Saturday, April 7, 2018

The bane of pharmaceutical R&D

A recent study (1) appears to raise red flags on pharmaceutical research, animal studies and the contemporary scientific process in general. Perhaps it could be new to the authors but most of what they describe have been known to the community for many decades. The following are important considerations in this debate. I state them without proof but there is plenty out there:

(a) A very large percentage of the published studies cannot be replicated
(b) Most of the published studies target proving something rather than the other way around
(c) The quantity of publishing (rather than the quality) is the most important metric for most educational institutions to determine the reward for academics
(d) Big pharma is run by outdated leaders who are trying to churn out incremental medicines to meet shareholder value targets
(e) The drug discovery and development processes are ably assisted by an incompetent regulatory agency with many conflicts of interest
(f) Hypothesis testing in life sciences still clings to a nearly 100 years’ old idea that uncertainty is normally distributed. And most statisticians, encumbered by the agency’s love for “p-value,” will not deviate from the framework. And in the process, they have approved bad drugs, rejected good ones and failed to identify sub-populations who could benefit from the NCE.

So, the authors’ contention that many animal studies are not published at all, albeit interesting, is just the tip of the iceberg. There is a much bigger problem to tackle. The leaders of life sciences companies and their regulators may want to consider retirement, say after 80, as they may need to yield to young leaders who have a higher appreciation of emerging technologies.

The correlation between animal studies that precede the clinic and what happens in humans has been incredibly low for almost a century. They have tried everything from mice, rabbits, dogs, and chimps in an attempt to prove the unprovable. In the process, they reduced animal welfare while simultaneously developing therapies that can only be called, “bad.” The finding that the therapeutic index of marketed drugs seems to decline over time is a warning signal that there are many inefficiencies in the R&D and approval processes.

Technology is advancing. We do not have to stick to regression slide rules to prove or disprove if a drug works anymore. It is time life sciences industry embraced ideas that are transforming every other industry. To make that happen, it will require cleaning the shop and starting over.

Old ideas die hard and older ideas are even worse.