R51/Sigourney oh I completely forgot! There’s actually a whole other category of sponsors for trials. The networks. We have networks like the HIV Prevention Trials Network (HPTN), The AIDS Clinical Trials Group (ACTG), we had the PACTG (for perinatal studies which merged with a subgroup from the HPTN and became IMPAACT) the HIV Vaccine Trials Network, MTN (Microbicides) and then more that are county specific. The cabotegravir trial was an HPTN trial and some of the PrEP trials may have been as well, but I can’t remember and if they did they’d have a name like HPTN 052 (which wasn’t PrEP but was one of the big studies on when to start and also behind Treatment as Prevention). So it was an HPTN sponsored trial but funded by NIH and ViiV partially funded it. I guess it was a network trial because it was comparing CAB (I’m already tired of typing out “cabotegravir”) to Truvada and both ViiV and Glenn Close donated the study drug.
So I was around for the beginning but I was long gone from PrEP by the time it was competed. (I left because I had to be near my old parents and it meant leaving my job).
All I remember about the beginning was being at one the first meetings where we knew the drug number but the drug hadn’t even been named cabotegravir yet much less Apertude when it came to market and we were talking about it in such abstract terms. They hadn’t decided to do a ramp up period with oral CAB yet so people were saying things like if someone has a bad reaction to an injection, what are we going to do? Dialyze them? Then they came up with the plan for a ramp up period using a pill. But I was out of there.
I have…feelings about all the 2nd generation PrEP studies. Most clinical trials are conducted on an Intention To Treat basis (ITT). If someone gets the pill and doesn’t take it (or the reverse, somehow is assigned a placebo and then gets their hands on the pill) you treat them as if they took the drug or the placebo they were assigned to regardless of whether they didn’t. PrEP studies used a Modified Intention to Treat (mITT) model where if someone tested positive after their first dose of PrEP but before their second visit, their first blood sample got tested with a better test and they were excluded from the analysis and considered not part of the trial (because they became HIV positive before the trial started but weren’t detected by a Western Blot which was the gold standard at the time and PCR isn’t and a whole other thing that gets under my skin and could be another book).
So the results of the PrEP trials in gay men were good enough for approval but the real world effectiveness was actually way higher, 100% after two years in a Kaiser Permanente cohort of gay men.
So the CAB trial was a non-inferiority trial and I believe it only had to be better than the 44% in iPrEX but not as good as the close to 100% in real life. I don’t know what number they actually used for the non-inferiority margin. It’s in the protocol but I don’t remember if it was actually in the paper.
On the other hand, it was also basically a Directly Observed Therapy (DOT) study because the volunteers had to come in and get a shot every two months and they directly observed if they did or didn’t.
In my mind, DOT > ITT, but a cohort of men for 2 years in real life > DOT.
So I’m just waiting for another KP cohort study before I decide what I think works best.
I know. A lot of jargon. I tried to explain what the jargon meant but it was still jargony.