New Drugs Trail Many Old Ones In Effectiveness Against Disease

Lasrick tips this report from Reuters: "Despite the more than $50 billion that U.S. pharmaceutical companies have spent every year since the mid-2000s to discover new medications, drugmakers have barely improved on old standbys developed decades ago. Research published on Monday showed that the effectiveness of new drugs, as measured by comparing the response of patients on those treatments to those taking a placebo, has plummeted since the 1970s. 'While experts agree that tougher trials and similar factors explain some of the decline in drugs' reported effectiveness, something real is going on here,' said Olfson. 'Physicians keep saying that many of the new things just aren't working as well,' and therefore prescribe antidepressant drugs called tricyclics (developed in the 1950s) instead of SSRIs (from the 1980s), or diuretics (invented in the 1920s) for high blood pressure instead of newer anti-hypertensives.'"

Comments

Re:Trail?

[K. S. Kyosuke]

I see you've been trialing your high school peers in English recently. :-)

True True

[Anonymous Coward]

Big Pharma Big Bucks is a decent documentary covering this: http://www.youtube.com/watch?v=zqCdZ19y39s

Additional Reading: Ben Goldacre's Bad Pharma, Jacky Law's Big Pharma, Marcia Angell's The Truth About the Drug Companies and Irving Kirsch's The Emperor's New Drugs Exposed.

Companies are out for profit. That in itself isn't bad, but due to stockmarket pressure that becomes all they care about and start chasing the easy money spinners. The easiest money is repackaging old drugs. New drugs are too risky.

BTW The Chaser's Checkout did a hilarious piece on Complementary Medicine: http://www.youtube.com/watch?v=QMYXKSy2fb8

Re:True True

[SharpFang]

Moreover: Promote new, weaker drug. Still keep selling the old, efficient drug.
People buy the new drug. They find it's inefficient. They switch to old drug.
Two packages sold instead of one.

Re:True True

[hedwards]

I'm not a fan of big Pharma, but this is horseshit.

Tricyclics are substantially more dangerous than the newer generation of medications, sure you can OD on any of the psych medications, but the newer medications tend to be more narrowly focused than the old ones. Have you ever looked at the listing of things to avoid when it comes to MAO inhibitors?

A lot of the problem with the newer medications is that since they target smaller parts of the brain, it's less likely that any one medication will work properly, but it also means that it's less likely that it will interact with some other medication. For instance you can't take Prozac or Paxil if you're taking stimulant medication for ADHD because they use the same channels in the liver, IIRC.

Ultimately, this is not likely to be a problem in the near future as brain imaging scans to see what exactly is going on in the brain become more prevalent and there's more formal testing of what the medicine is actually doing. At present there's very little attention paid to how much of the medication actually gets to the site where it's needed. Something as simple as an undiagnosed food allergy can result in little or none of the medication making it to the brain. Which also effects how much seratonin, dopamine and the rest are there for the medications to work with.

Re:True True

[h4rr4r]

Often it seems safety is traded for effectiveness. The best cough suppresent ever is herion, that was its original purposes. Since that was dangerous we moved to codeine, which was not as good but safer. Then we moved to Dextromethorphan, which is safer but works no where near as well and many folks cannot tolerate. Hallucinating while not getting good cough suppression sucks.

So now my options are to be accused of being a drug seeker by my doctor, take more powerful opiates I have left over from other procedures or going to canada and smuggling back Tylenol 3.

Sometimes the old stuff really was better.

Re:True True

[h4rr4r]

I do not smoke. Why would you assume I do?
Do only smokers get upper respiratory infections?

Old business ideas

[erroneus]

1. Can't make any money unless you hold patents (monopoly) and can charge any price you want even [especially] at the expense of loss of life for those who cannot afford it. (They are just dying to get a new drug!)
2. People won't buy your crap unless it has the word "new" on the label. (Microsoft has driven that notion out of us over the past few years though)

Real breakthroughs and discoveries are rare. It seems a month doesn't go by without my hearing some new kind of benefit of using aspirin or acetaminophen.

What really needs to happen:

1. People need to be more careful about their use of drugs -- a body less accustomed to drugs in it shows a better response to drugs when they are needed.
2. People need to be more careful about how they live their lives and to take responsibility for their bodies. I could go on forever about that.
3. More work needs to be done to discover the causes of the maladies plaguing our modern world. We already understand that lots of the cause IS our modern world, but no one wants to talk about it because we might have to give something up.

There's less or no money in any of these ideas. Consequently, it won't happen.

Re:Old business ideas

[blackraven14250]

Beyond the patent issues, there's also quite a few newer drugs that have reduced levels of side effects relative to the older ones. Tricyclic antidepressants vs. SSRIs is a particularly good example of this - SSRIs are less effective on many cases of depression, but they're one of the go-tos in cases of depression because their side effects are generally less severe than tricyclics. If you ignore the side effects entirely, sure, tricyclics are better - but keeping side effects to a minimum is always the preferred course of action.

Re:Old business ideas

[CastrTroy]

2. People need to be more careful about how they live their lives and to take responsibility for their bodies.

This is the major problem with most people I know. They do not even attempt to live a healthy lifestyle. They are in a complete complete fantasy world where eating a bowl of instant oatmeal with 15 grams of sugar in it is healthy, simply because it's oatmeal, or that it's ok to eat TV dinners for lunch every day because they are low calorie, nevermind the fact that they have half your day's recommended intake of sodium in a single meal. They don't exercise at all.

Now I'm not the healthiest person in the world, but I do exercise a fair bit, and try to eat healthy on most days. But I also don't delude myself, and I admit when I'm eating something unhealthy, or being lazy about getting my exercise..

Re:Old business ideas

[hedwards]

One of the problems here is that the doctors don't always bother to conduct the testing necessary when doing the prescribing. I wound up with nasty hyponatremia the first time my doctor put me on blood pressure medication because my sodium levels weren't the problem, and she just assumed that lowering the levels would help. All it did was cause severe memory impairment and concentration issues within days. I discontinued the medication pretty much immediately and felt better.

A better course of action would have been to run the tests and verified that it wasn't potassium deficiency or one of the other causes of high blood pressure. As a practice, doctors really need to avail themselves of tests more often in prescribing. It's the 21st century and there are tests, in many cases, to help inform the prescription of medication which would go a fair distance to eliminating the problems that TFA talks about.

Re:Old business ideas

[drinkypoo]

People won't buy your crap unless it has the word "new" on the label.

In truth, you have this exactly backwards. People want to buy the old drug, because the patents have expired and generics are available. The bar for bringing a modified version of an old drug to the market is far lower in the USA than bringing a new drug. You don't have to even prove that it is as effective as the drug it is replacing. Then you get the insurance companies and medicare to drop the old drug, which they do (I've personally experienced it on medi-cal, anyway) and you run some ads to scare people off the old drug. You know, "If you've been harmed by such and such drug, contact us for your shitty settlement". And since they buy the laws (Big Pharma always being one of the biggest campaign contributors for a broad range of politicians; Hilary Clinton got a record payout from them after giving up on single payer health care) they get to decide who is and isn't forced to run such ads, which also helps to keep competition out of the market.

The sole reason that new drugs often trail old drugs in effectiveness is that they only profit from patented drugs, and only new drugs are patented.

It is clear that the profit motive in medicine is a murderer.

Re:Old business ideas

[BoRegardless]

Guillotines cure depression 100% of the time, but side effects persist forever.

Re:Old business ideas

[femtobyte]

Assuming "cure depression" means "live a normal life, with standard healthy human emotional responses to events," the guillotine doesn't seem especially effective. In a sense, dead people express the symptoms of most extreme depression: an absolute nihilism, utterly unmotivated to do anything at all, don't even care about being dead, zero sense of self-worth, will just lie on the ground and rot.

Re:Old business ideas

[hairry]

+1 to this... The original source article says "In the early years, drugs easily beat the placebo: They were, on average, 4.5 times as effective, where effectiveness means how well they lowered blood pressure, vanquished tumors, lifted depression or did whatever else they were intended to. * * * Experts disagree on why that should be, but suspicions range from the U.S. regulatory process to basic biology." The standard wisdom in the industry, according to those who work in the field, is that the FDA is not terribly concerned with efficacy. Any new drug needs to merely be more effective that nothing at all. It cares first and foremost about safety- that's what politicians hear about ("My great aunt Hilda was on drug X and it killed her!!"), so that's what the FDA looks at. New drugs are not removed from the market because of failures of efficacy, but safety issues. Think of Vioxx- an effective pain drug that worked just like ibuprofen, but with better GI safety. It was pulled because of increases in the risk of adverse cardiac issues, especially in patients at high risk for cardiac events, at high doses of the drug. (to be fair, part of the issue was that the company looked like it had covered up the cardiac data... but "safety" killed that product.) This is different in other countries- efficacy is (relatively) more important in e.g., Japan, and drugs that are equally effective as older drugs have harder times being approved, and safety is not the end-all, be-all.

The inability to research?

[gallondr00nk]

This doesn't really address the whole issue, but remember that the war on drugs has stopped scientists from being able to conduct research for decades. LSD and Ecstasy both had incredibly promising properties in treating some illnesses, especially in the area of mental health. This was until research was banned by governments around the world. I wonder what sort of illnesses, diseases and conditions we'd have cured today if they hadn't banned it.

It pays to remember that through drug prohibition governments are not just waging a war against the individual's rights, but waging a war against scientific research.

Re:The inability to research?

[dpilot]

I remember reading somewhere that...

Thalidomide has 2 "rotations", left-handed and right-handed forms. One handedness was "effective" and the other caused the birth defects. The big Thalidomide crisis was because of bad quality control, there was significant contamination by the wrong-handed version, and we really didn't understand this stuff at the time. Therefore the "good Thalidomide" was banned along with the bad. The bad Thalidomide should be simply be considered a harmful manufacturing by-product that needs to be removed from the final product.

Re:The inability to research?

[VAXcat]

Not exactly true. Thalidomide does indeed have two mirror image isomers,. and there is some research to indicate that indeed only one of these isomers causes damage. BUT - thalidomide undergoes racemization in the human blood stream - that is, even if you start only with "good" thalidomide in your drug, it will be metabolized into a mix of good and bad in the bloodstream - so, even if you only ingest the "good twin", you wind up with the damage causing "bad twin" in your body anyway.

Re:The inability to research?

[h4rr4r]

Neither of those drugs work by killing brain cells. Nor should either of them cause those. You are likely correlating events that are not causally linked.

Re:The inability to research?

[justthinkit]

wiki explanation.

Re:The inability to research?

[DerangedAlchemist]

Medically, LSD is one of the safest drugs known. Pretty much any reference, like wikipedia, will mention the low toxicity.

Re:The inability to research?

[ultranova]

Low toxicity is not no toxicity,

Actually, at some point, it is. Even water will kill you if you overdose on it badly enough. So either you draw the limit at some nonezero level, or accept that every substance is poison, thus making the term meaningless.

and last I checked, which was admittedly a long time ago, the receptor molecules it binds to aren't a perfect fit, which does lead to the receptor molecules being damaged from time to time. That's not going to result in permanent damage, but it's unpredictable how long that will last.

Well, Tetanus permanently destroys certain receptors and takes a few months to recover from, so that would seem like a reasonable upper bound.

What's more the "repressed" memories that LSD was allegedly to help unblock don't exist

According to Wikipedia, it was used to unblock repressed subconscious material, not memories. It was also used to help anxiety, alcoholism, pain and cluster headaches. Also, the potential for increased insight inherent in psychedelics shouldn't be ignored.

No evidence, but...

[Telecommando]

Perhaps the older drugs were manufactured for maximum effectiveness and the newer ones for maximum profit.

Re:No evidence, but...

[RabidReindeer]

Perhaps the older drugs were manufactured for maximum effectiveness and the newer ones for maximum profit.

Close, perhaps. Cynical, certainly.

A lot of the older drugs were discovered more or less accidentally. Mostly because their effects were anything but subtle.

Unfortunately, so were the side-effects.

There are perfectly good humanitarian reasons for chasing new drugs.

First of all, drugs have varying effects depending on the patient. So the "go to" drug might not effectively - if at all - on some people. Or even harm them.

Secondly, the side-effects of the drugs may be prohibitive for some people.

So there's definitely a demand for drugs that are more finely-targeted than the original sledgehammer medications. Problem is, the more precise the solution, the more likely that the number of people it works effectively for is going to be very small. And, on top of that, the objectionable features become more objectionable, relatively speaking.

That's aside, of course from the all-too-common situation where the business decision is made to push a drug even when it's more of a medical liability than an asset just because it's more of a (potential) financial asset than a liability.

Re:No evidence, but...

[edremy]

> That's aside, of course from the all-too-common situation where the business decision is made to push a > drug even when it's more of a medical liability than an asset just because it's more of a (potential) > financial asset than a liability.

Then 5 or 10 years back there was also the case where a very effective peanut allergy drug was nearly finished with trials and approaching approval. The developing company was bought out by a bigger rival. The new owners squashed the new drug, because they wanted to re-purpose a drug they already had for peanut allergies. It wasn't as effective as the new drug they'd just acquired, and had worse side-effects, but it was more profitable.

Urban legend or true story - I don't know. The inability to know stuff like this is a problem in itself.

Almost certainly an urban legend. This behavior doesn't make sense in the context of the drug market. The first-tier drug companies like Merck and Glaxo fund everything from a few high priced, patented drugs. They have a limited amount of time to make money off of these before they come off patent and the generic makers cut the prices by 10x. This is why you see a constant stream of "me too" modifications of existing drugs- they need to something under patent to make money. Buying a drug and then burying it in favor of something existing would be stupid- you have a chance to reset the patent clock and get ~15 years of high profits as opposed to trying to compete against the generics

So what?

[swamp_ig]

So what?

Sure the old drugs are great, but there's plenty of new ones that are great too.

Take statins for example - relatively new class of medication that have dramatically changed the treatment of high cholesterol - which leads to the number one killer of heart disease. Another example - artemisinin - great treatment for malaria, relatively recent invention.

Not to mention the survivorship bias http://youarenotsosmart.com/2013/05/23/survivorship-bias/ - there's heaps of old drugs that just aren't used anymore because frankly they were no good and had a ton of side effects. You don't hear about those ones much simply because they aren't used. This gives the perception that 'the old drugs are better' when in truth they were just as bad or worse, and only the good ones have stood the test of time.

But even if it were true - should we then give up drug discovery? Give up the chance to find the next great drug just because the low hanging fruit are already taken? What exactly is the solution to this?

Re:So what?

[jo_ham]

The big problem with statins (from a pharma standpoint) is that they hit on the perfect one right away and the patent is soon going to expire, opening the door to generics. This is great for the patients, but it stops the money train.

All of the work on alternate statins that can be patented (throwing new function groups on there, changing the core structure but keeping the interaction with the target receptors etc the same) has resulting in a less effective drug.

With atorvastatin, and others like simvastatin going generic before a new patented, more effective (or as effective) analogue could be developed, the pharma industry has gone into panic. They were some of the must lucrative drugs of all time.

More than just effectiveness

[adoarns]

I am an epileptologist, and I would certainly love to see more effective anti-seizure drugs on the market. But although the newer anticonvulsants aren't necessarily better at stopping seizures than older ones (like the classic four: phenytoin, carbamazepine, phenobarbital, and valproic acid), they are better tolerated, have fewer severe adverse effects, have much more predictable serum concentrations, fewer drug-drug interactions, and require little to no routine bloodwork monitoring. For the 1% of the population suffering from epilepsy who have to take these drugs on a regular basis, this has been a significant change.

Re:More than just effectiveness

[drjoeward]

i was just going to say, most of the old medications were found to be very effective, but not very targeted in where they work in the body. Hence lots of side effects, Modern medicinal chemistry and molecular modeling allow for the design of better molecules that work only where they are supposed to. you don't even have to go that far to see one. Look at Benadryl and Claritin. both are antihistamines, but benadryl did not target the Histamine receptors responsible for the allergic response, it also affected others and made most people sleepy. Claritin on the other hand is much more targeted and has dramatically less side effects.

you can go on and on about side effects and how many older meds have such issues and with those issues a patient is going to weigh benefit vs side effect and likely not take the damn med. So is it is better to only target what is broken and to have a med the patient will comply with, even if it is somewhat less effective, because in the long run it is better!

More difficult now

[Anonymous Coward]

Several reasons for this:

1. Patent Law - Because all most all of the simple compounds have been patented, with the patent already expired, New drugs have to get more and more complicated in order to guarantee gaining a patent. More complicated means more expensive, but not necessarily more effective.

2. Increased safety - The requirements to get a drug on the market keep getting tougher and tougher. Almost everyone in the industry agrees that if aspirin was developed today, it would be a coin flip as to whether it would gain approval. (And certainly wouldn't be available OTC.)

3. Laziness - Many new drugs are just minor modifications of existing drugs made to get around patents. This is unlikely to provide any benefit to patients other than breaking the other company's monopoly. See Viagra vs Levitra: they are effectively identical.

4. Increased difficulty in animal testing - Years ago you could do anything to mice/rats, and the ethics committees only cared about larger animals. Now you have to argue in front of a panel that there is no way an animal could suffer as a result of your testing. I am talking about mice that are going to be killed at the end of the month anyway. And don't even think about using the word LD50: you will be looking for a new facility to do testing for you. This forces more testing back into the test tube, and in vitro environments are different enough from a real body that it is common to see something that works in a test tube to not work in a mouse, and vice versa.

5. Current failure of computer modeling: A lot of research money has moved from trial/error research by chemists to using software to model binding sites of proteins and trying to compute structures that may fit. While this may one day work, I know of no drug on the market or in clinical trails that was developed using computational chemistry as a primary tool. Note: Computational chemistry has brought some good things with it - see Lipinski's Rule of 5, but that was the result of a statistical analysis rather than modeling.

Yes, I am a medicinal chemist.

Re:$50 billion sounds like a lot

[KiloByte]

Wait, so government-granted monopolies such as patents are now libertarian fault?

The govt testing drugs and refusing those with harmful side effects, that's regulation I'm willing to accept. Denying people the right to do something just because someone else does the very same thing is flat-out oppression.

Re:shareholders

[Black Parrot]

He also told me that about 90% of all the new drugs actually come from research out of universities, not the pharmaceuticals themselves

I keep reading that from a broad variety of sources as well.

(Is it true?)

Re:shareholders

[edremy]

He also told me that about 90% of all the new drugs actually come from research out of universities, not the pharmaceuticals themselves

I keep reading that from a broad variety of sources as well.

(Is it true?)

Depends on what you mean by "research". A lot of the initial leads do come from universities, but the process to turn a lead into something you can buy over the counter is difficult, very long and hugely expensive. You frequently see a drug company buy the rights to the idea and then do the human trials. The HPV vaccine Gardasil is a good example- a group of people at several universities developed the concept. Merck then took over and ran the phase III human trials (the one that sees if it actually works in the field) as well as the R&D to manufacture it.

IMHO, this isn't a bad way to work- most drug companies can't really do the blue sky stuff and universities don't have the $$$ to bring something to market.

Re:shareholders

[femtobyte]

So, the big drug companies aren't doing the actual innovative parts of research. They're just grinding through the large and expensive trials to standards set by national regulations. So, why have the drug companies at all? Dump them and have the final large-scale drug testing procedures done by government agencies as a public service. Approved drugs get released to the public domain, so they'll be manufactured (cheap and competitively) as generics. The trials are already rigidly defined methods and standards --- not an area where you need the mythical "free enterprise innovation," just routine bureaucratic administration and recording of results. No profit motive for hiding adverse symptoms; no gigantic advertising budgets (which are much larger than R&D budgets); no obscene profit margins --- you'd be able to produce/distribute drugs at vastly reduced cost, with far more transparency about effects. "We the people" are already paying for the fundamental research (through government grants) that initially develops most drugs --- so why should we get gouged by big pharma to complete the routine testing cycle, and introduce profit-motivated conflicts-of-interest against full transparency and disclosure?

Re:Trail?

[JazzLad]

I know, right? I'm just glad I remembered to tick the 'Post Anonymously' box.

Crap.

Re:Money money money...

[davester666]

Old drugs = not covered by patents anymore = hard to jack up the price
new drugs = covered by patents = can charge an arm and two legs for them

Course, now they've figured out to just limit supply for common diseases and then let everyone bid for what little they make.

Sort of like the electricity "market".

Re:Money money money...

[davester666]

doxycycline

http://www.wsmv.com/story/21616095/sudden-increase-in-cost-of-common-drug-concerns-many