guidelines…

Posted on Monday 24 June 2013

I had just written this in the comments,
I have developed a reflex high alert whenever treatment algorithms or treatment guidelines are on the table. I’m sure my head is as filled with algorithms as any doctor, but I’m suspicious of them coming from the outside. They can be a way to “push” drugs for one thing. But they also can make people careless.
then I looked over the other blogs I follow and saw a reference to the article below on Pharmagossip. It’s in the British Medical Journal:
by Jeanne Lenzer, medical investigative journalist
BMJ 2013;346doi: http://dx.doi.org/10.1136/bmj.f3830 [Published 14 June 2013]
[full text @ BMJ or on Pharmagossip]

…Guidelines are usually issued by large panels of authors representing specialty and other professional organisations. While it might seem difficult to bias a guideline with so many experts participating under the sponsorship of large professional bodies, a worrying number of cases suggests that it may be common. A recent survey found that 71% of chairs of clinical policy committees and 90.5% of co-chairs had financial conflicts. Such conflicts can have a strong impact: FDA advisers reviewing the safety record of the progestogen drospirenone voted that the drug’s benefits outweighed any risks. However, a substantial number of the advisers had ties to the manufacturer and if their votes had been excluded the decision would have been reversed.

Biased guidelines can have powerful and wide ranging effects. Thousands of guidelines have been issued, and, when promulgated by highly respected professional societies, they sometimes serve as de facto “standards of care” that may be used to devise institutional protocols, to develop measures of physician performance, and for insurance coverage decisions. Guidelines may influence the medicines selected for inclusion on drug formularies and may be used as a “reliable authority” to support expert testimony in malpractice suits. Eighty four per cent of doctors say they are concerned about industry influence over clinical guidelines, yet the fear of malpractice suits puts many in an untenable position of following guidelines they believe are flawed or dangerous to patients. Despite repeated calls to prohibit or limit conflicts of interests among guideline authors and their sponsors, most guideline panellists have conflicts, making the guidelines they issue less than reliable…
Of course you ought to read this whole article. Maybe it should be tattooed to the inside of the eyelids of all graduating medical students. It’s a tragedy that it even had to be written.

I recall a time in my training when I had a little black notebook [we called the "ectopic brain"] with all kinds of protocols, algorithms, guidelines written in to remind me of all the things that needed doing in specific situations. They weren’t injunctions, just guides for a novice. Things like what to do for Pulmonary Edema, Diabetic Coma, the Acute Abdomen, Septic Shock, etc. My head and my book were full of such things. Then there were real guidelines pasted cut out and pasted in like the ADA recommendations for Diabetic Management or the work-up for hypertension and treatment guidelines. It was a book for the Intern I was and it disappeared by the end of the year, to be seen no more. My point being that part of what’s called experience is an internal collection of algorithms and guidelines gathered by anyone, doctor or auto mechanic, over the course of a professional life.

But this article is about something else. It’s about expert guidelines put together by biased experts – and it gives concrete examples of instances where those guidelines have been heavily compromised by the industry ties of the authors – examples resulting in unnecessary treatment and actual increased mortality. In psychiatry, there are plenty of examples – like the whole Texas Medical Algorithm Program [TMAP] that has never been fully exposed. If you’ve read this blog much, you’ve probably noticed that I have been unusually vigilant about the publications of Dr. Madhukar Trivedi like the last several posts. It’s because of his fixation on algorithms and guidelines. When I looked into the source for the algorithms in these computerized systems below, I never found them. They were just what he and unknown others thought. It was the same for TMAP or STAR*D. Opinions:

1. Computerized medication algorithms and decision support systems in major psychiatric disorders.
      Trivedi MH, Kern JK, Baker SM, et al:
      Journal of Psychiatric Practice 6:237–246, 2000
2. Computerized medical algorithms in behavioral health care, in Behavioral Health Care Informatics.
      Trivedi MH, Kern JK, Voegle T, et al:
      Edited by Dewan NA, Lorenzi N, Riley R, Bhattacharya SR. New York, Springer-Verlag, 2001
3. Development and implementation of computerized clinical guidelines: barriers and solutions.
      Trivedi MH, Kern JK, Marcee AK, et al:
      Methods of Information in Medicine 41:435–442, 2002
4. A Computerized Clinical Decision Support System as a Means of Implementing Depression Guidelines.
      Trivedi MH, Kern JK, et al:
      Psychiatric Services 55:879–885, 2004
5. Assessing physicians’ use of treatment algorithms: Project IMPACTS study design and rationale.
      Trivedi MH, Claassen CA, et al:
      Contemp Clin Trials. 28(2):192-212, 2007
6. Barriers to implementation of a computerized decision support system for depression: an observational report on lessons learned in "real world" clinical settings.
      Trivedi MH, Daly EJ, Kern JK, et al:
      BMC Medical Informatics and Decision Making, 9:6, 2009
7. A computerized decision support system for depression in primary care.
      Kurian BT, Trivedi MH, Grannemann BD, et al:
      Primary Care Companion, Journal of Clinical Psychiatry,11(4):140-1466, 2009
8. Using algorithms and computerized decision support systems to treat major depression.
      Shelton RC and Trivedi MH:
      Journal of Clinical Psychiatry,72(12):e36, 2011

And when I look at his Conflict of Interest declaration, the list boggles my mind. There’s no way I could trust his opinion [list from the article in the last three posts]:
Madhukar H. Trivedi is or has been an advisor/consultant to, or on the Speakers’ Bureaus within the past 3 yr and anticipates receiving fees in the near future for: Abbott Laboratories, Inc., Abdi Ibrahim, Akzo [Organon Pharmaceuticals Inc.], Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Cephalon, Inc., Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc., Pfizer Inc., PgxHealth, Rexahn Pharmaceuticals, Sepracor, SHIRE Development, Sierra, SK Life and Science, Takeda, Tal Medical/ Puretech Venture, Transcept, VantagePoint and Wyeth-Ayerst Laboratories. In addition, he has received research support from: Corcept Therapeutics, Inc., Cyberonics, Inc., Merck, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals [Epix], Solvay Pharmaceuticals, Inc., Targacept and Valient.
It’s not really fair to single him out, because there are so many COI lists that look like his. And in the article in the BMJ, they talk about panels of people on guideline committees with COI connections that relate to the specific guidelines. Here’s an example where one powerful person was the COI epicenter of a guideline:
In the early 1990s, high dose steroids became the standard of care for acute spinal cord injury, reinforced by a Cochrane review. The Cochrane Collaboration, is widely known to have strict standards concerning conflicts of interest, yet in this case the collaboration permitted Michael Bracken, who declared he was an occasional consultant to steroid manufacturers Pharmacia and Upjohn, to serve as the sole reviewer. He was also the lead researcher on the single landmark study, published in the New England Journal of Medicine, used to support the Cochrane review.

Neurosurgeons were not convinced. Many expressed concern about high rates of infection, prolonged hospital stays, and death with high dose steroids. One expert estimated that more patients had been killed by the treatment in the past decade than died in the 9/11 World Trade Center attacks. A poll of over 1000 neurosurgeons showed that only 11% believed the treatment was safe and effective. Only 6% thought it should be a standard of care. Yet when asked if they would continue prescribing the treatment, 60% said that they would. Many cited a fear of malpractice if they failed to follow “a standard of care.”

That standard was reversed this March, when the Congress of Neurological Surgeons issued new guidelines. The congress found that, “There is no Class I or Class II medicine evidence supporting the benefit of [steroids] in the treatment of acute [spinal cord injury]. However, Class I, II, and III evidence exists that high-dose steroids are associated with harmful side effects including death”…
The thing I find so frustrating is that these problems seem so obvious to me. It doesn’t take a moral giant or a bioethicist to see the impossibility of trusting guidelines constructed by doctors who are in the employ of these manufacturers. It is one of those things that comes under the domain of, "We hold these truths to be self evident." So that’s why I say that "It’s a tragedy that it even had to be written." And I don’t even think this is strong enough:
Concern about the credibility of guidelines led the Institute of Medicine to recommend that ideally no guideline authors should have financial conflicts of interest. If individuals who have professional conflicts that can’t be divested [for example, specialists whose career depends on treating a certain condition] are included, the institute recommends that they “should represent not more than a minority” of the panellists.
I see no reason for compromise here. The reason given for these softening remarks is that so many experts have conflicts of interest that they can’t find enough people to be on a panel. What I’d say in that case is either don’t produce the guideline, or give the task to a bunch of young idealistic medical students or early trainees walking around writing things in their "ectopic brains" – people who come from a more innocent time of life. What we’re doing now is embarrassing. Clinical Guidelines, like a lot of the CME, has become too corrupted to continue. One reason to read this article in full is that a lot of practicing physicians in the examples don’t follow these corrupted recommendations. Good on them. And a lot of people refuse to go to industry financed CME [see pharmed out]. Good on them too…
  1.  
    Bernard Carroll
    June 24, 2013 | 12:52 AM
     

    Reflecting on Jeanne Lenzer’s BMJ commentary and on your post, I am reminded of the great sociologist Jane Jacobs. In discussing the ethics of the guardian tradition, which includes medicine, and the ethics of the commercial tradition she has one of her protagonists say, “There are many fine points to medical ethics, and some difficult puzzles, but the most rudimentary morality is the line between the guardian and commercial (traditions). It’s as crucial that physicians understand it as it is that lawyers recognize that when they go into guardian service they can’t morally also be in service to clients seeking to influence legislation or regulatory decisions.” [Systems of Survival, Random House, 1992]

  2.  
    a-non
    June 24, 2013 | 4:42 AM
     
  3.  
    Steve Lucas
    June 24, 2013 | 7:32 AM
     

    And from the BBC:

    http://www.bbc.co.uk/news/health-23005367

    or, how do we harm children before they are born?

    Steve Lucas

  4.  
    wiley
    June 24, 2013 | 3:23 PM
     

    How is it that a medical treatment can be recommended when it is still, for all practical purposes, experimental? Perhaps it’s easier to accept a guideline than it is to admit that most new medical treatments are unproven. That medical doctors must deny the scientific observations in front of them while going by “the book”. When doctors knows that a treatment is harmful, but goes along with a recommendation out of concern that they’ll be sued, those doctors are doing harm to patients and medical science.

    Perhaps doctors are not being served well by the AMA and HMOs and could do themselves and their patients a favor by challenging all guidelines pertinent to their field.

    I’m beginning to see the point that what Ben Goldacre recommends is necessary, but it is not nearly enough. Perhaps we need a mechanism to put all new medical treatment on probation for ten years, requiring documentation and reporting by those who use it, and for all that information to be studied and evaluated before that treatment can be recommended as a first line of treatment.

    It should be clear enough by now that “new” doesn’t mean better, and that the clinical tests just scratch the surface of what new drugs, treatments, and methods are more beneficial than not. It’s understandable that a lot of medical doctors would be uncomfortable having to admit that a treatment is, for all practical purposes, experimental, and would have misgivings about presenting this to a patient; but since saving lives is the point of being a medical doctor, it seems obvious that killing patients with a recommended guideline should be the last thing they want to do.

    All our professions need shaking up.

  5.  
    a-non
    June 24, 2013 | 6:03 PM
     

    “Medical Devices Contract Research Organizations – Global Opportunity Assessment, Competitive Landscape and Market Forecasts to 2018″
    GlobalData-June 7, 2012
    http://www.marketresearch.com/GlobalData-v3648/Medical-Devices-Contract-Research-Organizations-7010840/

  6.  
    a-non
    June 24, 2013 | 6:13 PM
     

    “Community-Based Participatory Research”-NIH
    “Community-based participatory research (CBPR) is an applied collaborative approach that enables community residents to more actively participate in the full spectrum of research (from conception – design – conduct – analysis – interpretation – conclusions – communication of results) with a goal of influencing change in community health, systems, programs or policies. Community members and researchers partner to combine knowledge and action for social change to improve community health and often reduce health disparities. Academic/research and community partners join to develop models and approaches to building communication, trust and capacity, with the final goal of increasing community participation in the research process. It is an orientation to research which equitably involves all partners in the research process and recognizes the unique strengths that each brings.”
    “Advantages of community-based participatory research include:

    * Joining partners with diverse expertise to address complex public health problems
    * Improving intervention design and implementation by facilitating participant recruitment and retention
    * Increasing the quality and validity of research
    * Enhancing the relevance and use of data
    * Increasing trust and bridging cultural gaps between partners
    * Providing resources for the communities involved
    * Benefiting the community and researchers alike through the knowledge gained and actions taken
    * The potential to translate research findings to guide the development of further interventions and policy change”
    http://obssr.od.nih.gov/scientific_areas/methodology/community_based_participatory_research/index.aspx

  7.  
    a-non
    June 24, 2013 | 6:25 PM
     

    “The illusion of zero risk” from “Swimming with Great Whites? If you’ve got “Diabetes” look away now.”-David Healy

    “Companies are so adept at handling these issues that they probably welcome the appearance of controversy – it increases sales. If you’re a doctor, come to Amity Island where there is more action on the beaches than anywhere else. Doctors, have we got the deal for you, your very own heated infinity pool – to give you the illusion you are in the water without any of the risks.”
    http://davidhealy.org/swimming-with-great-whites-if-youve-got-diabetes-look-away-now/

  8.  
    a-non
    June 24, 2013 | 6:43 PM
     

    Mickey:
    “It’s the ultimate outsourcing solution. The CRO arranges and manages the clinical trials including writing the paper, finding authors to sign on, submitting the articles, etc. in whatever combination of services you want to pay for. They, in turn, interact with multiple Centers that recruit the subjects and do the studies – usually multiple centers in a given clinical trial. This is something of a new, multibillion dollar industry.”
    from “selling seroquel VIII: CRO-Charts…”
    Posted on Wednesday 2 March 2011
    http://1boringoldman.com/index.php/2011/03/02/5189/

    Raw clinical data will reveal the black box behind the CROs.

  9.  
    Johanna
    June 24, 2013 | 11:08 PM
     

    The really important place to run these Conflict of Interest statements would be in the popular press whenever these bums are quoted or interviewed. Outside the echo chamber of corporate medicine, it is still considered scandalous and scary that a doctor “researching” a drug or “educating” about it would be on the drug company’s payroll. Inside the echo chamber it’s so normal I don’t think these COI statements in the medical journals even register with their jaded readers. There could even be a perverse prestige in having a conflict-of-interest statement like Trivedi’s – “Look, mine’s bigger than yours!”

    “The bourgeoisie has stripped of its halo every occupation hitherto honored and looked up to with reverent awe. It has converted the physician, the lawyer, the priest, the poet, the man of science, into its paid wage laborers.” That’s from the Communist Manifesto of course. I keep pulling that thing off the shelf lately, more so than I have in years. Has someone made a smartphone app of it yet?

  10.  
    Gad Mayer
    June 25, 2013 | 1:45 AM
     

    Wiley: putting new medical treatments through a “probation period” sounds like a very good idea! It’s the exact opposite of the current NIH and FDA zeitgeist.

  11.  
    June 25, 2013 | 1:56 AM
     

    Johanna,

    Great point! It’s a pity that Marx the philosopher is so entangled with the disastrous social applications that followed. As a reminder of the pitfalls of Capitalism, he remains the breath of fresh air he always was. Speaking of old philosophers, your Freudian interpretation of the outrageous COI declarations and the CVs with hundreds of articles amassed by these same people [“Look, mine’s bigger than yours!”] can’t be wrong. The Trivedi list in this post to wit.

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