4 ms·

This is the full text of the study? http://onlinelibrary.wiley.com/doi/10.1002/hon.2437_7/full http://onlinelibrary.wiley.com/doi/10.1002/hon.2437_7/full Is th

by nonbel 9y ago

This is the full text of the study? http://onlinelibrary.wiley.com/doi/10.1002/hon.2437_7/full http://onlinelibrary.wiley.com/doi/10.1002/hon.2437_7/full Is that really it? Shouldn't they have to publish something substantive before approval? It doesn't have to be in a journal, but somewhere on the FDA site, etc.

nonbel 9y ago
Actually, not even "have to" do that. That makes it seem like the people coming up with these treatments should be an adversary to patients. Shouldn't they want to share as much info as possible? That would seem necessary to convince possible patients (and/or any advisers) that this will help them.
- refurb 9y ago
  Kite is a start-up in a very competitive field. It wouldn't surprise me that publishing data wasn't that high of a priority vs. getting FDA approval. That said, it's very common for biotechs to publish after the phase 3 is complete as they can put much more information in the paper vs. what their sales reps can say to physicians.
  - nonbel 9y ago
    >"It wouldn't surprise me that publishing data wasn't that high of a priority vs. getting FDA approval." I see, so the problem is physicians/patients are willing to act on very sparse information, so why bother providing it.
    - refurb 9y ago
      You clearly don't understand the pace of work at a biotech start-up. If you could only do one or the other, which would you choose? 1. All hands on deck to get the FDA submission completed so the drug can get to patients sooner. 2. Peel off a bunch of headcount to get a handful of papers published, knowing that will result in a delay in getting the drug to patients?
      - nonbel 9y ago
        When patients/doctors are willing to put all their eggs in one basket (FDA approval), this seems like a perfectly reasonable business plan. However, for the best chance to find out if your drug really is working the way you think it does, you will need actual public examination of the results. You'll want to see what critiques people come up with, make some predictions about future results, whether an independent group can replicate your work, etc. Although it is nowhere near a guarantee, sharing your results/methods is another of those heuristics (like do independent replications, and make precise predictions about future observations) that served as the basis of science for so long. More and more I see science being replaced by "something else". This something else is definitely a faster process...
jfarlow 9y ago
There are a LOT of papers out there about CARs [1], how they work, and what their effects are. The DNA sequence used here has been effectively frozen for quite some time as it runs through all sorts of examinations. Further, your link is to the description of an Oral Presentation, not even a paper. It's not supposed to have data associated with it. This is the paper from the Phase I results of the same therapy (I very much appreciate that the paper is open-access): http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016%2816%2945375-X http://www.cell.com/molecular-therapy-family/molecular-thera... [1] https://www.ncbi.nlm.nih.gov/pubmed/?term=chimeric+antigen+receptor https://www.ncbi.nlm.nih.gov/pubmed/?term=chimeric+antigen+r...
- nonbel 9y ago
  I followed the link from TFA: "The study that led to approval enrolled 111 patients at 22 hospitals; 101 of them received Yescarta. They had one of three diseases: diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or transformed follicular lymphoma." The study that led to approval is unpublished.
- nonbel 9y ago
  Thanks, here is an example of the type of questions I would expect a doctor to ask (which is impossible if no study is published). Looking at your paper I can't really tell what they did to determine CR. Did they only do PET-CT? The paper they cite[1] mentions some biopsies (for some cases), etc but they only show any results for that assay. Assuming it was only PET-CT for now, they say[1]: "Typically FDG-avid lymphoma: in patients with no pretreatment PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET negative." So positive/negative is apparently based completely on relative metabolic activity. Just looking at figure 1B in your paper, it appears that baseline vs 30 days is done perhaps using different exposures. Or for some reason the intestines were much more active at 30 days (patients ate more recently?). 1) How do they ensure there isn't some response to the drug/environment that has increased general metabolic activity, thus decreasing the relative signal from the tumor? 2) Were the people processing and examining these scans blinded to the fact they were part of a drug trial? There seems to be ample room to play with exposures, etc here. [1] http://ascopubs.org/doi/10.1200/JCO.2006.09.2403 http://ascopubs.org/doi/10.1200/JCO.2006.09.2403

by nonbel 9y ago

nonbel 9y ago

Actually, not even "have to" do that. That makes it seem like the people coming up with these treatments should be an adversary to patients. Shouldn't they want to share as much info as possible? That would seem necessary to convince possible patients (and/or any advisers) that this will help them.

refurb 9y ago
Kite is a start-up in a very competitive field. It wouldn't surprise me that publishing data wasn't that high of a priority vs. getting FDA approval. That said, it's very common for biotechs to publish after the phase 3 is complete as they can put much more information in the paper vs. what their sales reps can say to physicians.
- nonbel 9y ago
  >"It wouldn't surprise me that publishing data wasn't that high of a priority vs. getting FDA approval." I see, so the problem is physicians/patients are willing to act on very sparse information, so why bother providing it.
  - refurb 9y ago
    You clearly don't understand the pace of work at a biotech start-up. If you could only do one or the other, which would you choose? 1. All hands on deck to get the FDA submission completed so the drug can get to patients sooner. 2. Peel off a bunch of headcount to get a handful of papers published, knowing that will result in a delay in getting the drug to patients?
    - nonbel 9y ago
      When patients/doctors are willing to put all their eggs in one basket (FDA approval), this seems like a perfectly reasonable business plan. However, for the best chance to find out if your drug really is working the way you think it does, you will need actual public examination of the results. You'll want to see what critiques people come up with, make some predictions about future results, whether an independent group can replicate your work, etc. Although it is nowhere near a guarantee, sharing your results/methods is another of those heuristics (like do independent replications, and make precise predictions about future observations) that served as the basis of science for so long. More and more I see science being replaced by "something else". This something else is definitely a faster process...

jfarlow 9y ago

There are a LOT of papers out there about CARs [1], how they work, and what their effects are. The DNA sequence used here has been effectively frozen for quite some time as it runs through all sorts of examinations. Further, your link is to the description of an Oral Presentation, not even a paper. It's not supposed to have data associated with it. This is the paper from the Phase I results of the same therapy (I very much appreciate that the paper is open-access): http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016%2816%2945375-X http://www.cell.com/molecular-therapy-family/molecular-thera... [1] https://www.ncbi.nlm.nih.gov/pubmed/?term=chimeric+antigen+receptor https://www.ncbi.nlm.nih.gov/pubmed/?term=chimeric+antigen+r...

nonbel 9y ago
I followed the link from TFA: "The study that led to approval enrolled 111 patients at 22 hospitals; 101 of them received Yescarta. They had one of three diseases: diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or transformed follicular lymphoma." The study that led to approval is unpublished.
nonbel 9y ago
Thanks, here is an example of the type of questions I would expect a doctor to ask (which is impossible if no study is published). Looking at your paper I can't really tell what they did to determine CR. Did they only do PET-CT? The paper they cite[1] mentions some biopsies (for some cases), etc but they only show any results for that assay. Assuming it was only PET-CT for now, they say[1]: "Typically FDG-avid lymphoma: in patients with no pretreatment PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET negative." So positive/negative is apparently based completely on relative metabolic activity. Just looking at figure 1B in your paper, it appears that baseline vs 30 days is done perhaps using different exposures. Or for some reason the intestines were much more active at 30 days (patients ate more recently?). 1) How do they ensure there isn't some response to the drug/environment that has increased general metabolic activity, thus decreasing the relative signal from the tumor? 2) Were the people processing and examining these scans blinded to the fact they were part of a drug trial? There seems to be ample room to play with exposures, etc here. [1] http://ascopubs.org/doi/10.1200/JCO.2006.09.2403 http://ascopubs.org/doi/10.1200/JCO.2006.09.2403