The Truth About Generic Drugs

The truth is out there. Finally. The NYTimes has a piece on the problems and differences between generic and brand name drugs. Think they are the same? Think again. The article is excellent and I recommend everyone read it. As usual, I will quote liberally, with some of my own commentary.

But there is a gnawing concern among some doctors and researchers that certain prescription generic drugs may not work as well as their brand-name counterparts.

I personally believe that many practitioners have been aware of this issue for decades. But, you can only obscure the truth for so long.

The problem is not pervasive, but it’s something consumers should be aware of — especially now that more insurers insist that patients take generic medications when they are available.

Generic drugs are for the most part great. But they are not all created equal. The real issues here are about awareness, understanding, knowledge, and truth.

Some specialists, particularly cardiologists and neurologists, are concerned about generic formulations of drugs in which a slight variation could have a serious effect on a patient’s health. The American Academy of Neurology has a position paper that says, in part, “The A.A.N. opposes generic substitution of anticonvulsant drugs for the treatment of epilepsy without the attending physician’s approval.”

Small differences matter. Why this is confined to a 2006 paper regarding epilepsy, I do not know.

But insurers tend to argue otherwise. On Thursday, ExpressScripts, which handles drug insurance for big employers, put out a news release announcing results of a study it sponsored that found no difference in hospitalizations or emergency-room visits for people on brand-name epilepsy drugs compared with those taking generics.

No surprise here. A company with a huge monetary interest in providing generic drugs has come up with a study to support their stance.

The Food and Drug Administration, meanwhile, says it stands behind generic medications and its methods for approving them.

The American Medical Association concurs. A spokeswoman for the group told me in an e-mail message, “the A.M.A. position is that as a whole generic drugs do work as well as name-brand drugs.”

Naturally, after years of advancing the opinion that all drugs are created equal, the FDA and AMA are not about to change.

According to F.D.A. rules, the new generic version must “have the same active ingredient, strength and dosage form” as the brand name or reference product.

Sounds pretty good. So what does it really mean?

Generally, the only test that a maker of a generic medication must perform to receive F.D.A. approval is one that establishes the “bioequivalence” of the product. This test is done on healthy volunteers and compares the blood levels of the reference drug to the generic one. According to Mr. Buehler of the F.D.A., to be considered bioequivalent, the generic drug must reach a blood serum level that is 80 to 125 percent of what the reference product achieves. But Mr. Buehler said that in reality the spread was not nearly that large. He noted that the F.D.A. conducted a large study and found that the average difference in absorption into the body between a generic and brand name drug was only 3.5 percent.

Interesting. So 80% = 100% = 125% I think I get it. Make something similar and you are good to go. I don’t believe the 3.5% from the study is representative or necessarily relevant. There is still a problem. The differences may be smaller than we thought but the message is still the same, we need better standards.

Some specialists, though, worry that the allowable range for bioequivalence is too wide, especially for patients who are taking medication to control problems like arrhythmias or seizures.

I’m no specialist, but I have a problem with 80%=125% What about you? And it’s not just for arrythmias and seizures. Many psychotropic and hormonal medications exhibit dangerous variability in their bioequivalence as well. Want to increase your hormone levels by 50% I didn’t think so. Even a 5-10% difference can be significant when we consider non-linearity in complex systems.

Stephanie Ford, 29, who spoke on condition that she not be otherwise identified, had been taking Lamictal to control her bipolar disorder. When a generic version came out two years ago, her insurer switched her to it.

Ms. Ford found that the generic drug, lamotrigine, worked just as well as the name brand and cost her just $10 a month instead of the $45 copayment she had been spending on the brand name. (For a person without insurance, Lamictal can cost about $300 a month, depending on the dosage.)

But when her insurer then urged her to order her medication by mail, she received another generic version of Lamictal and her symptoms returned.

“After about a week,” she wrote in an e-mail message, “I noticed a difference in my emotional state (and nothing changed in my life) and by a week and a half, I had digressed to the state I had been before being on medication.”

Ms. Ford has found a local pharmacy that carries the original generic. She now buys the medication directly from that store. Because her insurer charges her a $5 penalty for not using mail order, her copayment is now $15.

She says her condition has once again stabilized.

I believe there are countless variations on the story above. I think doctors need to come forward, share their experiences, and pressure the FDA for more rigid measures of “bioequivalence.” Individuals need to be careful and self-aware when switching medications, even when the medications are supposedly the same.

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  • Rafe Furst

    Great post, Daniel. I’m curious though — excuse my not having read the original article, but that’s what a great summary is supposed to do: save me the time — the incentives are counterintuitive to me…

    I would assume that patent-holders don’t want any generics and thus they would lobby Congress / FDA hard to make the conditions impossible to comply with so they strangle the market.

    I’m clearly missing some key insight into the industry, please shed some light here…

  • danielhorowitz

    I’m not all that familiar with the history of the industry, so I don’t know exactly how we got where we are today. But here is my take. There is a conspiracy to provide inexpensive drugs to people. (not all conspiracies are bad) I don’t know when the best time to lobby congress/fda was, but I don’t think it’s a battle they can win today. The FDA wants to allow people access to low cost medications and big pharma and their patents are in the way.

    WRT patent-holders (mostly big pharma,) their only option would be to

    1) Run clinical trials against generics (costly)
    2) Run more clinical trials against more generics until the results come out in their favor (costly)
    3) FDA makes it harder to get generic drugs approved. (costly)

    I think in this situation the aggregate supply of generic drugs is temporarily reduced, but in the long run this only raises the costs to produce generic drugs. Competition decreases and everyone loses. Many people manufacture generics that are almost identical to the original. Assuming a fair trial, these generics will come out as good as the brand name. Perhaps a generic will fare better than a brand name in a clinical trial, then what?

    My guess is that over time the quality of generic drugs has decreased as the number of manufacturers has increased.

    Also, the business of patent holders and generics are now intertwined. Many big pharma have used their hordes of cash to purchase generic drug manufacturers. And the real kicker? The company may now produce both the brand name and generic that are significantly different. (The generic manufacturing subsidiary operates separately)

  • kevindick

    I have a solution. What you want to do is make sure that the generic companies have the incentive to make sure their generics are as close to the original as possible.

    So you have a challenge system. Third parties can put up the money to do a “challenge trial”. They pay a neutral laboratory to run a clinical trial of the generic versus the original. We set some sort of statistical confidence bounds to determine if the challenge “succeeds” or “fails”.

    If it fails, the challengers have to eat the cost. But if it succeeds, the generic company has to pay 3x the cost of the trial to the third party (or 2x or 10x-whatever an economic study shows is the optimal deterrent).

    My guess is that the generic companies would make darn sure they have good products. And if they ever slipped up, third parties backed by investors would jump at the opportunity.

  • MarkL

    You haven’t considered the possibility of simple fraud. Many generic drugs are produced in the same country that included Certain Highly Inexpensive Non-nutritional Additives <- (and some poisonous ones) in human and pet products to increase short-term profits with no consideration whatever for the health of their customers or the reputation of the producers. Such practices appear to be normal in that country, so why assume that generic drugs produced there are produced according to adequate standards?

  • MichaelM

    Another possibility is that placebo power makes the branded version more effective. Wired ran an interesting article on how new drugs in clinical trials are finding it harder to outperform placebos. For some reason, placebos have become more effective over the last generation!

  • Adrian

    I have spoken to two different MD’s who are both in agreement with the theme of this post: generics are usually just as effective, or very close to the brand version, but there are exceptions and you just have to educate yourself on what those exceptions are (and they may vary from person to person).

  • Kaiser Permanente

    Wired ran an interesting article on how new drugs in clinical trials are finding it harder to outperform placebos. For some reason, placebos have become more effective over the last generation!

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