Guidelines and the ‘glitazone’ problem

15

Category : Medical Rants

While I continue to work on formulating my grand plan for guidelines, several articles have driven me to write this entry.

More Studies Cast Doubt on Safety of Diabetes Drug

In addition to its deleterious effects on the heart, Avandia can cause blindness, and it doubles the risks of bone fractures in women, Dr. Singh said in an interview.

“If you use Avandia to treat patients with Type 2 diabetes,” he said, “their chance of getting heart failure due to Avandia is one in 30 and their risk of getting a heart attack is one in 220. All due to the drug.”

Dr. Singh added, “There are older and cheaper drugs that are far better to treat diabetes.”

A colleague, Dr. Stefan Kertesz, has written a commentary in the latest SGIM Forum (not yet available online). In that commentary he opines that part of the ‘glitazone’ problem stems from overly aggressive guidelines.

His point, on which I concur, states that our efforts to lower HgbA1c stimulated our willingness to try another drug to reach the magic number. Perhaps the zeal for lowering HgbA1c to below 7 stimulates us to use a second or third drug. Perhaps if we had a more realistic goal of 8 we would have less ‘glitazone’ use, and thus fewer bad outcomes.

Does our HgbA1c lead to negative externalities? Or is the problem that physicians are too eager to try a new drug class, accepting the hype from drug companies?

The editorial in the current JAMA has these interesting thoughts:

In an interview, Dr. Daniel H. Solomon, a co-author of the editorial, called Avandia “a drug of last resort.”

Dr. Solomon wrote that the Avandia situation should be used to improve the nation’s drug-safety system. Among his proposals is that when several drugs are available to treat a condition, new drugs must prove that they improve or extend people’s lives before they are approved. Now, many drugs are approved only after they improve laboratory results, like blood sugar or cholesterol levels.

This story highlights one of the problems of guidelines. Treating numbers, for the sake of guidelines, may conflict with treating patients. If you have not read Dr Rich’s piece on P4P (I linked yesterday), read it now. The “quality” geeks seem to have forgotten one of Osler’s basic thoughts.

“The good physician treats the disease; the great physician treats the patient who has the disease”

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Comments (15)

Doctors need to be very aware that even small changes in guidelines create very large changes in potential markets. In stepping back I think many doctors will find that new guidelines overlap older concepts of normal and often multiple medications aggravate the very conditions they are trying to treat.

In the Sept. 8th WSJ we find an article warning about the free lunch now being offered to prospective investors, Free Lunch? It Might Serve Investor a Scam. The point of the article is the blunt explanation that the attendees will then be obligated to participate in a high-pressure sales presentation.

When that drug rep comes in after providing lunch, doctors need to realize that the drug reps have all of your prescription history. When they speak of “underserved” populations, they in fact want you to meet their sales quota on a per unit basis.

Following on in the WSJ, we find race being used to promote a continuation of existing anemia treatments. Sept. 11th Kidney Clinics Cite Race to Fight Curb on Drug. The drug companies used an NBA basketball player to promote their position.

In the same paper we find Ad Campaign Fuels Debate On Breast-Cancer Gene Test. The sub-title: Critics Say Calling Attention To A Rare Risk Factor May Create Unnecessary Fear.

Again on the 11th we find Why Firms Tax Cuts Get Senate’s Attention. The point of this article is drug companies lead the list of companies with questionable tax policies. Merck being the larges at $7.4B.

My point is, pharma is a predatory industry. They will use any means to increase sales of their product, and customer/patient needs come in a distant second to this goal. Setting unrealistic guidelines is only one tool in their arsenal. Funding a group that advocates for a disease they sell a drug for, DTC ads, CME, etc. are all part of a very sophisticated marketing program.

I was reminded by a cartoon in yesterdays paper that: If you tell someone, something, often enough, they will believe it.

Steve Lucas

It was the ADA, not the P4P who pushed for A1c under 7. It was based on DCCT and UKPDF trials that said there was a direct correlation between A1c and complications (eye and kidney were the main thing, but also all-cause mortality). This is the thing that I wonder about. If a person with an A1c under 7 lives longer than one with an A1c over 8 (as suggested by both of these trials), and suffers less morbidity due to DM, does this offset the negative effects of the drug? Certainly GSK thinks so, but what do the data show?

It is very cynical to think that the A1c guidelines are a product of big pharma. The guidelines are held by many institutions and are considered, in general, very solid guidelines.

I really don’t know. It is something worth revisiting to see, but I am honestly not trying to get my patients’ a1c under 7 for the sake of P4P, it is because of the clinical evidence that this is actually a good thing for the patient (which is my real goal)

Rob

To make my point, here is the summary of the UKPDF trial in Uptodate, where the two groups were A1c control average of 7.9 vs. intensive control with A1c of 7.0:

* Over 10 years, the average A1C value was 7.0 percent in the intensive-therapy group compared with 7.9 percent in the conventional-therapy group (11 percent reduction)

* The risk for any diabetes-related end point (see abstract for definition of endpoints [2]) was 12 percent lower in the intensive-therapy group (P = 0.029) and 10 percent lower for any diabetes-related death (P = 0.34) . It was estimated that 19.6 patients would have to be treated to prevent any single end point in one patient in 10 years.

* Most of the risk reduction in the intensive therapy group was due to a 25 percent risk reduction in microvascular disease (P = 0.001) ; there was no reduction in macrovascular disease.

* The benefits of intensive therapy appeared to be independent of the type of treatment administered.

This was not as powerful as the DCCT trial for type 1 diabetics, but it clearly established that A1c under 7 is important to reach.

In our inderdependent world, I believe many of the clinicians who make the ADA recommendations are also consultants for pharmaceutical companies, and this can influence standards recommendations. I do not believe this is malicious, but I believe there is an influence.

If a particular medication increases macrovascular risk, it would likely not take much of an increase to wipe out the benefits of lower Ha1c. I agree with comment above; study needs to be done showing decreased overall risk before these drugs are used widely.

As a primary care doc in the trenches, I feel the pressure to get patient to “goal” using multiple medication, and I would hate to discover years from now that I am causing harm.

As an undergrad, I wrote a paper on use of DES in pregnancy; those docs in the ’50s thought they were doing good, turned out not to be so.

It is important to note that the ADA has a new CEO Laurence Hausner who came from the Leukemia and Lymphoma Society. With undergraduate and graduate degrees in marketing his major accomplishment seems to have been raising income from $165M to $270M for his previous employer, per the ADA web site.

I would have to question the ADA’s ability to withstand pharma’s influence given the CEO’s background and trumpeting of increased revenue.

Steve Lucas

Hi-

As the author of the commentary that first ran on Marketplace and then was reproduced in longer form in the SGIM Forum (and I will quote a bit here), I’ll pitch in my 2 cents.

As a matter of quality of care, the use of a binary standard of 7% was rejected (everyone hear that REJECTED) by the panel of experts convened by the National Commission for Quality Assurance, and indeed that same standard was also REJECTED by the Veterans Health Administration. The scientific rejection of that standard is a matter of public record and open to all, just by reading the statement of that panel online at:

http://www.nationaldiabetesalliance.org/

Experts like those on the Technical Expert Panel of the Diabetes Quality Alliance and the Veterans Health Administration judged that there could be adverse consequences to the use of an absolutist binary standard like 7%.

Is that counterintuitive?

One of the most important problems is that while reducing HgbA1c is generally a good thing (no matter where you start out), a binary standard of 7% sets up peculiar incentives that run contrary to where we stand to do the most good for our patients. I will simply paraphrase my argument here, which summarizes the arguments elaborated by many others in addition to myself:

The doctor who brings a very challenging diabetic patient’s hemoglobin A1c from 14% to 11% has done such a patient enormous good, far more absolute good than reducing a mild diabetic from 7.5% to 6.9%. However, a single binary standard ignores the former and rewards the latter. In fact, with a binary standard like 7% the best thing a doctor can do is test a lot to diagnose and care for mild diabetics, preferably middle-class people with good insurance to cover medication expenses. The one thing that will hurt that doctor’s quality rating is to take care of the true “difficult patients”, the challenging ones, the poor ones with lousy insurance, where getting from 15% to 12% would be an absolute triumph and objectively does far more good for kidneys and eyes. The latter patients will count AGAINST the doctor’s quality rating, however, because they enter the doctor’s denominator (i.e. diabetics) but don’t count as successful. Anyone can read the relevant analyses in an article by Vijay et al. Annals of Internal Medicine; 1997: 127:788-95. I am aware of current articles in press that will review these same issues in detail (not by me).

So I am just one primary care doctor trying to point out the utter perversity of the binary standard that has been enshrined by some major quality organizations that happen to receive lots of money from the pharmaceutical industry.

Helping the patient who has the greatest need, and who stands to benefit the most from help, is precisely what the 7% binary standard discourages.

Is there anything more paradoxical than a quality standard that punishes doctors who try to help the patients who most need our help?

On the other hand the standard does encourage writing 1, 2, or even 3 prescriptions for costly glucose reducing drugs in a desparate attempt to reach the standard, even for patients where the balance of cost, convenience, risk and benefits may be quite a bit more complicated that “7% or bust.”

The question should be how major organizations would have chosen an absolutist binary 7% standard, despite the scientific recommendations of the majority of their OWN scientific expert panels.

I don’t fully know that part, but some of it is alluded to an article in the American Journal of Managed Care at http://www.ajmc.com/Article.cfm?Menu=1&ID=3291

(NO subscription required).

All of the major organizations that influence policy see themselves as existing to serve the public good, obviously. But there is no reason to assume that any one of us is exempt from scrutiny for potential conflict, we all know that good intentions have paved many a hellish road.

So let’s not forget that the 7% standard was first aggressively promulgated in 2002 by pharmaceutical firms (see http://www.diabetesmonitor.com/dma1ci.htm), just as the scientific experts were beginning to argue that this was in fact not a good idea.

Speaking for myself, I serve on the Board of a service-learning organization that received a big grant from Merck. I can and should be subject to scrutiny too.

I don’t know how to fully disentangle the conflicts that beset us, but I do feel that every organization that influences the health of millions of Americans should strive for complete transparency on who interprets the medical evidence, and what procedures were followed, and where the monetary industries may lie.

Stefan Kertesz, MD

Rob,

When I looked at the evidence regarding tight control of A1C and outcomes, through a critical reading of the UKPDS studies, I was quite surprised. I encourage you to read these two papers from the BMJ.

http://www.bmj.com/cgi/content/full/320/7251/1720

http://www.bmj.com/cgi/content/full/328/7440/E280

Incidentally, the microvascular improvement you cite was primarily due to a difference in the rates of photocoagulation for retinopathy. This was unblinded, so there may have been a bias to treat those with higher A1Cs, thinking it may be more “important” for those patients. (Even if you think this is important, note this is a disease oriented outcome, not a POEM.)

I personally find it amazing (and unfortunate) that the UKPDS evidence has been used to justify tight control based on A1C values.

I forgot to mention the important point that the lack of evidence in UKPDS for tight A1C control applies to type II diabetics. Type I is a different story.

It’s one of the signs of a great mind that it can incorporate new data and change. You have a great mind Dr. Centor.

It wasn’t so long ago we were reading stuff like this:

http://medrants.com/index.php/archives/2942

Whose guidelines and for whom : The case of TZDs and HF

To illustrate by example the case of guidelines for TZD use in heart failure which have been endorsed by major medical societies AHA/ADA and widely disseminated which say that TZDs can be used in low dose in Stage I and II HF but contraindicated in Stage III and Stage IV.

– Clinical evidence–More than 1000 spontaneous reports of HF with TZDs even in people without HF submitted to FDA AERS

– TZDS contraindicated in all Stages of HF in Europe since approval.

-The current blackbox in the US based on spontaneous reports of AERS, despite our Meta-analysis of RCTs presented at SGIM and published in Diabetes Care submitted to FDA as well as the current paper in JAMA which shows HF in all stages with evidence from RCTS states ” TZDs contraindicated in symptomatic HF and in Stage III and Stage IV>?”

– It leaves Stage One and Stage 2 ambigous. Is this an attempt to expand the indication for this class.

-What evidence is the FDA and ADA/AHA looking at?

Note : I have no sources of funding.

If the ADA’s goal of 7% is too staunch, consider the AACE’s goal of 6.5%.

An a1c of 8% equates to an average glucose of nearly 210. I really don’t feel that’s what we should be aiming for to improve outcomes.

If OA’s are a problem, instead of just going to maxes one 3 of those, why not add insulin sooner?

I agree with Christine #11: Insulin is underprescribed and often used in a less than ideal fashion. Would you believe that there are still patients on twice-a-day NPH?

As for those who see the devil, or worse yet, the pharma industry, behind every corner, I have four letters: DCCT.

Claiming that a “binary” standard (above vs. below an HgbA1c of 7.0%) is in and of itself bad is a strawman argument; the actual standard is “as low as it can be pushed while avoiding excessive hypoglycaemic events”. 7.0% is just a convenient number that, in my experience, can be attained by even a mildly motivated patient.

And while getting a patient’s HgbA1c from 14% down to 11% may be an accomplishment, I say that it is not a reason to call for one’s laurel wreath: initial gains are always easiest, and 11% is still a catastrophically high average BG.

I wonder whether the proponents of such elevated BGs are paid off by the immunosuppressant divisions of the pharma companies!

(And if the last paragraph sounded ridiculous to you: It is. But no more so than the aspersions cast on doctors who actually try to guide their patients to better health instead of less rapid disease progression.)

Cheers,
Felix.

A1C may or may not be a good indicator of diabetes control. I ,as a patient, watch my 2hr post blood sugar reading I also don’t believe in listening to anything most of you docs have to say. You do not keep up with the role nutrition can make in a persons health. You are all about pushing dangerous drugs on people. so is the ADA for the matter, when it comes to diabetes.
My treatment of choice for my diabetes is simple, very little carbs. It only makes sense to eliminate the source of increased blood sugars in the first place.
It seems to me that all you doctors with your years of schooling would get that concept. I learned it in high school biology. But what do I know, I’m just a patient.

Christine,

I believe an A1C of 8 correlates to an average glucose of 180, not 210. Shooting for an average of less than 180 (A1C less than 8) doesn’t seem unreasonable, especially given the lack of evidence that tight control matters for Type II DM.

BamaGal #13: T2DM can, depending on circumstances, often be majorly improved and sometimes completely controlled just by lifestyle modifications; if that works for you, more power to you. (By the way, I claim exercise works better than a low-carb diet. It also has other health benefits.)

Those “dangerous drugs” that you decry are being pushed because most people are extremely resistant to lifestyle changes; the GP charges the same fee if he is telling us to drop fifty pounds by eating less and exercising more, or for telling us to take this little pill.

Oh, and despite all the hue and cry in this thread, you should note that the absolute incidence of major adverse effects is extremely low.

Cheers,
Felix.

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