Drug Patents and Generic Drugs: What Does This Mean to Us?

by Michael Jorrin, "Doc Gumshoe" | July 8, 2013 4:28 pm

Doc Gumshoe looks at the drug approval process and patents

Does the Supreme Court decision announced June 17th, giving the FDA the right to sue pharmaceutical companies that enter into “pay to delay” agreements with generic drug makers represent a blow to big pharma, a gift to the generic sector, and a boon to consumers? I don’t think so, and here’s why:

The situations where this ruling might apply are not that common. What happened in this case is that a generic competitor to Solvay’s Actavis testosterone gel challenged Solvay’s patent. Rather than slugging it out, Solvay made a deal with the competitor to keep the generic off the market until Solvay’s patent expired. How much Solvay shelled out to protect their patented version, I don’t know, but it no doubt struck the generic outfit as better odds than what could have been a protracted court case. And in the event of a court battle over the patent, who knows which side would come out on top. And how much it might cost.

However, in my opinion, the drug patent system is flawed, not to say dysfunctional. How it works is that the original developer of a drug absolutely has to file a patent as soon as they’re looking at any promising drug entity. They cannot, cannot, cannot wait until their drug is approved to get it patented – doing so would risk that somebody else beats them to the finish line, and all their work is down the drain.

Drug patent life is 20 years (under normal circumstances) from patent approval. So if it takes the pharma company 7 years to move their drug through the regulatory process, they have 13 years of remaining patent life. And if it takes 12 years to get their drug approved – which is by no means unusual – they have 8 years of patent life. That’s the patent cliff you hear about. And the approval process is arduous, as it must be, if the regulators are going to be able to assure the public that the drug is both safe and effective.

The Drug Patent Situation outside the US

A “pay for delay” case is currently underway in the EU. The Danish pharma, Lundbeck, is the target of enforcement by the European Commission because of a deal with a generic manufacturer to keep citalopram off the market until the patent expired, about two years. Citalopram is marketed in the US by Forest as Celexa. But more about Celexa below, under Phase IV trials.

Meanwhile, in India the Supreme Court refused to grant Novartis (NVS) a patent on their leukemia drug Gleevec, permitting Indian drug manufacturers to sell a much cheaper version. The decision was acclaimed as an important step in making low-cost drugs available in poor nations – Gleevec would cost about $70,000 per years, while the generic version costs about $2,500 per year. Novartis counters that it makes Gleevec available to huge number of leukemia patients in India at no charge, and that if drug developers are not compensated for the enormous costs of moving a drug from the first glimmer of promise to full marketability, then innovation will be stopped dead in its tracks.

And, of course, India is the biggest manufacturer of generics in the world. India could flood the entire world market with cheap generics, a matter of considerable concern to the entire pharmaceutical community. And India did not even have patents on drugs until 2005 – and then only for drugs introduced after 1995 – so the concept might be said to be a bit alien to them.

But, returning to the US …

The Drug Approval Process in the US

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First, the original developer identifies a promising agent that might have some useful activity. Let’s say, for the sake of inventing a case study, that they are looking around for antibiotics that might address some of these exceedingly troubling resistant microbes that are giving the infectious disease docs nightmares. They find that by tinkering with the structure of one of the existing antibiotics they can get it to penetrate the cell wall of some of these offending pathogens, and, by golly, stop these little devils from reproducing. So, immediately, they patent the new molecule.

Now they have to do a whole lot of lab work. They need to test against which pathogens their new agent will be effective, and they also need to make sure that the agent doesn’t harm the myriad human cells that are essential to life. (An essential difference between antibiotics and disinfectants is that the antibiotic specifically targets pathogens, while disinfectants tend to kill whatever cells they touch. You can put iodine on an infected scrape or cut, but you don’t want to take it internally or even cover it up, because the iodine will be absorbed and do a lot of damage to healthy cells.)

The lab work is termed in vitro – “in glass” – but early on they will also do a considerable amount of in vivo testing – i.e., in living animals. Small animals at first, and eventually larger animals, that, we hope, tell us how humans might react to the potential antibiotic. For example, they want to determine as accurately as possible what the minimum lethal dose might be. If it takes 10 milligrams to kill a mouse, and the mouse weighs 15 grams (about half an ounce), it would take about 6 kilograms (more than 12 pounds) to kill a 95 kilogram human, like me. Pretty safe.

Phase I Trials

Those tests (described above) are preclinical, meaning no human subjects are involved. But fairly early in the process, they need to start doing clinical trials. Phase I trials are short, involve maybe a few dozen subjects, and are focused mostly on safety and on determining things like dosage, how the drug is absorbed and eliminated, and how long it stays in the system.

Phase I trials also try to provide some information on whether the drug works in subjects with the target disease. This can be tricky, especially when there are already drugs with demonstrated effectiveness for that target disease, so sometimes the drug is tested in patients that have failed to improve with existing agents. In the case of an antibiotic, they might get the consent of a patient with a resistant infection. There are a lot of skin and soft tissue infections that don’t respond to standard antibiotics. They could obtain informed consent from a patient with one of those infections and try out their new drug on that brave person to see if it works.

Phase I trials do not compare the trial drug with another drug or with placebo, and they are not randomized or blinded. The level of information they provide is just a start. Needless to say, lots of potential drugs crash and burn in Phase I.

Phase II Trials

Now we start getting serious. If the drug didn’t raise any safety issues in the healthy volunteers in Phase I, and if it demonstrated some effectiveness in subjects with the target disease, the drug developer moves on to Phase II trials, which typically enroll a couple of hundred subjects with the target disease. These trials will be randomized, meaning that patients are assigned to different treatment groups at random, but at the same time making sure that the patient characteristics in the different treatment groups are similar (it wouldn’t do to have patients in one group be older or sicker than those in another group). The trials are double-blinded, meaning that neither the patients nor the investigators know which treatment they are taking. They may be placebo-controlled, or, in some cases, active-controlled, meaning that the new drug is being compared with an existing drug.

Phase II trials look for both efficacy and safety data. Efficacy data in Phase I trials, which are not controlled, can be deceptive. If we stay with infectious diseases as an example, patients recover from infections on their own, and it’s hard to be sure whether it was because of a drug they were taking or because their own immune responses came to the rescue. But if 100 patients taking the new drug recovered from the infection on average several days sooner than patients taking placebo, then the developer knows that the new drug is doing something.

When the new drug is being compared with an existing drug, it may be enough in Phase II trials to meet a pre-determined standard for non-inferiority. This would be a matter of falling within a certain statistical range

Phase II trials also look carefully for adverse effects, which drugs are almost certain to have. Because the subjects in Phase II trials have the target disease, and because Phase II trials can run several months (depending on the disease under treatment), these trials are more likely to detect the kinds of adverse effects that would emerge in the patient population that the new drug is intended for. Certain adverse effects (headaches, nausea) are very common and often go away after the subject has been on the new drug for a couple of weeks. Others are of greater concern, and if they are serious enough, may stop the development of the new drug dead in its tracks.

It’s worth mentioning here that if the drug is intended to treat a life-threatening disease, some adverse effects are probably worth putting up with. But if, on the other hand, it’s meant to do something like treat allergies, the safety standard is much higher.

Phase II trials (and this goes for all clinical trials) have predetermined outcome measures. In an infectious disease trial, the outcome measures are apt to be both biological (the drug eliminated a predetermined percentage of the target pathogen) and clinical (the patient’s signs and symptoms of infection diminished). The principal investigators and statisticians determine whether the trials goals were met, and the degree of statistical significance – i.e., could this have happened at random, or can they be confident that the results were really produced by the new drug.

Phases II trials, because they enroll many more subjects and run longer, start to run into real money. A trial with 200 subjects may require the involvement of as many as 50 investigators at different medical centers. It would not be unusual for a Phase II trial to cost $50 million or more.

Nor is it unusual for Phase II trials not to meet their outcome measures. When that happens, the money is down the drain, and it’s back to the drawing board. Although during the years that they have been working on that particular new drug, the drug developer doubtless learned something of value that might be useful in the development of another drug that might work better.

Usually several Phase II trials are conducted before going on to Phase III. Some Phase II trials are conducted by Big Pharma, but many are done by smaller biotechs, perhaps working with academic centers. And often, Big Pharma makes deals with the biotechs, subsidizing the cost of Phase II trials in exchange for rights to develop and market the new drug if the trials are successful.

An example of this is the deal that Celgene (CELG) just struck with MorphoSys (MPSYF.PK). The deal will total more than $800 million, and it gives Celgene some marketing rights to a drug that will treat multiple myeloma and leukemia. But that drug (so far unnamed) is only as far as Phase II. What we can take from that is that successful cancer drugs are rare and exceedingly valuable, and this one looks promising.

Whatever the arrangement, we can be sure that the eyes of Big Pharma are sharply focused on these Phase II trials.

Phase III Trials

When we get to Phase III, the stakes are high. Drug developers aren’t going to launch Phase III trials without serious expectations that the trials will meet their objectives, and that the drug will be approved for marketing. A Phase III trial might enroll as many as a thousand subjects and could take several years, depending on the target disease – if the disease is acute, trials are shorter, but trials in chronic or recurrent diseases typically last years. And costs, correspondingly, are much higher, frequently in the hundreds of millions.

The FDA looks very carefully at Phase III trials, and goes through thousands of pages of data with the proverbial fine-toothed comb. It’s not enough, in order to gain FDA approval, for the new drug to demonstrate that it’s effective and safe. The FDA wants the drug to be of value to the field – it has to be better in some way than the drugs that are out there already. Of course, there are lots of ways for a drug to be better. The obvious one would be that the new drug actually performs better on what are referred to as “validated outcome measures” than the drugs already in use. An easy example would be a cholesterol-lowering drug – if the new drug lowers total cholesterol by 40% compared with about 35% for a standard statin such as Lipitor, it would be highly likely to be approved, all other things being equal.

Other ways for a new drug to be “better” might include dosing, side effects, or absence of interactions with other drugs. And the FDA might look favorably on a new drug that had a different mechanism of action; for example, the cholesterol-lowering drug Zetia (ezetimibe), from Merck (MRK) works by inhibiting the transport of cholesterol from the intestines to the circulatory system. It doesn’t lower cholesterol as much as most statins, for the simple reason that most of the cholesterol in our system doesn’t come into our bodies as cholesterol – we synthesize it ourselves. But Zetia is another tool in the kit, so to speak, and it easily won approval.

Drug developers don’t go into Phase III trials unless their expectations for success are pretty strong. They most definitely do not treat these as a crap-shoot. They will have started to work with the FDA fairly early in the development process, and as it goes along, the FDA looks at the results of the clinical trials and may point to further information that is needed before the new drug gains approval.

That doesn’t mean that the drug developers necessarily conduct just the type of trials the FDA would most like. I am not privy to the FDA’s hopes and dreams, but a type of trial that the FDA would probably look upon with great favor is just the type of trial that gives drug developers the serious willies: a head-to-head trial between their new drug and an established drug. That would give the regulators the clearest indication as to whether the new drug should be approved or not – i.e., is it “better” than drugs that are already approved. The FDA is not fond of “me too” drugs – they just clutter up the marketplace, confusing patients and doctors alike.

But for the drug developers, this is a high-stakes gamble. They would much rather test their drug against placebo; then they can compare how their drug did versus placebo with the established drug’s record against placebo. And they can structure their clinical trial in such a way as to maximize the chances that their drug will do better versus placebo than the competitor drug did. But going head to head against the competitor drug – that’s risky. They would prefer to go with the noninferiority trials that they did back in Phase II, and hit the FDA with trials against placebo.

Which is not to say that head-to-head trials don’t take place; however, they tend to be the exception, and they’re usually conducted after the drugs have been approved for marketing, rather than as part of the New Drug Application. These tend not to be sponsored by pharmaceutical companies, but by academia or government.

Phase IV Trials

It doesn’t stop with Phase III. Let’s say the drug gets approved by the FDA and is being marketed. If it’s that antibiotic for skin and soft tissue infections, maybe the pharma outfit would like to get an indication for another kind of infection, perhaps lower respiratory infections (LRIs), many of which are caused by the same or similar pathogens. So now they need to study the drug in patients with LRIs.

Or say the drug has gone off patent, and generics are starting to eat into the revenue stream. Pharma has strategies to try to extend the patent life of drugs. One might be to change the dosing, from (for example) twice a day for a week to once a day for three days. To do that, they would have to run a clinical trial demonstrating that it works.

Another would be to replace the racemic form of the drug with an enantiomer. What do those words mean? Well, drugs are complex molecules, a lot of radicals (parts of molecules) bonded together however they happen to fit. They can have the exact same chemical composition, but be structurally different – mirror images. For many drugs, their capacity to do their thing depends on exact fit, like a key in a lock. Think of two keys with the identical profiles, except that one has the grooves on the left side and the other one on the right side. Only one key fits in the lock; the other one is useless. The racemic form of the drug is a mixture of the left hand molecule and the right hand molecule, but half of those aren’t going to be effective. So the pharma outfit figures out which is the one that works – which enantiomer – and markets a version of the drug that consists only of that enantiomer, and obtains FDA approval, based on the premise that there’s no benefit (and there could even be harm) in giving patients a drug half of which is not efficacious against the target illness. But to do that, they need yet another clinical trial.

An example is the development of Lexapro (escitalopram), which is the enantiomer of Celexa (citalopram), marketed by Forest (FRX) and others. It has been suggested by the European Commission that the motive for the development of escitalopram by Lundbeck was purely “evergreening,” i.e., keeping the patent alive.

Yet another strategy is to market a two-drug combination. An example is Lotrel, marketed by Novartis (NVS). It’s amlodipine – Norvasc , from Pfizer (PFE) – plus Novartis’s Lotensin (benazepril). Norvasc is a calcium-channel blocker, and Lotensin is an ACE inhibitor, both hypertension drugs, but with quite different mechanisms. When the individual patents expired, Pfizer and Novartis made a deal to extend the patent lives of their separate drugs by marketing a combination. The way Lotrel is “better” than the individual drugs is that the patient only has to take one capsule, and that’s thought to contribute significantly to patient compliance.

All in all, Phase IV can go on and on and on. There is no end to Phase IV.

Patient Protection with Generics

How much protection do patients have with generics? My short take is, slim to nil. Here are some basics:

Generic drug makers do not conduct trials or, really, test their drugs clinically in any way at all. What they do is copy the active drug molecule and package it as closely resembling the labelled drug as possible. Prescription generics are covered, supposedly, by the prescribing information (PI) of the patented drug. However, once the patent has expired, the original developer/manufacturer/marketer of the drug has no further obligation to update the PI. If they are going to continue to market the drug, they mostly do update the PI for their own protection. But, as often happens, they give up marketing the drug, they have no further interest in updating the PI, which means that if new adverse effects appear, these don’t get listed in the PI.

There was a landmark Supreme Court case on exactly that issue a year ago. A woman named Gladys Mensing of Owatonna, Washington, developed a seriously debilitating disease, tardive dyskinesia, that caused her to lose control of many muscles in her body. She had taken a generic form of Reglan (metoclopramide), initially marketed by Pliva, Inc, which is now part of Teva (TEVA). After the patent on Reglan expired, Pliva turned the manufacture of the drug to a generic drug maker. So when cases of tardive dyskinesia emerged, no warning was added to the PI. Gladys Mensing sued under state law, arguing that the drug maker had failed to warn patients about the risks, but SCOTUS ruled that Federal law prevailed, and the Reglan PI, although outdated, was the only warning label recognizded by law, so she had no recourse. At that time there were thousands of cases open having to do with metoclopramide and tardive dyskinesia, and none of those patients had any legal remedy available.

Another area where patient protection with generics is questionable is the actual compounding of the drug itself. The active drug molecule is supposed to be identical with the original patented drug, but every drug has inactive ingredients, sometimes constituting most of the content of the pill that we swallow. What the provenance and purity of these constituents of generic drugs might be is hard to determine, and there have certainly been cases of generics imported to the US with questionable ingredients. A lot of us remember the tainted heparin that was imported from China, which resulted in 149 deaths in the US about 5 years ago. When pharmaceutical companies in the US and Western Europe import ingredients from elsewhere, wherever that may be, they are required to test these ingredients scrupulously, and they certainly do this – for their own protection, not to mention ours. But the tests sometimes fail to detect dangerous and even lethal impurities, as in the case of the tainted heparin.

However, the distinction that I want to draw is between the level of scrutiny carried out by developers/manufacturers/marketers of patented drugs and the testing done by generic drug makers. I am not accusing the generic sector of having lower standards, necessarily. But the big goal for the generic makers is to be economical, not to say cheap, and the disincentives represented by hugely expensive lawsuits and reputational damage are simply not enough to guarantee equivalent safety.

How Can Drug Patents Be Changed to Address These Issues

My proposal (which has no chance of being adopted) would be to start the patent clock running from the time the drug is approved for marketing in the US, not from the date the patent is first granted, so that if it takes 12 years to get FDA approval, the drug developer still has 20 years to recover the costs of developing and testing the drug and still make a reasonable profit.

This might remove some of the incentive to reap huge profits in the short run, and the patent law could be changed with the clear understanding that more reasonable prices were part of the quid pro quo. It might also remove some of the incentive to look for ways of evergreening the patent. A 20-year lifetime for a genuinely valuable drug sounds like a boon to pharma. And by the time that 20 years has elapsed, chances are something better will come along anyway.

* * * * * * *

I look forward to your comments on this and any of my pieces. If there are subjects you would like me to rant and rave about, drop a little note in the comments. Or if you have questions … of if you think I am way off base and need to make amends… Just let me know. Michael Jorrin (aka Doc Gumshoe)



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Endnotes:
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Source URL: https://www.stockgumshoe.com/2013/07/microblog-drug-patents-and-generic-drugs-what-does-this-mean-to-us/


  1. Avatar
    David Krueger
    Jul 8 2013, 05:13:54 pm

    I don’t understand why Canada can sell the generic version of a product that is only available as a name brand in America. For example a Cialis sells for around $30 per pill in America but in Canada they sell for around $3 as a generic. If we can get those type prices in America we could save billions of dollars.

    • Avatar
      Kevin FitzGerrell
      Jul 9 2013, 06:09:25 am

      David,
      Generic alternatives to Viagra could be available in Canadian pharmacies as the patent for Viagra was overturned in Canada. Viagra reduced their Canadian prices, however, so generic alternatives were less cost effective and may not be available. Cialis is, I believe, still under patent in Canada. Of reputable Canadian online pharmacies (CIPA members or Pharmacychecker.com checked), some sell generics of both products but drop ship from dispensing pharmacies overseas in locations (ie Indian manufactured and dispensed in Singapore) rather than sell through their Canadian dispensing locations.

  2. Avatar
    vivian lewis
    Jul 8 2013, 05:44:59 pm

    dear Doc Gumshoe
    An excellent take on the gaps for both patients and patents in our US drug approval circus. But who is looking to improve the drug trial process, apart from you and me?

    • Michael Jorrin
      Michael Jorrin
      Jul 9 2013, 11:05:45 am

      Glenn, you’re right – miscounted the zeroes. All the same, I’d say that if the minimum lethal dose is 63 grams, the drug is pretty safe. Thanks, MJ

  3. 31 |
    Avatar
    Tzvi Yisrael
    Jul 8 2013, 05:57:23 pm

    Fantastic article about how drug companies get drugs to market….
    To bad not all countries are as sophisticated as the US process is…. No wonder why there are cost benefits to test a new drug outside of the US and maybe later patent it and bring it into the US…. At least they’d know whether the drug is effective by testing it out in some remote marketplace!

  4. Avatar
    art slesinger
    Jul 8 2013, 06:04:21 pm

    At some time the US citizens will have to decide if they want to support the research that leads to new drugs. The US is the last free market place in the world of any size. The others control price or availability. So we pay more for our meds because that cost covers all the failures that preceded it. The FDA is the most demanding approval agency so a US approval suggests no major problem in Japan or EMEA (Europe). On top of that, the manufacturing demands for quality and safety are far more stringent than many other places. In the end of the day, you get what you pay for.

  5. Avatar
    A. Fazio
    Jul 8 2013, 07:32:37 pm

    The generic vs. Brands very difficult for patients and their families. My husband has Parkinsons and a large pharmacy run by a large supermarket chain took it upon themselves to change all his meds to generics. He didn’t know the difference but the changes that took place in his body and brain were unbelievable. I took him back to the Dr. thinking he was really going downhill and then discovered what had happened. We went back to the brand name but t a great personal cost. We spend over $500 per month on brand name and he still has not recovered some abilities he lost while on the generics. I cannot tolerate any of the drugs made in China or India due to the fillers that are used. There are only certain generics like Watson and Teva that work for me. What a fight with most Pharmacists. The Generics are not the same as brand name.

  6. Avatar
    Allan Robinson
    Jul 8 2013, 08:28:40 pm

    As always, Travis, great in-depth takes on the topics covered. An educational joy to read the Gumshoe’s articles. Keep up the interesting work

  7. Avatar
    Suman Lal
    Jul 8 2013, 08:31:10 pm

    I thought generic versions DID have to be tested to make sure that equivalent blood levels are attained compared to Brand names with same dosage to qualify for FDA nod.
    And that biotechs such as Epogen and Neupogen are immune to generic competition supposedly because their molecules are too complex for comparison to generic versions. So there can never be any generic competition to them. I learned hard way after being burned in one Dragon Pharmaceuticals ( ticker DRUG.OB ) that had created Erythropoietin (AKA Epogen) but could not get FDA approval. The stock eventually ended up worthless.

    It is an irony because Erythropoietin occurs naturally in human body and should not even be patentable.

    But I guess who pays the piper calls the tunes.

  8. Avatar
    Bruce Bardes
    Jul 8 2013, 09:07:57 pm

    A minor point on the term of a US Patent. Prior to 1992, the term of a US Patent was 17 years from date of issue. After 1992, the term became 20 years from date of application. Also, there is a provision by which the term may be adjusted to reflect delays in the approval cycle.

  9. Avatar
    Peter
    Jul 8 2013, 09:32:46 pm

    Cher maître–

    Porter keeps intoning in his infallible way that there’s really no actual gold around so all our gold “investments” are bogus. Question: the reality of actual gold bullion in ETFs may be one issue, but what about our gold financers like Sandstorm–do they actually have gold under lock and key, or have they loaned it all out so they are no better than an ETF?

    Looking forward to your insight!

    Best regards,
    a humble irregular

    • 12558 |
      Travis Johnson, Stock Gumshoe
      Travis Johnson, Stock Gumshoe
      Jul 8 2013, 09:38:45 pm

      Sandstorm has the right to purchase gold that hasn’t been mined yet, and they can get physical delivery of gold when they make those purchases, but they don’t hold gold — they sell it pretty much as soon as it comes through the door. I suppose they could hoard it at some point, but they’ve shown no indication of that — they want to recycle that cash to buy more gold “streams” and grow the company.

  10. Avatar
    Rog Yocum
    Jul 8 2013, 10:41:31 pm

    Michael,
    Thanks for you for your educational article. I am a molecular biologist, but have little experience in the pharma universe, so I learned a lot. However, I think you got one fact wrong. Patents in the US are now valid for 20 years from the date of APPLICATION, not from date of issuance. Up until June 7, 1995, it was 17 years from date of issuance, but since then the US switched over to the “European” system of 20 years from filing. I agree with you 100% that drugs should get 20 years from approval. I had a European patent (not directly related to drugs) that I applied for in 1985. It took until 2004 to get it granted. It expired one year later in 2005…. -Rog

  11. Avatar
    sagenot
    Jul 8 2013, 11:07:08 pm

    Who is Michael Jorrin Travis. I’m not on the ‘net as often as before, but I wondered if he was your nom de plume? ROFL!

    BTW Travis, it was Congress who passed that pharmaceutical bill allowing the Pharma Cos. to charge Americans the full price for their drugs, while almost everywhere else the same RX is priced much lower. Just ask your Congressman.

  12. Avatar
    James Lowell
    Jul 9 2013, 03:37:46 am

    Great job, Doc Gumshoe, of explaining the approval process, including enantiomeric switches! I’m retired, with a PhD in organic chemistry, and quite a few years working for a lab that contracted with Pfizer, and I’d say you nailed it!

  13. 30
    Avatar
    Cathy Kandravi
    Jul 9 2013, 05:41:42 am

    You hit it right , the one stat I would like to see if it could be done impartial is the drugs under study and when some ones last few days or weeks are imminent. So they do the out of the USA doctor trip to try for a cure and come back to the USA, and same doctor or same doctor with several opinions before and after. Many wealthy try but the stats are not published until the results which are not a success , but there are many doctors that feed off that last hope with a $ sign. The FDA ,the Patents, the Moral Doctors, the Immoral so called $Doctors, the selling and stealing of organs, etc., and of coarse the Attorney’s all have there judgement day to. Then we have the all mighty piece of paper with the side affects that you get to sign and the Malpractice Insurance premium. But big Pharma is just that ( BIG ) and miracles are few if any. I like the comment J Lowell says including enantiomeric switches! I am curious on quality reading material that gets the attention of a retired PhD that separates the fact and fiction, it still seems time runs it’s coarse before what mostly seems a lot in cycles and then someone seems like they stumble through there work on something by mistake and finds a cure of coarse we are much more developed in the lab now, I finished a book a while back from Chris Martenson, PHD called The Crash Coarse and would recommend , a little long but interesting on the levels of time and the world advancement and the levels with all the studies Govt. and Private noticed to verify . Big on numbers but good reading and the time theory’s detailed but J Lowell and as he says Doc Gumshoe do you all have any special magazines with out all the hype and yet in laymans terms that you follow. Thanks

  14. Avatar
    Craig Wilson
    Jul 9 2013, 12:11:54 pm

    Comments reflect a career in Canadian trade policy, and a decade living in China (1984-2002):
    – shift to a 20 year patent period was the result of an intense decade long campaign, led by pharma, but supported by a lot of other research intensive sectors across most OECD members; main rationale was payback on growing investment required; there was concommittant undertaking that pharma in particular would increase R&D (important to remember, original patent period of 17 years was chosen at 1792 US Continental Congress, choosing the same period in which a slave manumuted to free status – the US patent innovation was the American effort to monetize and buy technology from emerging industrial revolution which Britain industrialists refused to share with its ‘upstart’ colony – -there has never been a scientific/business effort to assess what the best economic period for a patent should be to spur the greatest innovation; and, efforts to differentiate among sectors, despite clear evidence of faster payback in several key sectors – manufacturing, IT, etc
    – reality is that 2 decades since 1992, global pharma R&D has levelled off, while longer period of payback enabled major business shift in pharma sector to buyout of small R&D focused firms as research projects appeared close to viability; major productivity boost of late 90’s has not been repeated in bio-tech sector to date – while growth of low margin emerging markets has forced ongoing, painful adjustment in pharma business strategies in the west;
    – today, the huge cost hump of bringing new drugs through Phase III trial and approval has generated an industry focused on incremental change, and minimizing transparency…. The ability of governments to achieve a better policy framework and environment for innovation has been constrained by the fragmented and costly system big pharma has developed – beginning with the emergence of the industry in Germany and Switzerand 150 years ago.
    Travis’s ideal scenario might incorporporate a commitment to an independent scale drug testing capacity, sharec among national health authorities, which would deliver much better metrics on patient characteristics (as suggested above by Cathy Kandravi);
    Health sector has been relatively slow to digitize, a factor of both costs and fragmented industry, with an ideological overlay in the US which results in the most expensive health care system in the world, and the only developed economy not using a single government purchaser to leverage pharma bills down – 17-8% of GDP, with relatively poor health outcomes – often near the bottom of the OECD measures for a variety of standardized measures (Canada does better on these measures, but only marginally so, often falling in the bottom 10 in OECD or wider tests – Canada spends about 12% of GDP, 1/3 less than US…the average Chinese spends 1/40 th of what the average American spends on health care, but lives longer and healthier…better diet, less obese, more active..their reliance on cheap natural medicines and more self responsibility, including in interaction with pharmacists appears to have delivered, on average, better health care to many more people)
    – key point is that drug system focused on new drug/placebo comarison asbasis focconsumerchoice misses reality of human experience– and also basis of Asian herbal medicines, which are based on trial and error (like the West) but also standards of observation of patient impact which are worthy of modelling (Chinese pharmacopeia published about 1490 was superior to anything in West until after Osler’s landmark book on patient healthcare of 1912). Growing integration of western and eastern medical knowledge could hugely improve patient treatment world-wide, if the interactions of various practices were subject to common measurement.., eg aruyvedic Indian practices, Chinese herbal, acupuncture, European homeopathic and other natural practices against pharma solutions;
    – Modern doctors, west and east, would love to have access broad treatment data on specific patent types, with detailed metrics on characteristics from gene make-up to ethnic origin, to adverse effects of specific interactions on all of these variables- instead of the current narrow reporting standards which leave even doctors with specialized training confused with so much generalized info, making it extremely difficult to drill down on problems of specific patients reactions or needs.
    – Of course, pharma loves the rich US market, but in total just as many new drugs have come out of Europe over the past century. The recent surge in R&D and patents awarded in India and China will only continue….key question is will our North American healthcare decision-makers ensure sufficient flexibility and transparency to enable new and more efficient health care solutions, including the best pharma options, are delivered to our populations….and can we ensure efficient regulation to deliver safe products in our markets, but combined with higher comparative standards – so our doctors can compare and advise accurately on optimal health choices in the future….

    • Avatar
      Kiki
      Jul 14 2013, 02:14:38 pm

      Craig Wilson, thanks for your long, insightful comment. The idea of a global data base with comparisons of the effective treatments used by different cultures around the world would be an amazing step forward for health and safety. Any global approval process would have to secondary, after a global understanding of various effective treatments was accomplished. Unfortunately, most of the pharma world is motivated by $$$$, not necessarily the best health outcomes for all. Perhaps a group like the Bill Gates foundation could work on compiling such a complicated data base, starting with common maladies such as high blood pressure . There are many historical effective herbal remedies used for thousands of years that the West has only “discovered” in the 20th century.

  15. Avatar
    Ted Pass
    Jul 9 2013, 02:35:26 pm

    One of the most informative articles I’ve ever read online.
    Many thanks for the clear orderly explanation of how drug approval works.
    It does promote some understanding of the obstacles facing big pharma in bringing a new drug to market. For years they have been running ads explaining to Americans how we should be happy to pay exorbitant prices for their products because of all the research they do to create them (they don’t explain why the prices are much higher than in other countries). Your article makes their case much more persuasively than their ads do.
    Since you asked for suggestions for future articles, I’d like to see more details on Celexa vs Lexapro and what evidence there is (if any) that Lexapro is better.
    Thanks again.

  16. Avatar
    Eddie Mimbs
    Jul 9 2013, 07:46:38 pm

    Guys your insurance company or PBM requires the Pharmacy to use the least expensive drug in stock. They have what is know as maximum allowable cost for almost all generic drugs and it is getting very difficult to find a brand that is below this maximum allowable cost. Our government is trying to control cost at the retail level instead of looking a the real problem. For example the common antibiotic went from a low of $ 26.00 per bottle to over $ 2000.00. The PBMs only update their prices when it is to their advantage. For instance if a price goes down it is updated that day, but if a price goes up it may take them weeks to get in the system, so your Pharmacist loses both ways. In my opinion the drug companies and PBMs ( Express, Medco, etc) have bought and paid for your congressman. Go look at their contributors.

  17. 28 |
    Avatar
    Douglas Kandt
    Jul 10 2013, 12:08:45 am

    One simple question – at the beginning of the article, you talk about a couple “pay to delay” cases. What I don’t understand is: if the drug in those type of cases is still under patent, how can a generic manufacturer make a generic version of the drug (and so why would the original pharma company have to pay them not to do so)? Don’t they legally have to wait until the patent expires before generics can come out? Or are they doing this illegally? Thanks.

  18. Michael Jorrin
    Michael Jorrin
    Jul 10 2013, 11:39:40 am

    Quck replies to a couple of excellent questions:
    One – I don’t know that Lexapro is any better than Celexa. The assumption is that because it’s the enantiomer & contains none of the wrong-sided molecules, it’s better, but I don’t know that it’s been demonstrated to be more effective. However, I’ll poke around & see what I can find.
    Two – regarding the “pay to delay” cases, these are where the patent might be in question for any reason, and the holder of the original patent would rather shell out some cash than take a chance on a court decision.
    Three – yes indeed, the patent clock starts ticking from the application, not the approval.
    Many thanks for all your comments & best to all, Michael Jorrin (aka Doc Gumshoe)

  19. Avatar
    Ted Pass
    Jul 10 2013, 01:20:43 pm

    Michael,
    Thanks for your comment about Lexapro vs Celexa.
    It turns out there are whole websites devoted to this question, although not clear who is behind them. Lots of confusion regarding which is clinically more effective.
    I’d be interested in anything definitive you can find.
    The general question seems to be that if someone creates an enantiomer of a drug with established effectiveness, how much investigation should be done of it and what outcomes are acceptable? Should it be tested head to head against the original drug, and be required to be shown superior? Or is it sufficient to test it against placebo without reference to the original drug?

    Again, thanks for an excellent article.

  20. 14
    Avatar
    Marilyn Scott
    Jul 11 2013, 07:42:02 pm

    Hi Travis,
    What can you tell your subscribers about the “Hollyood Contracts” that claim to generate fast income involving no buying or selling of stocks. Is it another some kind of “put and call” deal? MS

  21. Avatar
    claudia
    Jul 14 2013, 06:07:38 pm

    Michael, thank you for the great article – I did not see anywere where generics verses brand when it comes to certain medicines and insurance companies – when on seizure meds my Dr. would not let me take the generics said they could be off up to 30% most phamacist say it really is only about 20% that makes you feel better right – the brand I had to take was very expensive even with insurance and there was no generic at the time wouldn’t made a difference – now the insurance companies at least blue shield of ca. is making it’s patients take the cheapest generic on the market = no more Teva generic = you have to take something like Qualtist which is very bad and does not work and makes me at least sick – the only thing I can do is pay up for a better generic = made here like Watson or Teva and pay like I’m buying the brand name – how can they do this when your Dr. says only use this generic – this is a whole new subject – everyone ask yourself it in the last 2 months you notice your generic was different or did not work the same and your pharmist will tell you your insurance will not cover the more expensive generics = they do not give a rats weight about how the new cheapest drugs work -where it is made or anything – news to me that the companies making generics do not have to test or have much or any quality control and only read the brands ingredients and make their version – has always been about money to the drug companies and it should since they are the ones putting money on the line that could break at any time – but to make the pharmist give you there cheapest one it is not right becaues they have to make a profit too – so it comes down to we are all getting washed and no one cares.

  22. Avatar
    Judy Appleton
    Jul 14 2013, 06:30:21 pm

    For one thing. If they would allow our pharmaceutical companies a 20-year patent when the drug goes to John Q, then the price would come down. They are the ones who put the millions of dollars into the drug. Generics are just copies with a different base possibly. I know many generics do not work for me. The real drugs do when I am sick or need them. Then again many companies do make their own generics. If you have a heart condition go ahead and take the generics and see if they work for you. I would not try it. It depends on if they work for you and what condition your have. Israel has been doing generics for years. To each his own.

  23. Avatar
    Roberta Glick
    Aug 30 2013, 10:46:43 pm

    I am delighted to have finally found your writings. For too long I have been expressing negative feedback on the effectiveness of many generic drugs. And, while insurance plans state they do not interfere with medical decisions, they most decidedly do by requiring that generics be used even when a physician clearly informs them that they do not work. The mailorder pharmacies which we are forced to use do not only require the generics, they often refuse to fill prescriptions unless they agree that what was tried before did not work, responding that they do not believe the drugs already tried were only for the specific condition. Given not only this attitude, but this reality, and combining it with the information that generic drugs do not go through trials etc. is not only troublesome, it is infuriating. Unfortunately I have multiple atypical diagnoses that only respond to specific medications. My physician has spent countless hours trying to get these dispensaries (the pharmacies that insurance cos reimburse) to listen and stop interfering with medical diagnoses when they do not know the patient, nor do they have medical credentials. The public suffers both physically and economically that is inexcusable. Perhaps if your information gets wider readership some changes will be forced to occur. Thank you for the job you do.

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