If a philanthropist wants to aim a lot of money at biomedical research, there's many good ways to do it, but I think the most high-impact, lowest-risk would be to fund clinical trials for non-patentable interventions. There are plenty of drugs and therapies that are well-known to work, but which can't be used (or can only be used through much-more-expensive variants) in clinical settings, due to the lack of anyone willing to fund the studies to formally prove their effectiveness to the FDA.
A notable example is recent efforts to fund a study on the use of corticosteroids and vitamin C to stabilize patients with sepsis [1]- this would be a huge impact on mortality for patients with all sorts of diseases, since sepsis is a common consequence of lowered immune system functioning or post-surgical infections, but since neither corticosteroids or vitamin C are patentable, there's no commercial incentive to fund trials. Another example is the use of MDMA as a psychiatric drug- any highschool dropout can tell you that it works as a powerful mood-elevating chemical with relatively rare and benign side effects (at least by the standards of psychopharmaceuticals,) but clinical trials were only recently begun after decades of agitating from psychiatrists.
The most potent benefits from philanthropic funding tend to be in areas that can't be reached by conventional for-profit commercial work. There's still much more low-hanging fruit out there.
Personally I was quite impressed by what I had read about the "drugs for neglected diseases initiative" (DNDi). I recall seeing an interview where they mentioned that trials are much easier conduct when the disease has very serious effects (i.e. death) and the existing treatments were poor since you needed far less statistical power to show that your treatment was better.
I don't know how Sepsis fits into this, but they specifically do trials that drug companies won't.
If FDA is a major barrier to bringing drugs to market, is it possible set up trial in other countries with less regulation as well as trial cost? I would imagine that for stuff such as cancer there should be significant demand for trying out drugs that are still on trial - especially in other countries because they don't even get to participate normally.
The FDA specifically (and famously) does not regulate the practice of medicine. They regulate the marketing of drugs and medical devices - mainly that you cannot market something as an safe and effective treatment for a disease/condition without proof of (a) safety and (b) efficacy (or effectiveness), which is obtained through clinical trials.
Adherence to "evidence based" therapy guidelines is typically enforced via malpractice claims. Obamacare tried to introduce incentives for outcome measurement/tracking and evidence based care by either cutting or supplementing medicare reimbursements, but even that has been difficult to implement nationally across the 5-7 most frequent and costly conditions and procedures (e.g. acute myocardial infarction, COPD, knee replacement, etc).
While the FDA's regulatory approach does slow the pace of innovation, they exist for a reason -- I acknowledge that GP is not calling for any policy change. Snake oil salesmen were a real thing, and still abound in the valley albeit in different form.
That the FDA does not regulate the practice of medicine is technically true- doctors can and do use (approved) medicines for non-approved uses. But as you also mention, this informal, "non-evidence based" approach has downsides such as the risk of malpractice suits. If a doctor tries treating a sepsis patient with corticosteroids and vitamin D, instead of with the current "evidence based" standard of care (massive doses of antibiotics,) and then the patient dies, the patient's next of kin can sue for massive damages, potentially ending the physician's career- despite it being the medically more effective thing to do. As far as the courts would be concerned, this could be equivalent to the doctor opting for homeopathic medicine in place of antibiotics; one treatment not supported by the evidential standards of medical care is about as good as another, to a lawyer. Since doctors can't risk their medical licenses on a daily basis and stay doctors, they treat patients with suboptimal methods, and people die because of it.
So to say that the issue is funding for FDA approval is probably an oversimplification- equally powerful studies without FDA involvement may or may not suffice, that's a question having to do with law and other non-science factors. But the FDA has established what is the broadly recognized "gold standard" of establishing the medical effectiveness of an intervention.
I don't quite understand this - what is the purpose of the FDA process for approval for "compassionate use" drugs? That is, what does completing this process let a doctor do that couldn't otherwise be done?
(My understanding was something along the lines of, the FDA regulates which drugs can be used/sold but not how, so if a drug was approved for any purpose a doctor can use it "off-label," but a new drug still requires FDA approval. Is that accurate?)
I tend think of compassionate use more in the context of medical devices and biologics (e.g. synthetic antibodies) than small molecule drugs. And to reiterate FDA regulation has more to do with marketing (and prescription/reimbursement) than use.
For example, nutritional supplements are often recommended by doctors and incorporated in their practices, but are marketed as "promoting general health and wellness" and not treating a particular condition. Here you don't need any evidence of efficacy (or even safety), you only need to be able to show a "history of use". Many "structure-function" claims push the envelope (ex promotes liver health), but are still legal and FDA has been pretty consistent and clear about where they draw line.
Compassionate use concerns drugs not yet FDA approved. The doctor needs permission to treat a patient with an investigational drug outside of a clinical trial.
Doctors can use anything already FDA approved off label but they don’t... unless there’s compelling evidence.
I couldn’t find a comprehensive treatment of the broader issue on a quick check- I suspect that the nature of an issue revolving around “what we know vs what we formally know” resists discussion in places like scientific journals. But there’s some overlap with more well-known issues, such as antibiotic development- even though new antibiotics can be patented, the return isn’t enough to stimulate nearly sufficient development (e.g. https://www.pharmaceutical-journal.com/news-and-analysis/fea... .)
Why fight one-by-one. The highest impact use of money would be lobbying to disolve the FDA or, failing that, eliminating the requirement to show efficacy (leaving only the requirement to show safety, which is relatively cheap).
Of course, I anticipate a number of replies telling me how wrong I am and that regulations are needed for safety; none of them will mention the trade offs involved.
For lack of a rebuttal to the FDA dissolution comment, which I'm sure others are more qualified to respond to, I wanted to address the efficacy/safety remark:
A growing number of people have voiced objections to the burdens of the FDA's efficacy testing requirements, but it's worth at least thinking about why they're in place. The main issue is that "safety" in the context of pharmaceuticals doesn't mean "perfectly safe" or even "non-lethal" — it really means, "safe enough, given the benefits". Side effects of a chemotherapy drug that can completely eliminate a tumor, for instance, could be acceptably substantial, because it cures an otherwise terminal illness. Side effects of a drug mildly lowering cholesterol levels, by contrast, must be strictly limited, because many Americans may take such a drug for much of their adult lives, sometimes in combination if the effects of a single drug are too weak.
It's hard to know if the benefits outweigh the risks if you don't know what the benefits are. Obviously, this efficacy testing carries a huge time and monetary burden, but without it, contextualizing acceptable risk would be difficult, if not impossible.
"We're having issues with users forgetting their login password. We could implement password-recovery protocols to solve this on a case-by-case basis, but it's much more efficient to solve these issues once and for all by eliminating the login system altogether."
Why would disolving the FDA fix the problem? If you don't do clinical trials to establish efficacy, then how will doctors know which treatments are effective and which ones are bogus? Randomized trials are important here due to the causality issues inherent in establishing efficacy in hindsight.
"Moskovitz, whose estimated net worth is more than $14 billion, and Tuna have said that they plan to give away most of their fortune during their lifetimes."
To get an idea of the money involved here, his life's fortune is about what is currently spent every 6 months on medical research that no one will ever double check (since it is impossible to do):
"Overall, the team found that poor materials made the largest contribution to reproducibility problems, at 36%, followed by study design at 28% and data analysis at 26%. The team estimates the overall rate of irreproducibility at 53%, but cautions that the true rate could be anywhere between 18% and 89%. That puts the potential economic cost of irreproducibility anywhere from $10 billion to $50 billion per year."
And irreproducible in principle studies are just the tip of the iceberg. Beyond that there are many problems that can render research useless or misleading (p-hacking, bias due to unblinding, misinterpreting results, incorrect analysis, etc). Just pumping more money into this system rather than trying to change the incentives and practices seems wrong.
For anyone else who was confused by the headline: it's "high-risk" research in the sense of "speculative" or likely to have null results, not in the sense of e.g. the lethal virus research that was on here a few days ago.
I'm surprised the "identified 11 priority areas in science" did not include antibiotic research, given that we are rapidly running out of antibiotics as resistance develops, all while virtually nobody is researching or developing new antibiotics.
I know that antibiotic resistance is a problem but can you elaborate on how were rapidly running out right now? I got strep last week and they prescribed me amoxicillin (or penicillin if i was allergic) which are both quite old and established, and still prescribed today.
No i know how antibiotic resistance works, i just haven't seen it have any effect on me or anyone I know, which makes the statement "we're rapidly running out" seem distant
We are running out of effective antibiotics. It's not the supply of amoxicillin that's the problem, but the rapid increase in bacterial strains that are resistant.
If you want to see concrete progress thanks to Dustin and Open Phil, read about Target Malaria, one of the research organizations.
I am seeing firsthand the need in Southeast Asia: an emerging drug-resistant "super-malaria" is spreading along the Mekong and is impossible to treat with standard medicine.
Big U.S. pharma has no answer for this, and the problem is accelerating. I believe Open Phil and similar independent science funding orgs can give us all a major avenue of research to help save many lives.
Exciting to see more funds going to research, but cringe knowing the efficiency in how it is spent.
Due to procurement not having a research background, they often due poorly negotiating prices for basic scientific chemicals and supplies. The result makes it very difficult for researchers to buy from the open market such as Amazon, etc.
For example, a contract gives the scientific distributor the right to match a price [1]. Scientists need to make this request through their procurement office or to a sales rep. which takes a couple of days and additional paperwork to complete. These extra steps create enough friction that researchers will often by through contracted providers despite them being more expensive.
A notable example is recent efforts to fund a study on the use of corticosteroids and vitamin C to stabilize patients with sepsis [1]- this would be a huge impact on mortality for patients with all sorts of diseases, since sepsis is a common consequence of lowered immune system functioning or post-surgical infections, but since neither corticosteroids or vitamin C are patentable, there's no commercial incentive to fund trials. Another example is the use of MDMA as a psychiatric drug- any highschool dropout can tell you that it works as a powerful mood-elevating chemical with relatively rare and benign side effects (at least by the standards of psychopharmaceuticals,) but clinical trials were only recently begun after decades of agitating from psychiatrists.
The most potent benefits from philanthropic funding tend to be in areas that can't be reached by conventional for-profit commercial work. There's still much more low-hanging fruit out there.