Over the Falls Without a Barrel: The Patent Cliff and Prescriber Impartiality

Randy Paterson, PhD, RPsych
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Imagine calling up your old college friend Science and asking her advice. She speaks softly, hesitantly, and with frequent caveats. You strain to hear what she says, but there’s a problem.
It’s a party line.
While you try to hear Science speak, two boisterous rowdies named Marketing are shouting at you, all but drowning her out. They butt in, answering your questions before she gets a chance, claiming to speak on her behalf. It’s tempting to give up and listen to them instead.
This is the situation for any prescriber. “Science” is out there, murmuring in the distance, while the boys from Marketing giggle, whoop, and exclaim in an attempt to attract attention. They sound like 15-year-old boys, and their understanding of Science is about as deep. There is a light at the end of the tunnel, however. At 16, they get bounced off the line.
Umm, what? A Primer on Drug Development.
When a pharmaceutical company discovers a potential new drug, they undertake a mammoth project designed to assess a) whether it really works, and b) whether the risks and side effects outweigh the benefits. The aim is to amass sufficient evidence that the Food and Drug Administration (in the USA) or other national organizations (such as Health Canada in, you know, Canada) will approve the sale of the drug, and the type of disorders for which it can be openly prescribed – the so-called “on-label” uses.
The process of gaining approval generally takes 5 to 8 years and can cost from several hundred million to more than a billion dollars. The figures vary widely, in part depending on whether one includes the cost of researching drugs that don’t ever make it to market. For every drug eventually approved, there are four to ten that start human trials and don’t wind up on the pharmacy shelf. So the true cost of development is not just the enormous cost of the trials for successful Drug A, but also the costs of failures B, C, D, E, and F. During the development period, the company is bleeding money and can only get it back once the drug is available in the marketplace.
In order to encourage companies to undertake this risk, governments place a pot of gold at the end of the rainbow. This is patent protection. The company that develops the drug has the exclusive right to produce and market it – in effect, achieving a monopoly on that medication. They can set the price to reflect not only the cost of producing the drug, but also to repay the cost of drug development and testing. If they have a “blockbuster drug” – one that becomes a major seller – they can also make huge profits.
The problem with this system is that patients and governments wind up paying enormous prices for the drug. The solution is to impose limits on patent protection – after which rival companies can produce generic versions of the same drug. Generics companies don’t have the same development costs, and so they price their versions much lower, which the original developers are forced to come close to matching. So when a drug goes off patent, the price drops sharply (often by over 80%) and the advantage to the original developer vanishes.
The period of patent protection is typically 20 years from the date of initial filing of the request. Given the delays in the approval process, the actual period during which a company can market the drug exclusively varies, but is usually around 15 years.
The result is that FDA approval essentially fires the starting gun on a race to recoup development costs and turn a profit. The finish line is the end of patent – often called the patent cliff.
The Expensive Elephant in the Room
There’s one bit of accounting that’s often left off these sketched reviews of the process, and that’s the cost of marketing the drug once it has been approved. Most accounts indicate that pharmaceutical companies spend at least as much on marketing as they do on drug development research. One account (below) suggests the figure is almost twice as high for marketing.
Well, fine. What’s the point of developing a new treatment if no one finds out about it and patients go untreated?
The marketing costs do not include the means by which prescribers are alleged to receive their knowledge about practice: reading journal articles. Here’s an estimate of total costs from Gagnon & Lexchin (2008) – all figures in billions of US dollars:
  • Samples (the provision of free packages of medication to prescribers, who can offer them to patients in the office to get them started, after which they will continue on paid prescription): $15.9b.
  • Detailing (essentially, visits by sales representatives to physician offices, plus the provision of pamphlets, swag, and related products): $20.4b
  • Direct to consumer advertising (advertisements in newspapers, magazine, television, and internet that is directed to the general public rather than to healthcare providers, often with the advice to “ask your doctor”): $4b
  • Sponsorships, displays, and the provision of speakers to professional meetings: $2b.
  • E-promotion & mailings (generally to prescribers), promotion-related post-approval clinical trials: $0.3b
  • Journal advertising (advertisements in publications aimed at professionals): $0.5b
  • Unmonitored promotion (estimated; includes amounts that do not appear in other categories including promotion to unmonitored physicians or in unmonitored journals and miscellaneous other marketing strategies): $14.4b
Of particular note here for the nonprescriber is the contrast between the amount for direct to consumer advertising (the seemingly ubiquitous and presumably expensive “ask your doctor” ads) at $4 billion, and the marketing to physicians, a much smaller group of people, at a cost 5 times as great at $20.4 billion.
One might be tempted to wonder how the firms can possibly spend so much money marketing to prescribers. Imagine that instead of producing television ads they sent the salesperson directly to your home to act out the advert in person – while making you lunch and providing golfing fees.
But All This Ends?
Once a medication “goes off the patent cliff,” profits decline precipitously and the motivation to promote the med to physicians and the public decline as a consequence. The drop can have a major impact on a pharmaceutical firm – just search using the terms “antidepressant patent cliff” to turn up a variety of business analyses like this one.
Let’s take a look at the names and patent expiration dates of some of the most well-known antidepressants.
  • Prozac (fluoxetine), 2001
  • Paxil (paroxetine), 2003
  • Zoloft (sertraline), 2006
  • Remeron (mirtazapine), 2010
  • Effexor XR (venlafaxine), 2011
  • Lexapro, Cipralex (escitalopram), 2012
  • Cymbalta (duloxetine), 2013
  • Wellbutrin (bupropion), 2013
  • Pristiq (desvenlafaxine), 2022 – of note, desvenlafaxine is marginally different from Effexor and is often regarded as little more than a patent extender on Effexor.
  • Viibryd (vilazodone), 2022
Overall dollar sales figures for antidepressants have tended to fall as the medications have gone over the patent cliff. Revenue for antidepressants peaked at about $15 billion per year in 2003, and is projected to decline to $6 billion in 2016. Depression, once a major money-maker for pharmaceutical corporations, is fading as a revenue opportunity.
Why is This Important?
Remember our party line? The marketing rowdies drowning out our friend Science get laid off when their drugs go off patent. The drugs are still around, but the distorting influence of their promotional activities (disguised as science) largely end. The air clears, and our prescriber is left undisturbed to examine the literature once more.
Of course, this doesn’t solve all the problems. Prescribers are likely still to have received most of their psychopharmacology education from the marketing team. And having been subjected to endless lectures about the wonders of various drugs, they may feel that they already understand the scientific backing and neglect to look again. As well, most of the articles in the scientific journals are funded and written by (guess who!) the pharmaceutical companies themselves, and there has been a marked publication bias favoring positive studies over negative ones.
Nevertheless, the end of patent means fewer free samples, fewer visits from pharmaceutical reps, fewer paid lunches, fewer “opinion leaders” making the rounds showing the companies’ own slides, fewer conference symposia lavishly funded by patent owners, and less general noise distorting the environment. Medical decision-making is likely to be based at least somewhat more on science than on enthusiasm and hoopla.
What About Newer Antidepressants?
There are still a few preparations on patent, and in the past there have always been new medications coming online. Once Prozac went off patent, everyone finally shut up about it and more profitable medications picked up the baton and continued the charade. Won’t that continue?
Well, that’s the thing.
The pipeline is just about empty. Some firms have given up on depression, and in the past few years a variety of preparations have bitten the dust before reaching the approval stage. There is a noticeable lack of enthusiasm about upcoming products, though the few that remain on patent will doubtless be promoted to death. So there will still be some rowdies on the line trying to drown out science, but there will be fewer of them and they seem to have become somewhat muted. Not even the pharmaceutical reps seem able to muster much enthusiasm for the newer products, and the usual claims of “revolutionary advances” are not being heard.
So, Science. It’s been a while. At last we’re (almost) alone. Whisper your ambivalence. We can finally hear you.
Resources
Gagnon M-A, Lexchin J (2008) The cost of pushing pills: A new estimate of pharmaceutical promotion expenditures in the United States. PLoS Med 5(1): e1. doi:10.1371/journal.pmed.0050001
York University. “Big Pharma Spends More On Advertising Than Research And Development, Study Finds.” ScienceDaily. ScienceDaily, 7 January 2008.

44 COMMENTS

    • Two videos on You Tube are worth watching to rule out vitamin B12 Deficency.
      – Diagnosing and Treating Vitamin B12 Deficency -Sally Pacholok and Jeff Stuart.
      Pernicious Anaemia Society Conference 2013 Part 2.
      Professor David Smith B12 as key player in preventing brain atrophy that leads to Alzheimer’s disease.
      In James Davies book – Cracked Why Psychiatry is doing more harm than good , he explains how a drug that is off patent changes colour, packaging and name to treat a different condition.

  1. Very interesting article Randy and thanks for the info. The dollar amount used to “influence” doctors is mindboggling.

    I though this piece of your article was also interesting…

    “Nevertheless, the end of patent means fewer free samples, fewer visits from pharmaceutical reps, fewer paid lunches, fewer “opinion leaders” making the rounds showing the companies’ own slides, fewer conference symposia lavishly funded by patent owners, and less general noise distorting the environment. Medical decision-making is likely to be based at least somewhat more on science than on enthusiasm and hoopla.”

    I guess my question would be…what science? The biased big Pharma studies fill many of the medical journals and alternative interpretations of the effectiveness (or non-effectiveness) of antidepressants is likely to be downplayed even after the “patent cliff.”

    I would like to think that the medical profession would reexamine the merits of these drugs using more unbiased non-industry studies and “science’ but I fear I have become fairly cynical.

  2. So interesting to see how all of this plays out between Big Pharma and physicians. It’s the clients I’d be concerned about, as of course, these drugs have absolutely nothing whatsoever to do with healing. The resources used for all of this is sheer waste. Thanks for an interesting read.

    • “So interesting to see how all of this plays out between Big Pharma and physicians. It’s the clients I’d be concerned about, as of course, these drugs have absolutely nothing whatsoever to do with healing. The resources used for all of this is sheer waste. Thanks for an interesting read.”

      I disagree. I am grateful for some of the meds they produce. Some of their drugs save lives.

  3. If you decided to start a drug manufacturing company, what would you do? Where would you get the capital, how would you pay it back, how would you promote your products and what would you try to produce first?

    Anyone can research any drugs’ efficacy. That the drug companies publish most of the literature about their drugs, means what? Who else would we expect to invest huge sums of money to do so? Take the profit motive out of making drugs and what do you think will happen? If corporations are psychopathic monsters who don’t mind killing people, like someone posted the other day, better not get in an airplane or a car or a bus, a ship, a train, don’t eat most food sold in supermarkets, drink coffee, or enter buildings or houses or use elevators, buy t.v.s, radios, R.V.s, and away we go.

    Some drug companies have produced some drugs that have saved lives and enhanced our health. As I constantly rethink my view on the drug industry, I can’t deny some of their achievements.

    • “If corporations are psychopathic monsters who don’t mind killing people, like someone posted the other day, better not get in an airplane or a car or a bus, a ship, a train, don’t eat most food sold in supermarkets, drink coffee, or enter buildings or houses or use elevators, buy t.v.s, radios, R.V.s, and away we go.”
      As for the foods it’s probably a good idea to avoid a great deal of it and yes the sh*t that companies sell as consumable products is killing people. As for the cars – there has been an ignition switch scandal recently and that killed quite a few people and it’s not the first and not the last either. Yeah, the whole society is corrupt so the regulations are lacking and/or not enforced. But it does not even reach the level of corruption in pharmaceutical industry, simply before it’s easier to spot and prove an error in a car than it is to prove medical error.
      Government funding has brought us many modern advances including the wonders of internet. It has also brought us the research which led to many drugs that actually help people. The mistake is then take the last step – commercialization – and give it away to private drug companies. It’s even a worse idea to give them power to develop new drugs and “self-regulate”. It’s a disaster.

  4. If I focused on the information Ralph Nader published in books about the poor design and construction of cars, I would never own, rent, borrow or ride in one, ever. I love Ralph Nader. He provided an important service. We were awakened as a nation by his single-handed efforts to alert us to the grave dangers we didn’t see. At the same time, percentage wise, most drivers avoided most of the perils he described.

  5. Randy ! Read Edwin Black’s most throughly documented book on the planet ” War Against The Weak ” then tell me how “PRO PSYCHIATRY” you are . Of course making some bucks within the field is all some need , to become true believers irregardless of anything else including mass harm to humanity.

  6. Right now, the drug class that is getting huge attention is the stimulants. While these are far from new, there are a number of patented formulations that are heavily marketed. What the companies – along with the psychiatrists KOLs – are doing is to expand the potential market. So ADHD now extends into adulthood. Doing the math, it is easy to see how this quickly broadens the market for drugs that were once promoted for use only in childhood. But Vyvanse just got approval for the new Binge Eating Disorder. So inattention and overeating – two ubiquitous traits of modern life – are now the potential target/market for these drugs.

  7. Profit margins and bottom lines have replaced any actual concern about improving the human condition. That is not only apparent in regard to psychiatric medications but society as a whole.
    The power imbalance in the field of mental “health” makes it abusive but no one talks about that sad reality. It would be criminal in most other facets of a democracy but it isn’t in this one. The mental health system has placed itself on a pedestal with the help of the drug industry despite the fact that it operates on sheer theory, wishful thinking and measures which, by and far, have been proven to benefit few asides from those making money in some form. It is a high stakes stock market that gambles with the lives of those who are most easily victimized (economically disadvantages, native and African Americans, the young, the elderly, those involved in the criminal justice system, etc) and there is no way to institute balance of power because it is a system which has never had such a thing. The sad fact that mental “health” has weaseled it’s way into every aspect of society (from schools to nursing homes) should give a reason to be alarmed as there are more numerous ways with which to lead one to the gates of the all mighty medication gods.
    Over prescribing, uninformed consent, off label marketing, prescribing drugs never intended for certain populations, the growing rift between the “us” (prescriber) and “them” (the non prescribing clinicians), the harm to millions of people from side effects and long-term use (including withdrawal and lack of support in tapering) among other issues keep the pathetic history of psychiatry intact. Medications are as effective as the other form of witchcraft that psychiatry has performed in it’s history (blood letting, psychosurgery, asylums, etc). It has never been about science but always about a select few being given free run to use the whole of humanity as a collection of lab rats with which to test theory. Even in the light of failure, the same beat goes on all in the name of “helping”. I cringe when I look at the future plans to use MDMA, Nitrous Oxide and other hallucinogens as “treatment” knowing that drug companies would abuse their power through medicine to profit at the expense of a few million more people and psychiatry would hold their hand while they do it.
    Abuse, no matter how subtle, is still abuse.

  8. Profit margins……have replaced concern for improving the human condition? When did that happen? No one cares any more?

    We live longer
    We live healthier
    We have better nutrition
    We have the finest doctors
    We have the best hospitals
    We have the best technology
    We have more self-help groups
    We have more information/access to information
    We have more choices
    We even have more brilliant, aggressive lawyers than one can possibly imagine who might pursue malpractice for us