1. Drug candidates seeking approval must show non-inferiority to gold standard, meaning they are not worse than the top choice for the same treatment. This non-inferiority is quite easy to game, as we all know statistics are fungible and may be manipulated. If all I have to show is no significant difference, and I can use one of 10 different outcomes or surrogates, well my job got a LOT easier than showing superiority on the primary outcome of interest.
2. Before approval, drugs are tested in non-representative samples, either because they are too small in sample size, the disease is too rare, or because there needs to be a VERY large (post-market) population to tease out rare side effects.
3. Doctors and geneticists should come together and provide genetic testing to ensure that patients and their drugs are appropriately matched. This could be done in cancer, for instance, as you can genotype the cancer and provide a drug cocktail specifically for it. Another instance would be depression, as some drugs do not work for people with certain neurotransmitter genotypes. Physically, this means that each of us may have slightly differently shaped receptors that different drugs bind to differently. This explains a lot of the difference in drug responses, whether it be SSRIs or alcohol or cannabinoids, people simply have different receptors/biochem.
4. Medicine has always been a battle between doing nothing, providing the placebo effect, providing beneficial treatment, and avoiding/minimizing harm. In medieval times, exposure to medicine was tantamount towards increased risk of death and complication (see leeching, blood letting, terrible hygiene in surgery/childbirth, etc). Even now in modern times, going into a hospital is risky: hospital-associated infection is a massive killer, never mind acute psychological stress leading to delirium. We demand improvements in healthcare, new drugs, innovations, and extending life, and yet that is a very complex and challenging process that we will work on for centuries to come.
Simply put, doing medicine well has always been very hard. We have many legacy treatments and practices which probably should be put on the back shelf, but as with coding practices and legacy code, it is very hard to stop practices with momentum and inertia, whether the field is energy (fossils dominate), medicine, coding, or anything.
> 1. Drug candidates seeking approval must show non-inferiority to gold standard, meaning they are not worse than the top choice for the same treatment. This non-inferiority is quite easy to game, as we all know statistics are fungible and may be manipulated. If all I have to show is no significant difference, and I can use one of 10 different outcomes or surrogates, well my job got a LOT easier than showing superiority on the primary outcome of interest.
Before they to the test they have to declare a primary outcome to avoid this issue. And most diseases just don't have that many outcomes relevant outcomes you can test for.
> 3. Doctors and geneticists should come together and provide genetic testing to ensure that patients and their drugs are appropriately matched. This could be done in cancer, for instance, as you can genotype the cancer and provide a drug cocktail specifically for it. Another instance would be depression, as some drugs do not work for people with certain neurotransmitter genotypes. Physically, this means that each of us may have slightly differently shaped receptors that different drugs bind to differently. This explains a lot of the difference in drug responses, whether it be SSRIs or alcohol or cannabinoids, people simply have different receptors/biochem.
They're trying, and they're failing hard. Precision medicine has been pretty useless outside of cancer.
Even in cancer precision medicine is pretty crap. It works, but only sometimes. Most of the time even a correctly targeted drug results in a resistant tumor.
2. Before approval, drugs are tested in non-representative samples, either because they are too small in sample size, the disease is too rare, or because there needs to be a VERY large (post-market) population to tease out rare side effects.
3. Doctors and geneticists should come together and provide genetic testing to ensure that patients and their drugs are appropriately matched. This could be done in cancer, for instance, as you can genotype the cancer and provide a drug cocktail specifically for it. Another instance would be depression, as some drugs do not work for people with certain neurotransmitter genotypes. Physically, this means that each of us may have slightly differently shaped receptors that different drugs bind to differently. This explains a lot of the difference in drug responses, whether it be SSRIs or alcohol or cannabinoids, people simply have different receptors/biochem.
4. Medicine has always been a battle between doing nothing, providing the placebo effect, providing beneficial treatment, and avoiding/minimizing harm. In medieval times, exposure to medicine was tantamount towards increased risk of death and complication (see leeching, blood letting, terrible hygiene in surgery/childbirth, etc). Even now in modern times, going into a hospital is risky: hospital-associated infection is a massive killer, never mind acute psychological stress leading to delirium. We demand improvements in healthcare, new drugs, innovations, and extending life, and yet that is a very complex and challenging process that we will work on for centuries to come.
Simply put, doing medicine well has always been very hard. We have many legacy treatments and practices which probably should be put on the back shelf, but as with coding practices and legacy code, it is very hard to stop practices with momentum and inertia, whether the field is energy (fossils dominate), medicine, coding, or anything.