In this first of a two-part MossRehab Conversation, John Whyte, MD, PhD,discusses his body of research, including seminal work on disorders of consciousness and more recent exploration into how to define and measure progress in rehabilitation more effectively. Dr. Whyte is retiring as director of the Moss Rehabilitation Research Institute later this year. ;
In this second part of a MossRehab Conversation with John Whyte, MD, PhD, Dr. Whyte talks about his work mentoring future researchers and his vision for translating theoretical research into treatment. Dr. Whyte is retiring as director of the Moss Rehabilitation Research Institute later this year.
Welcome to a MossRehab Conversation, part of a continuing series of discussions with pioneers in physical medicine and rehabilitation from one of America's top U.S. News-ranked rehab facilities. In this first of a two-episode series John Whyte, MD, PhD, who is retiring this year as director of the Moss Rehabilitation Research Institute, talks with MossRehab digital manager Larry Blumenthal about Dr. Whyte's research including seminal work on disorders of consciousness and more recent research into how to define and measure progress and rehabilitation more effectively.
Dr. Whyte, you have a long history of impactful research in neurorehab, but I want to jump in with a look at some of your current work. Right now you are deeply immersed in a project aimed at developing a system for defining rehabilitation treatments. Can you explain why such a system is needed?
Dr. Whyte: Well, if you think about how rehabilitation treatments other than drugs are currently described or defined, it's usually either by saying someone got a certain number of hours of a discipline - that person was in physical therapy for a six week course or something like that - or it's with reference to the problem that was being addressed - they had gait training or memory remediation. But none of those ways that we currently describe rehabilitation treatments tell you what the therapist did. And presumably there are effective and ineffective things that physical therapists and occupational therapist do. So just saying you had x hours of that therapy isn't very useful. Similarly, there are probably many different ways to try to help someone with a memory problem or gait problem and they probably aren't all equally effective or ineffective. So we refer to this as the black box problem that we know a lot about how to describe the severity of the problems that our patients come to us with. And we know a lot about how to describe how well they function when they leave us. And we know practically nothing about how to describe what the heck we did that is supposed to help them get from the beginning to the end. So it limits research and it means that when you want to replicate a particular treatment technique you don't know what's important to replicate - what really is the essence of that treatment. So it has enormous consequences for our ability to develop evidence about the most effective ways to treat our patients and to train clinicians to deliver treatments in the most effective way.
So how do you go about solving this problem?
Dr. Whyte: I'm part of a group of some people who've been involved in this for really more than 10 years and other people who entered the project around three years ago. But this group of people believes that we have to solve this problem with reference to what we call treatment theory which means that at some level a clinician or a researcher developing a new treatment has to say, "Here's the experience that the patient has to have for this to be therapeutic. Here's what must happen in the course of treatment. And here's the specific thing that I commit will change in response to that thing." So it's not even good enough to say this is a treatment for gait. Is it a treatment for gait speed, for gait stability and falls, for gait fatigue and effortfulness? You know there are a lot of things you might want to change about gait and you wouldn't go about them all the same way and measure the outcomes in the same way.
So treatment theory is a statement that this set of ingredients changes that functional thing that I want to change, and I will say how it does that the best I can. That's where often the treatment theory is much more sophisticated than "practice makes perfect" or something like that. But at least it's a commitment to, "these ingredients will produce that result. That's what I predict." And by grounding things that way then we can start saying, "Did those ingredients get delivered to the patient? Did these two treatments deliver similar ingredients or different ingredients or are they really just different names for pretty much the same patient experience?" and so on.
It all sounds like a simple process a simple concept on the surface. Once you get into practice, I'm sure that it's much more complex than that. I'm wondering what are some of the challenges that you're facing as you move through this work.
Dr. Whyte: In this most recent project that we're working on which is funded by PCORI - the Patient Centered Outcomes Research Institute - our goal was to produce an actual how to manual. If you adopt this frame of reference, if you if you agree with this analysis of the problem and what the solutions should be, here's how you would describe a treatment correctly quote unquote. And so it's a how to manual. It explains the concepts and then it leads people through the decisions that have to be made in order to lay out a treatment that adheres to this framework. We were somewhat naïve when we applied for the project in thinking that we could write this manual in such a way that you could just pick it up read it and do it. I think our experience from educating a lot of different rehab professionals at different professional conferences, as well as working with our own advisory board of thought leaders and rehab researchers and clinicians and educators, the general message we get is these concepts are incredibly valuable. This is the way to try to attack the problem. But it's quite a challenging thing to wrap your head around. And it's not a manual you pick up and do. It's going to require incorporation into curriculum and probably sort of training resources and train the trainer things and so on. So now we're in this phase of trying to plan future projects, which have to deal with a cart and horse problem of we need to know that there's a certain amount of demand out there for these concepts in order to develop all these materials but people can't be wild about the concepts unless and until they have the support to implement them in reality. So we're working through what the best next step is to handle that tension.
Let's move on to another research study that you're involved with and this is about developing more effective measurements than the current FIM scores for measuring functional improvement over longer periods of time. Can you describe that work?
Dr. Whyte: Sounds like all i do is think about how to measure things, but I actually use those measures to answer questions. I do a fair amount of treatment research with patients with very severe traumatic brain injury who start out essentially unconscious. But we've been interested to see that even patients who start out that impaired, if you want to look at how they turn out let's say a year later, a lot of them turn out very well. Not perfect but very well. So what we find is that the FIM, which is a good measurement tool that's used in a lot of studies of sort of global functional improvement, a lot of these very severely injured patients score at the floor of the FIM, meaning they get the lowest possible FIM score when they come in to rehabilitation. They all look the same, but they're not all equally impaired. None of them can yet dress themselves and the like, but they aren't all the same by any means clinically in their severity. Then - at the one-year follow up - a large number of our patients, those patients even, score the highest possible score. Again they're not all working. They're not all emotionally well-adjusted. They have varying degrees of residual problems. So if you want to do a clinical trial or any sort of treatment study where you enroll people early on and then randomise them to two different things or whatever - but you really want to know long term impact of that treatment which is a better question then how do they do you know a week later - you're limited by the fact that you don't have a measurement yardstick that can follow the person continuously from that most severe beginning point to that pretty darn good ending point and spread everybody out in a meaningful way.
So we are doing a project. This one is through our relationship with the Traumatic Brain Injury Model System Network funded by NIDDLR to take measurement items from other kinds of scales that are particularly tailored to very low level impaired patients or particularly tailored to relatively fine gradations in the upper range of functioning and to use a statistical method called Item Response Theory. If all goes well - and that's a big if - the method lays these items out on a quantitative yardstick. So you actually know what the easiest item is, what the hardest item is, how quote unquote far apart they are on this dimension of overall functioning, if you will. And what we're hoping in the end is that we will then have an instrument where you can actually measure scores and score change all the way along that yardstick and from the most severe beginning point to realistically at least that year post injury. We've done the initial work that used existing data sets where two or more measures had been given to the same patients. We used that to pick items that looked good. We're now administering that large set of items prospectively to patients at the very beginning and at one year to see how this yardstick concept is looking.
Let's look back a bit at some of your previous research. You and some colleagues have published research in the past showing that zolpidem (available under the brand name Ambien) could cause temporary recovery of consciousness after brain injury. Can you explain what you found specifically and why that work was important?
Dr. Whyte: We had seen case reports of patients where it was described that they regained consciousness fairly shortly - within an hour or two - of receiving a zolpidem dose and these were patients who had been unconscious chronically for several years. So whereas I don't often put a lot of stock in case reports of drug induced improvements, this was so unexpected that I had to take it seriously. We went on to do a couple of studies looking at how prevalent this phenomenon is. In other words I believe that it happened. I didn't know if it was incredibly rare or lots of people would benefit. So we first did a study with just 15 patients who we brought into our lab and administered zolpidem one day and placebo another day in a double blind fashion and we assess them hourly with a measurement tool called the Coma Recovery Scale Revised.
And we did a larger subsequent study where we enrolled 80 some patients and actually started with home administration. We coached their family by phone to administer the drug and the placebo again blindly and to kind of do a layperson's assessment over a few hours. If anything sounded interesting from that assessment we sent the research assistant to do the full protocol in the patient's home or nursing home. The results of both studies were about the same. Five percent of patients more or less seem to have a measurable degree of improvement after a dose of 10 milligrams of zolpidem. It starts within an hour or two and it doesn't last very long - couple hours on average but sometimes longer. That's as far as we've gotten. There are tremendously interesting questions to ask about this, but it's a hugely complicated problem to study.
Since those early results came out, what have you learned about this process.? Where do you see this research heading in the future?
Dr. Whyte: I'm not terribly optimistic that zolpidem is going to be a big clinically beneficial drug. There are some families that I know of who use it regularly and their family member seems to sort of benefit in an ongoing way. But other families tell me that the effects wear off if they use it too frequently and that really hasn't changed their life very much. But I think what it does do is point out a very important problem, which is that we define unconsciousness by the absence of behavior. But you can have absents behavior from damage in lots of different parts of the brain and more damage and less damage. And we're introducing biological treatments. It has to matter what the living brain systems available to interact with that drug actually are. And I think zolpidem is telling us that there are at least five percent of people who have some form of reversible unconscious.
We know that they have to have the machinery for consciousness to even show it for those two hours. Now we might have to find another way to get it more reliably, but it's a way of sorting people into biologically meaningful categories that you then might have some hope of making progress with.
Thank you for taking the time to talk with us, Dr. Whyte, and for your long and distinguished service as director of the Moss Rehabilitation Research Institute. Thanks also to Larry Blumenthal, digital manager for MossRehab, for conducting this informative conversation. Be sure to listen to part two of this conversation, where Dr. Whyte discusses his work mentoring future researchers and his vision for translating theory-driven research into treatment. Look for more conversations to come on our Web site at mossrehab.com/conversations. I'm Bill Fantini. Thanks for listening.
Welcome to a MossRehab Conversation, part of a continuing series of discussions with pioneers in physical medicine and rehabilitation from one of America's top U.S. News-ranked rehab facilities. In this second of a two-episode series, John Whyte MD, PhD, who is retiring this year as director of the Moss Rehabilitation Research Institute, looks back over his career with MossRehab Digital Manager Larry Blumenthal, including discussion of Dr. Whyte's work mentoring future researchers and his vision for translating theory-driven research into treatment.
You have a real interest in mentoring clinicians and others who want to pursue careers in research including an NIH-funded training program called Rehabilitation Medicine. Scientist Training Program. What drew you to that area and how does the program work?
Dr. Whyte: I did an MD/PhD program myself and - although I obviously benefited greatly from my PhD training and learned a lot of useful research ideas - I went straight from that MD/PhD program to a residency and then tried to start a research career. I was not in an environment that had a rich mentorship network. In fact, I was viewed as the most research sophisticated person in the institution and I should help get projects off the ground. And I floundered for several years and then I moved to my current job at Moss where I was fortunate to go to work alongside Myrna Schwartz, a few years older than me and already more established in research. And although I didn't have any formal training that relationship was able to turn me around. She was able to read my grants and show me what was wrong and give me suggestions for solutions to difficult research problems.
And it made a huge difference and I started getting my own funding and I developed my own expertise. But I saw around me that world of rehabilitation didn't have enough research. I saw this tension between the complexity and interestingness of the domain and the lack of training to take on actually very difficult research problems. So that motivated me, and I started doing this work through the Association of Academic Physiatrists - one of our two professional associations that is the more academic and training oriented one. We began developing this program that grooms people from an early point in residency, shows them what a research career looks like because they often don't have role models, helps them identify and define what their research interests are, helps them search for and negotiate with a mentor who can help them progress, and helps them structure an application for funding.
You helped found the Moss Rehabilitation Research Institute in 1992, and you're wrapping up your time as director this year. Looking back what are your thoughts on how MRRI has wound up where it is today and what it's accomplished over those years?
Dr. Whyte: I'm a little bit biased in that regard. I think that a thing that my colleague Myrna Schwartz, who I mentioned earlier, and I saw early on that has been important is the need for at the same time reliance on clear theory and commitment to real world importance. And that's a hard balancing act.
Our observation when we started was that an awful lot of rehabilitation rehabilitation research is not theory driven. It's, "Let's see if this works. Let's see if that works. Let's see if this works better than that." At best, that gives you one more thing that works. It doesn't really launch a science. People would do very successful theoretically important work by not studying any messy patients or things that might complicate your theory. That didn't seem like a good way to solve the problem. So for 25 years we have talked about - not that we have solved - but we have talked about how to bring theory to bear and where to bring theory to bear and how to make sure that what we're bringing theory to bear on is impacted in real people and in real ways. I think that that's, as I say, a very complicated problem, but at best a fascinating discussion to guide 25 years of work.
Looking back on your own career. What are some of the highlights that come to mind?
Dr. Whyte: I have kind of always operated on two planes in my research. I try to approach real research problems. What's the most effective drug for this or what kind of training is best for that. But I run into huge obstacles every time I do that which lead me to also think about write about and to work on those obstacles like measurement. We don't have a good way to measure this. We haven't defined what this thing really is that we want to care about and so on. So I think that in the end I'm probably most proud of the second plane that I just had i.e. methodologic things because those hopefully will have some impact beyond the one individual question and might offer tools or guidance across a broader set of questions.
Similarly for the training, it gives me tremendous gratification to see the people who have gone through the RMSTP and what they're doing now and to know that that's going to make a difference, I think.
As you wind down your time over 2018 as director of MRRI, no one's expecting you to start to dust off a rocking chair and retire from the world. I think we're all curious about what your plans are for the next few years.
Dr. Whyte: I'm curious about that, too. I mean I'm looking forward to kind of taking other things one-by-one and case-by-case. I am relatively newly the president of the Foundation for PM&R, that's a two-year commitment. So I'm at least doing that. I'm on the board of AAP for a little while yet. I'll at least be doing that. I'm going to sort of take it project by project whether I will wrap something up, whether I will be involved in any kind of renewals and so on because I'm going to see what this feels like. It is a new and different thing for someone who has been very work-committed for a long time.
Thank you for taking the time to talk with us Dr. Whyte and for your long and distinguished service as director of the Moss Rehabilitation Research Institute. Thanks also to Larry Blumenthal, digital manager for MossRehab, for conducting this informative conversation. Be sure to listen to part one of this conversation, where Dr. Whyte discusses his research including seminal work on disorders of consciousness and more recent research into how to define and measure progress in rehabilitation more effectively. Look for more conversations to come on our Web site at MossRehab.com/conversations. I'm Bill Fantini. Thanks for listening.
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