Too Many Medicines Simply Don’t Work
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But the DSM is full of illnesses that are really a half dozen completely different conditions with the same (or just similar) apparent symptoms, each with its own cause, and no reliable way to distinguish it from the others except that maybe drug X helps one, and drugs Y, Z, W, and V are useless for it. Likewise, the one that Y helps, and the one that responds to Z, and the rest where nothing seems to work. In double-blind trials, V, W, X, Y, and Z are all "shown" to be equally useless.
That does NOT mean V, W, X, Y, and Z don't work. The "gold standard" is as subject to GIGO as everything else. You simply cannot tell anything about what it means without looking at underlying facts.
Such a drug should be approved but with a big warning that it only works in some cases.
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.
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.
How can that be?
The answer is GIGO. Feed garbage to your Hamilton scale, get garbage out. The "gold standard" is no better than your diagnoses, and depression is the diagnostic counterpart to a "wastebasket taxon", polyphyletic. The only way we know to distinguish one "depression" from the next is which med fixes it. Now, design a "gold-standard" protocol to evaluate those meds.
Checkmate.
We're begging the question here.
Millions of people who have recovered some stability after a period of profound crisis were begun on a particular treatment at the nadir of that crisis. They very reasonably assign the recovery to that treatment - because they view that treatment as an individual, rather than as a cohort who endured similar crises, responded with various or no treatments, then had various degrees of recovery or mortality.
Additionally, they can't be evaluated based on their reaction after the treatment is withdrawn, because antidepressants are generally physically addictive, and you would expect a subsequent crisis even if withdrawn from a person taking them who had never had a crisis in the first place.
The effectiveness of antidepressant medication can't be assumed through the testimonial of the survivors, then types of depression reified through sorting the survivors by treatment type.
It becomes obviously self-justifying, because people who didn't improve clearly had the wrong depression for the drug. Instead, you have to evaluate the treatment against non-treatment; you can't just assume that survival indicates success, and work to refine tools that filter for the people will be helped by that treatment without material evidence, either of physical mechanisms or by already having strongly predictive tools, that the treatment is more effective than placebo.
I wouldn't deny that defining a disease by its effective treatment could be useful, but the margin for effectiveness would have to be pretty high if there were no other criteria for that definition.
That is permitted here, but I am likewise permitted to point it out. Please acquire some life experience before holding forth on this topic in the future.
You seem very sure of yourself, like you're unwilling to listen to any opinion that doesn't immediately conform to your own. And maybe this is a very difficult topic, charge with such intense emotion that it nearly hurts to hear someone so contrary. However, the man who proclaims the one truth will never learn again.
The epistemological difficulties around treatments for wastebasket diagnoses are very real, but it demonstrates a deep, fundamental confusion to conflate those difficulties with problems with the meds themselves. This failure of reasoning is only attractive to the inexperienced, hence my advice.
To understand the problem, consider the medieval diagnosis "ague". Numerous cases respond instantly to antibiotics. Others, viral, do not respond at all. Some can be prevented by variolation, some by refrigeration, some by hygiene, some by purifying drinking water, some with mosquito netting, some by quarantine, some apparently not at all. The only way to predict which will work for a particular outbreak is to know more details about the causative agent. Denigrating antibiotics because they fail to treat malaria is deadly foolishness.
Double-blind trials, where they work, are the cheapest way to obtain reliable information about a medication's effectiveness for a reliably identified illness. Where they do not work (for readily understood reasons) we are obliged to use more expensive, time-consuming, and idiosycratic methods to obtain the same information.
In the case of "depression", as for other similar diagnoses, such methods have been found necessary, and are used. Insistence that the so-called "gold standard" is the only arbiter of truth (because the name?) betrays ignorance of history and medicine that can be remedied only by deeper experience.
One does not always have time to explain all of the above in detail, and must distill the gist. The gist is better than nothing.
Agreeing with the person who outlines her viewpoints, just because she did so most recently, leads you to agree with falsehoods. Truth is not so easily discerned as agreeableness or articulateness, appealing as the idea may be. What matters is the facts, and to how many decimal places.
They aren't. The average might be small, but the range is wide.
What we do know about statins is that they have terrible long-term side effects that might not put off somebody worried about dropping dead at any moment, but should give everyone else the heebie-jeebies.
They interfere with the liver's production of cholesterol, but we (like every other animal) need cholesterol to live.
It also doesn't mention the drug company funding provided to some patient campaign groups. It's pretty cynical: you know your medication is not effective enough for the cost, so you give money to dying people and their families to campign to get your med provided by single payer systems and insurance companies.
> For example, for every thousand low-risk patients prescribed statins for primary prevention, only a single stroke is prevented per year. Meanwhile, you would need to treat more than a thousand people with antihypertensive therapy per year to prevent one death. This is a far higher NNT than that of many interventions GPs are advised against prescribing due to lack of efficacy.
https://www.bmj.com/content/348/bmj.g3458/rr/761453
> Enas bases his numbers on a 2013 Cochrane review. Enas reports that NNT equals 167 for low risk (less than 1%) and 67 for intermediate risk (1-2%) individuals. Enas reinterprets this as meaning 1000 low-risk people would need to be treated for five years to prevent six major adverse cardiovascular events. Enas notes the increased risk of type II diabetes from statin use and also estimates that 100 of the thousand people treated would have myopathy (that the same might occur with placebo is irrelevant as I will not be taking a placebo). Enas judged that the benefits of treatment in low risk subjects far outweigh any possible hazards and concluded that early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of coronary artery disease among Indians.
In an example from The NNT about PSA Screening for Prostate Cancer: http://www.thennt.com/nnt/psa-test-to-screen-for-prostate-ca...
No benefits were identified to PSA screening, while 1 in 5 will go on to have an unnecessary prostate biopsy (which can itself lead to complications, false-positive diagnosis, and further treatment with associated complications, and so on).
(I feel obliged to mention that I'm not a doctor, btw, just sort of a casual fan of medical science and stats.)
https://www.amazon.com/Medical-Nihilism-Jacob-Stegenga/dp/01...
You can listen to a recent EconTalk podcast for a one hour summary of the book.
This is what you would expect from a blind application of a 95% confidence interval only if 50% of tested drugs were good.
My understanding was that a 95% confidence interval implies the chance of a false positive of 5%.
From http://www.mit.edu/~6.s085/notes/lecture2.pdf
"In particular, we can ask for an interval around ˆp for any sample so that in 95% of samples, the true mean p will lie inside this interval. Such an interval is called a confidence interval."
You are likely to find the actual positive and 50 false ones.
However, that’s with a single test. If you run 5+ different tests you are likely able to distinguish the true positive.
Interestingly, the unexpectly effective placebo effect seems to be limited to the USA. Why nobody is sure.
That was my first thought.
When I took it, after pseudoephedrine was placed behind the counter, I never thought phenylephrine did anything. Turns out that it really doesn't:
https://www.jwatch.org/na39054/2015/09/17/phenylephrine-no-m... https://www.washingtonpost.com/news/wonk/wp/2015/11/04/the-t...
But then the war on opiates happened and they removed all OTC codeine. I understand the evidence on codeine's efficacy as an antitussive in the amounts used was mixed but the tablets seemed to work for me. Alternatives like dextromethorphan probably work as well or better but the pseudoephedrine containing cold and flu meds seem to have disappeared instead of being reformulated. I am guessing the market was getting too small and higher volume OTC placebos make more money.
I came across it on reddit a while back and it's basically solved my acne problem. You get a super dry face and chapped lips, but there are lots of products to help mitigate that.
The Accutane subreddit is full of tips and before/after photos - https://www.reddit.com/r/Accutane/
https://www.bbc.com/news/health-47952076?intlink_from_url=ht...
I approached my GP after suffering with acne who put me on tetracycline which has some horrible side-effects such as staining your teeth and it didn't work for me at all.
I bypassed my GP and bought accutane online. The side-effects are some of the worst I've had from a medicine, dry skin and eyes, regular nose bleeds, sensitivity to the sun etc. Nothing mental though. That said. It works.
Before I used accutane I had several acne spots turn into keloid scars which I have been treating over the last decade with corticosteroid injections.
I also wasn't used to chap stick before, but now I carry it all the time.
Accutane makes the “horrible side-effects” of Tetracycline look like a mild headache. Aside from being a powerful teratogen (i.e. it causes nasty birth defects), Accutane is linked to suicidal tendencies, liver damage, heart damage, and more. It’s not a drug anyone should be taking without supervision.
It's also been linked to increased suicide rates https://www.nejm.org/doi/full/10.1056/NEJM200102083440616
Remained acne free until suddenly getting cystic acne in my early 30s.
Here's what helped me:
- Do laundry more often ( Increase the rate you clean your: sheets and pillow cases!, face cloths, clothes. If this is impractical you can simply buy more pillowcases and swap out clean ones more regularly; especially if you're a prone to sleep drooling or have greasy hair. )
- Stop washing your face with soap ( Just use water and a wash cloth on your face; use firm pressure to get into pores but light enough to avoid giving yourself 'rug' burns or tears. This is great for exfoliating dead skin and removing surface oil. Do this twice a day; morning and evening. Buy multiple face cloths and use newly cleaned ones regularly; every 2-3 days. )
- Apply moisturizers twice a day; morning and evening ( My skin had an amazing response to Sea Buckthorn: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438513/ . Its coloring is very intense so for my twice daily moisturizer I cut it with Rosehip Oil usually only putting 5-10 drops per 2 oz of Rosehip; experiment for your skin color. To increase my skin's recover time and the effectiveness of the Sea Buckthorn I will take a regular long bath where I apply it directly, almost like a mask, and wipe it off after the bath. It has proved great at reducing redness and blemishes as well as healing open wounds such as exfoliated dead skin and bleeding pores. )
- Spot care for cystic acne with pure Salicylic Acid ( Only rub this on cystic pores. Avoid trying to pop any pores without a clear white 'head'. )
- Cold showers ( Or at the very least end the shower by holding your face under cold water to close your pores. )
- Exercise ( General health will aide skin health. Also great for hormone balance which can be a cause factor for acne. )
- Wrangle your hormones ( Through masturbating less, and eating a hormone nutrition informed diet. For example, if male, eat more cruciferous foods for Testosterone maintenance. )
Hope these suggestions can make the difference they made for me for you too.
I appreciate these tips and I do follow most of these so I can vouch for their value as they do seem to help. I will try the more unique suggestions...!
What do these words even mean?
Helping your body's androgens ( Testosterone ) to maintain ( maintenance ) their natural levels.
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Also, cruciferous plants are good sources of vitamins and minerals that appear to positively affect testosterone levels; for instance, Vitamin K and A and zinc.
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[1] https://en.wikipedia.org/wiki/Cruciferous_vegetables
For a list of cruciferous plants.
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[2] https://en.wikipedia.org/wiki/Testosterone#Regulation
> Nutrients: Vitamin A deficiency may lead to sub-optimal plasma testosterone levels. The secosteroid vitamin D in levels of 4001000 IU/d (1025 µg/d) raises testosterone levels. Zinc deficiency lowers testosterone levels but over-supplementation has no effect on serum testosterone. [2]
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[3] http://www.whfoods.com/genpage.php?tname=foodspice&dbid=9
> A third area of increasing research interest involves the metabolism of vitamin D. Broccoli is not a source of this vitamin, but it is an excellent source of vitamin K and also of vitamin A (in one of its precursor forms, beta-carotene). Many individuals have large vitamin D deficiencies that cannot be remedied through diet alone, and these deficiencies require sizable amounts of vitamin D to be provided through dietary supplementation. When large supplemental doses of vitamin D are needed to offset deficiency, ample supplies of vitamin K and vitamin A appear to help keep our vitamin D metabolism in the proper balance.[3]
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[7] https://en.wikipedia.org/wiki/Aromatase
> In particular, aromatase is responsible for the aromatization of androgens into estrogens.[7]
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[5] https://en.wikipedia.org/wiki/Androgen
> Testosterone, the major androgen.
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[6] https://en.wikipedia.org/wiki/Estrogen
> All of the different forms of estrogen are synthesized from androgens, specifically testosterone and androstenedione, by the enzyme aromatase. [6]
> Quantitatively, estrogens circulate at lower levels than androgens in both men and women. [6]
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[7] https://www.ncbi.nlm.nih.gov/pubmed/23090135
> The aim of this study was to evaluate the effect of white cabbage and sauerkraut juices of different origin and indole-3-carbinol (I3C) and diindolylmethane (DIM) on expression of CYP19 gene encoding aromatase, the key enzyme of estrogen synthesis. [7]
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[8] https://www.ncbi.nlm.nih.gov/pubmed/26840393
> indole-3-carbinol and diindolylmethane. These compounds occur as glucosinolate conjugates in cruciferous vegetables and are released when one chews or otherwise macerates the vegetable.
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[9] https://www.ncbi.nlm.nih.gov/pubmed/19524224
But of course this is nutritional science so there is lots of conflicting and grounding counter research.[9]
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My take away from all of this is that having a varied diet is the most important.
I said 'cruciferous plants' to actively avoid listing a single item as a cure all.
Also, my guess is that our diets have narrowed as we have stopped seasonally cooking for ourselves and buy processed foods with a lot of ingredient overlap likely confusing our bodies which were designed to function on the ingredients found in the varied foods we ate.
I hope this is less bleak than it reads.
If you are already in a healthy and happy relationship is hope you’d stay rather than seek a ‘new’ relationship solely to manipulate your T levels.
If you are instead implying that a single person should ‘get a new’ relationship I would hope you would get into that relationship for other reasons than to manipulate your T levels.
Unless I suppose you lead with that and both people are into it?
I want to note that ‘girlfriend’ is an unnecessary specificity.
Most of the literature simply refers to ‘sexual activity’.
Also, the link between sexual activity and Testosterone is rather varied.
Most of the literature tests on older populations where it is already widely known that age reduces T levels.
Also, there is still debate on which is the cause.
Some say less sex leads to low T levels. Some say low T leads to less sex. Others suggest it is feedback loop.
Either way it seems the results tend to peak and be short lived.
But anyone with an otherwise healthy, functioning, body is guaranteed through exercise and a varied healthy diet to set up their body for optimal Testosterone maintenance.
I think it was a tongue in cheek comment about how a man’s brain has a huge influence over their testosterone levels. Men see their testosterone levels drop after being in a relationship for a while, and drop further when they have children. Although, I guess it could be argued that they are likely having less sex in these situations.
Look, I agree with almost everything we’ve both said in this discussion. I even created a website that shows my agreement (http://max-testosterone.com - not designed to make money, rather to market the domain name which is for sale). I think I just didn’t like the phrase “testosterone maintenance”, implying it’s something that’s broken that can be fixed. For most men, low testosterone can’t be dramatically improved (double or triple) by simply improving their diet.
Update: Spironolactone (Aldactone) is an androgen blocker drug that, at a lower dose, can help with hormonal acne.
The customer who didnt research?
The physician who gets lunch twice a year from Accutane?
The government for stopping freedom?
Note: none of this is /s, I would like to discuss why this happens, and if there are any solutions.
Accutane worked amazingly, and very fast. Acne gone in a week, and never returned. I stayed on Accutane til I hit the target dose (maybe 3 months, I forget exactly). Twenty years later, I'm still acne free.
Though without a doubt, Accutane is the strongest drug I've ever taken. I needed a liver function test before starting, and monthly during the treatment. My nasal lining and lips were unbelievably dry. I carried lip moisturiser and creams with me everywhere, used them several times an hour. I remember my dermatologist telling me to avoid the sun, and treatment was over the winter months.
To anyone on long-term courses of tetracycline, I suggest trying Accutane. Be prepared for the side effects. And only do it under medical supervision.
We need to end off label use. Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy. One might as well not have fda approval.
The problem of tainted and ineffective generics confounds the analysis. A recent investigation shows the fda's proceedure of unannounced inspections only in the us means that 75 percent of indian and Chinese generics makers failed inspections during the few years when unannounced inspections were done. Now they have moved back to announcing. It is not sure that each failure meant there are bad drugs out there, but a majority of failures were 100 percent faked test data regarding the chemicals inside the drugs.
There are many cases where off-label drug use gives a minority of people tremendous benefit. Take a look at the people with various brain disorders using Ambien off-label. It can literally bring people out of coma-like states temporarily.
Other examples off-label use: * Propranolol for anxiety. * Guanfacine for blood pressure issues, now used on label for ADHD.
Is that off-label?
Paperwork for Propranolol in the US has on-label usages listed as: Hypertension, Angina Pectoris, Atrial Fibrillation, Myocardial Infarction, Migraine, Essential Tremor, Hypertrophic Subaortic Stenosis or Pheochromocytosis.
How would you propose doing that? Under the current system, we would simply be redirecting people to on-label prescriptions, which are higher priced but not better.
> Saying a drug is approved for one diagnosis and then allowing it for any other diagnosis is, in the modern age, simply crazy.
That's not what off-label is. Off-label just means that it's not an approved indication for the drug. The approved indications are what the drug companies are allowed to market / recommend.
> One might as well not have fda approval.
This is a fairly absurd comment to make, so I'm not even sure how to respond to it. Surely you are already aware that the FDA approval process requires studying the safety, contraindications, etc for a medication, and that these do not need to be redone from scratch for new applications?
Off-label use is just cutting through a small bit of regulatory box-ticking, box-ticking that doesn't add much value. Off-label use is common and standard of care often involves off-label use.
There are simply not enough resources to research the combination of every drug with every indication, not enough to provide the level of care that we can provide with off-label use.
But even from a more mainstream viewpoint, there are lots of examples of for-profit medicine where a drug company pays for an on-label use via a study where off-label use is cheaper and similarly effective. For example Ketamine and Esketamine. One is very cheap and widely available one is very expensive and not widely available.
I hope we can address the fundamental problems with for profit medicine, I think this is just one negative externality of our crazy system.
The approval process itself is what's crazy. Drugs are approved for treating disease X, but drugs don't work that way. They are chemicals that modify processes in the body to produce collections of effects that help treat some medical issue. What does prednisone treat? It's an immunosuppressant, an anti-inflamatory, and it reduces blood calcium levels. That's useful in treating a range of conditions like heart failure, cancer, autoimmune diseases, and many, many others.
One example of the insanity of this regime is the HPV vaccine. What does the drug do? It helps the immune system fight off certain strands of HPV. What was it approved for? Preventing cervical cancer. Since men don't have cervixes, it wasn't FDA-approved for men and any administration of that vaccine was strictly off-label. It took an additional approval and many years to get it approved for men, even though there was no reason to believe the vaccine would work in women but not in men.
Everyday in England 30,000 people with learning disability take a psychotropic medication when they don't have the condition that the medication is licensed for.
NHS England has a programme to stop this misuse of medication. It's called STOMP - STop Over Medicating People with LD. https://www.england.nhs.uk/learning-disabilities/improving-h...
This medication is often off-label use of anti-psychotic medication, used for a "sedative" effect.
People with learning disability are at increased risk of constipation (sensory issues around food; reduced range of food being eaten; not much say about what they eat; reduced access to exercise; etc etc), and these meds often have constipation as a side effect.
This combination causes harm. It sometimes kills people.
There's variable awareness of constipation as a side effect of clozapine. Most doctors know about agranularcytosis, and they're aware constipation can be a problem. But there are some doctors who don't know that the constipation side effect kills more people than agranularcytosis.
I agree. It's really important to stop misuse of medication.
This is patently ridiculous. The FDA just proved the drug was safe in therapeutic doses and that it treated what it said it treated. They didn't say that the drug wasn't safe to treat other things, and they didn't say the drug was generally unsafe. If doctors are prescribing non-therapeutic doses, yeah, that might be a problem, but there are entire clades of diseases that would otherwise be untreatable without off-label use. (And the frank alternative - labeling all of the drugs as being usable for all of the various conditions - can't keep up with reality. The FDA is slow and meticulous, and if we forced that on off-label used drugs, there'd be a lot more suffering for literally no good reason. And it probably wouldn't do anything for actually stopping off-label usage - doctors would just start lying and overclassifying their patients as having diseases to give them the meds. E.g. there'd be a whole lot of autoimmune patients with various "overlap syndromes" that suddenly have lupus and/or rheumatoid arthritis, despite not meeting the current diagnostic criteria, just so they could keep taking adalimumab, methotrexate and/or hydroxychloroquine. It's just red tape they don't need nor care about.)
We've done actual wonders in the world by simply scanning through approved drug combinations to find treatments for ailments. An example of this is in cancer treatment: it's fairly common one cancer drug will treat multiple classes of cancer, especially in combinations with other drugs (even ones not designed to fight cancer specifically). It's so commonly the case that this is now its own entire enterprise: high throughput scanning of drug combinations to fight tumors. https://www.biorxiv.org/content/10.1101/051698v1.full It's also been done to treat viruses and autoimmune diseases.
I'm not a super libertarian or anything, but I believe if a doctor has a reasonable belief that a drug will treat a condition, and therapeutic trial evidence bears it out, there's not a good reason not to prescribe it, whether or not it says on the bottle that that's okay. I've benefited from this in the past and I will continue to in the future.
We have a hard enough time keeping desperate people from trying things that we know for a fact are scams. Perhaps doctors could put the studies in clearer context when prescribing, but they are always clear that these drugs aren't perfectly effective and that it's kind of a crapshoot.
When you've got patients who will die anyway, it's no surprise that we end up treating them as a final stage of clinical trials. You need to be honest about that and get consent, but many will give it willingly.
And those Iowa farmers and shopkeepers and schoolteachers at the end of their lives sign the form. An unreasonable population of them. For no reason but to help.
That would allow outcome based decisions about keeping that approval or comparing new treatments to the actual efficiency of existing treatments.
I'm pretty sure we do this?
I mean I suppose we don't have laws which mandate this but medical researchers are constantly measuring and publishing how effective existing legal treatments are. I am sure researchers would love to find which treatments do not actually work and since publishing such work would affect treatment guidelines and have a huge impact.
Much of that would be addressed by having a single-payer healthcare system, which could mandate record standards and submission of specific portions of the data in ways that do not unduly risk identifying patients.