Evidence and Truth: WTF (Where’s the Fact?)

Inconsistency bothers me. When I’m interviewed, I answer that I wanted to build this website because there is so much “wrong” information about Rheumatoid Arthritis.  Too many common generalizations are actually incorrect. Truth about RA can be hard to find. Maybe this is an explanation in part.

I read something amazing today on The Scientist: Evidence: A Seductive but Slippery Concept.

disco ballFrom the article: “Finally, even some of the strongest proponents of evidence-based medicine have become uneasy, as we have increasing evidence that drug companies have managed to manipulate data. In the heartland of evidence-based medicine—drug trials—the “evidence” may be unreliable and misleading. All this doesn’t mean that evidence-based medicine should be abandoned. It means, rather, that we must never forget the complex relationship between evidence and truth.”

From the podcast on the same page: Larry Green: “A general critique growing… on rules of evidence… health sciences, most particularly medicine, have tended to become, I dare say, obsessed with internal validity to the point that they have put a finer and finer point on the degrees of certainty that the intervention being tested could be said to be the sole cause of the health outcome … & that obsession has caused the research to become more and more tightly controlled to the point that we have lost most of the external validity, the ability to generalize from the research to other settings and other patients and populations and… Left us with a literature that is … increasingly irrelevant… to most of what practitioners and patients are asking for.” In reply, Peter Frishauf, Founder of Medscape: “We’re missing the forest because we are counting all the trees.” Richard Smith, former editor of British Medical Journal: “We need research that will inform what happens in the real world.” Larry: “Am I represented in those studies? …They end up with an unrepresentative sample.”  Hear the full podcast on the Society for Participatory Medicine’s website.

Last week: 20 facts on RA I’ve learned from patients. Now: 3 RA truths?

  • A 30 year old article in Arthritis and Rheumatism states that RA patients cannot be labeled with remission status if they have “clinical manifestations of active vasculitis, pericarditis, pleuritis or myositis, and unexplained recent weight loss or fever attributable to rheumatoid arthritis.” How many modern sites don’t even list those as related to RA? How many doctors don’t connect these secondary diagnoses with RA? I hear them every day from patients. Did medicine un-learn these facts? I didn’t hear them mentioned in the remission discussion at ACR. See the post and comments on RA fevers for an interesting comparison.
  • It’s well documented that 30% of RA patients do not respond to treatment.  A 20% improvement is called ACR20 and many treatments can claim over 60% of patients respond this well. Considering the up & down nature of most RA, I’ve always thought 2 joints better out of 10 was not so fabulous. Anyway, about 40 or 50% of patients get to an ACR50 level and far fewer reach ACR70. Personally, an ACR70 response would still leave my own life disrupted, so what exactly is an “adequate response”? Why does one well-respected RA researcher from NYU state that only “10% to 15% of patients still do not have an adequate response to treatment”? Why under-state the non-responders by 2-3 times? He is co-author on another article that quotes the 30% measure.
  • Today, I did something I’ve never done before. I argued with medical personnel with regard to my own case. Once upon a time, a rheumatologist told me that CRP is the only measure of RA disease activity, a view becoming more prevalent. Today, a coordinator of a clinical trial told me that in order to qualify for a trial I would have to take all of my powerful CRP-suppressing prescriptions for at least 90 days and then have an abnormally high result. She stated that if the medications suppressed my CRP, then that is proof those treatments “are working” and I do “not need to be in a clinical trial.” I can hardly begin to say how many ways that’s wrong.  Start with the fact that nearly half of RA patients have a normal CRP.

It seems like some are paying attention to neither the forest nor the trees.

Recommended reading:

Kelly Young

Kelly Young is an advocate providing ways for patients to be better informed and have a greater voice in their healthcare. She is the president of the Rheumatoid Patient Foundation. Kelly received national acknowledgement with the 2011 WebMD Health Hero award. Through her writing, speaking, and use of social media, she is building a more accurate awareness of Rheumatoid disease aka Rheumatoid Arthritis (RA) geared toward the public and medical community; creating ways to empower patients to advocate for improved diagnosis and treatment; and bringing recognition and visibility to the Rheumatoid patient journey. In 2009, Kelly created Rheumatoid Arthritis Warrior, a comprehensive website about RA of about 950 pages and writes periodically for other newsletters and websites. Kelly served on the Mayo Clinic Center for Social Media Advisory Board. There are over 42,000 connections of her highly interactive Facebook Fan page. She created the hashtag: #rheum. Kelly is the mother of five, a home-schooler, Bible teacher, NASA enthusiast, and NFL fan. You can also connect with Kelly by on Twitter or YouTube, or LinkedIn. She has lived over nine years with unrelenting Rheumatoid disease. See also http://www.rawarrior.com/kelly-young-press/

24 thoughts on “Evidence and Truth: WTF (Where’s the Fact?)

  • December 9, 2010 at 7:08 am
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    Kelly – once again you’ve hit the nail on the head. Clinical trials are not really designed to produce “cures” OR to treat patients. They are designed to “prove” that the drug at hand 1) won’t kill patients, 2) or at least not kill too many, 3) while reducing some of the disease effects. In order to “prove” these things, they need to control all extraneous variables as tightly as possible. The definitions of “disease state” for clinical trials are not the clinical definitions and may not be related to clinical manifestations at all! They are simply used to limit the trial “tightly.” But frequently they are not even related to the disease!

    Reply
    • December 9, 2010 at 9:24 am
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      Good points on the purpose of trials, Elizabeth. On the other hand, half of the rheum docs I’ve met say that CRP is *the* measure of disease activity & that’s becoming more prevalent according to what I read. There are more 2 points where the CT intersect real / clinical life. 1) When an RA patient has no further treatment options – those 30% of patients who don’t respond to any of the approved treatments – getting into CT is the only option for treatment. 2) The recommendations for how to use the drugs and their so-called success rates are applied to the general RA population, even though they are not tested on a representative sample. This causes improper expectations about success rates w/ tx. This is why patients tell us they are not better, but the docs tell them that they are better since their numbers are improved – and since the statistics that come from the trials say they “should” be “better.” That was off the top of my head but I’ll think about this more.

      Reply
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  • December 9, 2010 at 9:49 am
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    More and more i find ur pages so interesting and learn alot from you…i already had my blood checked and went to the Rheumy and she wanted more blood! The nurse came in and said dont worry..she just wants ur crp..in a low voice! Whats the secret all about nursy? Cant wait to get my copy of med.records w/doctors notes!!!! I learned from you that half of all Rhuematiods(because i wont say arthritis anymore) have normal Crp levels!! This revelation is huge for me! Thanks again Kelly!! you work so hard for us! Im eternally grateful for you and this site!..

    Reply
    • December 9, 2010 at 11:50 am
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      Good luck with your crp Judi. whispering is funny – haha – who knows. As long as your doctor treats you either way, hopefully you won’t need to worry about it too much. (see Julie’s comments.)

      Reply
  • December 9, 2010 at 10:44 am
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    What huge discrepancies between reality and practice. I must say that my rheumatologist doesn’t take my normal CRP ,as evidence I am in remission. He looks at those other factors such as ongoing fever, synovitis, joint pain, fatigue, anemia, etc. It is a relationship of him knowing my disease pattern, over 15 years. His theory seems very contrary to the qualifications needed to get into a clinical trial.

    I don’t understand why there are not clinical trials designed for those RAers who have exhausted the current FDA-approved medicines, without the elevated CRP being that gold standard of clinical trial eligibility. I think Elizabeth had a pretty good answer, but we need to somehow bridge this huge gap. So many are going without any hope of new meds and are losing valuable time.

    Look at how many cancer patients (several who i know personally) who, having exhausted current FDA-approved chemotherapeutic agents, seem to commonly be able to move onto experimental drug trials fairly easily(if the patient desires and a clinical trial is available). I wonder if they have such an unobtainable lab standard to meet, before they are able to begin the drug trials.

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    • December 9, 2010 at 11:37 am
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      Julie that is a fantastic statement. I agree. My kids asked me about “compassionate use” even. With CT, there is sometimes something called “expanded access.” But i have no idea what is required to trigger that. It would have to come from the FDA, with the agreement of the pharm company, I suspect. I’ve never heard of it with RA yet.

      Reply
  • December 9, 2010 at 12:45 pm
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    Excellent read! I feel so privileged to have a provider that understands my medication will alter and suppress clinical labs. Despite having a relatively low Interluekin 6 result my physician stated it does not prohibit me from the trials. That my medications are most likely suppressing my results. He went on to state the negative lab results and why if any reason for them are part of the study as well.

    It is so refreshing to hear this for myself but disheartening as well knowing that is not the case for far too large of the majority out there.

    Reply
  • December 9, 2010 at 1:21 pm
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    You already have some of these points made in previous comments, but I wanted to give you the actual criteria that are used to calculate the ACR20, 50 and 70.

    The ACR70, ACR50 and ACR20 are criteria that have been developed to demonstrate the comparable effectiveness of certain therapies. It is used primarily in clinical trials. In order for a drug to be deemed effective and thus get FDA approval it needs to demonstrate that it actually works. Not only that it works, but that is significantly better than placebo or simple aspirin.

    So the ultimate goal is not to declare someone cured, but to demonstrate that one therapy has a higher probability of improving someone’s condition. It is important that all researchers use the same criteria for improvement so that we can compare the effectiveness of one drug to another.

    Unfortunately, these criteria are not as straightforward as they sound. While they do include an improvement in the number of swollen joints, this is not the only factor that is used to demonstrate improvement.

    The ACR criteria actually require improvement in tender or swollen joint counts AND improvement in three of the following five criteria:
    1. acute phase reactant (i.e. sedimentation rate)
    2. patient assessment
    3. physician assessment
    4. pain scale
    5. disability/functional questionnaire

    As you can see patient assessment, pain scale, and disability/functional questionnaire are all included in the criteria. These 3 areas are highly dependent on patient input. So rather than run a simple CRP and declare you have no disease, your physician should be familiar with these other parameters.

    For example, if a study reported that 55 percent of patients achieved ACR 20, that means 55 percent of patients in the study achieved a 20 percent improvement in tender or swollen joint counts as well as 20 percent improvement in three of the other five criteria.

    It is important to note that for patients to be assessed using ACR criteria, they must have participated in a clinical trial. These specific criteria are not used in everyday practice. You will not hear your doctor say, “Hey it looks like you achieved the ACR50 today.” The main reason for this is that when you participate in a clinical trial they take some baseline information and then future outcomes measures are compared to your baseline.

    The ACR web site actually has a nice collection of criteria and practice guidelines for various rheumatic diseases: http://www.rheumatology.org/practice/clinical/classification/index.asp

    Reply
    • December 9, 2010 at 1:53 pm
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      Thank you, Steve. I agree. Unfortunately there can be an intersection between what happens in clinical trials and real life in some ways as I mentioned to Elizabeth above.

      I guess this is off track somewhat, but many doctors label patients with “clinical remission” if CRP results are in normal range. There are of course treatment implications to that and most patients I talk with do not agree with the label.

      For the acute phase reactant, I’ve been reading that the CRP is interchangeable with ESR & more preferred now. Is that wrong?

      Reply
  • December 9, 2010 at 3:20 pm
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    My CRP has always been normal. Tell that to my shoulders, knees, hands and feet. Thanks for continuing to champion truth.

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  • December 9, 2010 at 3:56 pm
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    I know my rheumy goes by my labs and says I’m “stable” but she doesn’t take into account my fatigue, pain and my functional ability – I tell her about the first two, often overlook or understate the last one, as I work full time, and figure if I can “get out there and work full time, then I must be ok???” (I think I am deceiving myself there). I wish I could be taken seriously when it comes to my pain and fatigue with this disease….

    Thanks Kelly for another great article!!!

    Reply
  • December 9, 2010 at 7:53 pm
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    Facts do not cease to exist because they are ignored.

    – Aldous Huxley

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  • December 10, 2010 at 12:15 pm
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    Look at abstract 1051 from that meeting to see that those in clinical remission do still show signs of active disease on biopsy, ultrasound and MRI – though there was ‘less’ activity on those on TNF inhibitors. They all still showed active disease. Kelly, how’s the prednisone going, and have you considered adding plaquenil? I resisted that one for years, thinking it’s a whimpy DMARD and won’t do anything for me, and because of potential side effects, until my doc FINALLY corrected one of my misconceptions, and because I’m less controlled than before on mtx, and it IS helping some with pain levels. Not sure it’s stopping progression, but is helping some with pain if nothing else and I’m hoping I’ll be able to taper off prednisone with it. It’s still far from perfect, but is helping.

    Reply
    • December 10, 2010 at 12:54 pm
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      Yes, I attended the long sessions on remission. I hope to write about that soon. Yes, I’m considering certain dmards as options for a triple therapy. I’m glad you are doing better.

      Reply
  • December 11, 2010 at 1:10 am
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    Still, Dr. Bili and colleagues conclude, “Although HCQ has only modest disease-modifying effects in the treatment of RA (rheumatoid arthritis), its apparent effects on lipid profiles, and elsewhere reported inhibition of platelet aggregation and reduction in diabetes risk, along with its excellent safety profile and low cost, make it a beneficial first-line or an adjunct therapy for RA patients, particularly those with traditional cardiovascular disease risk factors.” http://www.medscape.com/viewarticle/733758?src=rss

    Thought you might like the above info.

    Reply
    • December 11, 2010 at 10:27 am
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      yeah I do like that info. The RA can & may often be attacking the heart in all patients, even those who don’t have bad joint symptoms – I saw similar reports at ACR about biologics giving protection regarding CVD. May be true even when we don’t notice a postive response to joint symptoms – that is why I say we ought to treat – even if the RA seems recalcitrant (like mine). Another reason to consider dmards.

      Reply
  • December 11, 2010 at 11:34 am
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    I have a relatively high CRP (whatever that means)…I didn’t know they knew anything about it, my doc’s certainly haven’t told me it means I’m “more sick” or anything.
    I just wanted to say as well that I have been battling pleuritis recently (think it’s gone now) and haven’t had any infections or anything – just from RA we think.

    Reply
    • December 11, 2010 at 11:43 am
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      I hope it’s gone for good Michael. “just the RA” – yeah. Well, at least you have that CRP in your back pocket if you ever need it. 😉 It’s when its normal that sometimes insurance or diagnosis or treatment decisions are affected. That’s what patients say.

      Reply
      • December 11, 2010 at 11:54 am
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        Never thought of it that way…maybe I can gift you some of mine – keep your eyes out for a package in the mail!

        Your right, the pleuritis better be gone – that was more painful than any pain from RA!

        Reply
  • May 17, 2011 at 4:34 pm
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    I am one of those who is seronrg withnl crp and sed rate. At diagnosis had visibly swollen joints and synovitis on mri of ankle. I did well on enbrel and mtx for 8 mos before symptoms started to come back. Did not have as much swelling this time but on medication. Grinned and beared it for a while then had bone scan that had 5 positive joints. So yes you can obviously be inflammed with normal blood tests. Too bad this point of view not more accepted even though it is taught in medical school. This is such a good educational point. If you are suffering and ‘tests’ do not geha with your symptoms, do not give up on yourself bc ur made to feel crazy!

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  • July 22, 2011 at 2:13 pm
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    I have had RA problems for 10 years. The treatment plan for me after an extreemly high RA factor was steriods large doses and very large doses of narcotics. It took 6 years to get and MRI that proved my hip pain was legit and had one hip replaced. It helped but one leg was shorter and I developed a terrible limp. In 2010 I had the other hip done and I am walking better but everything else is going to hell. I have started to use pain meds again after stopping the large doses and a new RA dr. visit in August promises new RA meds. At this point I feel like I am back at square 1 relying on Narcotics to get through the day. Everyone thinks I am being a drama queen when it comes to my pain level and it is really getting old. Has anyone had a noticeable change after starting the new RA meds and did you still need narcotics to help with pain and stiffness? Anything to look forward to will help.

    Reply
  • July 23, 2011 at 2:32 am
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    So you have never been other dmards or biologics? The combination of high dose, split dose methotrexate plus Plaquenil helped get me off of prednisone after being on it for over a decade. Of course this long dry/hot spell has probably helped too, and will have to see hOw I do this fall/winter being off of prednisone.

    Reply

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