Top comment from the reddit thread on the same article:
"Ophthalmologist here.
As a physician responsible for prescribing and injecting these drugs, I can tell you that this article glosses over the single most important factor involved in deciding between the three currently-available Anti-VEGF options: compounding pharmacies, and the lack of regulation thereof.
Any Ophthalmologist at this point is very familiar with the results of the CATT study which confirmed the equal efficacy and safety of bevacizumab (Avastin) and ranibizumab (Lucentis). The reality is that the actual drug injected into the patient's eye either comes from the manufacturer in a sterile, ready-to-inject form (Lucentis), or an appropriate amount was prepared for intraocular injection by a local compounding pharmacy (Avastin).
Compounding pharmacy regulation is notoriously poor, and the risk of an intraocular infection is not one many retina specialists are eager to take unnecessarily. Endophthalmitis frequently leads to blindness, even with early diagnosis and treatment. As much as everyone wants to think doctors are only interested in lining their pockets, the reality is that most of us simply don't want your grandparent going blind in one eye because a minimum-wage tech at a compounding pharmacy failed to follow appropriate sterile procedure. The American Society of Retina Specialists have been advocating for increased regulation of compounding pharmacies since Lucentis became available. Check out their website.
I guess I should also point out that we get paid the same for injecting any medicine into the eye, regardless of the cost of the drug. And we purchase and stock both drugs in the clinic, and bill insurance for whichever is used. So we don't benefit financially for injecting one versus the other."
The minute I started reading the article, I knew something was up, and then I got to that part.
It's not a $50 drug that treats as well as a $2,000 drug. It's a drug sold in large doses to treat cancer apportioned to a small dose to treat blindness.
Complaining about Genentech's price structure in this case doesn't make any sense. It's like complaining that a restaurant won't sell you half-sized portions at half price. It totally ignores the underlying cost structure of the industry.
Not really. It's more like a butcher selling a beef tenderloin in 40lb cases for $5/lb or a trimmed steak for $200/lb. Same product, just a cut that's too big for consumers to handle.
In the case of my hypothetical butcher, he would be out of business, as the free market will push prices down. In the case of Genentech, using patent monopoly and regulatory procedure as a weapon nets them massive profit.
No its not like that at all. Almost all the cost of beef is the beef. Cows are a certain size, overhead is relatively low, and so twice as much beef costs roughly twice as much.
With pharmaceuticals, cost is highly unlinked with volume. Marginal cost is almost nothing, but fixed costs are very high. Its like the restaurant: because most of the cost of the product is overhead and per diner rather than the food cost, half as much food sells for way more than half the price. This is true even though restaurants are in highly competitive markets.
They took the previous development costs and research for the cancer drug, made some relatively minor optimizations for ophthalmologic application, and packaged it appropriately. It probably cost them a few million to go through the regulatory process.
End result is that Doctors can write prescriptions on-label and avoid compound pharmacies (eliminating risk) and Genentech makes $1B/year, mostly off of Medicare. The only "fixed cost" is the cost to the Medicare taxpayer.
Do you really believe that going through all 3 stages of drug trials cost "a few million"?
A quick search found this page which lists all the studies and trials they did, including 3 year followups of the Stage III efficacy trials (pretty much required for this sort of drug, I'd think): http://www.lucentis.com/hcp/dme/clinical-trials-dme.html
Try hundreds of millions, from everything I've heard about what it takes to get a new drug to market. Now, you can question their decision to grab a fragment of the original and tweak it for what they thought would be better efficiency, something you know only after many years and $$$, but otherwise the costs are baked into the regulatory pie.
And even then a new indication for the original would not be cheap to get through the process ... given that it's injected into the eye vs. bloodstream, I don't think it would count as a "routine" new indication, but would require going back all the way to the first stage safety trials.
ADDED: Looking closer, they did 2 sets of Stage III trials for 3 indications, three different diseases that all have a symptom this drug treats. Around 800 patents total for each indication, and they did a 3rd Stage III trial for the first indication, looks like they experimented with less frequent dosing in that 3rd trial.
If you believe that Stage III trials, the ones that in theory prove a drug actually works, have any value, then just doing this science was worthwhile, vs. practitioners having much more rough knowledge of what the original drug could do after compounding. If you don't believe in Stage III trials, well, we can sure cut the costs of future drugs if the drug companies don't have to prove they work....
You don't even need to get to the expense of drug trials. It's simply nonsensical to proceed from a premise that costs in drug development are something you can divvy-up on a strictly per-product basis. Any given drug is the result of a broad research program that has a few hits and many failures. Everything is heavily cross-subsidized, and that's pretty much the only way to run a modern pharmaceutical company given the nature of drug development.
At the end of the day, Roche (the parent company of Genentech), has revenues and profits quite similar to Google. They're profitable, but not ridiculously so.
And yet we have a contributor https://news.ycombinator.com/item?id=6870282 saying "That said, Genentech is on the wrong side of the PR angle here and unfortunately for them, some internal documents got exposed which make them seem less than angelic here. If the cost differential of producing the drugs really is small, then they don't have a strong position, because it makes them appear as if they are using one of the drugs as a profit center to fund future R&D.", which he clarifies as "they are using one of the drugs moreso than another as a profit center."
In this case an appeal to abstract fairness in pricing based on production costs. Which the author recognizes is probably not practical in the real world.
But that such a thing, "using one of the drugs as a profit center to fund future R&D", can even be thought of as a bad thing ("wrong side of the PR angle") ... well, the very much not nice part of me hopes for all these people who implicitly desire or demand the end of new drug development that karma is for real.
Is the implication here that the technician at the "manufacturer" is not minimum-wage?
Or is the implication supposed to be that the minimum-wage technicians who work for the "manufacturer" are magically better at following appropriate sterile procedures?
I think it's a fair comparison for the following reasons:
1) Manufacturer techs get paid a hell of a lot better than compounding pharmacy techs. I knew guys in the pharma industry, nothing more than high school pulling down $100K/yr with overtime.
If compounding pharmacies perform so poorly in this area, then it is certainly in the interest of the manufacturer to provide a better product for at least two reasons.
1) If they know ophthalmologists will prescribe the safer product, and since the demand for this drug is relatively price-inelastic, they are able to raise prices drastically (hence the $1950 discrepancy).
2) If compounding pharmacies are the ones who are under-regulated, perhaps the manufacturer actually faces sufficient regulation. In this case, they face greater liability for sterility issues, and they have a strong incentive to enforce sterile procedures.
The problem with the pharmacies is not so much that the worker is paid low wages or under-skilled, but rather, that the lack of regulatory burden limits the incentive to ensure safe procedures.
The implication is that quality control is better at the manufacturer as opposed to the compounding pharmacy. It doesn't matter who is paid what. What matters is the quality and reproducibility of the product.
The implication is that the minimum wage technicians at the manufacturer were magically transformed into robots who happen to be very good at following procedures.
Eye doctor here. Avastin is currently used off-lable for eye conditions (most commonly wet AMD and macular edema in diabetes). It is only FDA approved for use in treatment of some colon and lung cancers. Generally speaking, even though it fits standard of care within the field of ophthalmology to use this drug, there are still some inherent risks in doing so for the practitioner, thusly, Lucentis is still preferred by some. Also, I've not encountered this (as MOST insurance companies would prefer practitioners to use the cheaper drug) but I've heard of difficulty with third party payer coverage/ reimbursement when using the off-lable drug.
Another thing to consider, as ajrw pointed out, they ARE NOT as the article mentions "the same drug." Some people respond more favorably to one versus the other. Commonly, the two will be used in succession on the same patient as though no double blind clinical trial has been done to confirm this; both drugs tend to exhibit a slight tachyphylaxis over time (diminished effect). Practitioners have found that when one drug starts becoming less effective, switching to the other VEGF inhibitor can show recapture of the previous level of therapeutic benefit.
I would advise all to take this article with a huge grain of salt. Most practitioners are not aiming to increase insurance costs (obviously, as generally speaking, the higher the bill, the harder it is to get the reimbursement.) Many are probably apprehensive to use an off-lable drug from a medical-legal stand point.
Note: I am not a surgeon. So some of this is slightly presumptive.
The rest of the world is very grateful for the US pharmaceutical market. Its unregulated and "free" nature, like consumer advertising for prescription drugs - something completely unheard of in civilized countries - allows for massive profits for the pharmaceutical industry.
those profits do not happen anywhere else. european agencies control and negotiate prices centrally, emerging markets seems to follow the european model (brazil, china, etc.).
those profits do get invested back into r&d, the patent system forces pharma companies to move forward. the recent patent cliff is a great indicator for the system working.
pharma r&d would be severly constrainted if not for the profits generated in the US market. on a global scale it looks like a subsidiy by the US people, paying high markups and taking way more drugs than needed - for the good of the rest of the planet.
The article left out a number of very good scientific reasons why lucentis and avastin are not bioequivalent and should not be subsituted.
I found it especially misleading that they used anecdotal evidence to claim that the cheaper drug is equivalent in function and safety.
That said, Genentech is on the wrong side of the PR angle here and unfortunately for them, some internal documents got exposed which make them seem less than angelic here. If the cost differential of producing the drugs really is small, then they don't have a strong position, because it makes them appear as if they are using one of the drugs as a profit center to fund future R&D.
Anyway, the article really glosses over stuff, but you'd need to spend about 5-7 years getting a PhD in pharmaceutical chemistry, plus working in industry for a few years before you understand the business and science of what genentech does.
they are using one of the drugs moreso than another as a profit center.
IE, given no other constraints, I'd expect a pharma to distribute its R&D cost over its drug profit centers weighted by the drug's profit margin, and that all the drug's profit margins would be roughly equal: naively, I'd expect them to raise the price of Avastin and lower the price of Lucentis, assuming the costs of producing them truly are similar.
The reality is, likely there are proprietary reasons we're not privy to that causes the cost differential. They could be technical (maybe it does cause much, much more to produce Lucentis), or the could be business (maybe increasing the price of Avastin could cause it to sell poorly against another drug from a competitor)
Doctors will typically prescribe the "best" drug to their knowledge which often means the newest drug with the least serious side effects. I don't think they are always out to bilk their patients.
If you are ever in a situation where you have to pay for drugs out of pocket or your insurance doesn't cover enough of the drug call your doctor and ask for a lower cost alternative. They can call the pharmacy and often times find a lower cost alternative to fit your budget.
At least this has been my experience with my doctors. I have also had my primary physician straight up tell me the price difference between the best choice and second-best choice doesn't justify the benefits.
> If you are ever in a situation where you have to pay for drugs out of pocket or your insurance doesn't cover enough of the drug call your doctor and ask for a lower cost alternative. They can call the pharmacy and often times find a lower cost alternative to fit your budget.
I think you hit the nail on the head. Most people just accept what the doctors, insurance companies, and pharmacies tell them, without asking for more affordable alternatives. My pool guy was complaining about how he got one of those "Your insurance is being canceled and your new insurance is 200% the cost" letters from Humana. I got the same exact letter a week ago. I asked him what he was going to do. He said "What can I do? Pay the high cost." I told him I got the same exact letter and I called Humana, talked to an agent for 5 minutes, and they put me on a plan that costs just a few bucks more than my old plan but covers a lot more and with similar deductibles.
It is in the best interest of every corporation to up-sell you the most profitable product. In case of insurance, Humana quoted both of us ACA-compatible plans that sound similar (similar/lower deductible) to the old plans but are actually different (no coinsurance, 100% Rx coverage etc.) and thus cost a lot more.
I also told him to call up BCBS, Aetna, and Cigna if he really wants to shop around because they all have good, competitive plans now. There is no reason to stick with Humana if they don't have a good plan for him. But I don't think he's going to do anything except blame the ACA law. There really needs to be a nationwide education campaign on healthcare. People really have no idea that there are better/cheaper alternatives, regardless of whether you are for/against ACA.
In this case, that is not true at all. I worked for a large retina group for 6 years and now consult for several different retina and general ophthalmology practices, so I'm a little biased, but I've also been lucky enough to see these new drugs through various stages.
First of all, Doctors are the ones buying the drug, and they have to keep enough inventory on hand to treat the patients that need it until the next delivery day. The introduction of these higher priced biologics has had a huge affect on the way practices (especially smaller ones) have to manage their inventory. The last practice I worked for was buying between $1.2 and $1.8 millon worth of lucentis, a few hundred grand worth of Eyelea and a boatload Avastin every month. If anything goes wrong during the reimbursement process and the practice isn't paid as expected, it can be devastating. When the use of these drugs started ramping up, there were definitely a few scary payroll periods for us. Putting the right inventory management procedures in place significantly helps this problem, but there's definitely some stress knowing you're on the hook for over 2mil each month.
Genentech's rebate and Regeneron's extended payment terms are efforts to alleviate some of this stress on providers while ensuring they are keeping enough stock on hand that they aren't having to bring patients back for a follow up visits just to order the drug. (some practices will see a patient, diagnosis, reschedule for follow up injection, then order the drug. This just wastes everyone's time)
Even more importantly though, as said elsewhere in the comments, these drugs are definitely not the same. A lot of us, even the docs, in the industry joked about the high price of Lucentis when it first came out and many doctors (though I'm not sure on the exact number, but I think I remember hearing 80% of anti-vegF injections were Avastin not lucentis) used avastin over lucentis specifically because of the price.
In the past few years however, this thinking has changed and it has very little to do with the reimbursement model. In the beginning, these drugs were simply awe inspiring. Before the availability of these drugs, a retina doc's approach to AMD was, "here's an amsler grid.. let me know if anything changes (it will), we'll see you in 6 months to asses how much more blind you've become. There are some vitamins you can take that might slow things down (barely), and oh yeah, there is this cold laser treatment we can try(PDT)that will just shut down that area and maybe prevent the spread. That treatment is going to require us to infuse you with a drug for 15 min, then shoot a laser in your eye for 83 seconds.. oh then after that, we are going to wrap you like a mummy because any form of UV is going to burn the shit out of you.. fun stuf"
Now all of a sudden here is a drug (Avastin) that takes half a second to inject, and not only preserves the vision that you have, but if we catch the leakage early, it can even dry it up and improve your vision! I was fortunate enough to work on some of the early trials and honestly the follow up visits were just breathtaking. NVAMD used to be a death sentence to vision.. now it's merely an inconvenience that can be overcome.
With that success came Lucentis (Avastin was being used totally off label) an FDA approved drug that was crazy expensive. Patient's couldn't afford it, no one really used it. Then medicare and some other insurances started having issues with off-label use and it actually became easier to get reimbursed for using Lucentis. The CATT trial started and some issues started being raised over whether or not Avastin was actually safe long term. Then there was the scare in Florida were a batch of Avastin from a compound pharmacy was contaminated and a ton of patients lost their sight to infections. So we started using Lucentis a little more frequently, just to see. While the Catt trial shows the two drugs are pretty equivalent.. in everyday practice, it's becoming more apparent that this is not the case. Some forms of AMD respond better to lucentis than Avastin. Diabetics with Macular Edema sometimes respond quicker to Lucentis (and even faster with Eylea!) It becomes more about finding the right drug for the individual patient than just choosing the cheapest option. Most doctors are not trying to screw their patients over, and have protocols in place for finding the best possible drug, and, in my experience at least, most of these protocols do consider the affordability to the patient as well as the effectiveness. (Personally, I think there are genetic variants of these diseases that determine the effectiveness of the drug, we just don't fully understand yet.. once we can more accurately test these variants and build trials around them, this will become more of a non-issue)
A few years ago, I would have totally agreed with this article, not anymore. The sad truth is profit drives innovation, it's a bitch developing new drugs, and their has to be enough of an incentive both financially and medically to encourage progress in that field. At the end of the day, the majority of the doctors out there just want was is going to be best for their patients and are continually re-evaluating their strategies to ensure that goal is met.
This has been my experience as well. There's almost always a cheaper, effective alternative. In the one case where there wasn't, the benefit of the medication vs. its cost was so out of balance that we just decided not to use it.
In this case, the doctors actually do buy the drug. Out-patient use of physician administered drugs is done through "buy and bill".
The physician purchases the drug and keeps an inventory. When a patient is treated, the doctors bills the insurance company and receives the cost of the drug (usually average selling cost) plus a mark-up.
Drug companies are allowed to offer rebates to physicians (it falls under the "safe harbor") as long as it doesn't create perverse incentives for use (as determined by the DOJ). The other thing to keep in mind is that any rebates gets subtracted from the average selling price, so in essence any rebate is clawed back with a few quarters.
I live in a small village and whe have two doctors. After visiting doctor A you'll leave with a bag of drugs, doctor B will not give you anything more than you need, even if you ask for it. The crazy part is people prefer doctor A..
When I was growing up my father told me a parable of three brothers, all of whom had grown to be doctors.
One brother was a miraculous curer of all injuries and ills. It did not matter how far a disease or injury had progressed, he could cure the patient. He was known throughout the continent.
One brother was exemplar diagnostician of all injuries and ills. It did not matter what was wrong, he could diagnose the problem and if he was unable to solve the problem he would make a personal introduction the most knowledgeable expert on the matter. He was known throughout the country.
The third brother was just a humble backcountry physician. He wasn't very good at diagnosing or curing diseases. But he visited his clients frequently, and gave them advice on their diet, and home and work conditions. On the rare occasion when his clients got ill or injured, he tended them back to health and when possible helped them to remove the conditions leading to the ill or injury. He was only known throughout the village.
And finally there is Dr. Oz, who talked well, was attractive, knew Oprah and was interested in talking about all sorts of diseases and conditions outside his training. He has a TV show, multiple book deals, is a millionaire, and doesn't have to see a patient.
No lay person (and a lot of 'experts') have no chance of judging the competence of a medical professional.
They don't know that though... Instead they will rely on all sorts of proxy indicators, and prescribing lots of tests and drugs is one of them. And no, it's not reliable. On the other hand, doctors have to appeal to these indicators in order to get patients to actually take their advice seriously.
I don't find that crazy at all: I would go to see doctor A as well.
Doctors should use their expertise to advise patients, but in the end people have to be allowed to make their own health decisions. Even if I did believe that doctor B knows better (which I have no reason to), I know I'll get at least the same treatment from doctor A and I'll be able to openly discuss my options.
A doctor whose patients always leave with a bag of drugs is likely not a competent doctor. The statistical chances of every patient having something in need of medication is slim.
Who says you can't discuss options openly with doctor B?
> Who says you can't discuss options openly with doctor B?
Exactly. In my case doctor B once took 30min to explain something I didn't understand, he also grabbed some books for it.. without charging me. One part is true, I can't certainly know who's better.
> Who says you can't discuss options openly with doctor B?
"doctor B will not give you anything more than you need, even if you ask for it" says that by implication: doctor B seems not to be open to ideas other than his own. That's (personally) not what I would prefer in a doctor.
Yes, exactly, I want a doctor who defers to my judgment.
I'm a scientist with significant relevant training.
I know more about my own medical history than any doctor I've met. (it may help to understand that locally that we don't have 'family' doctors and are assigned whichever general practitioner is available to bring the notes up on the screen)
I also confident that I'm a far better judge of my own risk and utility profiles than a doctor is. Who is the best person to decide which of a choice of treatments is right, given the costs and benefits? I believe a doctor shouldn't be (unilaterally) deciding that for me.
Even if those things did not apply to me, I would still want a doctor to advise me and then respect my judgment.
> I'm a scientist with significant relevant training.
That's nice and all, but most people aren't.
This is a little like saying because you're a theoretical nuclear physicist that you should be able to run a nuclear reactor - and so should any random yahoo off the street.
I believe I had already expressed that this was my personal preference.
If you scratch that line and read the rest, my other points would apply generally.
We aspire to give people personal choice in their lives. People have the choice to drink or smoke or get obese or even break the law and risk the consequences. People should have that personal choice in their medical treatment as well.
If that's your point of view then you are not part of the same argument as the grandparent commenter - we are talking about a doctor communicating with a patient. As such, you may infer that I'm talking about doctor-patient communication.
That's a large part of the antibiotic resistance issue. Plenty of doctors realized sending someone with a cold home with antibiotics would shut them up and have them leave happy, even though it has no actual (non-placebo, at least) effect.
I don't see the problem being that Doctor A gives you more drugs. I see the problem as Doctor A gives you more drugs at very little cost to the patient. Lots of patients would much rather pay the relatively minuscule co-pay to have three alternative drugs than just get one and risk having to go back to the doctor for a different prescription if that one didnt work.
It is all about incentives. Most PPO systems encourage everyone to spend more money.
- Doctor's want to sell more (and more expensive) drugs. They make more money that way.
- Patients on many PPO plans pay a small flat fee for each drug. Why not go with the more "expensive" one? Its all the same to the patient.
- The government and insurance companies work together to outlaw cheap plans and force people to over-buy for coverage the patients either don't need or expenses that are predictable.
If they were only reimbursed for exactly the cost of the drug, they'd lose money on expensive drugs because of inventory costs. Inventory costs include interest on money for the time they're holding it, damage and spoilage, security, theft, insurance, etc.
6% is probably a reasonable guess at the average costs. Large, high-volume operations can make a profit by keeping their costs below 6%, and that may create a wrong incentive. But the right answer isn't to change 6% to 0%, because nobody will want to handle expensive drugs.
For the most part prescribing doctors aren't the ones who have to deal with inventory costs, it's pharmacies that have the inventory costs. I've even had doctors send me to the pharmacy to pick up injectable medication, primarily because they didn't want to deal with an inventory. So why should prescribing doctors get 6% of cost?
Prescribing doctors don't get 6% of the cost unless they're also supplying it. Lucentis is injected with a needle into your eyeball, so you probably want your ophthalmologist to do it in their office.
It's actually 4% now that sequestration is in effect.
They get a 6% margin to account for all the other overhead associated with stocking the product. Someone has to order the drug, receive the drug, stock the drug, retrieve the drug and ready the drug for administration.
If they don't get that 6%, they lose money each time they administer the drug.
I don't see an interpretation of what was said in the article where reimbursement of the cost goes to a pharmacy and 6% goes to the doctor, though admittedly I skimmed.
What I found most interesting about the article was the complete lack of any idea of the patient paying for the drugs. The word "patient" literally does not appear on the first page, throughout the rest of the article, it only occurs in references to studies, except on the last page, were we find "many decisions are guided by whether the patient’s insurance covers the entire cost or just a portion."
It seems that patients aren't agents who have any involvement in anything, in the authors world. They're just objects to be pushed around by insurance companies, doctors, and drug makers.
Regardless of the details of these two drugs, right there you have the problem with health care in America.
"it’s the same damn molecule with a few cosmetic changes" pretty much tells you everything you need to know about this article.
As any chemist worth their salt will tell you, small differences to molecules doesn't necessarily make them just as easily produced. And similarly any biochemist worth their salt will be able to tell you that small differences can indeed matter a lot!
Reading the wikipedia article for the more expensive drug (http://en.wikipedia.org/wiki/Ranibizumab), it does appear that there are therapeutic differences between the two drugs in terms of associated infections.
Something most people fail to realise is exactly how expensive new drug development actually is. You've got experimental labs doing in-vivo tests of thousands of molecules (at least), animal studies to ensure the human trials will be safe, multiple stages of clinical trials in humans with associated insurance, etc. The sole means of recuperating the cost of all of this is through product sales. There are very few actual grants awarded for developing medicines all the way through to production. No tie-in marketing of lunch boxes. No crowdfunding from patient groups.
I do wholeheartedly agree, however, that there are perverse incentives on doctors to prescribe more expensive medication, and the modern pharmaceutical industry is messed up in so many ways. Most doctors too don't even understand properly what it is they are prescribing[1], and the 21st century medical representative system has more in common with jingles and home appliance sales than the clinical educators of the 20th century.
Disclosure: I have family and friends working in this field
[1] Reasons why people become doctors: money, power and helping people. Good doctors get to chose two of out of three. And to be fair to doctors, they have to remember a hell of a lot of academic material in a constantly changing field, and /then/ have social skills and physical skills to master
If the pharmaceutical industry didn't already turn me into a jaded person, I would still be feeling a bit of "so what" at what you're suggesting - and coming from an almost-biochem-but-CS major studying for the MCAT right now, I can probably appreciate what you are trying to say a bit more than the average layman.
Genentech have no problem at all whatsoever with most off-label uses of Avastin (e.g. ovarian cancer) and have subsequently added them to the label (and in some cases, like breast cancer, they had to be dropped from the label afterwards), but they actively refuse to do so for ophthalmic use presumably because it would chew into Lucentis profits which are practically an order of magnitude larger. Imagine if Avastin were wildly different from Lucentis - would this fingers-in-ears "lalalala" singing attitude (to be generous) to keeping the use off-label seem reasonable to you in the face of massive amounts of evidence supporting the idea that it is just fine? Literally their only excuse for doing so is that Lucentis exists, nothing else. Both drugs have a number of issues, both drugs could be used for a lot more than ophthalmic use, and both drugs are still kind of expensive ($50 vs $2000 in the US). Avastin is still a blockbuster for Genentech, don't forget - it is one of the best selling drugs in the US.
And yes, I appreciate that drug development is expensive and I know companies have to work for their stockholders, but it's really hard to watch patients trying to make a decision about Avastin vs Lucentis at the end of the day. Maybe I'm wanting to be a mediocre doctor that just wants to help people, haha. But my father has retina issues and I have spent way too much time in waiting rooms overhearing his specialist convincing other patients that he has had an excellent track record with Avastin use as well as Lucentis and he wants to prescribe whichever costs the least out of pocket first. When some of his patients decide not to go with either drug because off label use is too scary for them and they can't afford Lucentis even though he tries to reason with them - those are people giving up their fucking _sight_ and a practically miraculously effective treatment for want of money and a successful scare campaign. And he is a specialist that (I did my research before we went to him) has a good background in research and clinical practice, as well as participating in some studies for Avastin and Lucentis alike, so I hope he has appreciated your argument before doing what he does, too.
Perverse is an understatement here in my (not so honest) opinion.
> As any chemist worth their salt will tell you, small differences to molecules doesn't necessarily make them just as easily produced. And similarly any biochemist worth their salt will be able to tell you that small differences can indeed matter a lot!
As an example of this: thalidomide has two different enantiomers (see here: http://en.wikipedia.org/wiki/File:Thalidomide-structures.png) one of which is harmless (or at least is until it racemizes) and the other of which causes severe birth defects. These are literally the same atoms and same bonds with a twist.
If a twist in a molecule makes the difference between a healthy baby and a severely deformed one, then "a few cosmetic changes" can make a huge difference.
And for a more common situation involving "a few cosmetic changes" that makes me feel not so bad about talking shit about drug companies, take a look at levocetirizine.
My doctor tried for a couple years to push it on me while fully knowing that I would much rather just go to Costco and buy a year's worth of generic Zyrtec for the after-insurance cost of one month of Xyzal. There is literally no difference in effectiveness or side effects for me between the two. For many people there won't be much of a difference.
Tried to push it on you, or prescribed it and you filled it? Often doctors will prescribe the new drug to help patients save money: the insurance company doesn't yet realize it's the same as the cheap generic, and will pay the full cost for you because it's the only drug in its class available. (Buying the over-the-counter drug, you have to pay 100% of its cost from your taxable income, instead of paying $7 from your tax-free income. Then again, given a year's supply of generic Zyrtec is like $20 on Amazon... you'd have to have a pretty high tax rate for that to make sense.)
Obviously, insurers have wised up to this scheme with the "new" allergy drugs, but in other cases, it can be helpful.
In some cases it makes sense for sure. I'm guessing that or something like that is probably why Lucentis is also a blockbuster drug. If the price makes sense then what's the point in thinking any more about it? I would just go with the most affordable option.
In my case, he prescribed it and I asked for an alternative after a small case of sticker shock at the pharmacy (and the pharmacist was the one that mentioned it's practically Zyrtec). The next visit he dumped a couple months worth of samples into my lap and told me I should just stick with it and pay for it because it's worth it, so have some manufacturer coupons - you know, the same doctor that prescribed Zyrtec to me before Zyrtec was OTC, hahahaha. I'm still assuming that he wasn't after a kickback as much as it was just sticking with anything that worked at all in the months that I had bronchitis and sinusitis at the same time (with existing allergies and asthma, it was a terrible hell). Except he kept telling me to give it a chance after all that was over. Then I changed insurance plans and he wasn't in network so that was that.
I think the most unfortunate thing is that pricing is pretty opaque. Outside of that and a couple other situations, my doctors have been really helpful in trying to find cheaper alternatives but they don't know what is cheaper other than having someone spend time with the pharmacist going down a list of alternatives. Another anecdote from helping my dad: I used to set aside 2 hours every time he got a new prescription from his ophthalmologist. There were eyedrops that were literally $5/bottle/month, and then there were eyedrops that retailed for over $500 for a fucking 10ml bottle ~1 month supply (I'm looking at you Alphagan P). Every insurance company and plan would be different so someone from the doctor's office had to call the pharmacy and dealing with this took a couple extra hours on my end. Sometimes some brand name would be drastically cheaper than the generic (this happened with Adderall with my old insurance plan). Sometimes the price changed for no discernible reason (not even like anything to do with deductibles). It drove me nuts.
This kind of ridiculousness is yet another reason to be glad of the UK health system: flat charge of ~$10 for filling any prescription, and even that can be waived for large categories of people who have trouble affording it.
Having said that, certain categories of extremely expensive drug aren't available on the NHS; until recently Herceptin was the most prominent example of this.
> "it’s the same damn molecule with a few cosmetic changes" pretty much tells you everything you need to know about this article.
This is not like a small molecule where a little change makes a huge difference; Avastin is a giant antibody and Lucentis is a part if the same antibody. It's a hack of the FDA process to allow Genentech to sell an equivalent drug at a very different price.
Several of the "perverse incentives" are possible because of insurance/medicare hiding the true cost of medications from the consumer, so there is very little rational price-signaling back to the manufacturers. Other perversions are made possible by the very regulatory agencies that originally had the good purpose of ensuring drug safety and preventing snake-oil remedies but which have become complex, ever-expanding nightmares of bureaucracy with vast opportunities for corruption and political favor-trading.
another reason people become doctors is because they're interested in science and the human body. I've known a couple doctors that didn't care about money, power, or helping people. They were just really interested in how the body works.
This is hardly surprising, and it's unfair to try to turn it into a problem with "entitlement programs". There are many examples of this kind of thing -- and private insurers aren't pushing back on the costs, either.
Take the anti-viral drugs acyclovir and valacyclovir. They're both anti-virals used to treat diseases caused by the herpes simplex virus (e.g. shingles, chicken pox, cold sores, herpes, etc.), and are both commonly prescribed to patients of all ages. The only difference between them is that valacyclovir is a pro-drug -- it metabolizes to acyclovir -- and has slightly higher bioavailability, which means that patients can take three doses a day, instead of five. Otherwise, they're equivalently effective medications.
Granted, three doses a day is easier on patients than five doses a day, but that convenience comes at a cost: valacyclovir costs about five times as much as acyclovir. Your doctor won't tell you this -- she'll just prescribe the valacyclovir, in nearly all cases -- and your private insurance company won't do anything to encourage you to take one drug over the other. About the only way you'd know is if you tried to buy the drug without insurance, and your pharmacist told you that you could use this other, cheaper medication to save a lot of money.
Not only are "entitlement programs" not the problem here, they could actually be the solution: a single-payer health system would have an economic incentive to push back on providers, and encourage them to use more cost-effective drugs. Our current, private insurance system is almost totally blind to cost effectiveness, because nobody in the chain has any incentive to care. The final costs of the system get passed back to employers in the form of annual rate increases, when it's too late to do anything about them.
Errrm, it's my understanding that "compliance", i.e. people actually taking their prescribed medicines per schedule, is a terrific problem in the real world. The payoff in patient health can be substantial; in one area I'm familiar with, anti-depressants, there's a strong bias towards those that are normally taken once a day (one of the many advantages of Prozac, the first SSRI).
So I can see lots of physicians routinely prescribing the valacyclovir ... although for someone like me, to whom the whole idea of compliance was a new, almost unthinkable thing when I first learned about it, they'd like go with the acyclovir (especially after I looked up the drugs in question, read up on their pharmacokinetics, etc.; obviously I'm a special case, e.g. nowadays I tell my doctors what to prescribe me for allergies and sinus infections, having learned what works and what's cheap).
Hmmm, come to think of it, when I got an "early" (age early 40s) case of herpes zoster (shingles, and, yeah, it's no fun at all, get the vaccine when you can) in 2003 I was prescribed acyclovir, by a doctor who knew both my financial situation (not great then) and compliance patterns.
Yeah, I don't mean to diminish the importance of compliance -- it's a big problem, especially for things like antibiotics and anti-viral meds. And certainly, three times a day is a lot easier than five times a day. But as you imply, you might rationally make a different choice if you (the patient) know the facts. My point is that nobody has any skin in the game in the current system -- from the perspective of the decision makers, the costs are almost totally externalized.
Aside: I also learned about this when I came down with shingles. That was a bummer (not the least of which because I was on COBRA at the time, and the insurance company refused to pay the med costs without going through a complicated reimbursement scheme!)
Until then it's off-label usage. When the time comes, expect an absolute feeding frenzy to make a similar equivalent (with incrementally higher efficacy or slightly fewer side effects) or an alternative formulation to regain those patent rights. I would expect Genentech is already hard at work here.
Except that the problem doesn't take care of itself. By 2019, the same company will likely have on the market a new patented drug in the same family, with roughly the same efficacy as the other two. They can do this pretty much indefinitely.
Yes it does. For example, look at Clarinex. This drug is in no way advantageous over Claritin, and in fact is metabolized into Claritin in vivo. The only reason that it exists is because Schering-Plough's patent ran out on Claritin.
Or look at Vyvanse, a prodrug of Adderall. Shire Plc has been intentionally manipulating the market (using government amphetamine quotas) for years in order to push patients away from cheaper generic Adderall (despite the fact that many people find Vyvanse to be substantially inferior).
Or take the case of adrafinil, which metabolizes into modafinil (provigil). Adrafinil is just fine (not quite as effective, but nearly so), but its patent ran out. At that point, Cephalon pulled strings to get its approval revoked (this was in France; adrafinil is unapproved and unregulated in the US), so that people would have to move to their newer, patented drug. (And yes, adrafinil does tax the liver some, but no more so than plenty of other drugs).
Yes, it does. They add something like calcium carbonate (tums) to an existing med and patent the combo, or they find an isomer of the drug. Happens all the time.
Drug companies have tackled that in a variety of ways.
Outright bribery of generic companies to hold off on production (http://www.usatoday.com/story/news/nation/2013/06/17/supreme...), scaremongering over safety of the generic (the article being discussed in this thread), paying doctors for prescribing the more expensive versions, etc.
Yes, but those generics will be cheap, whereas the new drug will be expensive. Since the doctors are reimbursed based on a percentage of the cost of the drug, they will choose the more expensive one, just like they do now. A cheap competitor already exists. Adding another cheap competitor won't help when doctors are incentivized to use the most expensive option.
You're forgettingabout the incentives of the insurers. They will be the ones to require the cheaper alternative, similar to the way many insurers require the use of Avastin for AMD unless there is a good reason to use Lucentis.
Actually, it won't be so easy. Avastin is a biologic drug, so it's not possible for generic manufacturers to produce an exactly equivalent product.
Eventually, generic manufacturers may be able to compete (the generic clones of biologic drugs are called biosimilars), but it will take a long time and significant resources, because they will need to run new clinical trials to show that the new drugs are equivalent:
Because different manufacturers may produce slightly different products, they consequently cannot guarantee that their version is exactly as safe and effective as the original manufacturer's version. So, unlike most drugs, generic versions of biologics were not authorized in the United States or the European Union through the simplified procedures allowed for small-molecule generics. As a result, nearly all biologics have been brand-name therapeutics and required very extensive testing.
http://en.wikipedia.org/wiki/Biologic_medical_product#Biosim...
The FDA gained the authority to approve biosimilars (including interchangeables that are substitutable with their reference product) as part of the Patient Protection and Affordable Care Act signed by President Obama on March 23, 2010 - none have yet been approved.
http://en.wikipedia.org/wiki/Biosimilar#Approval_processes
Because at $75M to $250M a pop, they're way cheaper than developing a new Biologic ($1B-$2B) and that's because while none have been approved yet, the pathway in the Patient Protection and Affordable Care Act is shorter than that for a new Biologic. I think Big Pharma will do what it takes to make this happen myself. Just like Google will apparently do just about anything for the bottom line despite their corporate motto.
There will be no feeding frenzy; researching an alternative is a fixed cost, but with a competitor they will only be able to sell the drug for marginal cost. The upstart competitor would make more money investing the fixed cost amounts in treasuries at 1%.
(This is a joke; when there are just two companies they price-fix rather than compete. Not with actual price-fixing agreements, instead tit for tat signaling as in the iterated prisoner's dilemma)
Isn't that an example where the new drugs don't matter? Prilosec seems to be cheap and widely available.
I take the point that some of the motivation (I'm hedging here because I haven't looked into it...) for Nexium is a patent protected drug to market, but the tone of this thread would have me believe that Prilosec and equivalents are disappeared from the market.
It's their most commercially-successful medication, they did misleading studies in order to tout its comparative effectiveness, market it heavily and bribe docs to favour it.
Prilosec is still available, but if your doctor prescribes Nexium, you're unlikely to question it. Virtually all of the folks on it could likely be on Prilosec with equal effect and much less cost to the healthcare system.
The underlying problem here is that the consumer doesn't care what the cost of their drugs are; all they do is sign on the dotted line when the doctor recommends something.
Insurees are essentially paying a monthly cost for an effectively unlimited pool of medical funds. As long as the bill is above what their copay costs, they couldn't care less how much the drug costs - if anything, they will choose the drug that costs more than what the nearly identical drug costs so they can 'get their money back.' As long as the consumer is separated from the consequences of their choices, costs will continue to rise. Some kind of incentive for people to actually care about the cost of their decisions needs to be engineered into the system.
Suppose, perhaps, that instead of mandating that employers provide insurance to full-time employees, the government mandated that employers provide catastrophic insurance and contribute the remainder of the difference between the old system and the new to a kind of Health Savings Account: something that's tax-advantaged, and can only be used to pay for healthcare. Employees would then pay their medical bills directly from this fund, and funds will continuously build if they're not used. The kicker is that this HSA also doubles as a retirement fund, and any funds left over when retirement age is reached can be withdrawn without penalty. People will see the money as theirs, and will be much more careful about how they spend it, thus putting pressure on doctors and healthcare providers to reduce prices, rather than increasing them.
This took me ten minutes to think up. Give me half an hour, and I'll work out most of the kinks. Give a team of professionals a few weeks, and I'm sure that we could come up with something that makes infinitely more sense than the ridiculous hodgepodge of special interest legislation and twisted incentives that we have now.
Its the system and its players that overall are corrupt, not just the rules.
For example. Someone will be paid a bonus to make sure the average retirement account is emptied. The average american woman has about 2 kids, so we'll charge about 40% of an average lifetime account "earnings". After all we can either directly or indirectly select any price we'd like.
Another example would be some weirdness with plastic surgery where the cost would now directly correlate solely with human emotional response to a procedure rather than difficulty of the surgery.
Finally I think you'd have some pretty weird and borderline inhumane situations with respect to just barely under retirement age patients getting sick... Feel a lump? Well your grandkids will never go to college, or your kids will never live in a house, etc, if you seek treatment before retirement. Just wait a couple months / years, after all what could possibly go wrong with untreated cancer or heart disease or diabetes?
Now if you could roll over the treatment fund directly to your kids, that sounds great until (grand)parents start offing themselves so their kid can afford treatment.
"Give a team of professionals a few weeks"
Fox guarding the henhouse, you'll end up with something at least as corrupt if not more so than the existing solution.
You are ignoring that there are competing providers. In a competitive market, no one provider can maintain a price that is designed to "empty" an HSA account.
There is, of course, no competitive market in health care, its a natural monopoly and one side of the market is (intentionally?) completely uneducated.
This article seems to miss the bigger picture -- why is Lucentis 40x more expensive than Avastin?
The answer is that drugs aren't priced by how much they cost to manufacture a dose -- nor should they be!
Roughly, they're priced by the cost of R&D (a fixed cost) and the benefit to patients (a fixed benefit per patient). So it makes complete sense that Lucentis is more expensive, because the does size is so much smaller. It's still vastly less expensive to get eye treatment with Lucentis than cancer treatment with Avastin, which runs at ~$100,000/year.
The Post conveniently left out that the Pharm company found that "Avastin patients had a 30% higher risk of serious systemic side effects than Lucentis patients did". Why didn't they include the Pharm company's side?
The article does mention and debuffs it. Its the difference between 32 and 40% Its based off one study of small sample size and is not biologically plausible.
>The incidence of what are known as serious adverse events — a catchall category that includes hospitalizations for any reason — was slightly higher in the Avastin group: 40 percent vs. 32 percent. The adverse events included broken bones and urinary tract infections.
“The majority of the adverse events would be difficult to imagine being caused by the drug,” Martin said. Martin noted that while small, probably random effects favored Lucentis in some cases and in others they favored Avastin. Neither should be viewed as conclusively related to the drug, he said.
>
medicine is one of the areas where being economically driven causes problems.
medical research is stupidly expensive and companies need to recover their costs for their to be progress at all. incidentally its the /only/ valid argument i have seen for patents. it also explains a lot of the high expenses involved... its a shame, i feel that this is an industry that desperately needs to be nationalised because, even with the best of intentions, a business must be profitable to survive.
we regularly see layers of rhetoric and polical manuveuring attacking e.g. Obama care, the NHS and similar initiatives and from this i feel we lose out - they criticise the specifics for a political agenda. imo the spirit of these programs is exactly right - the problem is always sloppy implementation by politicians (as with any case where nationalisation is not effective - which is /provable/ almost in the mathematical sense). We can't expect them to do well though - they are winners of popularity contests which essentially boil down to competitions of rhetoric and salesmanship - they have no reason to have any of the prerequisite skills for us to expect them to do a good job in that arena - or even leadership in general. it is a massive failing of our particular flavour of democracy imo.
on the other side doctors are supposed to be bound by the Hippocratic oath. this utterly rules out not helping people because they can't afford it - and yet many physicians have to make that choice regularly - which is not just breaking their word, but against the entire spirit of medicine and morality.
all in all its a horrible situation, but one that i believe is incredibly fixable... however articles like this are attacking the institutions which currently allow us to have medicine and portraying it in a way that the common man will empathize with. its just another pile of rhetoric distracting us from being productive imo... if you dig into any of the details as other commenters have mentioned, the factual basis is weak.
I'll take a different angle from most of the comments and talk about the prohibition of Medicare negotiating the price of drugs. The article talks about how two other countries have negotiated discounts of 35-45% off the list $2000 USD price. If you want to help hold down prices, all that's necessary is to actually negotiate a volume discount with the drug companies. It's basically an indirect subsidy to the drug companies via Medicare.
It's well known that the pharmaceutical industry sends representatives to doctors to persuade them to prescribe their products. Frequently this is achieved with special "incentives" (read: bribery). Some doctors around here have put signs on their doors saying that they do not talk to representatives of pharmaceutical companies.
What isn't mentioned is that these drugs are actually injected directly into the eye. My grand father was prescribed both, and had no improvement in vision. When he switched to the expensive one, there were excellent results, and he can now see again.
I thought this sort of thing is what insurance companies are expected to handle: to advise on cost-effective alternatives for standard diagnosis codes.
It's no different in the US when it comes to generics. Most state have laws that force a pharmacist to fill a prescription with the cheap generic alternative unless the Rx specifically say to fill with the branded version.
However, in the Avastin vs. Lucentis case, they are no therapeutically equivalent.
"Ophthalmologist here.
As a physician responsible for prescribing and injecting these drugs, I can tell you that this article glosses over the single most important factor involved in deciding between the three currently-available Anti-VEGF options: compounding pharmacies, and the lack of regulation thereof. Any Ophthalmologist at this point is very familiar with the results of the CATT study which confirmed the equal efficacy and safety of bevacizumab (Avastin) and ranibizumab (Lucentis). The reality is that the actual drug injected into the patient's eye either comes from the manufacturer in a sterile, ready-to-inject form (Lucentis), or an appropriate amount was prepared for intraocular injection by a local compounding pharmacy (Avastin).
Compounding pharmacy regulation is notoriously poor, and the risk of an intraocular infection is not one many retina specialists are eager to take unnecessarily. Endophthalmitis frequently leads to blindness, even with early diagnosis and treatment. As much as everyone wants to think doctors are only interested in lining their pockets, the reality is that most of us simply don't want your grandparent going blind in one eye because a minimum-wage tech at a compounding pharmacy failed to follow appropriate sterile procedure. The American Society of Retina Specialists have been advocating for increased regulation of compounding pharmacies since Lucentis became available. Check out their website.
I guess I should also point out that we get paid the same for injecting any medicine into the eye, regardless of the cost of the drug. And we purchase and stock both drugs in the clinic, and bill insurance for whichever is used. So we don't benefit financially for injecting one versus the other."
http://www.reddit.com/r/politics/comments/1sdxz6/an_effectiv...