I was skeptical when I read this yesterday that a medical system with so much money and so many lives on the line could miss something so obvious.
Then today I run across a JAMA article from FDA researchers saying the same thing:
"Failure to determine the most appropriate dose for clinical use was a major reason for nonapproval. Dosing is frequently decided early in drug development, and optimization of doses to maximize efficacy and minimize toxicity is seldom formally explored in phase 3 studies. Adaptive trial designs and other strategies (such as tr... (read more)
I encountered this while I was reading about an obscure estradiol ester, Estradiol undecylate, used for hormone replacement therapy and treating prostate cancer. It's very useful because it has a super long half-life, but it was discontinued. I had to reread the article to be sure I understood that the standard dose chosen arbitrarily in the first trials was hundreds of times larger than necessary, leading to massive estrogen overdoses and severe side effects that killed many people due to cardiovascular complications, and yet these insane doses were typical for decades and might've caused its discontinuation.
In a world full of irrational people with availability biases, it is likely that seeing the effects of two weak nuclear bombs against Japan helped prevent the use of an arsenal of hydrogen bombs against Korea, Vietnam or the Soviet Union.
I was skeptical when I read this yesterday that a medical system with so much money and so many lives on the line could miss something so obvious.
Then today I run across a JAMA article from FDA researchers saying the same thing:
"Failure to determine the most appropriate dose for clinical use was a major reason for nonapproval. Dosing is frequently decided early in drug development, and optimization of doses to maximize efficacy and minimize toxicity is seldom formally explored in phase 3 studies. Adaptive trial designs and other strategies (such as tr... (read more)