A recent NYTimes op-ed made the case that the reason we don’t have more cures is no longer the science, but upstream trials bureaucracy within the the FDA. Data sharing, adaptive trials, platform trials, more flexibility can all help. I agree with some of this article, but think it oversimplifies and misses the elephant in the room.
Here is why we don’t have more cures.
The science is lacking. Contrary to the article— this remains an issue. It isn’t honest to pretend we have the science to “cure” every disease. Some diseases are caused by genes so large, and so broken, that we do not yet have a way to correct or insert or remedy the problem. Some diseases have targets, but our therapeutics cannot reach the target. Some diseases have targets that are shared by healthy tissue, and our therapies need more effort to be gated solely at the abnormality (LOH HLA CAR-T is trying to do this). Some diseases accumulate damage throughout a lifetime, so fixing the root cause might be too little too late. Some diseases are completely ill-understood. If I were to quantify the sources of not having more cures, I would say the number one problem remains: the science is lacking.
The science is misleading. Yes, we have science on a topic, and wow, it really looks like it has found the underlying error, but it is irreproducible, flawed, broken or worse. This matters because it is hard to train AI on these data and expect insights rather than confusion.
Early clinical trial regulations is broken in the USA. The central thesis of the author’s is definitely a factor. I am not sure adaptive trials are the answer. I think platform approaches can be better. I think some investigators, with proven track records, should be credentialled and be able to skip some FDA oversight. There are many efforts in this space, which we began at FDA.
Separate IRB boards. The author faults separate IRB boards as being redundant, but one irony she misses is often, despite several boards, none do a good job and unethical trials still happen. I would favor a single ethics clearance, but done competently.
Manufacturing standards are too onerous. I agree, and drafted many CMC flexibilities at FDA. It is a pity small companies do not often read and take advantage of them fully.
China is beating us. This is a double edged sword. Yes, you can try more things in China, and that means you can innovate faster, but also kill people in novel ways with failed drugs. China, spoiler alert, has a bit of a fraud problem. Hard to know what to trust with purely Chinese data, and that is why FDA has moved to reject 100% China registration studies.
Too many trials which actually don’t provide useful information. Not all trials give information. If I do a trial of 5 cancer patients, and I give each patient a different combination of drugs, and one has tumors shrink— have I proven anything? Maybe the other combinations would work in other people— I only tested in 1. Maybe the responder, responded because of one drug or a couple or all of them. One of the examples in the article- of a child with cancer who gets a bespoke MRNA vaccine in Germany- struck me as unpersuasive because I am unsure if the child was helped or hurt by the shot. More informative trials would be a boon, just giving things haphazardly is not science, it is Brian Johnson.
The bar for FDA approval is too high. I don’t think I would say it is "too high,” but, I would say in many cases it is irrational. As I explained, asking for 2 clinical trials, when one or both have an incorrect control arm, crossover, blinding, concealment, power, etc. is likely worse than the default we set at FDA of 1 clinical trial— which actually answers a scientific question.
When we do have advances, these have poor market diffusion because they are unaffordable. A cure that no one can afford helps no one.
When we have duds, these often steal considerable money because of rhetoric, advertising or worse. The amount of money you can make from a drug that doesn’t work is so astounding, it is hard to work up the energy to make a drug that does work.
I don’t think we’re ever going to find an answer in a pharmaceutical, though that is the system we have created. From the moment I arrived at the Mayo Clinic I knew my issues which turned out to be “a rare disease incurable brain cancer” was related to my teeth, which is a part of healthcare we ignore. We’ve created quite a system that ignores cause and will continue to ignore causes as long as we’re willing to pay it to create new drugs to find the cure.
Media has certainly conditioned us against science…media consumers get primed for demanding immediate answers, a true misunderstanding of science, and a mentality that promotes victimhood and shifts blame. In reality there is so much fluidity in disease, hopeful cures, and most importantly, we have to remember that each person is n=1. Perhaps that’s scarier for many.