Episode #11 - Mediation Analysis & OMT Blinding and Sham Treatments

Hello everyone and welcome to our eleventh episode of the OMM Research Podcast! 

Our panelists for this episode are Dr. Stephen Stacey and Dr. Alfread Amendolara.

In this episode, we are an article titled "Pain self-efficacy, kinesiophobia and health-related quality of life mediate pain and disability improvements with goal setting and education in people with chronic low back pain: a mediation analysis of a randomised trial" by Walkeret al. published in the Journal of Physiotherapy. The article can be viewed at this link: https://pubmed.ncbi.nlm.nih.gov/40987621/

We are also looking at an article titled "Meta-epidemiologic review: blinding and sham treatment in clinical trial design for osteopathic manipulative treatment research" by Irving 3rd et al. published in the International Journal of Osteopathic Medicine. The article can be viewed at this link: https://pubmed.ncbi.nlm.nih.gov/38312536/

You can also view this podcast episode on the DO-Touch.NET YouTube Channel and see what is happening in the DO-Touch.NET practice-based research network by visiting our website, which are both linked in this sentence.

Hope you enjoy and feel free to reach out to us at dotouchnet@atsu.edu!

Transcript

SPEAKER_01 0:12

Well, hello to you, our listeners, the manipulated and the manipulators. Welcome to the OMM Research Podcast. The OMM Research Podcast is produced by Dio TouchNet, a practice-based research network that focuses on osteopathic manipulative medicine research. Dio TouchNet is based out of the AT Still Research Institute, located at AT Still University in Kirksville, Missouri. Please note, as always, that the views and opinions of the panelists in this podcast are personal to each panelist and do not reflect the views or opinions of A.T. Still University. My name hasn't changed and is still Corey Lubring, and I am the practice-based research network of Deo TouchNet and the host of the OMM Research Podcast. And before we begin, we also just want to remind our listeners that this podcast recording has video recorded with it and can be viewed on the Dio TouchNet YouTube channel. Our episode, uh our episode, our panelists for this episode, uh are Dr. Stephen Stacy and Dr. Amendalara. So as always, Dr. Stacy, would you like to introduce yourself?

SPEAKER_02 1:20

I'd be happy to. I also have not changed my name. I am Dr. Stephen K. Stacy, D.O., Director of Osteopathic Education at the La Crosse-Mayo Family Medicine Residency Program. And while my name hasn't changed, uh, the astute listeners may have noticed that between the first episodes and now, my academic rank has changed from assistant professor to associate professor. So a little Easter egg there, but now we're highlighting it out loud. And I'm uh also the course director for the Mayo osteopathic research and education conference this September 18th and 19th, 2026 in Minnesota.

SPEAKER_01 2:03

And thank you for being with us again this month. And back with us again is Dr. Amendelara.

SPEAKER_00 2:10

Hi, yeah, I don't have any good uh title changes. Unfortunately, my name is the same as always, but uh my name's Al Amendalara. I'm a neurology resident at uh St. Luke's University Health Network in Pennsylvania. I'm also uh an adjunct professor in our clinical research department at Norda College of Osteopathic Medicine.

SPEAKER_02 2:30

Hey, there's one big I'd say there's one big change that has come, and you are uh PGY2 now instead of PGY1. In in about a week. I mean by the time this comes out, by the time anybody listening to it, it will be officially a PGY2.

SPEAKER_00 2:47

Yeah.

SPEAKER_02 2:48

Yeah, and you can get your license, sign your own controlled substances.

SPEAKER_01 2:55

That's a big step. That's a big thing. It's exciting. It's exciting. Well, we're gonna dive into our first article brought to us by uh Steven, which is looking at mediation analysis.

SPEAKER_02 3:07

That's right. This article is called Pain Self-Efficacy, Kinesophobia, and health-related quality of life mediate pain and disability improvements with goal setting and education in people with chronic low back pain, a media anal mediation analysis of a randomized trial. Honestly, I didn't think they let journal titles get that big, but here we are. The authors are Walker et al. It was published in October 2025 in the Journal of Physiotherapy. From the abstract, their objective was how much do pain self-efficacy, kinesophobia, stress, and health-related quality of life mediate reductions in pain intensity and disability in people with chronic low back pain receiving a patient-led global uh patient-led goal setting and pain science education intervention compared with general exercise advice. We'll unpackage that in a little bit, but their main findings are targeting pain self-efficacy, kinesophobia, and health-related quality of life may drive important reductions in pain intensity and disability following a goal setting and educational intervention for people with chronic low back pain. I know that was a lot of mouthful, so we'll unpackage that a little bit here.

SPEAKER_01 4:26

Sure. Well, but the first thing I want to unpackage for our listeners that may not know, could you give us a little explanation on what is mediation analysis?

SPEAKER_02 4:36

This was a strategy that they used to figure out what was the causal factor behind the improvement that they saw in a previously published study. So the original randomized controlled trial showed clinically meaningful improvements in pain and disability from patient-led goal setting and pain science education. So, what they did in that study is they randomized 75 adults with chronic nonspecific low back pain to one of two arms. One was the intervention arm, which was pain-led goal setting plus pain science education. So this was really an education intervention, not hands-on manual therapy, but we will definitely tie it back to OMM, I promise. The control was just standardized advice to exercise, sort of a typical, like, hey, get out there and you know do stuff kind of advice. And what they found was improvement in the in the intervention group. And this study now is an effort to statistically see what are the mechanisms behind the improvement.

SPEAKER_01 5:48

Interesting. So so what about this article? What did you made you want to bring it to this episode for us this month?

SPEAKER_02 5:55

I found that when we're doing manipulative medicine, a lot of the manipulation that we do is psychological manipulation as much as it is manual manipulation. And as we are helping our patients, a lot of the things that we do center around these ideas, these four things that they highlight pain self-efficacy, kinesophobia, stress, and health-related quality of life. So pain self-efficacy is the idea that patients can be in charge of their pain journey and find improvement through things that they are able to decide to do. And it's already been shown in multiple prior research studies that patients with low pain self-efficacy suffer worse pain outcomes. So their beliefs about what they're able to do with their pain actually drive outcomes. And so what they were seeing is whether that would apply in this case as well. Kinesophobia, similarly, is this idea that movement is harmful, therefore I don't want to move. And when I don't move, I get more stiff, and then when I get more stiff, I get more painful, so then I don't want to move. So this concept of not really wanting to move is kinesophobia. And stress and health-related quality of life, I think, are two a little bit more intuitive terms.

SPEAKER_01 7:25

Interesting. Uh, Dr. Minelaris, anything you want to add to that?

SPEAKER_00 7:32

Not particularly. This is an interesting study. Um, I like the statistical analysis they did with it. It's always interesting. This isn't something that I've done before, but my understanding of it, if it's essentially asking the question, um, the initial study kind of in a way asked, how do we get from A to C, or is there an effect on A to C? Uh, what this study is looking for is what is that B term in between the two? That is, I mean, as the title implies, mediating the effect. Uh, and I think that's kind of a useful analysis to do. Uh, as Dr. Stacey was saying, there's a lot of additional factors that go into manual therapy. It's it's not always a one-to-one. Um, you do something physical and there's a physical outcome to it. There's a psychological component, there's other variables. And I think in general, this kind of uh secondary analysis, which is kind of, you know, it's an analysis of an already published study, is really useful for filling out the entire causal relationship uh between a treatment and an effect that we're hypothesizing its its cause.

SPEAKER_02 8:37

And we sort of understand this intuitively because nobody thinks that just going and getting education directly causes pain to get better. There's got to be something that's happening to trigger that. And this is really hypothesis-based saying we would suspect that improvement in these other things would then mediate the improvement in pain. So that um pain self-efficacy, kinesophobia, stress, and health-related quality of life would cause would be mediating that improvement. So that's a real strength of this study, is it's digging deeper into an existing data set. Of course, the weakness is you have to have really considered a potential mediating variable for it to be manifest. Yeah. And so this doesn't explore things that they didn't think about.

SPEAKER_00 9:31

Hidden variables, right? It doesn't, it doesn't really explore hidden confounders.

SPEAKER_01 9:35

Well, we have to be careful, you know, educating people more because if you talk to anybody's kids, it just education in general causes more pain. Uh so that could be adding to more to this.

SPEAKER_02 9:47

I will say our kids are at the age of education where we uh as parents are at peak stupidity. They know so much more than we do about everything. Just ask them, they'll tell you.

SPEAKER_01 10:00

Absolutely. So so what more is this study? Like you all are talking about like, you know, how education is really uh benefiting these people with their ability to I don't know, cut better understand their pain and and be being able to mitigate it or address it and such. And so what can we take how is this go can be taken into a clinical setting, um, these results for people to be able to better improve their quality of care that they're giving their patients?

SPEAKER_02 10:32

Yeah, so the intervention didn't work by changing tissue the way that manual therapy might. And so we can add manual therapy to a lot of these educational type interventions by addressing things like confidence, fear, stress, and quality of life. What they ended up figuring out out of all of these is they were looking at all of these. The pain self-efficacy appeared to be the strongest mediator of disability improvement. And kinesophobia was the strongest mediator of pain improvement. But those two, by and large, stuck out. The pain self-efficacy and the kinesophobia stood out as better markers of pain improvement than reductions in stress or improvements in pain-related quality of life. And so, as we are making interventions with our hands, we can also make interventions with our minds to help people feel more pain self-efficacy. And I make this part of my personal practice to always give patients something that they can do for their own pain. I tell them my goal is to make myself irrelevant so that they are in charge of their own pain journey by having strategies for dealing with flares when they come up or improving themselves through stretching, strengthening, things like that. But then also the uh the kinesophobia piece. One of the things that I love about osteopathic manipulation is that we couch our treatment in terms of improved movement, which really helps with patients feeling like they can move. What I'm doing is helping you move. Now you keep moving and you're gonna keep doing better, contrasting that with other types, other models of manual therapy, which focus on um things like uh you know, subluxations or or things where you're out of alignment, out of place. And if something's out of place and then you put it back like a Lego set, what's the way to keep it there? It's to not move it. And that contributes to kinesophobia, which is actually counterproductive. And I've and I know that other practitioners aren't meaning to do that, but I have had patients feel like they can't use their back once it's quote put back in place by other providers. And I really try to avoid that language. So if if you take nothing else out of this, I would say focus on using your manual therapy to improve the patient's sense of their own self-efficacy and to reduce their fear of movement.

SPEAKER_01 13:13

Good takeaways. And uh, Al, if you were to uh take the study to a next step, where would you take the study from here? What would you see as the next step of this type of research?

SPEAKER_00 13:23

I mean, I I think this study does a really good job about uh of giving us a usable clinical outcome. I I think the idea that based on this research, based on the prior study, we can say, well, we know that pain self-efficacy, we know that kinesophobia are mediators in this, sort of these intermediate steps in helping their intervention be more effective. It lets us in a clinical setting pretty it's pretty low risk to keep those in mind as we're providing patient education, as we're providing treatments. So I think you can take that and run with that in a clinical setting. In terms of next steps for research, this is the type of um the type of study that I think can be repeated in with other primary literature. This is the type of secondary analysis that um if you've done a study where there's a high chance that there are mediators, especially if hopefully you've tried to address those or you were aware of them at the onset, this can give us more usable clinical information, which I think sometimes is lacking from osteopathic trials. Uh we get a lot we jump a lot from point A to like point Z sometimes, and we're missing a lot of steps in between. And this is really exactly what one of the ways that you can start to fill in those, those, um, the rest of the alphabet in between, essentially.

SPEAKER_02 14:46

That's a really good point. And they had to think about these things from the get-go. So you you can tell this was a planned secondary analysis from the beginning because they got information about these secondary endpoints from questionnaires that have been used in other validity studies or are widely used by the field to measure things. Uh, so they didn't just go straight from here's our intervention to here's our outcome. They gathered a lot of data along the way so that they could have this. And they didn't pick these at random. They really did a good literature search and and were very well aware of the kinds of mediators that have been shown in prior research. So this really builds on a foundation of a hypothesis that is already well on its way in the manual therapy research. So they're not just coming up with this willy-nilly, but but finding the the evidence to support or refute existing hypotheses and models.

SPEAKER_01 15:51

Awesome. Well, thank you for bringing this article to us this month. It's exciting to dive into. And before we dive into our next article, we do just want to remind our listeners that if you want to see our beautifully bearded, mustached faces, and then you can find us on the Dio touchnet. Sorry, I betrayed you guys. That's all right. The facial hair still exists in some form.

SPEAKER_02 16:13

But I grew taller than the rest of my hair, so my yeah, the top of my head is a little bit more barren.

SPEAKER_01 16:20

But that's Dio Touchnet. That's D-O-T-O-U-C-H dot N-E-T. You can find us on a YouTube channel or check us out on our website, which is spelled the exact same way. And our next article is based on a topic that we come to in a lot of our previous episodes, but the article is now just focused directly on it, and it's looking at blinding and sham treatment. And I'll pass it over to Dr. Mendelara.

SPEAKER_00 16:46

Yeah, so this article I thought was uh interesting. It's very relevant to things that we bring up probably a little bit too much on this podcast, but recurring themes. It's titled Uh Meta-epidemiologic review: blinding and sham treatment in clinical trial design for osteopathic manipulative treatment research. It's by Irving et al. It was published in the Journal of Osteopathic Medicine in 2024. The International Journal of Otec. International, I'm sorry, International Journal of Osteopathic Medicine. Um briefly to summarize it, uh, we won't get too much into the actual results of the study. I think their discussion is the more interesting part here. But they evaluated, they did a uh structured literature search and evaluated 83 blinded uh uh OMT randomized controlled trials published between 2009 and 2021. And they looked at a variety of different factors. They looked at sham categories, they looked at blinding, they looked at assessment of blinding, um, effectiveness of the blinding, and and all these kinds of different things. And then they sort of discuss it and they give us their their thoughts on it, and they had some interesting results. Um, in general, they found five big sham categories. Uh, most of these trials used light touch, some of these used unrelated sham treatments, meaning something like an ultrasound or a generic exercise. Um, a percentage of these uh used incomplete maneuvers, so they set up the treatment but didn't actually do any of the therapeutic movements. Um, and then they also did there were a handful that did either no-touch kind of sham controls or incorrect positioning, things of that nature. Um they did find that about 80% of these trials at least attempted to blind their subjects. Um, about 70% attempted to blind the data collectors, the evaluators, but only about 20% of the physicians delivering the actual treatments were blinded. Um, and interestingly, about only about 10% of these studies, out of the 83 studies, only about 10% actually assessed whether their blinding was effective. Um so that's kind of the general their general findings on it. But I this study to me really touched on all of the things that we bring up sort of over and over again when we're discussing the trials that that we that we bring onto this podcast to to sort of sometimes complain about, but to review.

SPEAKER_01 19:34

So to open the proverbial can of worms. Oh, sorry, go ahead, uh Dr. Stacy.

SPEAKER_02 19:39

Oh, I just think that this is great because it highlights, you're right, a lot of the things about what we would like to see in more manual therapies research studies. So we talk a lot about um, you know, increasing the N number, and that's great. Uh and people always say, though, um, you know, it's so hard to do manual therapies research because you can't do a placebo. And that's true in the strictest sense that, you know, a placebo sugar pill, yeah, doesn't really work. But there are lots, lots of interventional studies outside of manual therapy that use ways of analyzing it. And it's bringing a lot of those best practices into that. And one of those best practices is looking at your alternatives and saying what is the evidence behind their ability to maintain an appropriate control. This is really cool.

SPEAKER_01 20:32

Yeah. So so what about that discussion? What about uh this, you know, did you want to discuss here related to sham treatments?

SPEAKER_00 20:41

There's so much, there's so much to discuss. I think they bring up a couple good points though. Um, you know, the first is a general point that the way we talk about single blind, double blind, triple blind studies is not particularly standardized. One of the something that I thought was interesting was a number of the studies that claimed to be single blinded actually had sort of variations in who they were actually blinding, which I think as a reader is is very relevant. So uh about 43 studies uh claim to be self-blinded, 16 blinded the subjects, 18 blinded the evaluators, and 10 blinded both the subjects and the evaluators, which is really probably a double blind design. So, just as an example, there's a a lot of sort of uh inconsistency with how we're labeling these studies, which I think is something we usually talk about this more when it comes to calling something a pilot study or things like that. We we complain that it's not very standardized, but I think it's relevant to know that when you read the title of a study or or what the authors are claiming, you know that who they blinded and who they didn't blind and how that might manifest in bias or or how it could change the results and conclusions.

SPEAKER_02 22:00

conclusions and how blinding was performed and how successful it was.

SPEAKER_00 22:05

One of the things that the major yeah uh they they pointed this out even right in the abstract yeah they said the use of questionnaires to determine the success of blinding should be considered i i think if anything that's maybe too lightly phrased right i i think they should be mandatory really i i i think absolutely i i also think there's something interesting that they they acknowledge that there's difficulty in blinding the physicians who are performing omt for hopefully for obvious reasons but they also note that that doesn't mean that we should chuck that idea out the window and they also I think they make a really good point that there's a difference between blinding the evaluators or the people collecting the data and the person delivering the treatment. So you might say well we double blinded it because we blinded the participants and the people collecting the data but that's really controlling for different biases than if you blinded the the participants and the person providing the treatment. It it doesn't mean it's wrong or the incorrect way, but it it fundamentally you're controlling for different factors. And I think that's kind of relevant. We see a lot of of studies that call themselves double blinded but really what they're doing is blinding the participants and the evaluator not necessarily the osteopathic physician or or whatever practitioner is delivering the the treatment um which you're right that's not always going to be possible and probably most of the time it's not going to be possible but what you should definitely have a separation between is anybody who knows what treatment allocation is and anybody who is gathering data or processing data for the study.

SPEAKER_02 23:49

So whoever is making the primary outcome assessment really needs to be blinded. And in a lot of cases that's the patient themselves from like a self-reported questionnaire. And that's where we get back to this idea of knowing was the patient in fact blinded or uh or did they have evidence of unmasking such that they were very aware of treatment allocation.

SPEAKER_00 24:14

There's also there's also another point that they make that is again I'm gonna say we we say these all the time but the the the difficulty in choosing a sham because we know there is an effect there there is a placebo effect there is an effect of light touch there's a therapeutic effect to touch on its own which is has been documented in the literature and it really calls into question um just having two arms in these kinds of trials. I know there's big logistical issues but they make a really good point that when it's possible probably having three arms in your in your trial is really beneficial to separate positive effects from your treatment from just psychological effects or effects of light touch therapeutic effects uh that are different from your intervention but then also which may be separate from a a complete uh no intervention type control or a a different uh unrelated treatment type type thing i that was that was interesting to me that's something that I would like to see more of I I would even argue that for some of the types of studies that have been done much more than others like manual therapy and low back pain has been done a lot.

SPEAKER_02 25:32

We know that manual therapy can help in low back pain. So we have some unsettled questions there that really need to be part of any future investigations things like how much training does the practitioner need to deliver successful treatment? Could you have somebody that um uh took a 20-minute crash course that does as well as somebody who's been doing it for a whole career do you find differences there? Or other things like looking at these mediating factor analyses or comparing physician directed OMT versus protocol directed OMT and seeing in particular cases does it make a difference? These are the kinds of open questions that we have it's not really an open question anymore though does manual therapy help in low back pain? We know it does so let's start asking uh right more more informative questions. Other things, you know, we may not be there yet like do we know how well OMM really helps with things like chronic abdominal pain? I would say less so than with low back pain.

SPEAKER_01 26:38

Uh but even as you're starting studies that are perhaps a little bit more exploratory this last study that that I did and the one that you're doing now show the value of just gathering extra data along the way so that you can um explore hypotheses underlying potential mechanisms well this question that I've kind of been thinking about as you've been discussing this, I want to pause it towards both of you instead of really asking where would you take this research in the future more so related to you know blinding and sham treatment and the past conversations that we've had in it where would what would be the recommendations or practices that you would strongly recommend to those doing osteopathic research that would be able to bring the validity of the results to the next level uh as it relates to blinding and sham treatment. What would you like to see done as best practices?

SPEAKER_00 27:36

You know it's funny you should ask that because that is their entire conclusion. They give us some excellent recommendations that I don't want to pretend that I came up with these on my own because I think they do a great job of listing them out. They have four big recommendations. They recommend ensuring double blinding actually entails blinding the subjects and the evaluating clinicians um and additionally any other data collectors. And then their second recommendation is that you have someone uh independently providing the treatment so an osteopathic physician who is performing treatments but who really has no engagement in the actual data collection or analysis. So you you circumvent having to blind your treatment provider by having them as Dr. Stacey I think you already mentioned this having them separate from the data the collection analysis stages of the the study. They also mentioned uh their third recommendation is that post-study analysis to determine the success of blinding should be an integral part of the trial design. I think we harp on this a lot and that is an easy recommendation. And then they also recommend uh the general awareness of the fact that significant outcomes arising from sham techniques necessitates their deliberate incorporation into study design. Essentially again something that we've been saying that where it's possible the inclusion of a no treatment control arm, essentially a third control arm or at least the awareness of your choice of sham treatment can have a a large impact on your outcomes and your eventual conclusions.

SPEAKER_02 29:18

And you stay on the yeah absolutely yeah I would stand by those too and in answer to your question where do we go from here this is a big pie in the sky dream of mine but I would love to have a society supported internationally led process of finding uh of of creating reporting guidelines for manual therapies research that would incorporate all of these things because we have you know a lot of other disciplines have reporting guidelines we have reporting guidelines for every different kind of uh um survey study every different kind of um reviews yeah uh but we don't really have a good one for manual therapies research that that the journals could go to and say follow this guideline and in that guideline is something that says you know report on how you did this or report on the fact that you didn't do this as a weakness and and when authors look at that and they see oh to follow this guideline I needed to have done this that's really going to shape how trials get run.

SPEAKER_01 30:39

No that's a great point.

SPEAKER_02 30:41

Yeah yeah I couldn't agree with that more so if anybody out there listening to this wants to do that wants to spearhead it please please get in contact with me I would just be tickled pink to get this lifted off the ground awesome well thanks for this awesome article this month uh Dr.

SPEAKER_01 30:59

Mendelara it's a great conversation related to it uh and uh before we go uh we want to of course thank our panelists this month remind you all that if you want to find out more about what's happening within do touchnet you can always go to do to u c dot n e t to see what's happening within our uh network and um I believe uh Dr. Stacy this might be the last time for you to plug uh the conference that's happening up at the Mayo Clinic.

SPEAKER_02 31:29

That's right the Mayo Osteopathic Research and Education Conference or more in Rochester Minnesota come join us from September 18th to 19th 2026.

SPEAKER_01 31:42

Bring your research that you're doing we'll have one more uh one more episode that we can still plug it but yes absolutely you should you all should go if you can because you can and there's also going to be a residency fair so if you're affiliated with a residency uh find our website uh you can just google um more mayo uh osteopathic and it should show up um you'll see how to do that there if you're a medical student please come it's gonna be on Friday September 18th and if you haven't yet smash that follow and subscribe button follow along with this amazing awesome podcast as we continue to dive into osteopathic research and uh Dr. Stacy Dr. Mandelara thanks to you both again for being with us this month yeah and we will talk to you all next time