Dr. Santana frequently speaks on topics related to research ethics, including ethical considerations in pediatric research and educating medical professionals in the responsible conduct of research. We spoke with him about this.
Dr. Santana is a pediatric oncologist and clinical investigator at St. Jude Children’s Research Hospital in Memphis, TN, where he is Vice President of Clinical Trials Administration and Associate Director of Clinical Research at the Comprehensive Cancer Center, and the Charles B. Pratt Chair in Solid Tumor Research. He currently serves on the National Cancer Institute Central Pediatric Institutional Review Board, is a member of the NCI Cancer Centers Review Committee, and a past member of the FDA Pediatric Advisory Committee.
Tanya Verstak: What motivated you to be involved in clinical research? What brought you from being a practicing physician to also a research investigator?
Dr. Santana: Pediatric cancer and other pediatric diseases, such as the hematologic diseases like sickle-cell disease and hemophilia, are rare diseases in general. When you look at the incidence of cancer in the United States, children represent a small minority. The general number is between 16,000-17,000 new pediatric cancer cases in the United States per year, which is only a small fraction of adult cancer cases.
The only way you can make progress when you have a small, unique population is through research, because there is no opportunity to study thousands and thousands of patients. You are very limited, so you have to use your resources the best way you can to answer scientific questions. To me, the best way to do that is through a clinical trial because it brings together people to focus on an important question, given the limitation on the number of patients, to see if we can advance science.
I became a clinical investigator because of that: the realization that the way to make progress in cancer is through scientific collaboration, but also through clinical trials with other colleagues. I think that the model has worked: if you look at what has happened with cancer in the last 50 years, through clinical trials we have learned how to treat kids who have cancer. It has really reinforced that notion that through collaboration we progress.
Personally, I became interested in clinical research because I was interested in drug development and finding drugs to treat kids. I have always had a personal and professional interest in looking at new drugs, combining new drugs, and performing studies that would make those drugs become approved by the FDA and utilized as Standard of Care.
Tanya Verstak: Why are you interested in research ethics, particularly in the pediatric population? You wrote about this*.
Dr. Santana: That’s another interest of mine. The issue with research ethics has to do with the following: historically there was this notion that children should not be subjected to research because that can be perceived as exploitation, as they could not make decisions for themselves. They couldn’t have options to understand what a clinical trial was, along with its nuances.
So, there was that notion maybe 50 or 60 years ago that we need to protect children, and one way of protecting them was by keeping them away from clinical trials. But the reality is that if you are going to make advances in childhood diseases that are going to benefit children, then there is a need to apply the scientific method, which is what a clinical trial is, to learn more about these diseases and to discover treatments.
There is a tension between protecting children so that they are not the subject of a clinical trial versus providing them access to something that is potentially a benefit. I think that the pendulum has shifted beyond protection to include access, benefit, and justice, so that we can have clinical options which are likely to benefit them.
There is still a tension that not all clinical trials turn out to be positive — there will be trials that fail, so you do need to have certain protections for those populations who are more vulnerable. And that’s why there are regulations for populations that are more vulnerable, including children, the elderly, and the mentally-ill. There is a more rigorous process in reviewing these clinical trials — a more careful risk-benefit analysis for those populations so that there are additional protections that make sure that all those checks and balances are in place when a trial is approved for children. Children are therefore protected, but can also benefit from clinical trials.
For instance, in a lot of drug development, particularly for newer drugs where there may be a toxicity profile of concern, we start off in older children. We learn, and then as we understand the pharmacokinetics, side effects, and potential benefits, we move on to younger patients. Those are ways that one can protect children, but at the same time give them access to new medicine.
It’s a constant tension that we have: that’s why we have review committees, oversight, informed consent, assent, research advocates, and all those other additional layers that hopefully balance those two points.
*Devine, S., Dagher, R. N., Weiss, K. D., & Santana, V. M. (2008). Good Clinical Practice and the Conduct of Clinical Studies in Pediatric Oncology. Pediatric Clinics of North America, 55(1), 187–xii. http://doi.org/10.1016/j.pcl.2007.10.008
Tanya Verstak: At St. Jude then, since adults aren’t treated here, do you test new drugs in clinical trials somewhere else before testing them in older children here?
Dr. Santana: We don’t treat adults here because we have a certain age criteria, so if we were to do a Phase 1 clinical trial we wouldn’t do it here, we would do it at University of Tennessee or Methodist. We would not do adult trials here because we don’t have that expertise here. So I think that we do need to be careful in those kind of Phase 1 trials to assure that they are truly limited to the population at St. Jude.
We do have clinical trials that are non-interventional, non-treatment for older kids and young adults through our cancer survivorship program. So, there are trials here for adults who have survived childhood cancers, but those trials tend to be non-interventional cancer studies. These are survivorship trials, where you’re doing the research in the population most likely to benefit from it.
References to studies:
Tanya Verstak: You’re interested in educating new investigators. What do you think are some of the problems that physicians, study coordinators, and other staff face with regard to clinical research training?
Dr. Santana: I don’t know if this is a true statement, but I like to say that next to the airline industry, the clinical research industry is the most heavily regulated industry in the US. So, there are a lot of regulations in conducting clinical research, and I think that one of the deficits is that investigators, who are very well intentioned to advancing the science, don’t completely understand and comprehend that you can do that– but there are regulations that you should follow in the process of advancing science when you do clinical trials.
I think the purpose of training is largely for investigators and staff to become knowledgeable that these regulations exist, and that these are the processes that you need to have in place to have a successful clinical trial from the regulatory prospective.
Most of the education and training has to do with regulatory: what the regulations are, what are the criteria, responsibilities of an investigator, sub-investigators, ancillary staff, and investigational pharmacist, which is very different from the responsibilities that you may have on the clinical side.
I think that’s always one of the problems. Clinicians understand the responsibilities of doing clinical work – you do the best for your patient; you try to make the right diagnosis; you offer them the right treatment; the right follow-up; or advise them about prevention. That is very different from the research side. On the research side, you go beyond that. You have to do the clinical care, but you also have responsibilities as an investigator to ensure that you meet the regulations and standards that are unique to research.
I think that’s where education and training come in. We don’t learn this in medical school – you learn about clinical care. It’s the same way in pharmacy school- you learn the clinical pharmacy stuff, but you don’t learn the research regulations. That’s where intense training and education come in. You need to have those things in place.
A lot of people say, why do I need to do this training? Well, that’s something that you haven’t been exposed to before, there are different rules when you do clinical research, and you need to know these rules. This is not only to protect the patients, but also to make sure that the trial is conducted in a way to make sure that it is successful.
If the trial has to be closed or shut down because it has violated some regulations, no one benefits. For the people that participated in the trial, the trial was not completed, so you never answered the scientific question and the people that could potentially benefit could no longer benefit because there is no trial. So, I think it’s a no-win situation if a regulatory issue shuts down a trial.
Tanya Verstak: Would you then encourage anyone who is interested in clinical research to become receive formal training and become certified?
Dr. Santana: Yes, we do have some requirements here for people if they are going to be part of the research staff. They need to meet certain standards, either through a professional organization or one of these public websites that offer additional training. We have a very active program here at St. Jude that offers seminars, book clubs, conferences. We want to make sure that people participate in this program because the regulations change, or they get interpreted differently. We want to make sure that people get updated.
I always like to say that science is far ahead of the regulations. Sometimes you’re dealing with some new science and you want to do a clinical trial with new science, but there might not be regulations that address that, or the regulations might constrain it. There is a constant need to re-train, re-educate and get back to the federal agencies like the FDA to explain what the challenges are from the clinical investigator side.
The other thing is that academic medicine is very different than the pharma industry. The ideal there is that you as a clinical investigator partner with them, so it is a win-win situation. It’s very different here at St. Jude, because we are an academic center and we want to provide the best clinical care for our patients. On the other hand, we also want to advance scientific knowledge and science, so those two things have to co-exist.
Tanya Verstak: What brought you to St. Jude in particular?
Dr. Santana: What brought me to St. Jude? I have always wanted to do clinical research, and that’s what this place is all about. And I wanted to be surrounded by people that thought about science every day, that I could partner with. I wanted to see patients and understand the problems we are having in terms of advancing the science, and work with partners who would like to change things. It is an ideal place to do that. It is our mission. I am very tied to St. Jude’s mission, and that is what brought me here. Where else can you do this?
And then there are the resources. We do have a lot of resources here to help our patients. We always try to do the right thing and not have to worry too much. Although we have to be good stewards with the money we spent on clinical trials, I think there are so many resources here that make it better for me and my staff to support our patients through clinical research.
Tanya Verstak: What sort of advice would you give to someone who is interested in getting involved in clinical research or becoming an investigator?
Dr. Santana: There are different career paths. Some people go into the pharma industry, others go into academic medicine, and I think they all complement each other. I always tell young people who come for advice that you have to identify your passion, and then you decide which road best meets your passion.
You want to make sure that when you get up every morning to go to work you are doing a task that you really want to do because it is part of your passion and what you want to do.
So, whether you do it in academia, industry, at the bench if you are a scientist, or at the clinic, it all depends on your passion. I became a physician because I like to help people. I love coming to clinic: no matter how busy I am, I love seeing my patients and doing what I have to do for them.
For example, that is my passion. I became a physician because I have a passion for my patients. But there are people who love to be in a lab, go in there for 12 hours running experiments or taking care of mice, and that’s their passion.
So I think you need to find your passion and find a way that you can realize it. There are different venues you can take.
Interview conducted on April 6, 2017 by Tanya Verstak, M.S.
Victor Santana, M.D., is a pediatric oncologist and clinical investigator who has been devoted to developing new experimental treatment approaches for children with high-risk solid tumors, and to acquiring knowledge and expertise in clinical trial design and the regulatory aspects of clinical research for more than 25 years. His scientific interest and research has been in identifying promising new therapies for children with cancer. He is a past member of the FDA Pediatric Advisory Committee, and presently serves on the NCI Central Pediatric Institutional Review Board. Dr. Santana is also a scientific advisor to the NANT program project grant, and a member of the NCI Cancer Centers Review Committee. As a clinical investigator, Dr. Santana has participated as Principal Investigator and Sub Investigator in numerous clinical trials in children with solid tumors and specifically in neuroblastoma. He speaks frequently on protecting human research participants, including ethical considerations in pediatric research and educating medical professionals in the responsible conduct of research.
Tatsiana “Tanya” Verstak moved from the Bay Area to Memphis, TN to work at the Epidemiology Department at St. Jude Children’s Research Hospital three years ago. She then fell in love with clinical trials after working at the University of Tennessee Health Science Center and completing a M.S. in Clinical Research Organization and Management through Drexel University. Tanya continues to reside in Memphis attending pharmacy school with hopes of pursuing a career as a Medical Science Liaison.firstname.lastname@example.org
Citation for this article: Verstak, Tatsiana. “Interview with Dr. Victor M. Santana – Ethical Considerations in Pediatric Research.” Clinical Research Currents June 16, 2017. http://clinicalresearchcurrents.com