This is a lay explainer for my bioRxiv preprint Costing ‘the’ MTD.
What is it about?
In oncology, it is common to give all patients the same dose of a cancer treatment drug, say 200 milligrams. Even when adjustments are made for people of different sizes (for example, based on body weight or body surface area), this is done with one simple formula that ignores the many other differences between patients that aren’t related to size alone.
The result of this practice is that some patients get a lower dose than they could potentially tolerate, and so get less than the maximum possible benefit from the drug. Other patients, who can’t tolerate ‘the’ dose (because of bad side effects) get taken off the drug altogether, and don’t get a chance to try a smaller dose they might still benefit from. Thus, one-size-fits-all dosing creates two kinds of inefficiency:
- Some patients get less-than-full benefit out of the drug
- Other patients get no benefit from the drug because their course of treatment stops after the first dose.
This paper takes a big-picture view of this situation, and asks how much these two types of inefficiency detract from the value of the drug to society. The basic idea is similar to inquiring into the value of food wasted in restaurants, or electricity wasted by inefficient applicances. The math used may look prohibitive to some readers, but the key lesson is found in Figure 3 of the paper, which tells a fairly intuitive story.
The story is that the amount of value wasted by one-size-fits-all dosing (vertical axis) is driven largely by how much the best dose varies from person to person in the population (horizontal axis). In cases where there is very little variation of this kind (left side), then of course one-size-fits-all is a pretty good approximation and achieves pretty good results. But for drugs that have a large person-to-person variability in best dose (to the right), this paper shows that the magnitude of the inefficiency can be very great—wasting 50% or more of the value of the drug.
Why is it important?
One-size-fits-all dosing in oncology is obviously wrong. But history shows that many obviously bad ideas persist for a long time, despite widespread recognition of their flaws. This paper attempts to persuade an influential constituency—investors in pharmaceutical innovation, and the executives responsible to them—that it is in their financial interest to stop this practice.