Integrative Medicine Research for COVID-19

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This is a research review. It is not meant to diagnose or treat disease. For all things medical contact your healthcare professional. This video is meant for educational purposes only.

To add to the Traditional, Complementary and Integrative Health & Medicine COVID-19 Support Registry click here

All right. This is Dr. Joshua Goldenberg for Dr. Journal Club and we are doing a exciting interview with Dr. Ryan Bradley. Now Ryan and I have worked closely together for a while now. So we know each other well. Ryan, do you want to do a brief introduction about who you are for people, that may not know you yet?

Sure Joshua. I’m happy to do that. So I’m Ryan Bradley. I am a naturopathic doctor and, I have been practicing at different degrees for about the last 17 years. I also have a Master of Public Health in Epidemiology from the school of public health, University of Washington; I’m affiliated at a variety of conventional and naturopathic institutions. But my primary role right now is as the Director of Research for the Helfgott Research Institute at the National University of Natural Medicine.

Awesome and that’s where I work; that’s my primary affiliation now. So Ryan’s been really instrumental in directing the research at Helfgott and also in the larger naturopathic realm. Also spreading out to the integrative community as well. And so Ryan like we were talking a little bit before we went live, is a lot of people have been reaching out to Dr. Journal Club saying, “…well, it’s nice that you’re still reporting on the effect ratios of antidepressants and zinc for this, that, and the other thing. But we care about COVID, we don’t have any room in our brain right now for anything else besides COVID. At Journal Club, what we’re trying to do is bring high quality rigor and analysis to integrative approaches to health conditions. Problem is, this is just emerging so there isn’t high quality anything for anything right now. So instead of trying to review early emerging research, I thought it might’ve been, more informative to actually interview researchers that are actively trying to create this research and you are one of those researchers. You’ve had some really unique approaches and so I wanted to get your thoughts on how do we as an integrative medicine research community approach researching COVID and how are we doing it, how are you doing it, et cetera, et cetera.

Well, that’s a big question. I agree with you about the importance of doing research on integrative medicine in this time of COVID. With that comes a few challenges as you can probably anticipate. And I think one of the challenges is being realistic about where do we see the bulk of the energy in coverage as it relates to COVID. You know, putting on my primary or my public health hat for a moment, we really see that at this sort of tertiary stage of prevention, right? I’m looking at the acuteness individuals that have been diagnosed with COVID trying to reduce the impact of condition and in terms of their morbidity and mortality. But there’s a lot of other areas to research and that’s the approach that I’ve taken is really starting at one of a formative stage in developing new evidence in an area that we’ve never had to encounter before.

I’ve taken a practical approach to that I think with the help of many colleagues, doing work both in the evidence mapping/evidence synthesis stage of formative evidence development and then also collecting new evidence. Given that few of the academic medical centers for integrative medicine are conducting formal randomized control trials as they relate to integrative medicine or traditional complimentary integrative medicine approaches to COVID. I’m relying really on the clinicians out there in the field who we know are contributing to COVID and in a wide variety of ways. So the first structured project that I’ve taken on is designing, what I refer to as a COVID-19 clinical support registry, that is aimed to capture clinical observations and collect clinical observations from all categories of traditional complimentary integrated health and medicine providers. This is a project that has now gone internationally and has the endorsement of about 24 different agencies and associations that are connected to a complimentary integrated health and medicine in one way or another.

That’s amazing. That’s really wonderful. I mean, I remember seeing the initial emails going out maybe a few weeks ago now, but to see that it’s grown that much and I’m now seeing it getting emails from multiple different organizations promoting the registry and we will of course link to it, the show notes as well, so that clinicians can log in. So how does that work? And I’m very curious also. So if I’m a clinician out in the field and I’m seeing COVID patients and I’m trying different natural interventions and I’m seeing impacts, what do I do? How do I interact with this registry? Then what do you do on the back end? How do we see the forest from the trees at a certain point? Or is that still amorphous, ‘let’s gather the data and analyze it later’ type of thing.

Yeah. So we’re, it’s a little bit of both is the short answer. You know, let me first say that a clinical registry has its limitations in terms of a research methodology. You know, there, I’ve received a handful of emails from folks that are concerned about selection bias, you know, cherry picking, really compelling cases for one reason or another. They have a great outcome, et cetera and that’s true. There is absolutely a limitation in terms of the use of a clinical registry as a methodology. At the same time, as you’ve stated, this is a completely new area where really complementary, integrative health and medicine is on a level playing field with every other form and type of medicine and healthcare, and that we don’t have high quality evidence for any type of interventions for COVID-19.

So where do we start? We start at the bottom of the evidence pyramid, which is really in the collection of things like case reports and case series and relying on clinicians to document their observations in the field. This is really a starting point. As you well know, this is a starting point to guide the future design of randomized controlled trials or other higher level of types of evidence in order to you know, attempt to validate promising observations from the clinic. So I’ve taken an approach that has been inspired by my training in epidemiology and you know, when we think about longitudinal cohorts for example and collecting case observations, it’s very important to first define a case. And in many cases in many situations in epidemiology, we don’t necessarily have a formal biomarker that has been validated to identify a case and we require reliance on case definition that may be a consolidation of multiple inputs.

Maybe it’s the age of presentation, a series of clinical symptoms, responses to therapy. You know, we think about myocardial infarctions for example, or we have some symptoms present. We have some labs, we have EKG assessments. Those different evaluation strategies can be used to identify cases. I’m taking a similar approach with the COVID registry where there have been enough observations of COVID-19 that were pretty clear about some of the symptoms that are common in terms of diagnosed cases. And so we’re capturing those symptoms. We are capturing testing status for individual patients or clients that have been tested. But we’re also intending and wanting actually to capture unconfirmed cases as well. So these may be patients or clients that have known exposure but haven’t been tested, but exhibit a certain number of case symptoms, that they may still be considered true case positive.

So in terms of how clinicians may interface with the registry, it is a web based registry. It’s built on a research electronic data capture or red cap based platform. Red cap is a highly secure research data capture platform that we use for a variety of research methods, clinical trials, and ongoing cohort studies. It is web based, so there’s a shareable URL that is accessible anywhere in the world. The data themselves of course are captured on a computer server at the National University of Natural Medicine. Red cap has a lot of functionality in terms of being able to include, you know, quick to use radio buttons and build in branching logic. And so depending upon entries, different fields may open up to gather more information. The registry is quite simple. There are only four required fields and those required fields are the case symptoms, the testing status and the outcome of an individual case.

The registry has a capability with the individual recording a record where they get, an access code, that they can link to a medical record in case things change in the case. They can actually re-access the record, make updates, et cetera. So in terms of the clinician interface, it’s actually a very fast an individual record could take most clinicians less than two minutes to enter into the registry itself. Then you asked about the data and you know of course the hypothesis generated are only gonna be as good as the quality of the data entered and we are going to have to do some sifting of those entries in the back-end as we say. You know and that’s really going to result in a variety of subgroups. You can sort of imagine subgroups based on testing status based on, looking at outcomes based on different single or combinations of clinical symptoms. We may look at subgroups based on provider type to look at differences in treatment approaches, say between homeopathic providers versus naturopathic doctors versus integrative medicine medical doctors. We will make some definitions in terms of what do we consider a true positive case either due to a confirmed positive test or again, through a certain density of those case specific symptoms that we’re seeing the CDC endorsed in other organizations.

Gotcha. So what’s interesting I, okay, so from a clinician perspective is the thought that, okay, Josh, like anytime someone comes in where you think they might have COVID or they’ve proven to have COVID, just get all that data in. Track, good cases, bad cases, all cases, we just want to see what you’re doing. Or is it like, Oh, I had a really great case, it went well or went terribly and I should probably report it like a interesting enough for like a case report approach versus, no, you just want to capture as much data as possible out there.

Right. Good question. So we’re, we’re really interested in capturing as much data as possible. The overarching aim to the registry project is to document contributions to COVID support. So that could be at the preventative level. That could be again, for individuals that are known to be positive, individuals that are suspected due to exposure, we’re really interested in capturing all contributions to care. That’s the overarching goal of the registry project. A secondary aim is to then look at these subgroups that we think are truly positive, either due to establish testing or due to a certain constellation of clinical symptoms, pull those together and then begin hypothesis generation related to promising individual treatments or possibly protocols. You bring up an important point, which is that clinicians are able to download their entries to the registry on when a record is submitted.

Clinicians have the opportunity to download a PDF that records on their entries to the fields they have completed and that PDF may help augment their clinical record. It may help them organize a case report if they were interested in moving forward with the case report. We do not intend to publish individual case reports from the registry. So that would be up to clinicians. We could help clinicians publish case reports if they were interested, but we’re really looking at more composite data. Then you also bring up another important point, which is what about adverse reactions and what about the importance of collecting, you know, potentially negative outcomes. These are as or more important than favorable outcomes to document. Clinicians may have some reservations around entering, you know, case records that have adverse outcomes.

So we attempt to reassure clinicians by not requiring any contact information, any identifying information about themselves or their practices. There is an optional field that clinicians can enter contact information if they agree to be contacted in the future about something related to their case but it is not a required field. We do specifically prompt negative outcomes that they may have witnessed during the course of their care. And we also ask a separate question related to resolution of any untowards effect that they may have observed during the course of their care.

That’s cool. So, I think the registry is a great idea and again, we’ll link to it and we’ll try to promote it as well. One way I’m thinking about it, is it’s almost like a signal detection, right? Like a bunch of people desperately are trying ‘X’ herb they reporting good outcomes, and we don’t know anything about it in the literature. Let’s go study it or something. Then also this idea of case reports: you know, I’m interested like in this emerging situation, in different ways, I’ve never seen science move this fast, like it’s amazing to me. Right? Internationally everyone is coming together it’s, it’s quite fascinating. If it wasn’t so terrifying it would be quite fascinating. So I’m just thinking about how we do this research and especially in integrative medicine, we’re usually underfunded.

So you know, there is this registry idea, which I think is really exciting. We talked about case reports. There’s also a rapid reviews, which I’d like you to speak to if you can. I know we’re both kind of involved in that. Then, and I know we’re kind of close to time here, but are there other ways that you envision besides, you know, on the bottom level that you were describing the sort of the basis level of registries and case reports and the, you know, sort of hires, evidence synthesis, level of reviews. You know, are there other areas where integrative medicine research can play a role? Is funding a major limitation there? Like how, how else if appropriate, do we help in this situation?

Yeah, right. Great, great questions. Let me talk briefly about rapid reviews. As you know, there is an effort underway by the world naturopathic Federation and other agencies in support of the World Health Organization to synthesize available evidence on, a sort of hand selected grouping of natural therapies that have promise for COVID. The expectation isn’t in fact that there will be specific evidence to COVID treatment prevention or cure, but rather synthesizing the evidence about these products based on indirect evidence for other types of viral infections; respiratory system outcomes. For example, from, other types of viral infections, perhaps prevention of respiratory viral infections based on fundamental biochemical requirements for an individual nutrient that may be deficient or insufficient.

You know, we are well aware of things like zinc and vitamin D, we know that these are common deficiencies. We know that these nutrients are fundamentally required in many cases to immune response to viruses and or modulation of the immune system to tone down inflammatory responses and things like that. That’s where this group is starting with rapid reviews and I think really there’s a few goals with that. One goal is to be a part of the conversation and to show that we are able and willing to step up to this charge to contribute evidence in situations where there isn’t a whole lot of high quality evidence to date. You know, that brings up a really important point, which is you mentioned the rate at which science is moving right now.

It is moving very fast and part of me questions whether it’s moving too fast and that you know, we’re seeing, preprint servers getting populated with very early drafts of materials that have not been vetted by peer review. We’re seeing some weak clinical research designs that are leading too quickly to publication. Those publications are effecting policy and endorsements for individual treatments that may have on towards effects that have never been formally studied population wide. And there’s a lot of potential harm that could result from that type of practice. Then we also see of course a political influence on the research that is being published and where it’s coming from. Some filtering that is happening in science in general, where there may be pressures to not publish a negative result in some cases.

I do think that we need to be really careful. I’m enthusiastic about some of the changes as well because I think information is being shared more quickly. But I do think that the scientific community has a responsibility to make sure that the quality of evidence or the work being done at any stage is as high a quality and that limitations, if there are limitations, are disclosed really openly. So those are some concerns that I would have. Then finally, in response, how else can we contribute? You know, I think the traditional complementary integrative health and medicine community are subject matter experts in fields of medicine of care that other health professionals have very limited understanding of. I think especially in a time like COVID-19, where really societally we need to test every promising therapy that has a mechanistic rationale for treatment, for prevention or as you know, supportive care, rehabilitative care.

So I am hoping that there is some use of providers in this community for their subject matter expertise and that we actually see medical centers embrace some of these strategies towards, you know, repleting deficient nutrients and looking at, you know, natural therapy based protocols, formally in the context of randomized controlled clinical trials, whether they be in one setting or whether they be across clinical networks. We’ve seen some endorsement of integrative medicine protocols. I’m thinking of East Virginia medical center as one example where physicians in that medical center have openly endorsed and published treatment protocols that include many nutritional interventions in combination with any pharmaceutical interventions and they are innovative and they are also unproven and experimental. There’s already been some pushback with those protocols, saying that it’s irresponsible to disseminate those protocols in the absence of randomized controlled trials.

So I think that there’s a balance with that. Again, I think that we know that some nutrient deficiencies are bad when it comes to viral infection and outcome for viral infection and that it’s actually just part of medicine to think about replacing those nutrients. In other cases, I think this can go too far and you know, clinicians using therapies without appropriate assessment, or without consideration of interactions with medications. Then just the fact that, we really don’t know how many of these therapies might interact, especially in severely emergent cases.

Really good points. Well, thank you so much for your time, Dr. Bradley. I appreciate it. I think it’s neat. It’s interesting to think about us integrative medicine researchers interacting on the sort of, in the trenches level and up in the review level. Then I liked the idea of in the middle they’re serving as content experts because you’re right, I think that is a really excellent place for us and we should be collaborating. There are other perhaps better funded resources and other communities where they can knock out some randomized control trials or observational studies where they might need our expertise as well. So thank you so much for your time. Fascinating conversation, and we’ll talk to you again soon. Thanks for the opportunity, Joshua. I really appreciate it.