I was recently in The Netherlands for a few days, at an event for ERIBA. One of several interesting conversations at dinner merited a speculative blog post.
The topic under discussion was precision medicine (a recurring theme on the blog), and accidental motifs that could develop while trying to ensure that new drugs end up in the hands of those most likely to benefit. As a reminder, the purpose of precision medicine is the development of protocols such as biomarkers that predict drug efficacy, with the goal of matching patients to medicines. The use of Trastuzumab in HER2-positive breast cancer is a classic example.
Now all medicines must go through three phases of clinical trials, culminating in demonstration of efficacy in Phase III. Companies often develop biomarkers for use during clinical trials (these can but do not necessarily take the same form as the final precision approach), in the hopes that enrolling the “right” people will improve chances for a successful trial. It’s not kosher to run a trial and then post-hoc decide that responders and non-responders can be separated to yield statistical significance – it’s something you need to do right up front.
But even before the frequent use of molecular diagnostics, patients in trials tend to be biased in an important way – they are often very sick (especially in oncology). Which brings us to the dinner topic at ERIBA: is disease severity an accidental diagnostic in modern precision medicine? Are the marker levels chosen to accompany targeted medicines restrictive to the point where they unintentionally select only the sickest patients? This might be OK on the level of an individual drug, since it strives to only give drugs (expensive and with potentially nasty side effects) to those most likely to respond. But in aggregate across the industry, does it quietly bias away from moderate disease and towards the worst severity? Are we working our way into a corner that appropriately pairs medicines only at the extreme?
PS – Yes, it’s been a long time since the last post. I’ve been juggling a lot of travel with getting three papers out the door. The rest of the year will probably continue to be light on the blog. But teaching next semester will reduce my travel and give me plenty of opportunities to write blog posts while procrastinating lesson plans.