Moore’s Law: Can you imagine the current social distancing/quarantine/isolation without the internet or mobile phones? Technological advance has been robust and fueled by the exponential increase in the speed of the microprocessor. Moore’s Law, first coined in 1965 by Gordon Moore, a co-founder of Intel, states that the number of transistors you can fit on a microchip doubles about every 18 months.
Eroom’s Law: Unfortunately, in the area of drug development, we’ve seen an inverse of Moore’s Law. Eroom’s Law (Moore spelled backward), states that “the number of new drugs approved per billion U.S. dollars spent on R&D has halved roughly every 9 years since 1950, falling around 80-fold in inflation-adjusted terms.” Source.
Why is this the case? The researchers that coined the term “Eroom’s Law” in a paper titled Diagnosing the decline in pharmaceutical R&D efficiency propose four main reasons:
Better Than the Beatles Problem
“Imagine how hard it would be to achieve commercial success with new pop songs if any song had to be better than the Beatles, if the entire Beatles catalogue was available for free, and if people did not get bored with old Beatles records.”
This is sort of the situation with drugs. “Yesterday’s blockbuster is today’s generic. An ever-improving back catalogue of approved medicines increases the complexity of the development process for new drugs, and raises the evidential hurdles for approval, adoption and reimbursement.”
The Cautious Regulator Problem
A watershed moment in drug regulation was the Thalidomide scandal in the late 1950s and ushered in an era of stricter regulation. “Progressive lowering of the risk tolerance of drug regulatory agencies obviously raises the bar for new drugs, and could substantially increase the associated costs of R&D. Each real or perceived sin by the industry, or genuine drug misfortune, leads to a tightening of the regulatory ratchet.”
The Throw Money at it Tendency
Drug companies have reacted to increased competition and drug development difficulties by adding personnel and just throwing money at R&D. This may be partially driven by “a bias in large companies to equate professional success with the size of one’s budget.” The problem is that just indiscriminately adding resources doesn’t usually solve the problem. In an article on this topic, Scientific American quotes an analogy where administrators thought that “if one man dug a hole with a volume of one cubic meter in ten hours, then a hundred thousand diggers of holes could do the job in a fraction of a second…that a problem that five experts were unable to solve could surely be taken care of by five thousand.” This sort of thinking results in throwing money at problems.
Drug companies aren’t alone in just throwing money at problems. Throwing money at schools hasn’t been found to improve educational outcomes and in corporate America, adding personnel doesn’t create efficiency — instead, it reduces it.
The Basic-Research-Brute Force Bias
The researchers define this factor as “the tendency to overestimate the ability of advances in basic research (particularly in molecular biology) and brute force screening methods (embodied in the first few steps of the standard discovery and preclinical research process) to increase the probability that a molecule will be safe and effective in clinical trials.”
Another way to think of this factor is that when we had less knowledge drug developers just tried things to see what worked. Now, with greater understanding of molecular biology and the human genome drug companies are just trying things that make theoretical sense. Another analogy from Scientific American is that “we are turning into the guy who looks for his keys under the street light only because it’s easier to see there.”
The most disturbing fact is that Eroom’s law went on unchecked for six decades!
Jack Scannell, the lead author on the original Eroom’s law paper, recently gave an interview looking at what’s holding back drug discovery today. Life after Eroom’s law
And Nature Reviews just published another great article co-authored by Scannell, that goes into the factors driving the uptick in drug approvals over the last decade. Breaking Eroom’s Law