However, I am pleased to see that the Stanford researchers are interested in how much of this extra cost is due to costly new medications that may or may not be worth their price — a topic too rarely discussed in the Ivory Towers of academia. They cite Januvia and Byetta as potential cost centers, but I can't help but think that they're missing the mark just a little bit. In outpatient diabetes management — and I'm going to assume that institutions and hospitals are similar — Byetta and Januvia, while successful, aren't what I would consider blockbusters. They aren't super mainstream yet.

In terms of quantity and price, the TZDs — particularly Actos, since Avandia got thrown under the bus — are far more costly. Yeah, incretins, whether direct or indirect are the new CME hotness with the associated mindshare, but compared to your TZDs, biguanides, and sulfonylureas, they're a distant a second/third/fourth fiddle in volume, if not cost.

Drug companies market these new drugs with claims of greater convenience and better control of blood sugar levels, and physicians have increasingly used them as alternatives to injected insulin, Alexander said. Insulin use has correspondingly dropped from 38 percent of treatment visits in 1994 to 28 percent in 2007.

This particular sentence bugs me because the implication is that insulin is cheaper than most oral medications. This just isn't true, particularly with the modified human insulins that can be very costly indeed. At the very least, they're on par with the cost of oral meds, and let's not forget that most people with T2DM would prefer not to stick themselves with a needle, no matter how small.

Talk of direct costs aside, it is obvious that $1 spent in the name of public health has a greater marginal utility than $1 spent on a medical intervention — be that drug therapy, a procedure, or whatever. Ben Franklin was right, after all. Unfortunately, the long-run cost savings of public health programs are notoriously difficult to measure, and certainly nowhere near as sexy as a medical intervention. Perhaps that's why public health gets shortchanged? I've spent some idle moments wondering how much money we could save if we spent a third or even a quarter as much combating things like poor nutrition and obesity as we do on direct healthcare itself.

It seems like the bulk of the money spent on prescription drugs is spent to offset the poor lifestyle choices that we Americans like to make. Unfortunately we pay dearly for that privilege. Any sort of nationalized healthcare will have to take this God-given right tendency into account.

This is going to be quick and dirty because I've got some other things to do, but I've been putting it off far longer than I've meant to. (No time like the present, right?) In the January 2008 issue, CR ran a feature on how people could save money on prescriptions meds. Generally speaking, I am in favor of this kind of thing. I like people to know the alternatives, and how they can save money.

Generally-speaking, it's not a good idea to have word-choice errors in a piece that's supposed to be professional. (See image.) Maybe they should get a medically-trained copy editor and add them to the list of peer-reviewers. Ridiculous.

I've re-created the table they have:

I'll go through it quickly:

Zyrtec is now available OTC, and is comparable to the cost of Claritin. Claritin doesn't work for a goodly number of folks, so Zyrtec is a better option. Zyrtec went OTC the month after this was published — and it wasn't a big secret that it was going to happen.

For ADHD, Strattera is not a popular option. It doesn't work for many people, and ADHD people have a hard time remembering to take their meds consistently, which makes this option less desirable, particularly where it takes a little while for Strattera to begin working. I'm surprised this drug was listed at all, as it's rarely a first-line choice for ADHD spectrum disorders. Even comparing atomoxetine (an NRI) to methylphenidate (a stimulant) is a bit… off, and IMO, does the consumer no favors. Strattera is usually used where someone is at risk for drug abuse or has comorbidities like hypertension or anxiety (iatrogenic or otherwise) and so cannot tolerate stimulants.

Depression… don't have much to say there. Fluoxetine tends to be more stimulating than Lexapro, and there are other subtle differences (half-life, solubility, etc.), but for most people, switching from one to the other is probably not impossible.

As for Diabetes… well. Using a biguanide is usually the first step in treating metabolic syndrome, and then you add other meds on top of that. I'd be skeptical of any doctor who used Actos before using metformin without a given reason. Diabetes treatment tends to go in stepwise fashion like most other chronic illnesses. Removing a TZD from a pre-existing diabetic regimen can be done, but it's not as simple (or desirable) as this little blurb makes it seem. And a TZD isn't normally used as monotherapy. Frankly, I think suggesting Glucotrol rather than metformin would have made more therapeutic sense. And in terms of good use of space, I think think they would have been better going after the ARBs and hypertension in general here.

Heartburn and GERD? Nexium 20mg? Who even uses the 20mg strength Nexium? I see it maybe 3 times a year. They should have done 40mg Nexium and suggested 40mg of Prilosec. (Hilarious sidenote: 40mg Prilosec caps (the one without a generic) cost ~$60 more than 40mg Nexium caps.) Generally, though, this one wasn't too bad.

Insomnia: Eh, probably okay I guess. Insomnia is a poorly-treated condition in this country, and frankly, I'd rather see other methods explored before reaching for the BZRAs at all. But the BZRAs are the easiest, and they keep patients happy. Unfortunately, not enough time is spent diagnosing the underlying causes of insomnia, resulting in a poorly quality of life. There are differences in the polysomnograms of patients on eszopiclone and zolpidem, too, which are not talked about. I'd rather see ramelteon tried before any BZRA, and also see a psychologist about diagnosing an underlying cause for the insomnia in the first place, if a primary care provider cannot take the time (due to financial considerations) to do it themselves. And 5mg of Ambien might help with sleep induction, but the relatively short half-life will do next to nothing for those with sleep maintenance problems.

I'd rather have seen trazodone suggested, since insomnia is usually secondary to some kind of other psychiatric disturbance — a type of uni- or bipolar depression.

Not much to say about arthritis, but I hardly ever see Celebrex used anymore. Now that it stands alone as a COX-2 inhibitor, it's also the most expensive anti-inflammatory in the book and insurers are loathe to use it. I'd rather see diclofenac recommended over ibuprofen, and suggesting that 400mg of ibuprofen daily is anywhere near equivalent to 200mg of celecoxib is laughable.

Schizophrenia. SCHIZO-FREAKIN-PHRENIA? CR is going to tackle SCHIZOPHRENIA in an article about how to save money?!?! I am having difficulty wrapping my brain around that one.

But okay, here goes. Schizophreniform disorders should be managed by a psychiatrist or psychiatric NP, IMNSHO. Diagnosis is tricky, and management is always tricky. All that said… while first generation antipsychotics are often as effective as their second gen counterparts, I am extremely leery of merely saying that Y could be substituted for X. At least CR has the good grace to state "The antipsychotics have major side effects and response to them is highly variable" — AKA "Take our advice with a monster grain of salt." Not the least of the worries are akathisia, tardive dyskinesia, other extrapyramidal symptoms, weight gain, and about a bazillion other possible side effects. My mind is still boggled that they even went there.

Curiously, however, discontinuation rates of perphenazine in schizophrenic patients are lower than with any second gen antipsychotic save olanzapine (Zyprexa) — though people tended to d/c Zyprexa due to its metabolic effects and weight gain, and perphenazine for its extrapyramidal symptoms. Something to consider, I suppose.

–

All things considered, it's nice to see the mainstream media promoting saving money on drugs, but it bugs me that they did it in the way that they did.

What the hell is with that? You're going to make a guy with acid reflux, anxiety, depression, hypertension, hyperlipidemia, BPH, and T2DM split his fricken tablets?? Are you kidding me? This guy can barely remember all the medical conditions he has, nevermind what pills he takes at what time for which condition. (There's about 15 meds in all that he takes on a daily basis.)

I felt awful. I called UnitedHealth to no avail. I tried doing a prior auth — yeah, I do that sometimes when insurance companies let their little algorithms run wild without human supervision — nothing.

So now this guy has to remember to split his tablets as well when he's lucky he can get out of bed and tie his shoes in the morning. What assholes. This guy is NOT going to remember to do this right, and there's nothing I can do about it.

What about the money lost through patient non-compliance? I suppose that's not so easily measured when compared to a guaranteed savings of ~$5 per fill by instituting mandatory tablet splitting, so fuck it. We'll deal with the excessive cost of less-than-optimal therapeutic outcomes later.

(I'm conflicted about the idea behind splitting tablets for people since it destroys the tablet's integrity, and can confuse people when they open a bottle and see a bunch of little half tabs staring back at them. I would have asked anyway, but I was so pissed off at UnitedHealth when I got off the phone that it didn't occur to me.)

[tags]Medicine, pharmacy, HMOs, UnitedHealth, tablet splitting[/tags]

No, my fabulous pharmacy friends, these items are often considerably MORE expensive than gold… we're talking Americium expensive.

For comparison, the price of Ridaura — a gold salt in capsule form — is $295.79 for 60 caps.*

In no particular order:

1. Zyvox (linezolid): $1,546.78 for 20 tablets.
2. Cocaine HCl 135mg: $1,144.80 for 100 tablets
3. 1L of normal saline: $100**
4. Casodex (bicalutamide): $519.76 for 30 tablets.
5. Enbrel (etanercept): $7,500/ounce.
6. Lamisil (terbinafine): $435.84 for 30 tablets.
7. OxyContin 80mg: $662.31 for 90 tablets. (Street value is approximately $7,200 for these same 90 tabs).
8. Aldara (imiquimod) cream: $268.38 for 12×1 gram packets.
9. Vancocin: $651.85 for 20 pulvules
10. Iressa (gefitinib): $2,127.35 for 30 tablets
11. Gleevec (imatinib): $3,563.26 for 30 tablets.

Got anything to add?

* All prices are AWP.
** Except this one.

Exenatide (Byetta) is a glucagon-like peptide analog that responds to glucose by stimulating insulin release and inhibiting glucagon release. It also slows gastric emptying, inhibits synthesis of glucagon, and stimulates beta cell neogenesis by preventing beta cell death. It only responds in the presence of glucose, which means there's low risk for hypoglycemia.

Unfortunately, GLP-1 is broken down by DPP-IV, which limits native GLP-1 half-life to about 90 seconds. GLP-1 is also efficiently cleared by the kidneys. The other downside to Byetta is the fact that it's injected.

Sitagliptin (Januvia) prevents the breakdown of the body's own GLP-1 (and other incretin hormones) by inhibiting DPP-IV. As an oral tablet, patient compliance is likely to be higher, or at the very least, it's more convenient than poking oneself.

Despite having entirely different mechanisms of action, the net effect is the same: higher levels of GLP-1 in the body, with low risk of hypoglycemia. Both Byetta and Januvia are likely to help patients lose weight as well. There's been some talk about possibly getting Byetta approved as a weight-loss drug — I don't know how far along this idea is, however.

It's only a matter of time before we start getting insurance rejections for prior authorizations telling us that the doctor needs to try Januvia before they'll approve Byetta. This is good news for those seniors on Medicare Part D plans as well — Januvia can save them a pile of money because it's just so much cheaper than Byetta.

So to recap:

• Easier to store (no refrigeration)
• Oral tablet vs injection
• Once a day dosing instead of twice a day poking
• Cheaper

I think all the pieces are in place for Merck is going to eat Eli Lilly and Amylin's lunch here. It seems one investment house is also predicting something similar. (PDF)

Interesting post. Thanks for the analysis. It mirrors what I had suspected recently with regards to the "80mg Lipitor" reduces the risk of stroke. Emphasis on the 80mg part.

AstraZeneca did something similar with their marketing of Nexium, btw. You'll recall that Prilosec is typically prescribed as 20mg QD. Nexium is most common as 40mg QD. A drug rep (no longer with AZ) told me that they compared the two together — only Nexium was at 40mg and Prilosec was at 20mg. Naturally that part wasn't emphasized, and a lot of doctors were snowed by it. Hence Nexium's evergreened, un-deserved, excessively-costly popularity.

In the case of Lipitor, I think marketing will only work for so long. It's in the government's interest to conduct head-to-head studies comparing the generic statins to Lipitor because it can save them money. It's only a matter of time before this is done — and I think the results are not going to be in Pfizer's favor, which is why I think Lipitor will largely be irrelevant by the time it loses protection in 2010.

And another comment I left on PharmaGossip about a week or so ago:

It seems likely, to me, that this study was conducted with an eye toward generic competition in the form of simvastatin. Pfizer knew Merck was their largest competitor in the statin market, and conducted this study in the hopes of finding this correlation at around this time.

Why?

In the last month, I've seen Express Scripts (one of the largest pharmacy PBMs) move toward making Lipitor available only with a Prior Authorization where before it was the preferred statin of choice. Several other PBMs have done the same thing.

The only exception in the case of Express? 80mg Lipitor. I think that's why Pfizer is emphasizing the "80mg" part as much as the "Lipitor" part: the strength is just as significant (for them) as the drug itself.

My experience is anecdotal in this case — and should be taken as such — but there it is nonetheless.

I should add an addendum that I have since seen Express Scripts cover lower doses of Lipitor, and that different plans probably have different formularies. (Or doctors simply bothered to call in a PA before the patient filled the script which is equally possible.)

Yay marketing!

[tags]Medicine, pharmacy, marketing, Pfizer, Lipitor, cholesterol, statins[/tags]

Specialty drugs are typically biotech medications that treat complex, chronic conditions and often need to be injected. Spending on such drugs reached $40 billion last year or 19 percent of the total on all medicines, according to Express Scripts Inc., a Missouri-based pharmacy benefit manager.

[...]

The explosive growth is spending on specialty drugs is especially problematic because there is no pathway for generic competitors to enter the market.

While it's true that it is somewhat more difficult for biologic generics to be approved, the vast majority of them are still protected by patents in the United States, so the issue is largely moot for now.

An average prescription for an inflammatory disease costs $1,417.

Drugs to treat blood clotting factor deficiencies such as hemophilia registered a 25 percent spending increase, the second largest rise in the group. Annual treatment costs about $100,000 per patient.

Spending on cancer drugs known as antineoplastics, which were administered outside a doctor's office, rose 19.2 percent, the third largest jump. The price per prescription rose by almost 15 percent to nearly $1,600 on average, making inflation the primary driver of the spending increase.

The points missed by the AP article are that the number of hospitalizations is reduced, spending on marginally-effective drug therapies reduced, complications from multi-drug regimens is reduced, and most significantly, the overall quality of life for these patients is HUGELY improved because of the reasons stated above, as well as the fact that their therapeutic outcomes are better.

While it may cost $1,417 for a month's supply of Humira, it can cost that much for one night's hospitalization. A fact conveniently left out of the article.

Everyone is winning with these advanced new therapies: patients, doctors, insurers, and drug companies. But only if you look at all of the factors involved. Articles like this one make me cringe: just last week I heard a patient say to someone else as she was waiting that she "read it in the paper, so it must be true." People have enough FUD in their lives without the MSM adding to it with horribly slanted "news" articles which are nothing more than regurgitated press releases. (You'll notice the press release says nothing about about the lack of generics being a problem, and mainly talks about how Express Scripts is saving money in the face of higher prices. I guess tossing throwaway additions into a press release counts as journalism these days.)

[tags]Medicine, pharmacy, drug spending, drug prices, bad journalism, journalism, biotech, biologics[/tags]

It's a clear victory for Big Pharma, and a loss for consumers and any company that's not Sanofi-Aventis or BMS. Plavix was #2 on the top 200 list in 2005, with sales totaling $5.2 billion. Had Apotex been successful and not settled out of court, there would have been a generic Plavix available relatively quickly. Unfortunately they settled for the guaranteed money, and exclusive rights for 8 months. As I've said before, the value of the generic drug market is tiny compared to Big Pharma — by taking the settlement BMS, S-A, and Apotex all win. (Personally if I was Apotex, I'd have pushed for a higher figure, just because Plavix is so valuable.)

As soon as the results were announced, ten lawsuits by health plans, unions, and other businesses were immediately filed in retaliation, alleging the deal violates federal antitrust laws. The FTC has said that they will examine the case to see if there are any laws being broken. Frankly, I don't know enough about antitrust law to speculate whether the new round of litigation holds any water. It will certainly be an interesting case to watch, and has implications for further back-room licensing deals between major pharmaceutical companies and generic drugmakers, though nothing as unique as this has happened in recent memory that I am aware of.

Don't be surprised to see the number of similar lawsuits mushroom over the next five years as pipelines run dry and patents expire — it will be the only way Big Pharma will be able to maintain their otherworldly revenues for a precious few extra years. I have not seen a change in the way Big Pharma conducts their R&D efforts, and even if they did, there would still be a multi-year dearth of new drugs in the near-term. The path Big Pharma chose back when direct-to-consumer advertising restrictions were lightened has resulted in fat profits when their focus shifted to marketing instead of R&D. Unfortunately for them and everyone else, this more litigation and fewer breakthroughs.

[tags]Medicine, Pharmacy, Sanofi-Aventis, BMS, Plavix, clopidogrel, Big Pharma, antitrust law[/tags]

Before I even begin, I should state that Americans, by and large, have absolutely no idea what health care costs. This means doctors' visits, prescription costs, and anything else you can think of. Insurers have added a layer of abstraction to health care equation that insulates the public from what drugs, in this case, actually cost. (As a result, you'll find patients complaining about insurance companies far more often than you'll hear them complain about anything else.) By and large, this insulation is probably a good thing — when one is sick, worrying about what something costs should be the last thing on one's mind. Many HMOs charge a flat copayment for long hospital stays. Rarely does a patient see an itemized bill.

The downside of this is the "Holy crap!" factor that a patient experiences when a particular treatment is not covered. I see it every day, and I've grown immune to it and the string of complaints that usually ensues. (What I do find funny in a sad sort of way is that the patient often blames the wrong entity for their misfortune — for instance complaining about Blue Cross when they should be complaining about Express Scripts.) Every once in a while, the media catches hold of a particular drug or class of drugs and focuses in on how exorbitant the cost is, and how it shouldn't be that way. Sometimes they're right, and sometimes they're wrong.

This time, the media was wrong.

The WSJ recently shined its influential spotlight on the cost of several cancer drugs — it was the top story on the first page of section B — the article examines the cost of several medications, and makes erroneous comparisons to the backlash against HIV meds. Yes, Erbitux is expensive. Revlimid is expensive, and so is Avastin. But you don't see lines of terminally ill cancer patients picketing oncology clinics. (And it's not just because they're terminally ill.)

The value that these drugs provide is real. Erbitux, the most expensive drug named in the WSJ article, has been shown to extend the median survival rate for patients suffering from certain head and neck cancers from 28 to 54 months. I do not know how much Erbitux cost to develop — I can't seem to find that information — but I do know that the "average" cost to bring a New Chemical Entity (NCE) to market is about $500 million. Erbitux, being a monoclonal antibody, probably cost closer to $800-1,000 million to develop. Sales of Erbitux for 2005 totaled some $281 million worldwide. (It's also interesting to note that North America only accounts for 2% of Erbitux's sales!) Calculating the costs of manufacture, transport, and recovering R&D costs, and you'll find that Erbitux hasn't even paid for itself yet, so it's not as though ImClone is getting fat on Erbitux profits. Yet.

Drugwonks has some additional food for thought about some of the other metrics involved:

Indeed, the entire article ignores three important questions: Are the new generation of cancer drugs better than previous therapies? What would the economic and medical impact be if all these therapies were used in treating various forms of cancer? Are oncologists using these new treatments in an optimal fashion?

Their basic conclusion is that these drugs are significantly better than previous therapies — a longer lifespan is certainly easy to measure. In purely financial terms, the cost of Erbitux runs about $120,000 for a year, whereas a human life is estimated to be worth about $300,000 a year. (Disclaimer: I have no idea how that figure was arrived at.) The point stands that $120,000 for a year's worth of treatment is expensive by anyone's measure, but the question of whether it's too expensive (in moral and ethical terms) is far from answered. In my opinion, it has not reached that point yet.

[tags]Erbitux, journalism, bad journalism, pharmacy, R&D, ImClone, WSJ, Wall Street Journal, Avastin, Revlimid, Tarceva, oncology, cancer[/tags]