2 ms·

Luckily the article linked to the clinical trials.gov record for this trial [1] which suggests that the first approach (editing vs selection) is being used. 1.

Luckily the article linked to the clinical trials.gov record for this trial [1] which suggests that the first approach (editing vs selection) is being used. 1. https://clinicaltrials.gov/ct2/show/NCT02793856?term=crispr&rank=4 https://clinicaltrials.gov/ct2/show/NCT02793856?term=crispr&...

nonbel 10y ago
That seems to be the favorite interpretation. We need to see what data they present that favors it (ie % survival of the treated cells, number of initial cells, % mutants at that location detected in control cells). Also, this is kind of weird, because they say it is non-randomized: Study Design: Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment But later it says: Progression free survival - PFS [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months ] [ Designated as safety issue: No ] Overall Survival - OS [ Time Frame: The time from randomization to death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ] So is the treatment randomized or not? The info on that site may not be reliable... maybe it makes sense somehow though.
- ejstronge 10y ago
  I would be surprised if this safety trial were randomized with respect to the CRISPR manipulation. I agree with your assessment of needing more data to believe that the gene editing manipulation was successful. I suspect the randomization relates to the allocation to the experimental arms as described on the reporting page: This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose
  - nonbel 10y ago
    Nice catch, why do you think a safety trial should not use randomized allocation of the treatment (but it does make sense for dose) though?

nonbel 10y ago

That seems to be the favorite interpretation. We need to see what data they present that favors it (ie % survival of the treated cells, number of initial cells, % mutants at that location detected in control cells). Also, this is kind of weird, because they say it is non-randomized: Study Design: Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment But later it says: Progression free survival - PFS [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months ] [ Designated as safety issue: No ] Overall Survival - OS [ Time Frame: The time from randomization to death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ] So is the treatment randomized or not? The info on that site may not be reliable... maybe it makes sense somehow though.

ejstronge 10y ago
I would be surprised if this safety trial were randomized with respect to the CRISPR manipulation. I agree with your assessment of needing more data to believe that the gene editing manipulation was successful. I suspect the randomization relates to the allocation to the experimental arms as described on the reporting page: This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose
- nonbel 10y ago
  Nice catch, why do you think a safety trial should not use randomized allocation of the treatment (but it does make sense for dose) though?