Is off label use woo?

[ponderingturtle]

Should having a drug prescribe for an off label use, so that it was not actually studied for its effectiveness for that use, be considered evidence based medicine?

I have wondered how much off label use is effectively a placebo for a while. I am sure for some it is and some it isn't, and the safety of the medication is known, so it is not like say herbal supplements. But with out real studies who convinced are doctors that off label uses are not the exact same as the quack treatments and they are having the same biases regarding it?

 

[Cuddles]

What drugs are prescribed for things they have not been studied for? Isn't this illegal?

 

[ponderingturtle]

What drugs are prescribed for things they have not been studied for? Isn't this illegal?

No. Doctors can prescribe drugs for what ever use they want. It could in some instances be against the standard of care, but it is legal.

In my case I was prescribe Inderol for an off label use as a child. It was for rage attacks and was prescribed by a neurologist.

 

[casebro]

What drugs are prescribed for things they have not been studied for? Isn't this illegal?

No, in most states doctors can prescribe any thing for anything. But don't expect the mfg to cover liabilities.

"Off Label" is a legalistic term, not a scientific one. So, off label is not neccessarily unscientific. It just means that the mfg has not certified it's efficacy for that use. That doesn't mean there is no scientific basis for the off label use, only that the mfg hasn't jumped throug the hoops required to sell it for that purpose. There may even be bona-fide studies showing it's effectiveness. I would google up the drug and the condition, and see.

 

[Ichneumonwasp]

I wouldn't say "woo".

Off label uses serve to promote new investigation. Drug companies have caught on so that many new drugs emerge with multiple indications. Lyrica, for example, has indications from resless leg syndrome to add-on therapy for partial onset epilepsy to various pain complaints. Because of physician experience with Neurontin the company knew there was a good chance that pregabilin would have many of the same properties as gabapentin, so the prior off-label uses of Neurontin became labelled uses for Lyrica.

As far as the placebo effect, well sure. Take Neurontin again. Parke Davis pushed the drug on psychiatrists as a good treatment for bipolar disorder whithout actually studying it, banking on the fact that many other anti-epileptic drugs are used to treat the condition. Neurontin was useless for bipolar disorder and Pake Davis paid for it. Regardless, there were some patients, I am told, who distinctly benefitted from Neurontin when used to treat bipolar disorder.

I think Botox with migraine is another good example of a placebo effect. I don't think it is possible to run a trial in which those receiving the botox don't know they are getting it.

But, from one perspective, does it really matter? Especially when it comes to pain without a clear underlying cause that can be removed, like migraine, what difference does it make if the 'cure' is placebo or not? What we want are people without pain for whatever reason. Botox is an awfully expensive way to go about it, though.

Of course all off-label uses should be subject to placebo controlled double blind testing. But I can see clear benefits from off-label uses of drugs.

Technically, if we were only allowed to use drugs as they are tested, then we would never be able to use any of the newer anti-epilpetic drugs as first line therapy (with a few recent exceptions). These drugs are typically tested as add-on drugs since no one wants to remove an epileptic from medication and increase their seizure frequency. Every time we put someone on one of the newer drugs that clearly works for them as an add-on agent and remove the original drug to limit side effects (with the exception of Lamictal and Topamax) we are using the drug off-label.

 

[drkitten]

Should having a drug prescribe for an off label use, so that it was not actually studied for its effectiveness for that use, be considered evidence based medicine?

Hell yes, for several reasons.

First of all, there's lot of evidence out there about the usefulness of drugs for various conditions that haven't yet made it onto "the label." Case in point : it's now more or less indisputable that red wine (in moderation) is good for heart disease prevention and cholesterol levels. But there's no "label" for red wine at all. If the doc tells me to have a glass of dago red with dinner, that's technically an off-label use, but it's evidence-based.

There are a lot of studies suggesting that low-dose aspirin may have a cancer-preventing effect. In twenty years, with still more studies, that may make it onto the label. But I have patients I need to treat today. Is it not "evidence-based" if I read the journals as well as the FDA bulletin?

Secondly, a lot of off-label use is validated simply by analogy. The label says that such and such has only been validated for adults (e.g., 12 and over). But if a patient who is 11 years and ten months presents with the appropriate symptoms, it makes sense to believe (based on evidence) that it will have a similar effect as it would on a 12 year old. If I know that drug A (to which the patient is allergic) is approved for use against diseases X, Y, and Z, but that the newer drug B (which has a very similar mechanism to A, but the patient isn't allergic to it) is only approved for use against X, and Y,.... well, that's evidence that it might well be useful against Z as well, even if the pharma company hasn't gotten around to running the tests yet.

 

[Modified]

Ever see those ridiculous commercials where they claim "such-and-such allergy medication is only approved for outdoor allergies, but ours is approved for indoor and outdoor allergies". We're talking about antihistamines or steroids here; if it dries up your nose it dries up your nose.

 

[ponderingturtle]

I was not aware that there could be real studies demonstrating effectiveness, and have it considered off label.

But the point does stand to an extent, what about when a medication is used for something it has not been tested for, because of reports of effectiveness at treating such a condition? Is this really evidence based medicine, as it has all the problems with bias that a naturopath would have.

Basically I am having problems resolving these issues with the general claims about evidence based medicine, when there are drugs prescribed based on anecdote. Now I understand more that off label encompasses more than this though.

 

[drkitten]

But the point does stand to an extent, what about when a medication is used for something it has not been tested for, because of reports of effectiveness at treating such a condition?

And where do you think those "reports" come from?

Is this really evidence based medicine, as it has all the problems with bias that a naturopath would have.

Except for the fact that naturopathic medicine isn't peer reviewed and doesn't have the quality control of traditional medical journals.

Basically I am having problems resolving these issues with the general claims about evidence based medicine, when there are drugs prescribed based on anecdote.

So a report in JAMA is now an "anecdote"?

 

[Orangutan]

What is woo is claiming effectiveness when there is no scientific data to suggest that effectiveness.

For example "The hormones in "the Pill" can be used to treat some medical conditions, such as polycystic ovary syndrome (PCOS), endometriosis, adenomyosis, anemia related to menstruation, and painful menstruation (dysmenorrhea). In addition, oral contraceptives are often prescribed as medication for mild or moderate acne.[71] The pill can also induce menstruation on a regular schedule for women bothered by irregular menstrual cycles and certain disorders where there is dysfunctional uterine bleeding.

Combined oral contraceptive use reduces the risk of ovarian cancer by 40% and the risk of endometrial cancer by 50% compared to never users. The risk reduction increases with duration of use, with an 80% reduction in risk for both ovarian and endometrial cancer with use for more than 10 years. The risk reduction for both ovarian and endometrial cancer persists for at least 20 years.[34]"

Wikipedia. http://en.wikipedia.org/wiki/The_pill#Non-contraceptive_uses
[34] Speroff, Leon; Darney, Philip D. (2005). "Oral Contraception", A Clinical Guide for Contraception, 4th ed., Philadelphia: Lippincott Williams & Wilkins, pp. 21-138. ISBN 0-781-76488-2.

However, for breast enhancement, no reference = woo.

 

[joobz]

There is the flip side to off-label use. Drug reps for awhile were touting and promoting off label indications for some of their products. However, this turned out to be disaterous for one drug (can't remember the one, and which company was guilty: I think astra zenica)
There is the flip side to off-label use. Drug reps for awhile were touting and promoting off label indications for some of their products. However, if an off label indication results in unacceptable incidences of health effects that wouldn't be approved by FDA, this can be disasterous for the drug manufacturer. (I think this actually happend for a drug, but I can't remember which one).

Anyway, drug reps are barred from promoting ANY use that is specifically approved by the FDA. However, the Dr. is still free to read literature and use medications as best he/she sees fit. This just means that the Dr. bears full responsibility if there is a terrible or unexpected side effect.



related link: http://www.insidecounsel.com/issues/insidecounsel/3_circuit/

 

[ponderingturtle]

And where do you think those "reports" come from?

So you are claiming that all off label use is supported by studies?

 

[EternalSceptic]

Should having a drug prescribe for an off label use, so that it was not actually studied for its effectiveness for that use, be considered evidence based medicine?

I have wondered how much off label use is effectively a placebo for a while. I am sure for some it is and some it isn't, and the safety of the medication is known, so it is not like say herbal supplements. But with out real studies who convinced are doctors that off label uses are not the exact same as the quack treatments and they are having the same biases regarding it?

I don't know if it matches your definition, but when I came out of hospital mid 2003 I had lost over 7 kilograms and had severe RLS (restless legs syndrome) not only in my legs, but in the arms as well, which hindered me to fall asleep for hours every evening, making me still more weak and exhausted which in turn made the RLS worse.

In that situation I "pushed" the doctor to prescribe some (pretty heavy) sleeping pills, took them half dose for about one week, slept well every night for nine to ten hours, and when I noticed no more RLS during the days I stopped taking them. No more RLS, no sleeping problems anymore, I gained weight again and no RLS since that time.

 

[Ichneumonwasp]

So you are claiming that all off label use is supported by studies?

I think the claim is that we need direction to begin to find off label uses. Anecdotal evidence is used to suggest further study.

Here's another example. The Vagus nerve stimulator (not a drug obviously) was FDA approved for partial onset epilepsy. Many clinicians noticed two things about VNS -- folks with tremor (usually from Depakote) seemed to shake less and those with depression seemed less depressed. The tremor studies didn't pan out. But the FDA recently approved VNS for medication resistant depression based on studies performed from anecdotal evidence of clinician observation. I won't go into the very severe problems with that study and the approval process, but the point should be clear.

Basically we begin with anecdote. Then someone decides to perform a study and see if that anecdotal evidence can hold up to investigational rigor. Approval is a company related issue. Someone has to want FDA approval for it to happen. Many off-label uses have been investigated with good double blind procedures. Only if it is worth it for a company to seek FDA approval based on these studies is approval granted.

 

[ponderingturtle]

I think the claim is that we need direction to begin to find off label uses. Anecdotal evidence is used to suggest further study.

Here's another example. The Vagus nerve stimulator (not a drug obviously) was FDA approved for partial onset epilepsy. Many clinicians noticed two things about VNS -- folks with tremor (usually from Depakote) seemed to shake less and those with depression seemed less depressed. The tremor studies didn't pan out. But the FDA recently approved VNS for medication resistant depression based on studies performed from anecdotal evidence of clinician observation. I won't go into the very severe problems with that study and the approval process, but the point should be clear.

I am not saying that the observation of side effects and their study is not an important part of medicine, I am wondering how much off label use is backed by sound science. Understanding that it might be most is one of the things I have learned in this thread.

 

[Cuddles]

No, in most states doctors can prescribe any thing for anything. But don't expect the mfg to cover liabilities.

Fair enough. Does anyone know if this is true in Britain as well? It seems that even if you're not breaking the law you must at least be breaking codes of practice if you prescribe something with no evidence to back it up.

 

[drkitten]

Fair enough. Does anyone know if this is true in Britain as well? It seems that even if you're not breaking the law you must at least be breaking codes of practice if you prescribe something with no evidence to back it up.

I believe off-label use is legal in Britain (and most of the rest of the world) as well, and for the same reason. The drug regulation process is slower than the scientific research process.

On the other hand, "malpractice" is not really defined by "the law." In technical terms, malpractice is generally a civil offense --- I sue you directly for hurting me via delivering sub-standard care -- while "breaking the law" usually refers to criminal matters, resulting in the Crown prosecuting you. If you prescribed a drug for me off-label, and something went horribly, horribly, wrong, the fact that you had written an off-label scrip would be one of the pieces of evidence that I would introduce to help support my contention that the care had been substandard.

Presumably you would introduce the reasons you figured that the drug was appropriate. If you don't have any reasons, God help you with the jurymen. On the other hand, a simple statement like "this drug has been successfully and safely used with adults for decades, but no studies have been done about its use on geriatric patients; The patient simply had a previously unsuspected allergy to the active ingredient in the drug" is likely to be an argument the jury will accept.

The ethics of off-label prescribing have been a topic of a lot of debate in the medical profession. Few would argue that it shouldn't happen, but a lot of people would like to see some regulation and restriction. This article, although centered on the USA, not Britain, defines and describes a lot of the issues.

The basic idea, though, that everyone seems to support, is that a physician who genuinely has the patient's best interests at heart and has a rational basis, even if not formal evidence, supporting the off-label use should be able to use the drug in any manner she sees fit.

 

[Dancing David]

Should having a drug prescribe for an off label use, so that it was not actually studied for its effectiveness for that use, be considered evidence based medicine?

I have wondered how much off label use is effectively a placebo for a while. I am sure for some it is and some it isn't, and the safety of the medication is known, so it is not like say herbal supplements. But with out real studies who convinced are doctors that off label uses are not the exact same as the quack treatments and they are having the same biases regarding it?

Very interesting idea and one that bear pondering. In the psychiatric community there is a lot of off label use, especialy with atypical antipsychotics as mood stabalizers.

Sometimes there are follow up studies.

But often they are just used for marketing such as "this medicatioon is the only one shown to effect mood related symtoms" or in the case of antihistamines "the only one effective in the treatment of indoor and outdoor allergies."

I think the FDA studies are a good thing but i think there also needs to be more follow through on the use of medication in general, there should be random sampling and surveys of all medications in use.

 

[Dancing David]

What drugs are prescribed for things they have not been studied for? Isn't this illegal?

Sort of is and sort of isn't. A doctor assumes a different level of liability when perscribing off label. But they can always claim mis-diagnosis.

 

[Dancing David]

I was not aware that there could be real studies demonstrating effectiveness, and have it considered off label.

But the point does stand to an extent, what about when a medication is used for something it has not been tested for, because of reports of effectiveness at treating such a condition? Is this really evidence based medicine, as it has all the problems with bias that a naturopath would have.

Basically I am having problems resolving these issues with the general claims about evidence based medicine, when there are drugs prescribed based on anecdote. Now I understand more that off label encompasses more than this though.

Now having seen about fifty people who were given atypical anti-psychotics to treat bipolar disorder and thier sysmptoms reduced significatly, I can attest to the off label effect of drugs. However typical antipsychotics are already used to treat bipolar disorder, quite often.

There was a doctor who also perscribed mood stabalizers to people with treeatment resistant scizophrenia, he felt that it lowered the threshold of treatment or that they had undiagnosed schizoaffective disorder. However if the medication was not helpful withing 6-8 weeks he would discontinue the usage.