting requests to pull some information out. How do you enter patients into the registry? Is there any exclusion criteria? All patients that are scheduled for a cardiac cath are eligible as long as they’re able to give informed consent. There are, of course, always issues where people don’t speak the language or for personal reasons, don’t care to be involved in research, but there really aren’t exclusions for medical reasons. How are you ensuring patient confidentiality? We’re approaching this research with much tighter restrictions in regard to confidentiality than with some other research studies. For example, we don’t write a note in the chart. With most research studies, you will see a notation in the clinical notes for the patient that this patient is involved in research and has a research protocol. Most of the time, the research is for a drug or device and anyone caring for that patient would need to know that information. However, genetic research and the whole idea of collecting DNA results are a sensitive topics. Usually patients would rather not have their participation made known. We do not make a note in the chart. We do the informed consent, attach it and write what we would normally write in the chart (how we spoke with the patient and had a conversation about the research, and the patient agrees, etc.). This notation is written on a separate piece of paper and kept with the consent. If you were to pick up the patient’s chart after enrollment, you wouldn’t know from the chart that they were involved in any kind of genetic research. Of course, we use code numbers to identify the patient’s sample (which is not the patient number at the Clinic or the patient’s name). What do you find are some of the challenges in maintaining the Genebank? I would say, keeping up with the potential that the project holds. Ever since we got up and running, we have been constantly running across new angles for collecting information. The sky really seems to be the limit as far as the information researchers can gain from this project. From the beginning, we want to make sure that we’re including every clinical and historical question that researchers are going to need, and all the laboratory results that people may find necessary to do their future research. Also as you’re going along, new things come to light constantly, and genetics is such new territory that we’re always finding things that we want to make sure are included. However, it’s really hard to predict what data points might be significant in the future and thus, we should collect. It’s been a challenge to ensure that Genebank is comprehensive and yet still workable. The project has also keenly tested my organizational skills. There are so many details that I had to develop an elaborate filing system to keep things straight. At a moment’s notice, I may have to pull out details of what we decided on a specific lab or perhaps just another detail on the project. Maybe I need to put my hands on notes from a meeting that happened six months ago. The magnitude of information has been incredible. Can you talk about your collaboration with Millennium Pharmaceuticals? Yes, we are working in partnership with Millennium Pharmaceuticals. They are a leading biopharmaceutical company, headquartered in Cambridge, Massachusetts. There’s great mutual benefit from our collaboration. We take advantage of the Clinic’s expertise in clinical practice and state-of-the-art phenotyping and combine this with Millenniums genetic, genomic and technologic expertise. We expect to enroll our first patient under the agreement in just a few days. Our partnership includes sharing data and blood samples on 2,800 Genebank patients. You’re also creating a registry for peripheral and cerebrovascular disease? Yes, we are working out the logistics right now. We expect to probably begin enrolling patients into the project within two months. Would these patients be a subset of the patients you’re using right now for the Genebank? Yes, they will be enrolled in the Genebank and identified using the unique numbering system we’ve devised. This system will identify them as either the peripheral or cerebrovascular patients, and there will be a few different data points that pertain more to their disease state, but they will also be part of the main registry. What’s your role in Genebank? I’m the project manager, and that means I’m responsible for coordinating all aspects of the project. I coordinate efforts by all of the personnel involved in doing their piece of the project. Everything from the regulatory and IRB issues, to finding space to put the freezers and making sure they are up, running, and connected to our alarm systems. I’ve dealt with a lot of things I haven’t dealt with before, in a lot of areas. What was your background before you started this project? I’ve spent 20 years in the cardiology department at the Clinic. I have a certification in clinical research and have been doing clinical research at the Clinic for 13 years. A few years ago, I was the study coordinator for Cleveland Clinic in the Gene Quest Study, which was also done in collaboration with Millennium. Gene Quest resulted in the discovery of genes linked to early heart attack. Of all the exciting projects I’ve been involved in over the years, Genebank certainly has been the most challenging, but also the most rewarding and the most promising.

NULL