I read the report by Migliorini et al. The report concludes “prasugrel is associated with increased inhibition of platelet aggregation and with a better clinical outcome than is clopidogrel.”

I would like to raise the following points for the authors’ comments.

• (1)
  

  The study is stated to be sponsored by the investigators. How, why, and by whom was this particular study design developed?

  
  
• (2)
  

  What was the reason that prasugrel had the greater antiplatelet effect? Is it possible that the observed differences in antiplatelet effect and outcome were the result not of any basic differences between the 2 drugs but simply the result of the specific dosage regimens of each drug that was given in that study?

  
  
• (3)
  

  How can one use the data obtained to optimize the entire process of antiplatelet therapy?

More information could have been obtained from the data collected in this study. One can take each individual subject’s data, his age, gender, height, weight, renal function, and dosage regimen, and make a population pharmacokinetic—dynamic model of each drug, including serum concentrations (if available) and antiplatelet effect. Actually, such population models of each drug may already exist.

There was great variation in the observed antiplatelet effect in each of the 2 patient groups, as shown in Figure 2. It would be useful to compare the antiplatelet effect observed in each individual patient with that patent’s final clinical outcomes. One could then obtain the distribution of the effect responses and the various clinical outcomes. One can find a specific value of antiplatelet effect that separates the various good and bad outcomes optimally and which can then serve as an optimal therapeutic target of antiplatelet effect to be achieved for each new patient in the future.

In future clinical use, initial dosage regimens can then be developed, individualized for each patient to important clinical covariates such as age, gender, height, weight, and so forth, to achieve the desired target goal with maximum precision (minimum expected weighted squared error). Each future patient can then have his antiplatelet effect monitored and the dosage adjusted appropriately, especially using nonparametric drug models, multiple model maximally precise dosage design, and Bayesian adaptive control, to most closely achieve this target value. In this way, each individual patient can be positioned to maximum advantage during his or her course of antiplatelet therapy. One can avoid the “one-size-fits-all” approach to therapy currently described.

It is a pity that the pharmaceutical industry, the Food and Drug Administration, and the wider medical community appear not to have taken advantage of the opportunities and tools described in the references here, to facilitate such an approach.