MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Recently, I received this comment from a reader:

Edzard-‘I see you do not understand much of trial design’ is true BUT I wager that you are in the same boat when it comes to a design of a trial for LBP treatment: not only you but many other therapists. There are too many variables in the treatment relationship that would allow genuine , valid criticism of any design. If I have to pick one book of the several listed elsewhere I choose Gregory Grieve’s ‘Common Vertebral Joint Problems’. Get it, read it, think about it and with sufficient luck you may come to realize that your warranted prejudices against many unconventional ‘medical’ treatments should not be of the same strength when it comes to judging the physical therapy of some spinal problems as described in the book.

And a chiro added:

EE: I see that you do not understand much of trial design

Perhaps it’s Ernst who doesnt understand how to research back pain.

“The identification of patient subgroups that respond best to specific interventions has been set as a key priority in LBP research for the past 2 decades.2,7 In parallel, surveys of clinicians managing LBP show that there are strong views against generic treatment and an expectation that treatment should be individualized to the patient.6,22.”

Journal of Orthopaedic & Sports Physical Therapy
Published Online:January 31, 2017Volume47Issue2Pages44-48

Do I need to explain why the Grieve book (yes, I have it and yes, I read it) is not a substitute for evidence that an intervention or technique is effective? No, I didn’t think so. This needs to come from a decent clinical trial.

And how would one design a trial of LBP (low back pain) that would be a meaningful first step and account for the “many variables in the treatment relationship”?

How about proceeding as follows (the steps are not necessarily in that order):

  • Study the previously published literature.
  • Talk to other experts.
  • Recruit a research team that covers all the expertise you need (and don’t have yourself).
  • Formulate your research question. Mine would be IS THERAPY XY MORE EFFECTIVE THAN USUAL CARE FOR CHRONIC LBP? I know LBP is but a vague symptom. This does, however, not necessarily matter (see below).
  • Define primary and secondary outcome measures, e.g. pain, QoL, function, as well as the validated methods with which they will be quantified.
  • Clarify the method you employ for monitoring adverse effects.
  • Do a small pilot study.
  • Involve a statistician.
  • Calculate the required sample size of your study.
  • Consider going multi-center with your trial if you are short of patients.
  • Define chronic LBP as closely as you can. If there is evidence that a certain type of patient responds better to the therapy xy than others, that might be considered in the definition of the type of LBP.
  • List all inclusion and exclusion criteria.
  • Make sure you include randomization in the design.
  • Randomization should be to groups A and B. Group A receives treatment xy, while group B receives usual care.
  • Write down what A and B should and should not entail.
  • Make sure you include blinding of the outcome assessors and data evaluators.
  • Define how frequently the treatments should be administered and for how long.
  • Make sure all therapists employed in the study are of a high standard and define the criteria of this standard.
  • Train all therapists of both groups such that they provide treatments that are as uniform as possible.
  • Work out a reasonable statistical plan for evaluating the results.
  • Write all this down in a protocol.

Such a trial design does not need patient or therapist blinding nor does it require a placebo. The information it would provide is, of course, limited in several ways. Yet it would be a rigorous test of the research question.

If the results of the study are positive, one might consider thinking of an adequate sham treatment to match therapy xy and of other ways of firming up the evidence.

As LBP is not a disease but a symptom, the study does not aim to include patients that all are equal in all aspects of their condition. If some patients turn out to respond better than others, one can later check whether they have identifiable characteristics. Subsequently, one would need to do a trial to test whether the assumption is true.

Therapy xy is complex and needs to be tailored to the characteristics of each patient? That is not necessarily an unsolvable problem. Within limits, it is possible to allow each therapist the freedom to chose the approach he/she thinks is optimal. If the freedom needed is considerable, this might change the research question to something like ‘IS THAT TYPE OF THERAPIST MORE EFFECTIVE THAN THOSE EMPLOYING USUAL CARE FOR CHRONIC LBP?’

My trial would obviously not answer all the open questions. Yet it would be a reasonable start for evaluating a therapy that has not yet been submitted to clinical trials. Subsequent trials could build on its results.

I am sure that I have forgotten lots of details. If they come up in discussion, I can try to incorporate them into the study design.

 

 

39 Responses to Designing a decent trial of low back pain

  • Edzard- thank you very much for your detailed exposition of what will constitute a reliable trial of a treatment for LBP. Grieve’s book or any other is not a substitute for anything. It is a compendium of his life’s work and experience in the field. There can be no objection to a well conducted clinical trial of anything BUT it’s results cannot be a final word on such a complex subject as LBP ( or most other things also). Grieve’s book (2nd edition) lists more than 2500 references and recognizes the galaxy of opinions and conclusions and conflicting hypotheses that they contain. Assuming for the moment that no such trial meets or has met your satisfaction do you think that Grieve’s and others’ lifetimes work in the field and the positive experiences of countless patients count for nothing and have no validity for efficacy? If you do think ‘there may be something in it!’, on what evidence would you base this view or conclusion?

    • Oscar Wilde said: “Experience is the name we give to our mistakes.”
      I’d say that experience can often be the name healthcare professionals give to their mistakes; it is far too unreliable to be taken for evidence in healthcare. that is not to say that it is useless – quite to the contrary! It can be an invaluable starting point for research.

      • Another quote is germane to chiros and evidence:

        “It is difficult to get a man to understand something, when his salary depends on his not understanding it.”
        ― Upton Sinclair, I, Candidate for Governor: And How I Got Licked

        • Alan-Sinclair’s quote of course has some validity, more so with some than others, but comes nowhere near close to all the other psychological and many other factors that result in our ‘understanding’ of something. It might be considered an extreme oversimplification.

          • It does raise the question as to where is the persuasive, robust evidence for chiropractic? If it is as effective as many chiros claim, where is the evidence that would convince even the most skeptical of skeptics? Why are chiros not striving to produce the evidence for the practice that so many are making their daily living out of? If they were able to produce that evidence, we might quickly see chiropractic departments opening up in every NHS hospital, relieving the burden on so many other departments, not to mention relieving the suffering of patients.

          • Alan- I have made no claim for persuasive, robust evidence for chiropractic in anything I have written nor will I. Nor do I answer for most anything they do except in the right hands have some expert competence in manipulative skills. I think what I have written should be clear: I asked about 4 repeated questions, all very easy to answer and received no reply from Edzard, except finally an ad hominem ‘twit’ reference. That’s OK because I don’t think it denigrates me but does make public flaws in his approach to these matters. I repeat, your concerns are not something I have alluded to nor have to answer for.

          • Alan- I have not , will not and cannot provide robust, persuasive evidence for all that is encompassed by chiropractic. All I originally contended was that in well trained chiropractic hands it was reasonable to assume they were capable of manipulation of joints are than those of the lower back. With the dialogue expanded this and most other straight forward questions of mine, although repeated, remain unanswered by Edzard. It has resulted in his ad hominem aside about a ‘belligerent twit’ . This attempt to denigrate me , sadly, publicly demeans him.

          • Chiropractic is a multimodal approach.

            Regarding the daily living…

            https://www.ziprecruiter.com/Salaries/What-Is-the-Average-Chiropractor-Salary-by-State

            IMO the main issue re lack of robust research falls upon the colleges. When i was doing my research residency i was told that the research dept was not profitable…the college lost money every year on the dept. Of course grants and patents are the way to go if one can get them.

            Most chiro students enter to become chiropractors, not researchers.

            The CARL program is a good start IMO.

          • Leonard Sugarman said:

            I have made no claim for persuasive, robust evidence for chiropractic in anything I have written nor will I.

            I never said you did. But I hope you agree that the elusive nature of the evidence for what so many chiros are making a living out of is, at least, perplexing.

            I have not , will not and cannot provide robust, persuasive evidence for all that is encompassed by chiropractic.

            I didn’t really ask for that: but it would be good if chiros could make a start sometime.

            All I originally contended was that in well trained chiropractic hands it was reasonable to assume they were capable of manipulation of joints are than those of the lower back.

            Do you mean “other than those of the lower back”? But anyone can ‘manipulate’ joints: the question is whether any benefit outweighs the harms.

          • I am always amazed how people who are essentially my GUESTS on my blog behave and then go into a sulk when I tell them to go yonder and multiply.
            anyway, I have stopped this now because:

            Twelve simple rules must be observed when commenting on my blog.

            All posts should be in understandable English; with rare exceptions, I will not post comments that I find incomprehensible.
            Libelous statements will not be posted.
            Personal insults will not be posted and trolls will be banned.
            People who keep insulting others will be banned.
            Comments must be on-topic.
            Nothing published here must be taken as medical advice.
            All my statements are comments in a legal sense.
            Conflicts of interest should always be disclosed.
            I will stop discussions on any particular topic if I feel that enough has been said and things are getting boring or repetitive.
            I will not post comments which are overtly nonsensical.
            I will prevent commentators from monopolizing the discussion.
            Please use the same name you’ve used before when commenting — it doesn’t have to be your real name, but it helps others who are trying to follow the discussions.

          • DC said:

            Chiropractic is a multimodal approach.

            And? All that might mean is that there are a number of different practices that chiros need to be researching and providing evidence for.

            Regarding the daily living…

            https://www.ziprecruiter.com/Salaries/What-Is-the-Average-Chiropractor-Salary-by-State

            Not sure why that is relevant. It redirects to the UK site for me but this site gives the median salary for a chiro in the US as $154,000.

            IMO the main issue re lack of robust research falls upon the colleges. When i was doing my research residency i was told that the research dept was not profitable…the college lost money every year on the dept.

            It isn’t necessary that research be profitable: what matters is whether chiros have the evidence that what they do does more good than harm and that the training establishments are teaching what they know there is good evidence for.

            Of course grants and patents are the way to go if one can get them.

            Grants are not the only source of funding, of course, but what have patents got to do with it?

            Most chiro students enter to become chiropractors, not researchers.

            I don’t doubt it, but that’s just another excuse.

            The CARL program is a good start IMO.

            “A good start”…

          • In my experience, chiro-research rarely gets funded because the applications lack scientific rigor.

          • @Edzard

            You’d have thought all chiros and trainers with an ounce of integrity would be doing all they can to publish robust evidence for what they do…

          • integrity seems to be the keyword here…

        • May not be limited to chiropractors…

          “Trial evidence for the other six procedures showed no benefit over non-operative care.”

          https://www.bmj.com/content/374/bmj.n1511.long?fbclid=IwAR3Tb4kWqGzZh5jgVl8HH2_ONijr-04ga2HcgrVQRpIrKqFfRdUdRJqIIzI

      • Edzard- 2500 + references represents a whole lot of experience beyond any one person e.g Gregory Grieve: in fact not just experience but a whole variety of varied and conflicting evidence. It seems in answer to my question ‘is there something in it?’ that the only value you place on say Grieve’s work and many others is that it can be an invaluable starting point for research. And by that I presume you mean the RCT of which you expound so well and is of great value when possible. Without say any positive trial outcomes, so far, are there ANY other types of evidence that you could accept for the confident practice of a health care intervention? Without the ‘certainty’ or benefits outweighing risks trial or epidemiological findings, would you allow any treatment for a possible medical condition of your own? Where do you stand or what do you think about any acceptance of ‘doubtful’ medical practices? We would all prefer SBM but is it always possible? You will know by now that I think not!

        • of course, when no sound evidence is available one has no other choice than to go with less sound evidence.
          the principle is this: if you can, go with the best evidence that exists.

          • Edzard- I could not agree more with that sentiment but there may be, and we have, some disagreement about ‘sound evidence’. You may consider it possible to produce a RCT that will/could provide better evidence than other possibilities: in fact you seem to think it IS the best evidence , for or against a procedure. Better than all other evidence? I would agree IF it were possible to know exactly the anatomical and physiological location of the cause of the symptoms and have reproduceable exact skills , forces used etc. and in enough equivalent patients and therapists. In my humble view it is a minefield of uncertainty and will not produce the ‘best’ evidence for a procedure- for or against. It will be evidence but perhaps of no more strength than an expert clinician applying his skills and scientific knowledge to help an individual patient(s), and reporting the results. Far from perfect, but useful. The RCT, double blinded or not, is most suited to distinguish therapeutic value, among options, for example pharmacological substances and anything where the variables are controllable. I know you disagree .Oh and that question: ‘do you think there’s something in it and if so why’?

          • the best evidence is the one that is least open to bias.
            I have tried to show you in my post that the variables you mention are controllable.

          • Edzard-if the variables are controllable and the diagnosis of the origin of the cause of pain is established ( and there can be numerous possible structures involved with no consensus on these matters) then there must be some very good RCT( in your view?) regards low back pain. Do they establish any validity or otherwise of therapeutic manipulative treatments? Have you had experience within the ‘manipulation’ field that caused you to read 750+ pages of Grieve’s Common Vertebral Joint Problems,2nd edit.? His eclectic approach, using abundant scientific references and much else would seem to have minimized his bias. From your experience do you think there is any value , beyond placebo, in manipulative therapy of painful, restricted motion of vertebral joints and surrounding tissues? If not then we have nothing more to exchange on the subject but if you think there is some value- then WHY? So far you have not answered this question!

          • sorry – too many questions and no time

          • Edazard- there were just two crucial questions 1. anything in it? 2. if so why? There is a smatter of intellectual dishonesty here by avoidance of the questions that have been asked at least 3 times. I have enjoyed our exchanges.

          • “a smatter of intellectual dishonesty”
            oh dear!

          • Leonard,

            The man wrote a whole blog post just for you, patiently addressing your previous posts. And all you got to argue about is a 2nd edition of some textbook that was written in 1988 with no new edition thereafter. Other than hanging on to this 30+ year old textbook, do you not think that the field of chiropractic advanced in the last 30+ years? If you are unable to cite any new scientific studies in the field, then I seriously question as to what you are arguing about. Other than arguing for argument’s sake.

          • Jack-no new edition after 1988 because Gregory Grieve died, 2001. He had developed and progressed with and on giants shoulders and he wished for this to continue with a younger generation coming through. I only chose his book because it impressed me among so many other books in its organization, very clear writing and a great deal more. I am sorry that you do not understand the arguments and in future I will try to express myself in a clearer manner. If you read my original question to Edzard it stemmed from his comment about the competence of chiropracters to manipulate other than for the low back. The discussion expanded. I make no claim for chiropractors other than they use similar techniques ( although not necessarily identical) as osteopaths, physiotherapists, some orthopedics and other practitioners of the arts. In skilled hands they can be very effective for relief of painful and ‘stiff’ joints. Their science I will leave to others more qualified to comment.

          • Jack-no new edition [of Grieve] after 1988 because Gregory Grieve died, 2001.

            There is little hindrance to a reference of quality to be continued to be published in new editions, provided the copyright holders agree. Gray’s Anatomy continues to be published in new editions, even though its author, Henry Gray, died in 1861 and its illustrator, Henry Vandyke Carter died in 1897.

            It was first published in 1858 and is currently in its 42nd edition, published in 2020.

  • Usual care? That could get messy.

    “Those studies estimated that 28% (95% confidence interval, CI: 19.7–38.6) of health care for low back pain in Australia (based on 164 patients receiving 6488 care processes)5 and 32% (95% CI: 29.5–33.6) of health care for low back pain in the United States of America (based on 489 patients receiving 4950 care processes)6 was discordant with clinical guidelines.”

    Bull World Health Organ. 2019 Jun 1; 97(6): 423–433.

  • Jack- advances in manipulation therapy will mainly be in the scientific domain not the actual physical techniques. To know about what I argue go back to my original question to Edzard which was simply about the reasonableness of allowing some competence of chiropractors in manipulation of joints other than the lower back. The discussion expanded- and yes Edzard was very patient and informative, until the very end when he dodged my two questions. If you think that a 30 year old medical textbook- which was just one of a selection- has no value in contributing knowledge to treating patients I’m afraid I will leave you in your ignorance.

    • Leonard, I am not commenting on whether a old text book can contribute to treating patients or not. But rather I am pointing out that when repeatedly asked to cite any new studies you dodge that and keep going back to a 30 year old textbook. It is hard to believe that are no advances in the fields that can add to the knowledge presented in the old textbook. All this makes me think that you don’t know of any new advances in the field or just don’t care to bring any to the conversation. Anyway, I will let you wallow in your outdated information.

      • Jack-thanks for that profound understanding of all that has transpired on this blog. Whoever said or was arguing that more modern texts wouldn’t have more up to date references. Suppose I select a more recent text ( of which I have many), not on chiropractic particularly, but manipulation in general and matters related, and notice numerous references, maybe hundreds, sighted after 1988, which ones would you prefer me to quote? If you like I’ll give you some text references and you can check for yourself. Your call.

        • Oh..so you do know there is more up to date information available! You probably also know where to find it but choose not to cite any in two dozen or so posts you wrote in this discussion that spans multiple threads.

          Why are you asking me which up to date references you should be quoting? You started this discussion and you should be able to do that yourself without anyone’s help.

          While you were bickering and beating a dead horse with an old textbook, EE wrote a blog post on designing a trial on LBP and reviewed a trial on LBP. Maybe we call learn something from EE. I will take EE’s que and not engage with your any further. have a nice life!

      • Of course there is continued research. A simple place to start is a Google Scholar search.

        https://scholar.google.com/scholar?as_ylo=2021&q=spinal+manipulation&hl=en&as_sdt=0,50

  • Edzard- you took time to write ‘oh dear’ so why not instead answer the questions? Let me rephrase them. Do you dismiss manipulative treatment with the same strength as you do say homeopathy? If not, why not?

      • Edzard-you clearly have some difficulty with my questions and I think I know why you will not answer. I have read a bit on this very question in the past and was trying to get your opinion, which to the death you won’t answer. If I’m a twit by asking repeatedly a few questions you haven’t the courage to answer then I know I am in some very good company and do not take offence at your ad hominem aside.

      • Edzard- I have just finished your fascinating and informative book ‘A Scientist in Wonderland’. In the Addendum you state ‘Chiropractic or osteopathic spinal manipulation might well be useful for back and neck pain…’ which is part answer to the main questions I posed you. I would still like an answer, which I now know will not be forthcoming, to why you should think such a heretic notion!

    • That is Edzard typical response when he doesn’t want to answer a question.

      All one has to do is look at the many SR and MA on the topic re back pain. Most come to the same conclusion…SMT is as good or better than other approaches.

      Do we know exactly how it works? Nope. Some evidence of reduce muscle spasms, overall reduction in inflammation and activates descending inhibitory pain pathways.

      Best when combined with other approaches like rehab and exercise…which most chiropractors do.

      Current research is looking more into subgrouping and subtyping, responders vs nonresponders, clinical prediction rules, other conditions, etc.

      • not really!
        my standard response: when someone behaves like a bot and tries to insult me (“intellectual dishonesty”) I send him/her my blog post that indicates I had enough.
        I did answer about a dozen questions of this chap, had I continues answering what he called his last one, I fear, it would not have been his last.
        it certainly has nothing to do with me not wanting to answer a question.

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