HeartBeats Episode 4: Clinical Research Trials at Shipley

Welcome to heartbeats I'm Cathy Murtaugh-Schaffer and I'm your host for this episode this podcast is brought to you by Shipley cardiothoracic center and the educational series dedicated to providing our patients and the community with information and education about but our cardiothoracic surgery program. Today we have with us Dr. Brian Hummel one of our founding surgeons of the cardiac surgery program and principle investigator for the multiple research studies being performed at Shipley and Michelle Deckard who is one of our research nurses. Thank you so much Dr. Hummel and Michelle for being with us today.

One of the hot topics in medicine right now is clinical trials with the advent of the COVID vaccine, so Dr.Hummel I'd like to ask you what exactly does it mean to have a clinical trial and can you talk a little bit about the significant clinical trials that have helped refine heart surgery?

A clinical trial is utilizing or investigating a device or a drug that has already been evaluated through an earlier basic process, if you will. So, this isn't the primary research of science where we would come up with some new drug and then tested in a laboratory setting and then provide it to an initial segment of patients. The kind of research were offering our patients and through the Shipley Center are devices that have already been at least preliminarily assessed some already FDA approved, or, perhaps not for the cause or the disease that we are providing care for and those are the things that we're doing. We have some drug studies, the drug has been evaluated, but we're testing it in a clinical situation that we may prove an additional benefit to that drug other than what it was initially designed for. So, basically we want to think of the things that we're doing as secondary research, not the primary or basic research of academic institution.

Can you think of any particular studies in our history of cardiac surgery that have really refined or changed what has happened for cardiac surgery?

Well ultimately, all of the advances in medicine have come about through trial and error if you will. As we've gotten more sophisticated in medicine and management of patient diseases we recognize the newer devices, for the sake of discussion, can be utilized in a different setting. So we have had, for instance, a long period of time where surgical valves where we would sew the valves in after we cut the old valve out. We've now evolved to where we have valves that can be delivered through catheters utilizing very similar, if not the same technology in terms of the tissues but having a different frame that are mounted on that can be compressed into a catheter and then delivered to the site of need whether it's aortic position or mitral position or tricuspid position and so that evolutionary process and the advancement of technology and micronization of instruments and devices allowed us to progress in that instance. The other things that have gone on that we're dealing with the COVID vaccine, the monoclonal antibodies, that theory in that making of monoclonal antibodies has been around for a long time but now we've kind of refined it so we can take it to a different disease a different infectious problem and treat it in a much more directed fashion

It's all very exciting stuff for sure I know that Shipley’s been involved in multiple clinical trials and in fact it's part of shipley's mission to engage in research that will improve and refine the care of surgical heart patients. I'm curious though have you always been interested in doing research and was there something or someone in your residency training that influence that curiosity?

Well research, I think is kind of one of the clinical parameters that most physicians at least have an interest in. Now, they don't always have the opportunity to participate in it. When I was a general surgery resident I spent a year in the lab looking at heart perfusion under an adverse conditions and it was interesting and allowed me to at least get my feet wet if you will, in terms of research protocols and actually how primary research was done. As I alluded to earlier we were looking at microscopic levels of heart profusion so that that was my first real exposure I had done some clinical research studies as a Med student so that interest has always been there now with the foundation of the Shipley center and the strength that we have in Michelle and Jane or other researchers in our capabilities in terms of personnel we we can expand our research efforts great deal and its fun.

Michelle how long have you been a research nurse?

I've been here two years and prior to coming here I did some research in my previous job for about the last four years so that's been as long as I've been in research. Jane on the other hand has spent decades in research.

Are there any special qualifications that a research nurse needs to have?

There's a certification for it, you don't necessarily have to do that. There's different types of research nurses, there's some that will just do certain types of research or different phases of the research, some will just maybe just do the clinical side up others you end up doing some of the regulatory and the financial and things like that. Here at Shipley, Jane and I kind of are jack of all trades. We do all of those different aspects of it, so it just depends on your background. Jane and I are both Masters prepared so I've had some research training in our Masters degrees and things like that so you definitely want to at least have had some type of influence and experience in research of some sort.

I personally think that the transcatheter aortic valve replacement or TAVR trial is incredibly interesting that it started in its infancy here at Shipley and it's evolved into a multi level research trial for high risk, medium risk, and low risk surgical patients. Would you mind telling us about this trial a little bit and what made you want to participate in this trail in its infancy?

Well we were fortunate that the FDA approved the transcatheter valve in November of 2011. We had a team prepared to begin immediately and I mean immediately, we put one in the day after approval. Which supposedly, we were the second in the country. I believe that to be true but I don't have any actual proof across this country but that being said we were active in the program and believed in the therapy. The initial valve was for only inoperable patients or exceedingly high risk patients, they had to be cleared through our TAVR team, which we had put together and as I said we're waiting for FDA approval. Because of our success in that, we were offered a number of trials that came to follow. One being, looking at the intermediate risk patients, that was the first drill trial after the initial FDA approval and we participated in that and then we participated in the low risk run and with each step the valve proved to be durable and proved to the therapy to be of equal or better than open surgical procedures that were being done and so it really we've participated in helping define where these valves should be used and are involved in a number of publications that have arisen from these efforts so we're very proud of that.

Did you imagine then when you first started that trial that it would lead to this highly successful technique and device that ultimately changed the lives of those that would have otherwise died because they were deemed in operable in the traditional fashion?

With the first generation valves that we were putting in it was a little bit hard to imagine where we would be today and again I give credit to the companies that have been involved in this. Medtronic and Edwards were two of the early ones and they invested a great deal of resources into getting the 1st generation out and subsequently trying to refine their devices to make the second and third generation valves, which were now on in the 4th generation or coming very quickly. So, I give them all the credit but to have predicted where we are and those first valves which were somewhat big and cumbersome and difficult to deliver to now where we can literally we can put a valve in not infrequently in under 30 minutes from the time we start to the time patients ready to leave the room (host) that's impressive and half of our patients can now go home the day after the procedure so that is really a game changer in terms of having heart surgery that being said we are involved in trials now involving the mitral valve and also looking at tricuspid valves so having that experience and the technical expertise that we do we've done approaching I think 1500 the TAVR valves now here and not very many places can claim those sorts of numbers so we've been lucky and we're on the radar for companies looking for assistance now

(host) yeah those are impressive numbers for sure

Michelle, our listeners are probably totally unaware of the incredible amount of work required to do a clinical trial from meeting regulatory requirements to keeping track of data making sure patients don't get lost, don't get billed for procedures, coordinating with sponsors, this adds up to tremendous man hours. How do you keep up with all the regulatory requirements and care for patients?

Multiple techniques, our electronic health record which is EPIC has actually some things for research that we have very individual reports for each study that we have built, so that we can keep track of a lot of things that has the calendar for schedules and stuff like that in there that we can help with all of that. IN EPIC we create order sets for each study so that all of the tests and the visits and everything like that are done on time and correctly and that the right things done and through EPIC are also able to route things correctly as far as from the finance side and stuff like that. It still requires some oversight but it makes it a whole lot easier that way. We also utilized multiple spreadsheets for just keeping track of everything from scheduling and qualifications of patients whether or not they meet the the different requirements and stuff for the studies. From the financial side, you know we're dealing with the sponsors and invoicing them and getting stuff back and then getting it to the correct places and stuff like that too. We've got all of those different types things and then of course there's always the post it notes, and the to do lists, you know the the good old fashion stuff too

Well what I'm hearing is that it sounds like you both have an incredible eye for detail.

(Michelle) We are both very detail oriented.

(Dr.Hummel) I will attest to that the other thing that Michelle didn't mention is the IRB. Even though these devices have already been FDA approved, as I said we're utilizing them in clinical situations that may or may not be previously recognized as appropriate for their particular device or drug. Every time we involve a patient, that patient and this whole study must be placed before what we call the Institutional Review Board or IRB and that's composed of physicians on the staff and administrative members that review every aspect of every trial and ensure that patient safety is paramount and maintained throughout as well as anonymity and that there is no financial incentive to be doing the trial. That's important, we don't want patients to believe that we are somehow getting rich off of doing these trials or were being paid exorbitant fees to do something that that hasn't yet been proven. So, they maintain at arms length to be sure that everything is being done aboveboard and appropriately so I think that's important aspect of all the trials. (Michelle) Then from the finance side also is you know part of that is also that if a procedure or a visit or something like that is for the research itself, we make sure that that visit isn't billed to the patient or their insurance or anything like that and that it's taken care of from the research itself and not to the patient

I just want to throw into your comment Dr. Hummel that your IRB is governed by federal regulations and a couple of federal bodies that oversee research on human subjects as they put it. (Michelle) Everyone who's involved in the research has certification in human subjects and good clinical practice that are governed by the National Institutes of health and things like that that you know in order to be in research you have to have certification in those things. That you're protecting the research subject is first and foremost. (host) The ideas that you're protecting the patient at all times yeah

I understand you have a trial an Apollo trial coming up, can you tell us a little bit about that study? actually we are involved in the Apollo trial it got put on hold with COVID, the pandemic has certainly put the brakes on things that we were doing simply because we couldn't get our research staff in to see the patients etc. The Apollo trial is basically the another catheter based valve to replace the mitral valve. The current generation is the valve is delivered through a small incision in the chest that the valve goes directly through the heart muscle into the appropriate position and then it is released. During the time of this pandemic the companies have been able and this one is particularly with Medtronic, has been working on delivering it through a vascular access as supposed to direct chest wall penetration. So, we have looked for patients, screening the patients is exceedingly difficult in this trial. The anatomy has to be good, the patient criteria is pretty strict so up to this point been a little bit difficult in order to enroll patients. There was a meeting we were part of within the last couple weeks and the enrollment criteria has been altered a little bit so I'm thinking that we will begin seeing patients that we believe appropriate for that trial. (host) Great excellent and this is for mitral regurgitation? Correct, yes

A final question Dr. Hummel, with the speedy development and rapid FDA approval of the covid vaccine do you foresee changes in the way research is going to be approached in the future?

I don't, based on simply this pandemic response. The reason that we were able to rapidly devised vaccines is that the companies already had the H1N1 and bird flu, which is that virus on the shelf so to speak. So, it was a very similar virus and having that in stock allowed these companies to make genetic modifications very quickly and move on to a trial. Now, that being said I think there's more of these viruses that are going to be coming down the road to us as humans, and we're interacting more with the Animal Kingdom if you will, that these viruses are housed in, so, I would anticipate continued backlog of similar viruses that will allow a rapid development of a vaccine. The actual trial process was the standard; you have to look at the patients. The follow-up may not be quite as long as one would have normally had, in terms to ensure that there's no side effects of the vaccine long-term side effects but again with the prior history in the prior vaccine that allowed them to fast track this. So, we were fortunate in that regard. Could we have done better? Probably, I'm not making a political statement I'm just saying it as a human and putting our resources, you know, there's only X amount of dollars and so only X amount can be allocated to each and every need that we as a government or as a population require so decisions were made and I suspect as we look at things in retrospect over this particular pandemic they'll be some subtle changes that the go forward in terms of government response and healthcare response so hopefully will learn from this.

Is there anything that either one of you would like to add as we come to a close for this podcast?

I would like to say just briefly that we mentioned innovation research and education is the three mission statements of the Shipley Center and we take great pride in trying to focus our resources that we have on each one of those aspects and our research has been very robust for the relatively short period of time that we've been able to do it and that kudos again to go to Jane and Michelle for their efforts and their ability to take multiple ideas and distilling down into something that can be done in a reasonable fashion and in our clinical setting so I think that Shipley is going to continue to provide and promote health care and research here in this community for many years to come so we're proud of that.

And I have to say I do love working with the Shipley team for sure thank you for sure well thank you so much doctor Brian Hummel and Michelle Deckard for being with us today to talk about the clinical trials that are on going in Shipley until next time I'm Cathy Murtaugh-Schaefer and this has been heartbeats Shipley cardiothoracic centres podcast dedicated to bringing research innovation and education to our patients and the community have a good day