Eroom’s Law: Diagnosing the decline in pharmaceutical R&D efficiency
There is a terrific article in Nature Reviews Drug discovery on drug development, and possible reasons for why pharma appears so much less efficient that it once was. A stark figure is shown below. What is frightening is the fact that the scale for graphs a and c is logarithmic. The article discusses a number of reasons for the problem of Eroom’s law (Moore’s law backwards — sorry it took me a while). These include what the authors call the ‘better than the Beatles problem’ for new drugs (imagine the Beatles catalogue was free, and if people didn’t get bored with the old songs, how difficult it would be to bring new songs to market); regulatory changes; and what I take to be a model of basic-to-clinic that is horribly wrong (and don’t start me on translational medicine……).
They put a nice twist on things. Pointing out that the number of new drugs approved per billion US dollars spent on R&D gas halved roughly every 9 years since 1950, falling around 80-fold in inflation-adjusted terms, they note that there have been a numb of technical advances that mean that developing new drugs should be cheaper. But, as they say:
Eroom’s Law indicates that powerful forces have outweighed scientific, technical and managerial improvements over the past 60 years, and/or that some of the improvements have been less ‘improving’ than commonly thought. The more positive anyone is about the past several decades of progress, the more negative they should be about the strength of countervailing forces. If someone is optimistic about the prospects for R&D today, they presumably believe the countervailing forces — whatever they are — are starting to abate, or that there has been a sudden and unprecedented acceleration in scientific, technological or managerial progress that will soon become visible in new drug approvals.
One area that I think they are right about is how the diminished clinical input into drug discovery has lead to a reduction in clinical breakthroughs. Anybody who knows something of David Healy‘s work will know how critical clinicians were for major drug discovery in psychiatry. I and others have argued that the same is true in dermatology ((1) and (2))
However, the ‘cautious regulator’ problem and the ‘basic research–brute force’ bias have pushed most of the drug industry towards a narrow clinical search strategy. If a drug has an effect but this is not the precise effect that the trial designers anticipated, then the trial fails. Opportunities for serendipity are actively engineered out of the system. Perhaps it is too risky to let bright doctors with large numbers of patients make broad clinical observations, or to let creative scientists rummage around in rich clinical data sets, in case they find something unexpected, which has to be explained to the cautious regulator who then kills the project. Modern multicentre trials tend to spread the patients so thinly that a doctor who did want to look for patterns might miss them.
Chilling phrase: Opportunities for serendipity are actively engineered out of the system.