The article didn't get much attention in the American medical community, and that's no surprise. The title of the British Medical Journal article was "Evidence Based Medicine: Why we can't trust clinical guidelines." In the June 2013 article, author Jeanne Lenzer describes how drug companies can negatively influence members of committees that create clinical guidelines, to the detriment of patient care.
What are Clinical Guidelines?
According to the Institute of Medicine, clinical practice guidelines are "statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options."
Ideally, these guidelines should be based on rigorous analysis, good science, and the best possible evidence and patient outcomes, without any influence from the manufacturers of the drugs being reviewed, and procedures or medical devices involved in the treatments. In reality, however, as Lenzer identifies, most clinical guidelines are corrupted by the bias that results from strong and pervasive ties to drug companies on the part of the committees that create the guidelines.
What is Causing the Bias?
When researchers, committee members and committee leadership who create clinical guidelines and policies have ties to drug companies, bias is almost inevitable. And the majority of the players involved in these guidelines do have financial connections to drug companies. One recent survey found that 71% of chairs and 90.5% of co-chairs involved in creating clinical guidelines had financial conflicts. In general, the majority of guideline committee members and leaders have direct financial conflicts.
Lenzer cites an example from neuroscience. In 1990, neurosurgeons were given guidelines recommending high dose steroid treatments. At the time, a poll of more than 1000 neurosurgeons found that only 11% believed that the treatment was safe, and only 6% thought it should be the standard of care. Despite their concerns, almost two-thirds said they would follow the guidelines, out of fear of being charged with malpractice. Now, decades later, the new guidelines warn against the very same high-dose steroid therapy.
Lenzer also cited the example of the Food and Drug Administration (FDA) review of the safety record of the progesterone drug drospirenone. Many of the FDA advisers had ties to the drug's manufacturer, and if their votes had been excluded, the drug would not have been approved as safe by the FDA.
Even the Institute of Medicine has recommended that no guideline authors should have financial conflicts of interest, and that if committee members have professional conflicts that can't be removed, the institute recommends that they "should represent not more than a minority" of the panelists. This recommendation has not been adopted as policy.
The advisers, doctors and other experts with the financial conflicts of course argue that their financial ties to drug companies have no influence over their decision-making vis a vis guidelines, and that they are unbiased. But the evidence does not support them.
A 2006 study released by the Journal of the American Medical Association (JAMA) found that 90 percent of the $21 billion marketing budget of the pharmaceutical industry was directed at physicians. And that money is strong influencer. The JAMA study reported that the rate at which physicians prescribe a particular drug increases substantially after they see drug representatives, attend company-supported symposium, or even accept something as simple as samples of that drug, or a coffee mug with a drug company logo.
Dr. Ashley Wazana, in a January 2000 JAMA article titled "Physicians and the Pharmaceutical Industry: Is a Gift Ever Just a Gift?" found that meetings with drug company representatives were frequently associated with requests by doctors to add those drugs to the hospital formulary, and changes in the doctors' prescribing practices. Doctors who went to educational sessions sponsored by drug-companies preferentially highlighted the sponsor's drugs, compared to other continuing medical education (CME) programs. And attending free educational sessions, accepting funding for travel or lodging for educational symposium were all associated with increased prescription rates of the sponsor's medication, and what Wazana refers to as "nonrational prescribing."
Why Does This Matter to Patients?
For patients, the presence of biased clinical guidelines has a number of negative effects on the nature and quality of care you receive.
First, due to fear of malpractice suits, your doctors are often prescribing drugs and treatments that are not in your best interest, going against their own best medical judgment. That means that you may not get proper care, or the best possible treatment, and instead be subjected to treatments from guidelines that are based on the financial influence of the drug companies, not sound medical decision making.
According to Lenzer, "Doctors who are skeptical about the scientific basis of clinical guidelines have two choices: they can follow guidelines even though they suspect doing so will cause harm, or they can ignore them and do what they believe is right for their patients, thereby risking professional censure and possibly jeopardizing their careers. This is no mere theoretical dilemma; there is evidence that even when doctors believe a guideline is likely to be harmful and compromised by bias, a substantial number follow it." Said Lenzer, "Eighty four percent 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."
Second, the guidelines often end up being adopted as "standards of care" - being incorporated into your insurance company coverage, your HMO's procedural guidelines and reimbursement policies, coverage for your prescription drugs, and even raised in expert testimony in malpractice suits. So not only is your doctor likely to recommend a guideline-approved treatment — even if they disagree with it — but it may be the only treatment that your insurance or HMO will pay for or offer.
Third, by "committee stacking," these guidelines groups — and the drug companies that are funding them — fill these groups with biased decision makers. This enables them to achieve a desired outcome: pushing a particular drug or treatment on you, even if it's not in your best interests.
Clinical Guidelines: The Impact on Thyroid Patients
The American Association of Clinical Endocrinologists (AACE) and the American Thyroid Association (ATA) put together a task force on adult hypothyroidism, and published their "Clinical Practice Guidelines for Hypothyroidism in Adults (The "Guidelines") in 2012.
The result was jointly published in 2012 in the journals Thyroid and Endocrine Practice.
According to the authors, the Guidelines present "evidence-based recommendations" that, according to the report, "were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational and optimal medical practice for the diagnosis and care of hypothyroidism."
The authors included Jeffrey R. Garber, Rhoda H. Cobin, Hossein Gharib, James V. Hennessey, Irwin Klein, Jeffrey I. Mechanick, Rachel Pessah-Pollack, Peter A. Singer, and Kenneth A. Woeber. In the published guidelines' reference to financial disclosures, only Jeffrey Mechanick was listed as having any financial ties, in this case to Abbott, parent company of AbbVie, which manufactures Synthroid. While the other guidelines committee members claimed they had "no relevant financial relationships with any commercial interests," this is not true. A search of the ProPublica "Dollars for Doctors" database shows that committee member Rhoda Cobin has financial ties to drug companies. Peter Singer has disclosed in other venues that he is a consultant for Abbvie Pharmaceuticals, maker of Synthroid. Hossein Gharib and James Hennessey have also been speakers at AbbVie financed symposia. Not only do many of the guidelines committee memers have clear ties to the drug industry, and in particular, the company that makes the top-selling brand of levothyroxine, but the guidelines' disclosures were less than forthcoming.
AbbVie, a spinoff of Abbott Labs, is the key player in the levothyroxine market, as it manufactures thyroid drug Synthroid, the top-selling brand name of levothyroxine. AbbVie spreads around millions of dollars a year financing workshops, symposia, training sessions, and other industry events, and providing direct support to many physicians in the form of honoraria, speaker's fees, drug samples, and other payments. Levoxyl, owned by pharma powerhouse Pfizer, is a secondary, but important player. In contrast, the makers of T3 and natural thyroid drugs have limited marketing budgets, face heavy regulations on what sort of marketing they can do (especially for regulatory-grandfathered natural thyroid drugs), and are not typically involved in financing thyroid and endocrinology guidelines members or their organizations.
So did the industry ties of the committee members, and the influence of the levothyroxine manufacturer, show up in the Hypothyroidism Guidelines?
Take a look at the following recommendations from the Guidelines:
- Patients with hypothyroidism should be treated only with levothyroxine drugs.
- The evidence does not support using levothyroxine-plus-T3 combinations to treat hypothyroidism.
- There is no evidence to support using natural desiccated thyroid hormone — i.e., Armour, Nature-Throid — in preference to levothyroxine in treating hypothyroidism. The Guidelines conclude that "therefore desiccated thyroid hormone should not be used for the treatment of hypothyroidism."
The Guidelines also include the following statements:
- Thyroid Stimulating Hormone (TSH) is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations.
- The standard treatment is replacement with levothyroxine (T4).
- The decision to treat subclinical hypothyroidism, when the serum TSH is less than 10 mIU/L, should be tailored to the individual patient.
Are the guidelines "current, rational and optimal?" We would argue that they are emphatically not, for these reasons.
First, the guidelines appear to be heavily biased toward levothyroxine, and against any other drug treatments, suggesting that the link between levothyroxine manufacturers and some of the Guidelines committee members has had an impact.
Second, the guidelines also disregard a host of journal-published research that has shown that patients prefer T4/T3 combination therapy - versus levothyroxine-only treatment, and some clinical parameters are improved on the combination therapy.
Third, the guidelines make an illogical and unscientific leap. They claim that there is no evidence to support natural desiccated thyroid drugs over levothyroxine drugs, and then conclude that the two categories of drugs are not equally effective options for treatment — even though some recent research has shown that natural desiccated thyroid is equally effective as levothyroxine. Then they conclude that "desiccated thyroid hormone should not be used." This makes no scientific sense: it's like saying that there is no evidence to support ibuprofen over aspirin for headaches, therefore, ibuprofen should not be used.
Fourth, in claiming that the TSH test is the single best screening test for thyroid dysfunction, they are ignoring increasing scientific evidence that measurement of a pituitary hormone (TSH) can't identify many cases of thyroid dsyfunction, including:
- Hypothyroidism and related symptoms that result from autoimmune thyroid disease, detected by testing for elevated thyroid antibodies
- Hypothyroidism that results from deficiencies in Free T4 and Free T3, the actual circulating thyroid hormones
- Hypothyroidism that results from inability to effectively convert T4 into T3 — and T3 is the active thyroid hormone at the cellular level
- Hypothyroidism that results from elevation of Reverse T3, which can block the transport of T3 into the cells
We can only speculate about the specific extent to which the financial ties to pharmaceutical companies influenced this particular committee in developing the Hypothyroidism Guidelines. But we know that bias clearly has a negative effect on clinical guidelines in general. And it's hard to overlook that the Hypothyroidism Guidelines — developed by a committee with some members who have financial conflicts — show a blind allegiance to levothyroxine — and ignore contradictory evidence. And in the end, it's the patients who end up paying the price.
Lenzer, Jeanne. "Evidence Based Medicine: Why we can't trust clinical guidelines." British Medical Journal. 14 June 2013. Online.