James-Freeman-facebook wrote: Hello Jolie,
I will start this with a disclaimer - my experience with Hep C the new DAAs only goes back to March, and the entire world's experience is really only a couple of years. Data is lacking and the margins of error in the encouraging trial data is large.
First the guidelines say 12 weeks Sof+Dac is appropriate for you.
Now let's consider some hypotheticals.
Fibrosis is not "you have cirrhosis" or "you don't" but our guidelines deal with the issue of fibrosis in that way because of the need to group people to get statistically meaningful numbers. We know that longer 24 week treatment is often recommended in the context of a high level of fibrosis, but why is this?
My working model goes like this. Fibrotic tissue has a very poor blood supply, therefore getting medications into fibrotic areas is harder. You might imagine fibrosis as like the walls of a castle protecting the areas inside. Fibrosis is a spectrum. You might also imagine that F4 represents strong castle walls made of bricks and F1 represents weak walls, like the straw house the little pig made to hide from the wolf.
Now consider that for an antibiotic/antiviral to work we need to reach what's called the MIC (Minimum Inhibitory Concentration) - below this level it does not work, above this level it works. Like fibrosis this is a spectrum.
Now imagine to kill you I have to make you wet with rain. If I send you out in the rain stark naked it will not take long (low fibrosis), and if it's raining heavily (high doses) it won't take long either.
Now imagine I put some clothes on you. Now it's going to take longer to get you wringing wet. This is like mild fibrosis.
Now imagine I put a cheap spray jacket on you. Now it's going to take longer again and this is like having higher fibrosis.
Now imagine you have a Gortex Jacket. This keeps you dry, but over time water leaks in through the cuffs, around the neck. This is like cirrhosis.
So you could intuit that the optimal treatment times might really look like (total speculation)
F0 8 weeks
F1 12 weeks
F2 16 weeks
F3 20 weeks
F4 24 weeks
Now I just pulled those numbers out of my ear, but I hope you can see what I'm saying. More fibrosis probably needs more treatment and a binary division < F4 = 12 weeks and F4 = 24 weeks does not make a huge degree of logical sense.
Now when we look at treatment duration we know that it's too long.
It's supposed to be too long because we can't know exactly when to stop.
All we can ever know is that we probably stopped a little early if it comes back. Unfortunately this knowledge is only available in retrospect.
So moving on to Government economics. The goal is not maximal cure rates, it is maximal cure rate PER DOLLAR SPENT.
Consider
12 weeks treatment $60,000 (so 8 weeks is $40,000)
Cure rate @ 12 weeks 95%
Cure rate @ 8 weeks 90%
Take a group of 100 patients.
8 weeks treatment will cost $4,000,000 for 90 cures = $44,444 per cure
12 weeks treatment will cost $6,000,000 for 95 cures = $63,157 per cure
Let's assume that we can retreat with 24 weeks @120,000
In the 8 week group that costs another $1,200,000 and sees only one patient not at cure. $5,200,000 for 99 cures = $52,525 per cure
In the 12 week group that costs another $600,000 and sees only 1/2 a patient not at cure. $6,600,000 for 99.5 cures = $66,331 per cure
So the shorter treatment time, although it does not provide the best cure rate is 25% cheaper per cure, even with retreatment.
If you were planning to spend billions on treatment then 25% is a huge number.
When politicians talk about making hard decisions these are the sort of decisions they are talking about.
Thank you for this,
I always had a question about the fixed duration of the tx being either 12 weeks or 24 weeks, why not 16 weeks ? or 18? or 21? so your explanation makes a great sense to me, although I too am not a Hepatologist.
Maybe it has to do with the size of packagings? that they are in packets of 12??? so you can have either 1 or 2 packets ?
But how a size of packaging can determine the length of treatment ?? that's silly, still why 12 or 24 but not 18-21 weeks??
I think adding Riba to the mix would not add anything from what I researched so far including Dr Foster's theory that Riba in tx experienced patients might actually be contra indicated due to possible resistance.
Yes, I get that economic perspective for rationing the tx, piety that human beings, their health & well being is so low on the list of priorities for our Western Gov. political agenda's & very low on the list of priorities for Western Pharma's, where only the highest profit & keeping the shareholders happy is the no1 priority.
