Hauser: Dr. Rabago, can you tell us briefly how you got into Prolotherapy?
Rabago: I was in residency at University of Wisconsin, Madison and Dr. Jeff Patterson is on faculty here. He is pretty forward about including residents in that experience. He includes residents in clinical Prolotherapy at the UW, and invites them to join him on the medical service trip that he makes to Honduras every year to provide Prolotherapy there through the Hackett-Hemwall Foundation. I went on the trip in the early 2000s and was impressed by the apparent effectiveness of Prolotherapy but also by the lack of evidence in a clinical trial context of its effectiveness. When a person who is interested in clinical research sees a therapy that is doing apparent good but is supported by very little evidence in the literature, it’s a natural magnet to think about clinical trials and investigation. So we picked a likely candidate in terms of clinical scenarios and submitted a grant that we were fortunate to get. That indication was knee arthritis. We applied to the NIH (National Institutes of Health) in the form of a career development grant early in my research career. We submitted that to the NIH Center for Complementary/Alternative Medicine (NCCAM). They were interested and they funded us. Those studies are nearing completion now and we hope to publish those within a year or so.
Hauser: Congrats on that, David. Can you tell us what was involved in that study?
Rabago: We’ve done a few things in terms of clinical trials so far. The first was the knee arthritis study. It uses a so called “full knee” Prolotherapy intervention with dextrose, (intra- and extra- articular injections), compared to a blinded placebo control group that gets saline, compared to an un-blinded home exercise therapy control. It’s not formal physical therapy with a therapist; rather it’s a home protocol that subjects perform based on an informational pamphlet. Injection subjects had three to five injection sessions at the knee for their pain, and one year follow up.
Hauser: Since you currently don’t know the outcome or results, let’s move onto another subject. Do you have a private practice? Do you do Prolotherapy in your practice?
Rabago: No, I’m an assistant professor in the department of family medicine at the University of Wisconsin, so it’s not private. It’s a university teaching based practice. I split my time between research, with Prolotherapy being one of the research interests, teaching, and general family medicine. I have gradually stopped doing most injections because it was simply too much breadth to keep up with all aspects of a research career, full spectrum family medicine, teaching and also focus on injections. I depend on colleagues who do Prolotherapy interventions in the research projects and I have mostly become the research person. Prolotherapy research for me is a very collaborative enterprise.
Hauser: Let me just congratulate you again. You’ve probably written more on Prolotherapy as far as reviews as it relates to the traditional doctors getting the word out on Prolotherapy.
Rabago: It’s been fun. It’s been very positive. I’m a believer in the need to identify which patients are most likely going to benefit from Prolotherapy, as it certainly appears that some do. Injection therapy is hard to study; others have found that too. The folks that did the back pain studies realized this was a difficult thing to study. I think that’s one reason the protocols are so complicated. Dr. Michael Yelland has done a great job. He’s probably the best researcher of Prolotherapy in the world, in terms of clinical trial design and conduct. We’re happy to be in the game, for sure. Knee arthritis is a very compelling indication for Prolotherapy. It’s very common. It’s not the one that Prolotherapists probably do the most, but if we can make a dent in arthritis, that’s like making a dent in back pain since it’s so common, so debilitating.
Hauser: Regarding one challenge as it relates to doing research that you alluded to in the NIH grant study you completed, is the whole notion of the placebo group and doing the saline injections. As you’re familiar with Dr. de Vos’ study where they did a kind of Prolotherapy, PRP, for Achilles tendinopathy, both the Prolotherapy group and the placebo group had statistically significant improvements in pain.
Rabago: Compared to their own baseline but not compared to one another.
Hauser: Right. So, your thoughts?
Rabago: Research is difficult. They did, I think, a fine study. The problem is injections are interventions no matter what you put in the syringe. The fact that both groups got better is good for patients. The fact that they weren’t statistically significant compared to one another isn’t particularly damning for the PRP intervention group. It may be that the effect size between the groups was smaller than anticipated because both groups received eccentric exercise, an active therapy, and because of effects from needle trauma, blood and pressure volume relationships. Also it was a very small study and they didn’t follow them for all that long. All of those things can limit the effect size between groups. We actually wrote an editorial to JAMA, which can be found via Google, that lays out our argument that that study shouldn’t muddy the water too much with respect to PRP and injection therapy in general. We only were allowed 400 words in that letter, but if I was given another 400, I would argue that what we should be doing is comparative effectiveness research and not double blind placebo control trials for Prolotherapy because any injection control is going to have those problems. Comparative effectiveness research is just like it sounds. It would pit Prolotherapy against something else that we do for chronic MSK (musculoskeletal) pain and compare the effectiveness of two different but actual therapies. It takes away blinded-ness usually but we may simply have to accept that because it does seem that injecting anything does something. Saline seems to have an effect, whether it’s placebo response that has a mind-body interaction or weather there’s tissue response, we don’t really know but it does seem to do things. The initial intent of placebo was to have it be a non-physiologic intervention. It doesn’t seem that that’s true with injection therapy.
Hauser: I think you bring up a good point. So thus, in your study that you did, you had the exercise group. In essence, that might end up being your placebo group though you’re calling it more comparative effectiveness research.
Rabago: Right. The NIH, and traditional clinical trialists have always placed value on comparison groups that can be labeled as blinded placebo control arms. And we indeed have that in the saline group, but we also have this additional comparison group, the at-home exercise subjects. Comparative effectiveness research makes common sense and is getting more attention lately. The notion of comparative effectiveness research has its own acronym (CER) which you can Google to find a host of articles on the principles of comparative effectiveness research and the fact that it’s being talked about at the highest levels of clinical trials work. I think it’s a step forward for assessment of musculoskeletal therapy. I think it’s smart.
Hauser: If you and others find, from a comparative effectiveness perspective, that Prolotherapy is as effective or more effective than some other therapy, such as exercise, do you see that it might help Prolotherapy in its quest to get more accepted in traditional medicine?
Rabago: The short answer is yes. If Prolotherapy is compared in a strong trial to another therapy that is credible, and if a researcher found and reported that Prolotherapy did better than that therapy, sure. That’s a head to head trial and that’s a good thing for Prolotherapy. An example is Dr. Mike Yelland’s Achilles tendinopathy trial published in the British Journal of Sports Medicine last year. It’s a very interesting, well designed study that compared Prolotherapy to eccentric exercise to both. It’s terrific. It was a pilot study, not powered to be a definitive trial. But even given that, the authors were able to report some better outcomes for the combination of Prolotherapy and eccentric exercise than for either one alone. That’s impressive. That study should not be overlooked. Great trials can be designed and conducted. It’s hard work but better is better. He’s shown that you can do it and that you can detect effectiveness compared to other therapies using relatively small numbers.
Hauser: David, thank you again for all the work you’ve done in getting the message out with Prolotherapy.
Rabago: You’re very welcome, I’ve appreciated being able to do it, and have had tremendous help from colleagues along the way.