I'm gonna try and make this understandable without mentioning specifics. We all know that many trials on new drugs are done first for treatment naive patients. It seems that lately a number of previous non-responders to SOC have been in certain trials. I am assuming this information was not given to the pharma's or the patients would have not been able to get into the trial. With a disease like HCV, I can certainly understand patients doing anything to get in.
So, my question is, if the pharma company does not know about this, and the trialed med is not for previous non-responders or relapsers, wouldn't that skew the results and make the drug look less helpful for treatment naive patients? I'm wondering because one of the most exciting drugs looked a lot better in the early phase 1 trials, with more people responding, than it does in the phase 2 trials.
As I have said, I am not questioning what any particular patient has done, just wondering what you think about the skewed results. I remember years ago in the original combo trials, that people were overdosing on the interferon. I'm sure that skewed the toxicity results in that bone marrow had to be more suppressed than it would have been with regular dosing.
Susie: It seems that lately a number of previous non-responders to SOC have been in certain trials. am assuming this information was not given to the pharma's or the patients would have not been able to get into the trial.
Curious, what makes you think that folks aren't telling their doctors that they were previous non-responders?
I'm sure that it's happened on occasion -- it's a big world -- but I doubt it's very common. Certainly never saw anyone here mention they did that.
We do have prior non-responders here in Telaprevir trials for prior-non responders, but I don't think you're talking about that, or maybe that' s it?
I do agree, however, that you should be upfront about your HCV treatment history before entering a trial, or for that matter when speaking to any doctor about treatment. And yes, it would skew trial data if true, but again, I haven't seen any evidence of that at least here.
I'm not saying they aren't telling their doctors. I'm saying that no one is telling the trial people. However Jim, you are saying there are telaprevir trials for non-responders in Prove 2. I did not realize that. So I am very wrong. Sorry for the confusion. For some reason I thought that it was only phase 3 trials that would be for non-responders.
This is for the sake of argument. I have no knowledge of the above but look at it either of two ways;
I'm a treatment naive patient that wants to get into a treatment failure trial
I'm I prior non-responder, relapser, or otherwise past treatment failure who wants to get into a trial for treatment naive patents.
Either way....... would not my medical records show my true status and therefore make it difficult or impossible to get into either such trial?
One plausible answer to lesser results in trials is that it's simply the nature of the beast. Pharms are always banging on the drums touting the public to invest in the latest miracle drug. It's one reason for the trials; do actually discern the effectiveness of the drug. Trials are where ther rubber meets the road. Pharms may be able to construct initial tests to make things look better. It may be much harder in heavily defined 1000 plus trials seen in Phase 3.
You are certainly correct that it would corrupt the data. Of course..... some people are trying to simply stay alive. The may not have insurance or may have advanced liver disease and may feel that they don't have much time. Trials are interesting. They are constructed so that both the Pharms giving the trials are trials are kept from tampering with the results and they do their best to keep the participants from doing the same. I feel that both parties often are tempted to skew the results. It's why the trials are run by 3rd parties.
Prove 1 and Prove 2 were for treatment naive patients (and all geno 1)
Prove 3 was exclusively for prior treatment failures. (also geno 1's I believe) To my understanding it was for all types of treatment failures; inadequate response, slow response, discontinuations of many sorts, breakthrus and relapses.
The Phase III studies are supposed to be primarily for treatment naives geno I's but until it's posted in clinicaltrials.gov or announced by Vertex who really knows? Vertex seemed interested in a BID dosing at one time, treating harder to treat groups, co-infected and genotype 2 patients. We should soon see what that may look like.
I thought that might be it. But your general point about people not being honest with their trial doctors is a vaild one. Suppose for example, someone with drug "x" takes Procrit outside the trial protocol and no one in the drug "y" group does. When those two drugs are compared against each other, drug "x" might be favored in terms of a lower drop-out rate, for example. I'm sure you can think of many similar cases.
Also curious about your comment about folks "overdosing the interferon" in the early combo trials. Are you saying they were getting the interferon outside of the trial, or maybe just "dialing" in higher numbers on the RediPen. If it's the latter, it's quite understandable someone might due that -- I mean they made it so easy. You would think in a trial setting they would only give people the correct dose and not have them dial in a number. Human nature is human nature :)
I was in Prove 3 and is was for non-responders/relapsers. I was completely honest with the trial site and told them of my many times of treating and my lack of clearing. I feel that it was their decision as to whether or not to approve me for the trial...everything I did was above board. I unfortunately, have not been able to get my unblinding reports-which as I've said before-tics me off. There's no reason for them not giving me my reports as I've been off the drugs since the first week of July and I was in the Group C-which only ran for a total of 24 weeks. I was taken off trial on week 5. I already know that I had breakthrough on my virus, so why can't they release my reports so that my doctor can have them. I see my regular Gastro., when I'm not involved going on the 3 hr drive to the trial site and my regular Gastro., has no idea what those reports show and neither do I. I was completely done with any follow-up appt.'s as of Oct. 1st, so why no reports? This is the problem that I have w/the clinical trials. I also have a problem with them not allowing rescue drugs. I will be pretty hesitant to get involved in another trial unless it's a broad scale (non-randomized) large amount of people trial, that allows rescue drugs. I don't even care if they pay for the rescue drugs-just that they allow you to take them outside of the trial.
Regarding the concept that some people may be "cheating" their way into a trial or engage in behavior that violates the rules (like taking procrit, riba etc), and because they might be doing this it skews the results in a possibly downward manner: I've come to believe that your expected chances of SVR are usually higher than are predicted by the standard “drug trialed” sources. By that I mean during large "controlled" drug trials, typically you're looking at the antiviral performance of a healthy cross section of humanity. And by that I mean you would be amazed at how irresponsible, ignorant, lax, or even downright stupid many people are when it comes to their healthcare (even when it comes to a life threatening disease like HCV). I've heard of many people over the years that have cirrhosis and yet keep on drinking even knowing they have cirrhosis. And some of these same people eventually take on treatment, but once the effects of the drugs set in and they start feeling bad (possibly interrupting their drug/alcohol abuse schedule). And when confronted with this unpleasant/inconvenient situation they simply shrug their shoulders and stop taking the thing that's making them feel bad. It’s really that simple, and it’s really natural selection in the works. Or they may not even be deliberately not taking it, they just "forget" and only take their meds when they think of it. Or they don't show up for doctor visits, or they don't keep their IFN refrigerated, or they engage in ongoing drug/alcohol abuse or do other things to themselves that significantly hurts their chances of being cured (like prostituting and sharing needles with other infected people while they treat).
I was in the Vertex trial and I heard through the grapevine about this woman (who was also in the Prove 1 trial) that was from a low socio-economic class and was very uneducated. She thought her elevated liver enzymes were her viral load, and she was under the impression that when they went to zero, her viral load was zero. And when her viral load was zero she was cured and could stop. She said the pills made her feel bad, so she only took them “some of the time”. She had an old empty jar that she would put her pills into after she popped them out of the blister pack. Sometimes she would take them, sometimes she would put them in the jar. You had to take your empty drug containers into the trial center so they could perform a basic inventory to see if you were taking your drugs. She dutifully returned her empty pill packs, which gave the appearance she was taking the drugs as required – but she wasn’t. She also apparently thought she might lose her disability/welfare payments if she were cured, and that apparently also played at least some role in her non-compliance. On some level she apparently wanted to remain infected for this reason. This woman eventually dropped out of the trial altogether (and obviously was not cured).
Anyway, this is just one example of what can happen during drug trials and how the reported results can seem more dismal than they really are. This woman is just one amongst the percentage of folks who treated and statistically shows up as being a non-responder, and is included amongst those that discontinued early as well (possibly categorized for “adverse effects” too). Who knows how many more people in this trial (and others) have behaved in one manner or another like this? The number is probably larger than we imagine, especially considering the relatively high correlation between HCV+ patients and a “drug colored” past, or present (with “present” having obvious implications for non-compliance). So the moral of the story is, if you’re a reasonably intelligent, responsible, well-informed and compliant patient, your odds are almost certainly better for getting an SVR than the average reported SVR percentage. Furthermore, many of these drug trials (including Prove 1/2/3) preclude rescue drugs and/or custom dosing regimens. Lets remember that when these restrictions are lifted, the SVR rate will be even higher, and this of course goes for SOC alone as well.
Great post. That same dynamic also occurrs when one "predicts" how long we will live if we remain infected with the disease. The majority in the USA don't even know they have HCV.
Another thing that comes to mind is that boards such as this may be in a love-hate relationship with trials. One one hand the trial coordinators might grimace if they knew that members in their trials were on line reading and getting their heads filled with dangerous or even outright "wrong" ideas.
The flip side is that people who read at such boards may represent a sort of pinnacle of those treating. They understand the virus and treatment well. The have an excellent support base. They have people riding their butt encouraging them to stay on full dose, get medical treatment where it may be needed, share what often world class doctors are doing in their own HCV treatment. I believe that participation in boards such as this may end up raising the response rate a bit compared to people who are unconnected to anything other than a local and sometimes less than world class hepatologist.
People such as yourself (and many others here) help raise peoples HCV IQ and (I believe) help them understand their treatments and options better. Kudos.
I also believe that those here may have better SVR rates, because just the fact of being here, shows a proactive stance, that should only help. As to whether trial results are better (or worse) than out of trial results, I suppose it can cut different ways. On one hand, the rescue drug issue certainly must be factored in, but on the other, the trial doctors are no doubt on the whole more knowlegeable and experienced than your average treating doctor. Also, trial patients -- and I hate to use this word -- are "cherry picked" in the sense that the inclusion criteria may be more stringent in certain regards than in a general clinical setting.
I have to say in my own defense, that I thoroughly and totally complied with all the dictated regimens, took all of my medication on time and even with the 300-500 calorie snack which was required to take the pills with. I recorded in my diary faithfully. I have not been a drug user in over 20 years, not have I drank alcohol in over 11 yrs. I do not smoke. I exercise every day. So, there was NOTHING that I did to keep me from getting a good response, except for the fact that the trial managers decided to randomize me and I ended up getting into a non-Riba group. That has nothing to do with me..... There are ALWAYS exceptions to the rule and no one should generalize that because I did not clear the virus that it was something that I was doing wrong!!! IMHO, Susan
Susan, (I hope you don't think I was talking about you). I was not pinpointing anyone at all. I simply forgot that the Phase 2b trial was for non-responders/relapsers. I'm sure you were very compliant. I think that people who have tried to clear so many times, would be extra careful. I know I was and so was Miles. I never did anything wrong and that makes me pretty sure I am interferon resistant. I didn't even try to get into a Vertex trial because I knew you couldn't use the rescue drugs. Their excuse was that it was using two unapproved drugs and the FDA wouldn't allow it. That was a bit of BS.
Jim, they say that the trial SVR rates are always better than in real life because many times the patients are picked because they show certain characteristics. I just don't know which way is the truth. Also, there was no pen available in the original trials. It was a diluent mixed with interferon powder and rather than 1.0 cc in the vial, it always came out to about 1.3 so people could actually give themselves a third again more than they were supposed to get.
Mre, that is some story about the lady in the trial. I can't imagine being lucky enough to get in a trial and not taking the drugs. Sheesh.
Willy, I agree with so much of what you have said. Especially about the support and knowledge of the people who post on boards like this.
not saying it is impossible for a previous treater to get into a trial for naive's but i do not think it can happen that easy. i do not think a trial will let you in if you have no records, even if you just found out and really dont have any records they would still want the primary docs report.
My comments about non-compliant patients were not directed to anyone specifically, certainly not you. My only point was to point out that trial test results are the product of sensible, compliant patients like yourself (and pretty much anyone on this forum) AND non-sensible, non-compliant patients like the one described above. And the person described above is a pretty extreme case, so it's likely someone with that particular makeup is relatively rare. But I'm sure there are a significant number of other people who commit "lesser crimes" during their treatment that also chips away at the final reported response/SVR ratio. For instance, I've seen people sign up for and start treatment, take their first shot, get the fever and chills and shakes and then go "ohh this is awful" and just quit right there = tx wimps skewing the grading curve. And I imagine there are a fair number of people who often do not eat a fat rich snack with their riba (or research drug if in a trial). That seemingly simple and innocuous act of non-compliance right there can result in a dramatic downward shift in riba/VX etc blood serum levels, which could easily make the difference between eventual RVR/EVR/SVR and relapse/non-response...and yet that person could be perfectly compliant otherwise. There are countless other examples of how people skimp or skip or do not take their treatment as seriously as they should. Again, my point is to point out that this IS going on, not everyone is an apple during these trials, some people are oranges. And although it's impossible to quantify how much the non-compliant oranges degrade overall *possible* collective SVR rates, there's absolutely no doubt in my mind that if a trial was exclusively populated with your average hepatitis forum "medhelper", those SVR rates would be measurably and notably higher.
Anyway, no need to personalize what I said. If I recall Vertex put you in the non-riba group(?), and that was a mistake on their behalf. You should have been given the riba - no matter how compliant you were (or virtually anyone else was within that same group), you would not have cleared the virus without the riba...but that was not to be. So your non-response was obviously not because of non-compliance, it was because of being put into a bad (riba-less) regimen.
Hoping the best for you when you finally lay waste to your dragon.
Susie2007 - Prove 1 and Prove 2 are for tx naive people only. Prove 3 is for realpsers, non-responders, drop-outs, etc. To your point, NULL responder is an entirely different category. Null responders get no VL drop or something less than a 2log VL drop at Week 12 on SOC tx. You said that you are in this group. Again thanks for giving us the scoop from AASDL first hand.
Susan400 - Before being accepted into the Prove 3 trial you had major problems finding your past treatment records from a doc who had moved, retired, died or something. Vertex wouldn't accept you unless you coughed up the records, right? I'm curious....other than your honesty, how did Vertex know how many times you previously treated and with what drugs? My 1st SOC tx was with Doctor Local Idiot who changed practices half-way through my tx...we had a hard time getting records from him too. Prove 3 knew that I had treated though because Dr. Idiot referred me to the center. One last question; on Prove 3 Vertex is offering the real medicine to Group A who got the placebo and didn't respond...any chance that you get another try only with Ribarvirin this time? Right or wrong on Day 1 of Prove 3 I made my mind up if they didn't issue Ribavirin, then I knew that I was in Group C and would opt out Day 1 because of the early data of VX950's lower success without Ribavirin. I joined the trial to advance science but it's still my body, my family and my life.
Mremeet - How long have you been off Prove 1 tx and how are you feeling? I'm three weeks off Prove 3 and still have the Interferon "hangover" of that speedy sensation, sore neck & back. I too had the VX rash (not the rash from hell like you had) that cleared up entirely on tx. Now I get bits of what looks like the same rash only not as angry popping up in places where there isn't much body fat (hands, ankles, feet). It goes away after a couple days of hydrocortisone 10%.
That's a great point - without the riba the vertex is pretty much a wash. I think susan's rash was too bad for her to continue onwards, she was one of the lucky 18%. The girl can't get a freaking break.
Susan400 is a trouper and inspiration. How she endured so many treatments is beyond me. Andiamo1 too.
When I first read about the rash I was like, "How bad can that be?" It's bad and I had like 25% of what some people had. It drove me nuts as it moved around my body from place to place and always looked different. Lidex steroid cream finally cleared it up but the pharacist would only give me one tube at a time. I needed like a hand pump on a jug of Lidex.
I'll be 24 weeks post tx at the end of this month. I'm feeling great overall, basically I feel "cured" in every sense of the word. I feel better than I have since I was infected 24 years ago, it makes me realize what I've been missing all these years. The only after effects I seem to have had so far is that the joints in my feet and ankles hurt sometimes, especially when I get up in the morning. Makes me limp around a bit until I get warmed up. But that seems to be fading a little bit, hoping it'll eventually go away altogether (which I'm optimistic it will). Put on about 25 lbs since stopping the meds, but I'm pretty tall and thin so I wear it well. Food and find beer are my siren song now, I just gotta stay away from those rocks they're luring me to ;-) I also had a light rash pop up a few weeks ago. You could barely see it, but I could feel the bumps on my forehead and throughout most of my body, and it itched some. Fortunately it went away, but it did have me scared for a while there. In my darkest fears I keep thinking maybe I've permanently screwed up my immune system with all that IFN/riba/VX and prednisone/solumedrol I had to take...and "the rash" would somehow come back to haunt me with its long horrifying tentacles ;-) But so far I seem to be doing very well, I just can't get over that I'm in all likelihood SVR-ed and cured now. I still can't believe it.
Anyway, hope you're coming around real soon. Those residual "rashies" right after treatment are pretty normal for many folks, they'll probably subside in time. In a few months time after you learn of your SVR status, your biggest challenge will be figuring out what you want to do with the rest of your life!
Thanks guys, I guys I'm feeling over sensitive on this subject. Mike, as far as my records go, yes, you're right I did have one heck of a time getting my hands on records. I had some records, but the doctors had not taken good notes and the trial site wanted more. I had a pharmacy record, showing that I'd picked up and paid for the drugs (the different ones on different treatments cycles), I had some insurance paperwork showing where I've been approved for the drugs and then, the 6 mon. re-up, I had some labs (but, unfornately they were not spelled out w/adequate doctor's notes with them) and I had my biopsy reports and ultrasounds all my PCR's, things like that. The doctor's instead of dictating things like "Pt continues on meds, has had XXX amount of drop in her viral load, this is what's going on w/her LFT's and white cells..., blah, blah". I had records like from the beginning of treatment then, where it's just dictated-PT follow-up HEP-C at 3 mon. and then, another copy of a prescription for the interferon at 6 mon., but, not enough documentatioin as to what was happening with my labs and their decisions about my treatment and why they took me off, etc. And also, on a few of my earlier treatments, like from 1997-2001 time frame, alot of those records are missng or I can't get ahold of. In the beginning of my treatments, back then, they didn't take you off of treatments prior to the 48 day treatment cycle and my doctors were also only having me come in like once every 3 months with just getting labs monthly in between appts. Anyway, I did manage to have enough in my stack of documentation for them to convince the trial managers that I had treated and not responded. I had good records from my current doctor, but that was treating with the Infergen, and they didn't want that. They wanted Peg-Intron or Pegasys records. Anyway, it's sort of a sore subject for me and I guess I'm oversensitive about it. Susan
your point is well taken, I was in a trial, and did not know that I had the disease, nor did they test me, it was for a different disease I was being treated...however, having this disease probably effected my trial outcome.
I think the biggest concern with this disease, as it concerns the trials, is that a much larger percentage of indigent/still alcoholic people may be in the average trial for the numbers to not be effected by that fact, and their general state of declining health.
It's not so much to woorry with the avererage person; but I have noticed a lot of trial are even being taylored specifically to deal with alcoholics and their treatment.
In other words, trials designed just to deal with that group are myriad.
That is not to say
that a few would not make it into any trial, and perhaps skew the results downward because of the continual damage they create with their drinking. However, that will only mean the rest of us have a better than the numbers show chance, regardless of whether it's personal denial or out right lying.
In any case, It's very frustrating to see a trial you want into say treatment naive...yet if someone has treated bunches it would skew the results and really mess things up for the millions who might be helped by a new drug.
I'm very sorry you ended up in a non-riba equation, it seems now that the verdict is in on that outcome. Unfortuantely that's how all cures get discovered, there has to be good research, guinea pigs, and double blinds to get accurate stats on whether something helps at all.
I guess, when I see diseases where little children have to endure far worse trials for extra horrid diseases that one day may cure the most of them....well it helps us remember brave is a very special word, that's all.
haa this is funny i know this thread is old but i had to bring it back to life as someone just asked me how i might be getting on a trial for vx950 for tx naive when i tx'd before on a trial for virimadine 4 years ago...
i tried several times to get some records about that first trial to absolutely no avail after i was dropped i couldnt even get a return phone call from the trial people
... there is absolutely nothing that i can show anyone as far as results from this first trial so, as far as I'm concerned, I am TX NAIVE... what else am i supposed to do????? and, since i was never on SOC (peg/riba) i am tx naive to that...
i did mention on the phone to the current VX950 trial people that i was on a trial 4 years ago and they want to see me anyway ......but, im not mentioning it again when i see them this week, if they ask i will tell them exactly what i posted here but if they dont ask, im not volunteering
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