Most Fibromyalgia Research is Worthless

Most Fibromyalgia Research is Worthless

I make it a point to try to be aware of all fibromyalgia research that is published by using PubMed’s free subscription service (http://www.ncbi.nlm.nih.gov/pubmed/). I get to read all of the abstracts this way and if I find articles that are of special interest to me I try to download them. PubMed reports 659 publications in the last 12 months relating to fibromyalgia. For those who are interested, there are 9,366 articles listed in the all the years that data are available. For 1990, the year the American College of Rheumatology 1990 fibromyalgia criteria were published, PubMed cites 95 articles. If you think that after all these years of research you and your patients are much better off, think again. A kind, conscientious physician treating a fibromyalgia patient in 1980 or 1990 will have done as well as the 2016 health workers with access to all of these new publications and expensive if not very efficacious medications.

Of all the 9,366 articles on fibromyalgia indexed in PubMed 1,268 have an attached tag of “clinical trial.” You can get a flavor for the research by looking at the two most recent articles. The first is titled, “The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial.” That led me to ask myself. “Why would anyone want this information or want to do such a study?” The authors sav, “Patients with fibromyalgia frequently present with symptoms similar to those experienced by patients with gluten-related disorders, raising the possibility that a subgroup of these patients could be experiencing underlying gluten sensitivity. This study aimed to evaluate the effects of a gluten-free diet (GFD) compared with a hypocaloric diet (HCD) among patients with fibromyalgia? Well, the reason they did it was [they say] “…the possibility that a subgroup of these [fibromyalgia] patients could be experiencing underlying gluten sensitivity.” One reason for publications like this one is not quite the old “publish or perish.” Instead, think that the authors like a little of the glory that comes from being “scientists” and publishing “research.”

The second article is “Safety and efficacy of pregabalin in adolescents with fibromyalgia: a randomized, double-blind, placebo-controlled trial and a 6-month open-label extension study.” This is a special class of article,” one sponsored, funded, written and analyzed by Pfizer and led by physicians with a very long conflict of interest list. Pfizer has a long history of government fines, corrupt practices and ghost (or semi-ghost) written articles. The article concludes, “while this trial did not meet its primary efficacy outcome, improvements in secondary outcomes of pain and impression of change, together with a safety profile that was consistent with the known profile in adults with FM, suggest that patients might benefit from pharmacological treatments.” This isn’t the first time in Pfizer clinical trials that the authors point out the effectiveness of drugs that failed to meet their primary outcome goals. Few know that “Pfizer” is an old Klingon word that means beware.

Bad study design is a big problem

1) Normal controls. Most non-treatment studies of fibromyalgia make use of “normal” controls. This turns out to be a fatal flaw because persons with fibromyalgia virtually always have more severe abnormalities than healthy persons. They will suffer more, have greater costs, social disruption, pain, comorbidity, psychological distress. It doesn’t matter what you study if it is perceived to have some internal meaning. Studies against normals will tell you just what you always knew, fibromyalgia patients have more problems than those without fibromyalgia. Additional studies showing that patients with fibromyalgia have more of A, B and C are valueless. More than valueless, they tend to make clear that the authors don’t really understand the nature of fibromyalgia. Pfizer sponsors many studies that show how bad it is to have fibromyalgia.

If one wants to understand how those with fibromyalgia differ from those with pain who do not satisfy fibromyalgia, then controls have to come from pain groups. Because persons with fibromyalgia also usually have other comorbid illnesses and differences in psychosocial status, good studies of fibromyalgia need to seek similar (not normal) controls and have sufficient appropriate covariates. Many MRI studies, for example, that use normal controls may find differences that are not so much due to fibromyalgia as to other common comorbid symptoms. An example of this problem is that published studies began to report peripheral nerve abnormalities in fibromyalgia compared with normal controls. However, non-fibromyalgia pain controls also had such abnormalities. A number of early studies touted fibromyalgia vs. control data as examples of underlying abnormalities in fibromyalgia.

2) Biased studies and blinding. Convenience sample of volunteers with fibromyalgia as well as normal controls are usually biased, often in ways that are difficult to fully understand. Such biases are very common and truly invalidate studies, and statements by authors that there may be “limitations” never solve the problems. Fibromyalgia studies often have diagnosis and outcomes evaluated by persons who have an interest in the outcome. Studies that do this often get the results that the authors want.

3) Fibromyalgia studies are often underpowered, poorly analyzed and described. Only a small fraction follow guidelines for proportion publications.

4) Fibromyalgia studies often ask participants to remember events from many years in the past, something that always leads to unreliable data.

5 P-Hacking or taking multiple looks at the data before picking the analyses is common.

Why do “investigators do fibromyalgia studies? Because it is easy to find patients and there are always abnormalities. If you look hard enough almost any question can seem publishable.  As I sit here with a cat at my side and sun streaming in the window, I wonder if cats or weather have something to do with fibromyalgia? Not a bad guess; more than 2,000 hits on pets and fibromyalgia in Google scholar. Weather and fibromyalgia? More than 5,000 hits. Chinese food? Not so good. Only 103 hits.

11 Comments

  1. I love the humor with which Dr. Wolfe scalds the cumulative fibromyalgia literature. Everything he says is accurate.

    Impaired reasoning and scientific rule-breaking have marked the studies on this subject since 1967.

    One key problem over the years, as Dr. Wolfe emphasizes, has been that the popular study design (“normal controls”) has allowed flagrant nonsense to be spoken. This nonsense was compounded by the failure of peer review to expose the lack of credibility in such studies. Fundamental flaws vitiate 99% of everything written about the patients labeled as fibromyalgic — and that’s speaking conservatively.

    Do you know of any studies whose design truly aims at finding whether pain perception, psychology, behavior, neurology, immunology etc are truly different in fibro-labeled persons than in matched persons with various well-understood pain disorders? They are few indeed.

    To support Dr. Wolfe, I’ll resort to quoting myself: “… use of a normal control group eliminates, at the design level, the possibility of determining whether brain circuitry alterations in patients labeled as having fibromyalgia differ from those in patients with pain-causing disorders known to be peripheral and nociceptive.”

    Lampman, J. H. (2014), What is the Proper Control Group for a Fibromyalgia Study? Comment on the Article by Loggia et al. Arthritis & Rheumatology, 66: 1684. doi:10.1002/art.38397

  2. Firstly, I realise that this thread is related to research , however , it caught my eye and I was compelled to type.In my limited experience of Fibromyalgia research the problem has been the research has looked at treatments without actually finding the cause. My interest has been drawn towards the work of John C Lowe , who likened Fibromyalgia to undiagnosed hypothyroidism , affecting all tissues and systems of the body. In the UK we use an inadequate pituitary test to diagnose hypothyroidism which does not address the state of tissue hypothyroidism .Looking at the blood profiles of patients presenting with FMS , the majority do not have a standard screening , the screening was deemed to be negative and the FMS diagnosis was slapped on. Patient treatments proceed according to NICE guidelines ( don’t we all love EBM) , which frankly do not help the underlying condition ( whatever that may be) What a waste of resources and scant disregard for patients. Interestingly ,some patients who are concurrently treated for hypothyroidism, adequately, see an improvement in their FMS, cholesterol, BP and anxiety , all of which , when treated separately add to the NHS drugs and benefits bills.In this day and age we should be doing better.
    The American Journal of Medicine (2009) Vol 122 no 12A
    A. Lowe, J.C., Honeyman, G., and Yellin, J.: Lower resting metabolic rate and basal body temperature of fibromyalgia patients compared to matched healthy controls. Thyroid Science, 1:T1-T18, 2006.
    B. Lowe, J.C., Yellin, J., and Honeyman-Lowe, G.: Female fibromyalgia patients: lower resting metabolic rates than matched healthy controls. Medical Science Monitor, 12(8):CR1-CR8, 2006.

  3. ” More than valueless, they tend to make clear that the authors don’t really understand the nature of fibromyalgia. Pfizer sponsors many studies that show how bad it is to have fibromyalgia.”

    Dear Professor Wolfe, your comment raises the important question – What is the nature of fibromyalgia?

    I have always found it difficult to know whether my rheumatology colleagues were referring to a symptom, a syndrome, or to a distinct disease. As you know, in my opinion the constellation of clinical phenomena are best classed as a “symptom cluster”.

    But given that fibromyalgia now has its own ICD-10 code, this question needs to be addressed with some degree of urgency. Otherwise many of those suffering from persistent pain of unknown cause are at risk of being classified as having “fibromyalgia”. Furthermore, as it has been claimed that fibromyalgia can co-exist with any other painful condition, it may prove well-nigh impossible to delineate fibromyalgia from the other condition .

    I sincerely hope that the American College of Rheumatology can sort out the current state of diagnostic confusion before third party funders of diagnostic and treatment services decide to “pull the plug” on fibromyalgia.

    • And as you know, in my opinion the constellation of clinical phenomena is best classed as “a symptom cluster” of diverse and varying standard myotendinous ailments clarified by close and concrete physical examination and careful history.

      Common in this cluster are kinetic ailments such as trapezio-cervical, iliolumbar, gluteus medius, humeral epicondylar strain disorders. These may develop sequentially and cumulatively, fluctuating over the months and years, and may evolve into a clinical-level issue perceived by the individual as “pain all over.” Humanity has a myotendinous resiliency spectrum and those people on the farther end of this spectrum can get into more or less continuous physical annoyance. Only the prepared clinician can deconstruct and evaluate the several contemporaneous problems and show that the patient’s suffering is not the result of a mystic brain disorder. If he/she fails in this responsibility, the result is the nonsense of the “fibromyalgia” diagnosis.

      I feel that the code assigned to fibromyalgia needs to be reassigned to multiple-site myotendinous pain disorder, with subcodes for the top 4 sites of biomechanical pain sources.

      • With respect, Dr Lampman, in my opinion the appellation of “myotendinous pain disorder” is mere conjecture, as is your concept of “kinetic ailments”. But I do agree with you that the proponents of “centralized pain” have not been successful in defining such a “mystic brain disorder”.

      • Apologies for this delayed question, I just read this thread after the Sarno thread grabbed my attention. How, if you would kindly explain, does one identify/diagnose the “strain” of which you speak? Are there clinical signs other than pain, or tests? Thank you.

  4. Dr. Wolfe:
    I have always enjoyed your candor:) Do you think that the extremes of fibromyalgianess/PSD [1] are anything more than pain catastrophizing by another name[2,3]. In a similar vein, might not the right-ward extreme of any subjective pain self-report – DAS28, NRS, VAS, Wong-Baker, WOMAC, MIDAS, ODI/NDI, etc – be better thought of as a measure of catastrophizing rather than disease activity.

    Thank you for keeping this blog up to date.

    1. http://www.ncbi.nlm.nih.gov/pubmed/24497433
    2. http://onlinelibrary.wiley.com/doi/10.1002/art.21865/full
    3. http://www.ncbi.nlm.nih.gov/pubmed/27584819

  5. We need to take the study and treatment of fibromyalgia away from rheumatologists, many of whom don’t want it anyway. That specialty was assigned it in error, as we know, based upon faulty assumptions. I hesitate to suggest an appropriate specialty as my experience with various specialists has also been less than enlightening.

  6. This article hits the nail on the head. I have been a fibromyalgia sufferer for about 30 years, and upon reading about new research, discoveries, and so on, I become more frustrated. One small example: Using a TENS machine to relieve pain. Well, anyone with FM wouldn’t want a TENS machine near them when they are in pain and hypersensitive, even to touch. Another, treating with analgesics. I could take a bottle of OTC pain meds, and it does nothing.
    Thank you for writing this article. It helps to confirm that my frustration and yes, anger, is justified.

  7. The situation is really crazy. The new EULAR guidelines recently came out. They suggest that the first line of treatment FOR EVERYBODY should be physical exercise. Yet there is no adherence, the studies have no long term follow-up, and no intention to treat analysis. Everybody “knows” that they should get more exercise, the problem is that they cannot bring themselves to do it. Also there is evidence in CFS that exercise may show enhanced negative gene expression and the marathon runner in pain, needs to do the exact opposite and relax. The pain network and neuroscience is ignored. A bit of education, but no diagnosis. How can this be??? At least they no longer recommend pharmacological products which just make things worse, over time, for chronic pain.

Leave a Reply

Your email address will not be published. Required fields are marked *