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Hi miko3,
What we should keep in mind with these slides is that they are intended to provide GIs and heptologists at the conference with the latest available trials results rather than being a means to decide treatment options.
The correct place to be looking for treatment advice is the EASL or IDSP recommendations as linked in the”Getting Treated” section on this site. Those contain a consolidated view of the best recommendations by genotype, liver condition, prior Tx experience taken from a larger database of trials and will have factored in more data recorded during the trial that we are not aware of in the slides. Things such as maybe the cirrhosis patients in one arm of a particular trial turned out to be more forgetful (or headstrong) making them less compliant to the dosage timing causing a biasing of results. Even then you will see that there is a scaling of the recommendations such as Grade A, Class 11 as to how much confidence should be placed in the recommendation.
As to the sample sizes of the dataset, I agree it is not ideal but there are a number of factors that can cause this such as:
– willingness to participate in a trial with a “new” medication
– availability of genotype groupings e.g. Gt2 is relatively easy to treat so less Tx experienced Gt2s around.
– availability of researchers and monitoring staff
– cost of trial (yes I know, but given limited dollars do you trial 1 or 2 new DAAs with thousands or multiple DAAs with 10s or 100s)As a former trial participant I am very much aware of the massive amounts of data collected during these trials, both physical and psychological. I seemed to be constantly filling in forms, daily forms, weekly forms, monthly forms. What time did I take the tablets? the injections? (within 5 mins), What side effects today? How did I feel physically today? Emotionally? For the week? For the month? All cross referenced with further control questions. Blood tests, physical exams. That was for the 6 months of the trial then continued at a reduced pace as follow up for 18 mths. It exhausted me, goodness knows how the researchers felt! And at the end of the day that trial didn’t prove up the Tx under test so went nowhere*. Oh, and I didn’t end up clearing.
*But gradually all that data comes together in the EASL/IDSP recommendations.I liked your recent post about real world reporting of results of treatment and hopefully someone is actually doing that diligently other than in the Doc’s Redemption trials.
PS looking at your sig your treatment is going well too!
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
Hi miko3,
I also like hard data and definitive answers so I can’t really disagree with you. But as Nezam says, it is a rapidly changing field and the guidelines also need to take into account a number of different variables, so yes, it is a (hopefully) educated guess.
But this isn’t all that atypical of a lot of medicine. How often do we hear of new advances that change the face of treatment whether through technology advances or just a better understanding of the human body and/or mind……and then look back and wonder at what we did previously?I think Yoda sums it up well so when I was given the opportunity……To treat, I chose!
As did you.
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
Well, I’m not sure this discussion detracts from Dr James’ post as I suspect he posted so we are aware of the latest information available to the experts while understanding that none of it is definitive at the moment. So we are just fleshing that out a bit here. But yeah if anyone wants to move it to a seperate area I’m comfortable with that.
Let me paint your meeting with your specialist in a slightly different light:
A new patient has just walked into the specialists consulting room and asked him his attitude to generics. The doctor has responded that he is fully supportive of anything that can restore his patient’s health.
Said patient has a large pile of paperwork with him which the doctor notes and then smiles as he thinks “ah, here’s a patient who is taking charge of their own health and has researched rather than expecting me to just cough up the answers”. Respecting that autonomy but wanting to make sure that he doesn’t have a voodoo follower on his hands, he has asked the patient what they think are their best options. The patient’s responses have reassured him that there are no chicken entrails involved.Now, at this point he could have leant across the desk, God like, and stabbed his finger down onto any one of the options and said “This Is The One You Need!”
But instead he respected your intelligence and was honest with you……the options you had chosen were all good ones which would be just as likely to work as each other and he wasn’t going to try to pretend to you that there was enough evidence to favour one significantly over another.
I do suspect that if you had been less sure about generics, uninformed about your choices or just plain off track then his approach would have been different.Though I understand why you could be uncomfortable with the outcome of the meeting based on the age old instilled beliefs we have that the medical profession must have all the answers.
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
Which goes to show how long that post took me to put together. Much more succinct response from the Doc and he didn’t need an hour to write it.
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
To answer 2b’s first question in laymans terms. Yes, one of the traits of the HCV virus is that as it replicates it creates lots mutations some of which are different enough in structure that the DAA can no longer lock on to the receptor parts on the virus that it would normally use to block replication. So you then have DAA resistant virions in you which sounds bad; the good news here is that like most mutations they tend to be weak in some way and that particularly applies to their ability to reproduce or in this case replicate. So they tend to die out naturally or your immune and garbage disposal systems cleans them up. The problem occurs when a mutation occurs that is resistant to a DAA and can replicate reasonably well. Then because Hep c replicates so fast you soon end up with an infection with some immunity to the DAA and also other DAAs that work on the same receptor. This immunity will apply to whichever receptor that particular DAA works on so to re-treat you need to preferably use a DAA that works on other receptors if available for the genotype or hit it longer and harder and/or add riba or all of the above. It isn’t a huge problem but is the cause of some of those few percent who are non responders or relapsers.
Hope that makes sense.
The second answer is…..too bloody long! Or, I have no idea so hope someone else has an answer.
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
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