How Common Is It For New Drugs To Fail?

When a new drug is under development, I am sure that preliminary testing is done, to be sure that the drug is effective. Later, when animal testing is done, there must be a fair degree of certainty.
My question: is it common for a new drug to fail during human trials?
Developing new drugs is a very expensive process-and I see a lot of start up pharma companies, that seem to be one-product operations.
So, if their drug fails, it is usually the end of the company.
Is this type of debacle common in this industry?

I recall an article in Nature magazine and they said only about a third of all drugs that are successful in animal trials go on to be successful in humans. But that is somewhat misleading because this article only deals with published findings and certainly not all clinical trials are published.

So the result is probably even lower.

I recall when I worked a temp job at U of Chicago and the staff was all excited about a new cholesterol drug that worked miracles in mice, rabbits, monkeys and chimps. Unfortunately it didn’t do a darn thing in humans. But it’s nice to know that if a monkey or mouse has high cholesterol he/she has a pill for it


As someone who works for a medical center doing testing under contracts with pharmaceutical companies - I don’t have any data, but from what I’ve seen, it happens a lot. It’s really common for a medication to show one effect in animals and something different in humans, which is why you do different phases of testing on humans after animal testing and scientific reasoning/individual case studies of accidental use/whatever to show a potential effectiveness in humans. With a larger test population, unfortunate side effects might show up, or it might be shown that the drug isn’t all that helpful after all once you get down to the realities of how it works in people, and so on.

If it’s a one-trick pony company with only this new thing to their name, and human subjects trials prove a lack of efficacy and/or safety, they’re probably screwed. If it’s a huge pharma company, they’ll most likely be just fine, but of course they have to have a continuing track record of drugs that do succeed and do sell to keep funding their other research.

Speaking very obliquely here for confidentiality - years ago my department contracted with a very small pharma company to test a device that had a great theory behind it, genius inventors, and promising animal tests. There were no effective treatments for the terrible problem that it was hoping to solve, and so sufferers were eager to get in on the ground level for early testing, even when told it hadn’t been tried on humans. A very small number of people had it tested on them and there were some potentially promising results. So it went into a larger test. After the data was analyzed, it seems like the early results were just flukes; the analysis showed no significant help for the condition, and some people had bad effects from the device. The company floundered financially after the investors found out the results, and eventually another company bought the technology and ended up putting it on the proverbial shelf.

So here we have an example of a medical device that, when a bigger statistical population was analyzed, showed a lack of efficacy, not to mention safety concerns. The FDA wouldn’t approve the device with those results, and the investors wouldn’t agree to fund more studies or changes to the device.

What some companies do is figure out what other, similar problems might be helped by a treatment, and test it for health problems X, Y, and Z. Maybe it works for X only, but at least then they’ve got something they can release and hope to recover the millions and millions of dollars they spent on drug development and testing over several years or decades.

There are many ways to “fail” clinical testing. The first is to fail phase 1, or “safety” testing in healthy volunteers. If the drug is unsafe, or has side effects that are dangerous or discomforting out of proportion to the drug’s benefits, it has failed. Phase 2 testing is usually the “dosage phase”; if the drug is not effective in any reasonable dose (“reasonable” by economic, medical, or any other standard), or if it proves to be unpredictable or if some safety issue is revealed in the patient population that wasn’t clear before, then it has failed. Phase 3, a large-scale test of the final formulation in many patients, may reveal any of these, or may simply indicate that the drug isn’t good enough – no statistically significant difference exists between the drug and a placebo, or at least not enough to justify spending the additional money to bring it to market.

Finally, there’s another variety of failure: if the testing was so poorly run or poorly designed that the FDA or other agency rejects the results, it may simply be too expensive to try again – again, based on the potential market for the drug.

Drugs can also be pulled from the market after they are approved. A recent example is Vioxx which was linked to heart problems. And there are drugs some doctors want off the market such as Avandia.

There are a lot of big differences between lab animals and humans. Animal testing is an important step, but there’s still a huge leap to make into humans.

I wonder how many of these one trick ponies get bought up by big pharma if the drug does do well. Also I’d wonder how many of them get their start-up money from a drug company (with a contract that says if the drug does well said lender gets the option of buying out the company (or right of first refusal). In other words, I wonder how many of these one trick ponies are just there to protect one of the bigger drug companies. For example, Pfizer comes up with a new drug. They’re not sure if it’ll work, and even if it does they’re not sure if it’ll do well in the market. So they create a new company to develop and later market the drug. They put some money in, they find some investors, they get some loans etc etc etc. Then if it does well they can buy the smaller company and if it doesn’t do well and the company is in the red they can bankrupt it and be protected.

A drug can also fail the toxicology testing in animals which means it’s harmful. Those tests don’t measure whether it works for a disease, they measure any damage to the animals such as cancer. It’s sounds strange but they often don’t do those tests until after it looks like it will work in humans.

(adding a bit more to the already great info provided by others above)

During the clinical trials mentioned by Nametag, the real efficacy proving happens in Phase II clinical trials (Phase IIb). Not sure how much you are into industry jargon, but the clinical trials process is very well defined and is followed all across the industry; the Wikipedia page has lots of useful stuff.

As others have mentioned, drugs can fail in Drug Safety, which really begins in preclinical. Even if a compound has proven to have “druglike properties” (some industry standards and others proprietary guidelines) and has not been shown to be toxic, a living organism might generate dangerous compounds during the metabolic processes.

One of the things that happens in Drug Safety is they use tracers to follow every last bit of a new drug that is introduced in an animal to verify that they have identified the metabolic chain; all strange bits that come out tagged with tracer must be accounted for.
This helps them determine if metabolites that are known to cause problems, such as teratogenicity, are being formed.
To make matters worse, animals metabolize things differently than humans; hence the phase I and phase II trials to prove safety, dose, and efficacy in humans.

These are just a few of the places where failures can happen, before the drug makes it to market.

One of the intriguing concepts to me is the way in which, at the very beginning of the pipeline, enormous quantities of compounds are whittled down to, eventually, a primary and a backup compound, hopefully ending up being a successful drug.
Among many other tools, scientists use mechanisms such as combinatorial chemistry to make lots of neat things to test and high throughput screening to test millions of compounds looking for a few thousand potential leads, which get secondary screening, and then followup screening to eventually produce a handful of leads. That’s before the drug even begins animal testing.

And after 14 years and $800 million, a new drug is born. Hopefully it doesn’t fail.

It’s interesting to think though, how many drugs are unsuccessful in animals that would be miracles in humans. Of course, I have no idea whatsoever we could do to tap that resource. I sure as hell am not going to be a guinea pig, and I don’t think it’s acceptable for anyone else to be treated that way.

Very true. Some work can be done in cell cultures, of course, but yeah, no one’s going to be OK with accidentally killing a few dozen people in hopes of finding a new boner pill.

Well, I mean, I would, of course, but not most people. :stuck_out_tongue:

As stated above, yes, it’s common.

That’s why there is so much preliminary testing before they start testing the drug on people. Sometimes they’ll test their one drug against a bunch of different conditions so if it fails in one, there are other options. By the time they’ve gotten that far and spent that much money they’re reluctant to give up.

If they’re not bought out, they make partnerships. A smallish startup doesn’t have the ability to distribute a drug around the world. I think the plan for a lot of them is to develop one drug or one type of drug, and if it gets into human testing and looks good, to get bought or enter a partnership with one of the big companies.

And if it does fail…hoo boy. Pfizer had a potential blockbuster cholesterol drug - Torceptrapib - in late clinical trials. Over a weekend in 2006 the whole ~$900 million program was flushed down the drain when an interim analysis of a huge trial showed increased mortality in the study arm with torceptrapib.

There was another Pfizer program - inhaled insulin (Exubera and it’s “insulin bong” delivery system) - that was scrapped after it came onto the market. It never caught on and they just canned the whole thing.

This is actually a disturbing thought. If chocolate were unknown and deemed a potential drug, it would kill some test animals (namely dogs) and we’d be in the dark as to its safety.

Maybe we ought to entice prisoners with shorter sentences if they’re willing to be guinea pigs on these sorts of substances. Maybe.

Presumably there would be scientific means of identifying the exact mechanism of the toxicity and then evaluating whether the response was possibly specific to one species.
I imagine that drug safety issues in primates would stop the drug in its tracks.

I wonder how many examples of successful drugs there are out there that follow your chocolate example. It would be interesting to know if there are counterexamples to the argument.