I’m fond of saying that the most important single statistic about the drug industry is the clinical failure rate, which is (by any reasonable standard) appallingly high. To my mind, everything that is infuriating or inexplicable to outside observers (or patients!) about the biopharma industry traces back to that number, which represents a rate of failure that no other major industry operates under.
Here’s a new paper bringing together estimate of that failure rate since the 1960s, reviewing every data source the authors could find and assessing them for scope and reliability. They find that slightly more clinical candidates were making it through in the 1970s and 1980s as compared to today (or even as compared to the 1960s), but that the rates have always been very high indeed.
Here we go: in the 1960s, the clinical failure rate was 90%. In the 1970s, 81%. In the 1980s, it was 80%, and in the 1990s it was 88%. In the 2000s, 91% of all clinical candidates failed, and in the 2010s, it was 91% as well. I have rounded the decimal points here, because there are of course error bars on these numbers (and those spreads are naturally higher on the older numbers). But the numbers for the last three decades all lie within the same bounds, so if you quote a failure rate of 91% you cannot be far wrong.
The 70s and 80s numbers are interesting. The authors don’t speculate on the reasons for those rates being somewhat lower. If those data are really representative, my guess is that this was the final pre-molecular-biology era for clinical candidates, when compounds were more likely to be evaluated in tissue-slice assays rather than with isolated proteins (and quite possible when more preclinical development work was guided through phenotypic approaches in animal studies than later on). And it might well also represent the intersection of modernizing techniques with the available “low-hanging fruit”, an era when some classic drug targets got their first clinical development.
One way or another, I think it would be a mistake to look at these numbers and think that we could go back to 80% failure rates but turning back the clock somehow in our techniques. This is after all scientific research, and some of those clocks just cannot be turned back. We have already worked over those great earlier targets and moved on to harder ones; resetting the calendar is not going to bring back ACE and HMG-CoA reductase as new clinical programs (to pick two big winners that led to whole series of marketed drugs).
You can look at it by therapeutic area as well, using those as an example: whole disease areas like high blood pressure, high cholesterol, type II diabetes, HIV, hepatitis C and others now have multiple effective drugs to treat them. You can always do better, but you’re going to have to beat what’s already on the market, which is not so easy. Or you could always try to dig deeper into the underlying causes of these diseases and outdo the existing drugs that way, but you’re going to hit a lot of brick walls when you try that, too. Meanwhile, the disease areas that *don’t* have such lists of effective drugs are in that category because they have proven harder to crack - it’s not that we don’t see them! Alzheimer’s disease is a perfect example.
So it’s 2026 and there’s nothing we can do about that. We know a lot more about the biology of disease - although God knows, not nearly enough - and we don’t get to ignore the difficult pathways full of proteins lacking obvious small-molecule binding sites just because they’re harder to work on. We have been discovering whole new therapeutic modalities in recent years, and it’s for sure that many of the candidate programs in these are not going to work out, for reasons that we are soon to discover and then to learn how to deal with.
But let’s think about that 91% failure rate for a moment. When I bring this up in presentations, I invite the audience to consider what the auto industry would look like of 91% of new car designs proved unable to roll out of the factory, or if 91% of new airliner models were unable to leave the ground - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them. No cutting-edge restaurant could survive if 91% of its innovative dishes proved inedible or outright poisonous. What other industries operate under these bizarre conditions? So when we do get something to work and something that people are willing to pay money for, we try to squeeze every dollar out of it because we never know when the next one will come along. It’s a nerve-wracking way to live, but there’s no alternative in sight.