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Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - N155H: new scenario (DOMONO) - Nevirapine and Mono-DTG Switch: the Hunchback Trap - calculation error in the primary hypothesis - DOMONO and the benefit for the patients (not for BigPharma ...) |
This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.
At first, we provide a Google translation, then we work on proper translation, which will come soon.
Patients lose confidence in medicine ...
Overmedication is on! Be confident... Inhibitors are not toxic, taking a treatment in advance is safe. Then comes the obligation to get tested, then that to get treatment. The same drama as with vaccines! And, it is much more profitable!
To make believe that it is necessary to treat at any level of CD4, one has adulterated a trial: START. By construction, it could produce no other result than the advantage to early treatment. The trick? Introduce a large group of pre-tuberculosis patients. If we exclude them, the result is reversed, as had been shown by years of British practice to initiate only below 350 ... CQD
The S230R mutation is associated with resistance only if it is associated with others. All of them do not necessarily confer resistance ... According to Stanford, here: S230R is a non-polymorphic mutation [...], which seems to have minimal effect, if any, on INSTI sensitivity.
It is not causal in the VL rebound, and, alone, does not confer resistance (cf: here). It has a NUL score for DTG, but not for RAL or EVG (see here). Achilles' heel? Go figure...
S230R can only be identified as RAM (mutation associated with resistance) only if it is not alone; But here it is alone! So, not a RAM. VL rebounds, it calls for action. Which? A resumption of TRItherapy (Eviplera®), as the authors did ? Or an addition of 3TC, as they recommend at the end of the trial? In the long run, ICCARRE still remains possible.
Here, it was not a RAM justifying a trial interruption...
As with DOMONO, the BMM + P study excludes patients who had failed INI; BMM + P shows that more than 50% of failures are avoided by using the Achilles' Heel selector, which DOMONO does not. Unsurprisingly, we get as many failures as in BMM + P? Mostly avoidable failures!
The primary hypothesis is validated
Despite this, the non-inferiority hypothesis is validated! If the Morlat group is consistent, it could allow Mono-DTG in its next revision ;-)
Lorgeril explains, here, that we must define the primary hypothesis, in advance, and stick to it! And concludes: A trial stopped prematurely is worth no shit! Trash !
The trial has been interrupted due to a safety trigger, on the pretext that the number of RAM exceeded the number of allowed RAMs, as per predefined safety conditions. Predefined conditions that we could not find anywhere... It comes out of nowhere: it is done with a wet finger.
This is quite debatable: indeed, the S230R, seen at S30, is not strictly speaking a RAM. But the two other resistances N155H and R263K are seen at S60 and S72, ie while the patients, technically, are no longer part of the study, which lasts for 48 weeks.
The error originates from that patients remain in the study beyond the time allowed, without releasing the bridle. This safety constraint is calculated from a permissible frequency, say 2 per year, that is multiple by time (1 year), which gives 2 ... But if the study lasts 2 years, then the trigger should be set at... 4.
Why are there S72 patients in a 48-week study??? They had difficulty recruiting: the recruitment was spread over approx. 1 year!!!
The main reason for stopping the trial was that there were too few participating centers, and that the investigators, who have defulted their expectations, had not reassessed the safety conditions to take into account the delay. Hopefully Hocqueloux, in MONCAY, who also has trouble recruiting, will be smarter!
All the statistical analyzes are based on the (doubtful) hypothesis that resistance is random, with randomness constant in time ... Therefore, advancing the date of initiation of treatment increases the time the patient is exposed to risk of resistance or suicidality. But, no one talks about it ... Of course...
The summer is coming to an end, our summer series will have one last episode, and then it's back to scholl, full lights on our victory, remissions, post-treatment controllers, bi-cycle short cycle (BiCycle Strategy), new results with Mono-DTG ... Oh, we'll have fun!
Hurry to the sea, the beach, sun and Love!
Overmedication is on! Be confident... Inhibitors are not toxic, taking a treatment in advance is safe. Then comes the obligation to get tested, then that to get treatment. The same drama as with vaccines! And, it is much more profitable!
To make believe that it is necessary to treat at any level of CD4, one has adulterated a trial: START. By construction, it could produce no other result than the advantage to early treatment. The trick? Introduce a large group of pre-tuberculosis patients. If we exclude them, the result is reversed, as had been shown by years of British practice to initiate only below 350 ... CQD
S230R in DOMONO
It is not causal in the VL rebound, and, alone, does not confer resistance (cf: here). It has a NUL score for DTG, but not for RAL or EVG (see here). Achilles' heel? Go figure...
S230R can only be identified as RAM (mutation associated with resistance) only if it is not alone; But here it is alone! So, not a RAM. VL rebounds, it calls for action. Which? A resumption of TRItherapy (Eviplera®), as the authors did ? Or an addition of 3TC, as they recommend at the end of the trial? In the long run, ICCARRE still remains possible.
Here, it was not a RAM justifying a trial interruption...
More than 50% of failures are preventable
The primary hypothesis is validated
Despite this, the non-inferiority hypothesis is validated! If the Morlat group is consistent, it could allow Mono-DTG in its next revision ;-)
Lorgeril explains, here, that we must define the primary hypothesis, in advance, and stick to it! And concludes: A trial stopped prematurely is worth no shit! Trash !
Fatal error: the undue safety interruption
The trial has been interrupted due to a safety trigger, on the pretext that the number of RAM exceeded the number of allowed RAMs, as per predefined safety conditions. Predefined conditions that we could not find anywhere... It comes out of nowhere: it is done with a wet finger.
This is quite debatable: indeed, the S230R, seen at S30, is not strictly speaking a RAM. But the two other resistances N155H and R263K are seen at S60 and S72, ie while the patients, technically, are no longer part of the study, which lasts for 48 weeks.
Why are there S72 patients in a 48-week study??? They had difficulty recruiting: the recruitment was spread over approx. 1 year!!!
The main reason for stopping the trial was that there were too few participating centers, and that the investigators, who have defulted their expectations, had not reassessed the safety conditions to take into account the delay. Hopefully Hocqueloux, in MONCAY, who also has trouble recruiting, will be smarter!
All the statistical analyzes are based on the (doubtful) hypothesis that resistance is random, with randomness constant in time ... Therefore, advancing the date of initiation of treatment increases the time the patient is exposed to risk of resistance or suicidality. But, no one talks about it ... Of course...
The summer is coming to an end, our summer series will have one last episode, and then it's back to scholl, full lights on our victory, remissions, post-treatment controllers, bi-cycle short cycle (BiCycle Strategy), new results with Mono-DTG ... Oh, we'll have fun!
Hurry to the sea, the beach, sun and Love!
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