by Derek Lowe
April 6, 2007 at 7:20 pm
· Filed under Uncategorized
In response to the question from David Williams below, I’d say that the pharmaceutical industry is (unfortunately, perhaps) about as innovative as it can stand to be.
The cost of developing new drugs is indeed high, and rising - but it’s not rising because we like it that way, believe me. We’d much, much rather it be a lot cheaper so we could make more money, not to put too fine a point on it. But we’re in a technological rough spot: we know enough to check for (and worry about) a long list of potential problems, but we don’t know much about how to fix them when they come up.
An example is the cardiac side effect known as QT prolongation. Used to be, no one even knew about this, and drugs just came on the market which could cause heart trouble in a small susceptible population. Now we’re alert to the problem, but we don’t have any magic wand to change a drug’s structure to avoid it (and it’s not like we know what changes to make, either). The early assays to detect potential QT problems could help us avoid getting painted into a corner like that - if they were reliable, which they are only some of the time, sort of. Even tests in dogs (generally the most sensitive model for heart effects) aren’t completely predictive, either positively or negatively. But if your compound comes up with dog QT trouble, your cost for clinical development has probably just doubled. You either spend that, or just eat the cost of the preclinical work and do something else for the next few years.
We have plenty of situations like that, and I wouldn’t use the words “inefficiency” or “bloat” to describe them. The bars for development and regulatory approval are set a lot higher than they used to be: you’d be surprised at how many commonly used drugs probably would never make it through the current hoops. Some people see drug discovery as a mature field, but I’d say that we’re actually in adolescence: the awkward years. How we get out of them, though, I’m not quite sure yet. . .
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Thanks for taking this question on, Derek. Re: the QT prolongation issue I’m right with you (which is one reason I’m on the board of ECG biomarker company iCardiac Technologies.)
It’s too bad when drugs get knocked out because they have the potential to hurt a “small susceptible population.” It won’t be easy but I’m hopeful that the pharma and diagnostics industries will find ways to identify those populations and keep them away from the drugs rather than keeping the drugs off the market for everyone or slapping on black box warning labels that limit access.
I do think there are areas where pharma could be more innovative, especially in clinical trial design. For example, as a neuropsychologist told me, “Anxiety trials use the Hamilton Anxiety Scale, which has been around for forty years. At best this is a weak indicator and companies need to be defining markers of disease against which results can be better measured .” Protocol writers tend to use whatever’s been accepted in the past rather than pushing ahead. Yes, they have to engage with FDA as they try new things, but too often there’s an overemphasis on not rocking the boat.
Agreed on clinical trial design - I’m a fan of Bayesian designs myself, but they’re still rare outside of the medical devices area. I think that no one wants to have a drug trial fail where the new neat-o trial design (or the person who championed it!) could be seen as the culprit. As you say, it’s safer to use what’s been done in the past.
In the past the pharma business model has been based on developing blockbusters. The basic idea is that substantial up-front R&D can be recouped through many years of back end patent protection. This model is fading….
How does pharmacogenetics (the study of inherited differences (variation) in drug metabolism and response) affect the trends you raise?
I like the idea that drugs of the future theoretically will be designed with my specific genes and body chemistry in mind. However, this seemingly also would tremendously further complicate and increase drug development costs?
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