Why the cancer "moonshot" is a bad idea

[TownieDeac]

I picked this out because I think it highlights the biggest problem for moonshot cure. Besides the fact that cure is probably the wrong word to begin with, cure for most cancers is thrown out where in reality delayed should probably be the better term. CML for example (known or unknown by townie that he is talking about Philly again, as its a translocation of the "Philadelphia chromosome") the drugs attributed to Sawyer aren't like take this antibiotic and you are good. The five year survival rate is still only 60% or so for those two drugs.

For a lot of aggressive cancers that people work on technology that gets them to 30%+ survival rate is consider amazing and tons of money is poured into the research. For example CAR T cells which are very hot right now. The list of problems for CAR T cells is massive yet dozens of specialized companies have popped up overnight using specifically this technology, based off some very poor survival rates and the easiest possible targets out there, non-solid blood cancers.

I think the biggest promise right now is in immuno-oncology since current regiments even for what are considered simple cancers rely on treatments that in themselves give multiple hits to people that are clearly already susceptible to the development of cancer. Yet, like I said before the excitement for the technology to survival rates doesn't align. People will be surely disappointed in the future if the purpose of all of this is to get towards most cancers being cured when in reality its delayed death of 5-10 years. Maybe not though since people love to think organ transplants are a save all and the 10-20 year survival rate for those is about 50%. Life over death I suppose.

Good point. Cure is a misnomer in many cases in cancer - mostly we should say "extending life."

Cancer treatment is hard for a lot of reasons. Tumor heterogeneity is a big one - no two tumors are really, fully alike. Communication between clinics on tumor genotypes is going to be huge.

I agree that Immuno is the way to go (and CRISPR). Here's a good review of the state of the field, prevention, precision medicine, and immuno-oncology: http://cancerpreventionresearch.aacrjournals.org/content/9/1/2.full

 

[TownieDeac]

Nice. The ICMJE (a bunch of medical journal editors on a committee) are proposing a data sharing initiative for clinical trials - http://www.nejm.org/doi/full/10.1056/NEJMe1515172

As a condition of consideration for publication of a clinical trial report in our member journals, the ICMJE proposes to require authors to share with others the deidentified individual-patient data (IPD) underlying the results presented in the article (including tables, figures, and appendices or supplementary material) no later than 6 months after publication. The data underlying the results are defined as the IPD required to reproduce the article’s findings, including necessary metadata. This requirement will go into effect for clinical trials that begin to enroll participants beginning 1 year after the ICMJE adopts its data-sharing requirements. (The ICMJE plans to adopt data-sharing requirements after considering feedback received to the proposals made here.)

Enabling responsible data sharing is a major endeavor that will affect the fabric of how clinical trials are planned and conducted and how their data are used. By changing the requirements of the manuscripts we will consider for publication in our journals, editors can help foster this endeavor. As editors, our direct influence is logically, and practically, limited to those data underpinning the results and analyses we publish in our journals.

Should help make sure that clinical trials are reporting accurate data and help move Phase 1 trials to Phase 2 more safely.

Some boring journal logistical stuff that's actually really important:

Just as the confidentiality of trial participants must be protected (through the deidentification of IPD), and the needs of those reasonably requesting data met (through the provision of useable data), the reasonable rights of investigators and trial sponsors must also be protected. The ICMJE proposes the following to safeguard these rights. First, ICMJE editors will not consider the deposition of data in a registry to constitute prior publication. Second, authors of secondary analyses using these shared data must attest that their use was in accordance with the terms (if any) agreed to upon their receipt. Third, they must reference the source of the data using a unique identifier of a clinical trial’s data set to provide appropriate credit to those who generated it and allow searching for the studies it has supported. Fourth, authors of secondary analyses must explain completely how theirs differ from previous analyses. In addition, those who generate and then share clinical trial data sets deserve substantial credit for their efforts. Those using data collected by others should seek collaboration with those who collected the data. However, because collaboration will not always be possible, practical, or desired, an alternative means of providing appropriate credit needs to be developed and recognized in the academic community. We welcome ideas about how to provide such credit.

The first point is key. One major reason authors of trials haven't published their data openly in the past is because data deposits into registries have been considered "prior publication," which for most journals means authors can't then submit a paper with that same dataset. The last points about "credit for their efforts" is important too. We need to figure out a way to incentivize this data sharing other than just "it's the right thing to do." It means extra work for labs, and it doesn't meant their papers are going to be read more or cited more or anything like that, so journals and the academic community need to figure out how to develop that credit system.

 

[pourdeac]

hm, pour says that big data and computer modeling can't help us do real science

Never said that at all. Big data and modeling have limitations that need to be understood and respected. It's really not that hard to comprehend.

 

[ImTheCaptain]

c'mon, that's a terrible misrepresentation of your stance when it comes to climate science

 

[pourdeac]

Here are a couple links for people to peruse:

HealthNewsReview
NY Times
Ars Technica

Cliffs:
Cancer is not one disease, and there's not going to be one cure for it.
We have recent history to tell us that fast injections of lots of money are a bad idea for basic research goals.
There are systemic problems in science, medicine, and technology that need to be addressed first.

My thoughts:
Scientists in particular are thrilled with this news. It sounds, on the surface, like a great idea. But cancer is more complex than we ever imagined, and the more we discover about it, the more we realize we don't know. Injecting a bunch of money in the short term accomplishes a few things: it allows us to train a lot more new scientists on the career path of PhDs > PostDocs > Associates AND it comfortably funds established labs. Both of these are, in essence bad. Unless there's a long term, sustainable plan to fund the NIH/NCI to cure cancer, this means that in a generation, we'll have a ton of trained scientists and no $ to fund them. As for funding existing labs, that too sounds good, but a little competition is a good thing here. Opening up the purse strings has traditionally meant relaxing standards for grants and outcomes.

We've already spent about $36BN on cancer. I'm not suggesting we haven't made a lot of progress, or that cancer research doesn't deserve more funding. But most of the basic research (yes, most) is not reproducible and therefore hard to build on. What should be a feedback loop between the clinic and the bench is mostly flowing in one direction. And we need to make insurance companies foot the bill for genetic testing of tumors - passing off these costs to consumers or taxpayers just doesn't make economic sense.

I work at an organization that funds (and fundraises for), promotes, and publishes cancer research. We work very closely with policymakers, scientists, and patients. Money is simultaneously the one thing keeping all this moving forward, and at the same time, a potentially dangerous force in the field if applied incorrectly.

5 years ago I would have agreed totally with all of this. Today, I'm not so sure. While the kneejerk reaction was to pan this announcement as naive because it's far more complicated (which it is), there are some advancements in biology/drugs that might mitigate a lot of those complications. People including myself are targeting the natural response to tumors/abnormalities...as a more generalized approach. Inflammation, T-cell rejuvenation, etc can be targeted as ways to help the immune system deal with tumors and other abnormal cells. Boosting the natural ability to protect..including tumor induced suppression of immunity..can cross over many of these cancers and even other disease states. The Programmed Cell Death 1 inhibitors that have recently come on the market are a good example (see below). A strong push in that direction might actually result in the "moonshot" we've been looking for....probably not one but a few that cover a lot of these disease states.

https://en.wikipedia.org/wiki/Programmed_cell_death_1

 

[pourdeac]

c'mon, that's a terrible misrepresentation of your stance when it comes to climate science

Bullshit. My stance is, climate modeling is not predictive but is treated as a holy grail. People keep thinking that more data and more modeling will somehow make it predictive. It fundamentally can't be accurate because the data going into the model has greater error/variance than the end result being modeled, there are factors/drivers/data not included, etc. It's a lot like "bacon is worse than smoking" BS. So models have severe limitations and are only useful if that is understood. Big data does not mean better results. It often hides the true correlation/connection (see NSA trying to look for terrorist activity in communcations...and finding them not) and it is highly manipulative leading to extreme bias.

I even posted this pic in the past. It was used in a in silico drug discovery modeling conference I was at to describe model accuracy. The lego version is as accurate as any model can get...but we're treating climate modeling as if it's the actual painting..and the end change in climate is like a tiny hair width variation of the painting.

 

[ImTheCaptain]

no one treats it like a holy grail except skeptics.

 

[pourdeac]

no one treats it like a holy grail except skeptics.

Oh please...what an epic dodge! LOL. Anyone that believes in the CO2 correlation......which is 100% modeling.....believes said model to be the holy grail.

Lucky for us, cancer treatments can actually be....ya know...tested experimentally using that thing called the scientific method.

 

[ImTheCaptain]

there it is: if you can't test it in real life, it's not to be taken seriously!

 

[pourdeac]

there it is: if you can't test it in real life, it's not to be taken seriously!

If one wants to invoke "science'...that's pretty much the case. You either have to (1) experiment on it via the scientific method including the null hypothesis; or (2) develop a highly accurate, predictive model describing the observation..with solid causation evidence. Neither is true in most of climate research.

But again, lucky for us that's not the case for cancer.

 

[TownieDeac]

Welp, 21st Century Cures Act passed the House - http://www.nabr.org/2945-2/

Helps pharma/biotech/health IT a LOT, which, meh, fine. Cuts $3.5BN from Prevention and Public Health Fund, which is just awful. Nominally gives $1BN to fund opiod abuse research, which is great. $4.8BN to NIH over 10 years, subject to annual appropriations decisions, which is good.

 

[Liquid Karma]

Welp, 21st Century Cures Act passed the House - http://www.nabr.org/2945-2/

Helps pharma/biotech/health IT a LOT, which, meh, fine. Cuts $3.5BN from Prevention and Public Health Fund, which is just awful. Nominally gives $1BN to fund opiod abuse research, which is great. $4.8BN to NIH over 10 years, subject to annual appropriations decisions, which is good.

Only 30M for regenerative medicine using stem cells is what jumped out at me.

 

[TownieDeac]

we have all the SCOOPS on who is gonna vote against it in the senate since we spent like $10MM lobbying for it

elizabeth warren says it's a BAD DEAL and bernie will abstain or vote no

otherwise it's likely a landslide in teh senate too

 

[Liquid Karma]

we have all the SCOOPS on who is gonna vote against it in the senate since we spent like $10MM lobbying for it

elizabeth warren says it's a BAD DEAL and bernie will abstain or vote no

otherwise it's likely a landslide in teh senate too

I don't really see a problem in splitting the appropriations for research funds up between the private sector and the NIH, which is what is happening here right?

 

[ThinkingWithMyDeac]

It's a pretty bad bill all around, the usual for science in America.

 

[Deacfreak07]

Why do you think there is a resistance to getting serious about prevention? Lobbyists? Difficulty?

 

[Liquid Karma]

It's a pretty bad bill all around, the usual for science in America.

In your opinion what's wrong with it?

 

[TownieDeac]

I don't really see a problem in splitting the appropriations for research funds up between the private sector and the NIH, which is what is happening here right?

Not really. The way that the private sector is financially benefiting is through allowing the FDA to choose what kinds of trials they will require for preclinical/clinical tests of drugs and equipment. Should save the private sector billions.

Private sector spent about $192MM lobbying, hospitals/schools/health research orgs like mine spent $120MM.

Health IT really stands to benefit because the bill has unfunded mandates for upping EHR usage.

 

[Liquid Karma]

In other words I need to start up a company that is involved in EHR software.

 

[TownieDeac]

Why do you think there is a resistance to getting serious about prevention? Lobbyists? Difficulty?

In the case of HHS Prevention programs, lobbying from Big Sugar basically single-handedly defunded CDC Diabetes Prevention funding (around $73MM in 2016 will be $0 in 2020). Big Tobacco lobbied against the CDC Office of Smoking and Health, which will see its $126MM 2016 budget reduced by 25-30% per year for the foreseeable future.

More or less a public health disaster, though these programs will apply to get their funding privately like they do every time a bill like this goes through.