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475555 tn?1469304339

Trial pitfalls

Hi, everyone! It's been a looong time since I posted here, but I hope some of my friends in the forum will remember me. I'm the wise-a$$ (some say "funny") New Yorker with HCV gt1b A2F2 who's living in Buenos Aires, where my hospital isn't giving me tx so far.

A woman at another hospital called me a coupla days ago and offered to let me into their tx trial. It seems they're part of an upcoming international protease inhibitor trial and need subjects. She wouldn't answer any questions over the phone (natch) so I made an appointment with her. I want to get my questions lined up before going over there, which is the reason for this post. I know this stuff has been asked a million times before. So be patient with me, okay?

What are the main pitfalls of the trials, aside from that you aren't told which leg you're in?

I seem to recall that one of the bad things that can happen is that you have a side effect like severe anemia and sometimes they won't give you the meds to counteract it so that you can go on with the tx. Is that right? So should I ask if I can get something in writing about save drugs? (Maybe I should bring my lawyer with me...Ooops, there I go again...)

I guess another problem could be that their viral load test isn't sensitive enough to read down to a true "undetectable' amount (which I believe is now considered to be below 10/ml).

Then there's the question whether or not they're going to do the viral load PCR - even if they have the right test - at 4 weeks, to see if I'm having an RVR.

That's all I could think of. What are the other things I should ask about?

Help here will be much appreciated.

50 Responses
9648 tn?1290091207
1. what phase trial is this? (1, 2, 3?)

2. if you are on a placebo arm and don't clear will they give you the trial meds later so you have a chance?

3. do they give and pay for rescue drugs? (procrit, neupogen)

4. what is the name of the PI?

5. can you have a copy of the consent form (do they do consent forms?) so you can review it before you need to sign it

That's all I can think of right now but yesterday was shot day and . . . I'm shot.
751342 tn?1534360021
I'm in a trial, and I DO know which arm (or leg as you call it lol!). I didn't know before I got put in it, but I was told before I ever starting an Tx. The one I'm in has no placebo arms, so you get treatment, it just depends which arm your in, whether you get Peg/Riba only or the study drug in addition to Peg/Riba.  I am in Peg/Riba only. My trial does Pcr at 2, 4, 8, 12 and I think monthly after that, if your still in. I will get option to add the study drug at week 12 if I made the 2 log drop, but not UND. If you don't have the 2 log drop at week 12, Tx is discontinued. I was told my doctor will prescribe rescue drugs if I need them. I'm in one of the Schering-Plough studies by the way. Hope it helps some, even though I'm not sure if things are different outside of US.
475300 tn?1312423126
Hey, I do remember you.  I can't help you with your questions but am wishing you luck!!

Avatar universal
I'm the wise-a$$ (some say "funny") New Yorker with HCV
I probably would have stuck with "wise a$$", nevertheless :)

Of course you are remembered. How many people commute from NY to Buenos Aires to get their teeth cleaned and as long as they are down there have their liver's checked at the same time?

As to the trial (Buenos Aires or NY?) first of all you want to know what particular trial you may (or may not) be getting into. If you can get the specific name of the trial before you appointment, then you will have a little more heads-up time to do some homework and maybe ask some questions here to some who may have been in that particular trial.

Some things to be considered in a trial are what drugs are used, what doses, what phase trial it is, how many "Arms" or subgroups and what is the protocol for each Arm.

You also want to know if helper drugs (Procrit/Neupogen) are allowed and with what criteria. Also, when you will be tested for viral load, with what tests will be used and at what sensitivity.

You also want to know any "stop" criteria such as if you don't have a certain viral response by week such and such. Another question might be what will you be offered if you don't meet the requirements and/or relapse. Will they roll you over into another protocol or simply say sayonora.

Anyway, a lot of these answers should be in the trial particular which hopefully you can get in writing at your meeting, but if not perhaps someone here can fill in some blanks if you give us the trial's name. If I remember correctly, you still had not gotten a biopsy (or perhaps it was a recent biopsy?) . Any movement in that area?

As to "pitfalls", first and foremost it's a "trial", in other words you're more of a guinea pig than the rest of us guinea pigs who are taking drugs out of trial. You also could end up in a placebo arm, meaning you won't get the super PI that the trial is focusing on. Also, you might get the PI but at a less than optimum dose or time frame which may not be discovered until the trial is over. Helper drugs may not be available and if you don't like your medical team youre more or less stuck unless you drop out of the trial. That's for starters. Still, some very promising trials out there and if someone finds the right trial to match their stats it seems a very reasonable way to go these days. Lots of success stories here.

All the best,

-- Jim
476246 tn?1418870914
I don't know anything about trial, just wanted to give you a big 'holllllleeerrrr'. Good to see you posting my friend.
Avatar universal
Hi Mike, no advise either because I'm not in a trial but just want to say Hi and hope you are well.   Hmm, I notice all us ladies just want to say Hi.  That should make you feel good my friend.

Avatar universal
I may not be a lady but I also want to say hi.

Avatar universal
Nice to see you again.

Request the trial agreement.  Much will be spelled out in that.

Look the trial over also in Clinical trials (could it even be FDA?) but generally speaking there will be lots more info in the trial agreement.

I would read up on the drug, compare it to other drugs and see what else may be in you area.  You don't say; could this be FDA approved in B.A.?  I assume not but you may also have to evaluate the agency.  Trials are probably safer in the USA.  The downside with safety is it can also take more time for approval.  You may not want to participate in a trial where intro to approval takes 16 months.  ; )  I joke but you follow my drift.  You need to make sure that you are comfortable with the approval agency.
If it's the "chinese FDA" I might pass.  ; )

Google the PI and see if you can research it.

Generally I agree with whatever everyone else said.  You have to think the process through; what happens when "X" happens?  When "Y" happens, etc.  

A few examples; having rescue drugs paid for or allowed makes no difference if they reduce dosing first; what are the cut-off levels?

IF you are exposed to a PI and get underdosed, or pulled of the trial before clearing, or treating at sub-optimal levels so that you are more likely to break through, respond slowly or relapse....then you may be burning a bridge that you will need in the future.  If you fail this trial and were exposed to PI's you may come to wish you had not participated.

Play detective and you can always report back here with questions but I would have the agreement first, the name of the compound before even casually considering it.
I hate to question the agency but that could also factor in my decision.  There was an absolutely *from hell* trial about 3-4 years ago that pretty much damaged or killed everyone who got the compound. It was phase 1, caused extensive organ damage, and the company went bankrupt.  Lest you think it can only happen in "the third world"....this happened in Great Britain.

Sometimes it's good to get the placebo...  


751342 tn?1534360021
Willy's right about that agreement.  I've had about 3 addendums to mine so far due to some minor change in verbage.  I have to intitial every page, and sign and date the last page. My study coordinator gives me copies. I've never had to ask. They spell out the study in detail, and with the signing, I think they really want you to have read it.  I think mine actually is a clinical trial. Not sure of the difference?? I can't complain about it. I'm sure even with the good insurance that I have, being that there are no generic equivalents of these drugs, I'd be paying a pretty penny. Getting free meds and being watched a bit closer because of the study.  
Avatar universal
Hiya Mike.  Good to hear from you again.  Trials have "arms" Mike .. not legs. :)

I'll end up repeating some things but it's too much work to go back and look through everyone's submissions...so my apologies for any repeats.

Get the name of the drug and look at the past trial history of the drug - you're looking for side effects and you're looking at statistics on effectiveness.

Read the trial agreement and look closely at the various arms.  See if there are any arms that are dealbreakers and that make SOC look to be a better option.  Check out the interferon and ribavirin dosages and compare them to SOC to see how much of a risk you're taking.

Ask if they'll be letting you know the results of your PCR's and when.  Some trials won't tell you the results of your PCR's at all until you're well along in your treatment.  My trial told me the results of my PCR's all the way through from Day 1.  

Ask how often you'll get a PCR and if it's qualitative or quantitative and what the sensitivity of the PCR is.

Ask about rescue drugs - do they allow them and will they introduce a rescue drug before they will reduce dosages? Which rescue drugs will they allow and who pays for them?  How long will it take to get them if you need them?  Here in Canada, it can take awhile to get the government approval to cover the cost of the rescue drugs so you're either paying out of your pocket for awhile or if you can't afford them then you have to wait to get them until the approval goes through.

Ask about dosage reductions - what scenario would necessitate a dosage reduction?  For example, at what point will they automatically reduce your ribavirin or your interferon or both as in what's their threshold for your hemoglobin (ribavirin impacts this) or your ANC - Absolute Neutrophil Count (interferon impacts this).  In my trial, if HGB dropped below 10.0, it was automatic riba reduction.  If ANC and lymphocytes dropped below certain amounts it was automatic interferon reduction.  The level at which they will force a dosage reduction on a trial is usually higher and more cautionary than it would be on SOC.  They're dealing with a trial drug combined with SOC drugs and they don't call it a trial for nuthin.  So trials are more cautionary when it comes to how much risk they'll take with these things.  

What Phase is the trial?  Phase III trials are the best of course because they've got most of the kinks worked out compared to the earlier Phases and are refining their best dosage combinations by that point.

Who pays for the drugs?

If you end up relapsing or not responding for whatever reason, do they offer a rollover into SOC at their cost?

Is the drug known to build up a resistance to it?

At what point will they consider that treatment has failed?  

Study the arms of the trial, Mike.  See if there are any that are too reckless.  And study what's known of the drug and it's past history.  Pay really good attention to that, Mike.

And...post it here.  I did that before I went on my trial and I got really good feedback.  Everybody had different opinions and insights and it helped broaden my thinking towards making a decision that was good for me.

If I remember anything else, I['ll post it.  If you wouldn't mind, post the details of the trial.  It's good to know what's going on in the world of Hep C out there these days.

Take care and all the best to you, Mike.  Nice to have you back again. :)


233616 tn?1312787196
of course we remember you...look 2 main things....if it's not phase 3 run, don't walk away.
Unless you are desparate or at deaths door you don't want be the first of 20 human guinea pigs...sometimes what looks good in a petre dish or mouse turns out to be Darth Vader in human tissues.

2. All the PI's knock the virus out faster, which is why everyone is pushing in invent the first great PI....but PI's also have a nasty rep for knocking the blankety blank out of your white cells...and the riba, usually still on board albeit at reduced dosages is heck on the red cells....so make sure they will allow rescue drugs. You might recover or survive ok without them if treating only 6 months, but don't bank on that, especially with the PI's..
Usually on SOC people see a gradual drop in WBC but NOT true with PI's..nosedives are common there.
plus a couple PI's have been pulled in phase 1 or 2.....I'd want to know which company was making it and whether they had substantially changed the molecule from the one pulled...if they had the bad drug...sometimes they just remove one isotope and try again, until they get it right..it would be better to get in a good trial that treats their patients compassionately...like the Shlering-P does.

anyway, those are my 2 biggies, phase 3 and recue drugs.
Hope the study can help you.

475555 tn?1469304339
Thanks a million, everybody. This is a great help. I´ve got to run off to the hospital now for my interview, and at least I feel ready to ask the right questions and stick up for myself. I´ll post back with some answers to the above posts, and a few more questions, after the interview.


475555 tn?1469304339
Hi, everyone! I'm back with the trial particulars.

First I want to thank you all again for the help with questions for my trial interview. I went in there not only prepared but secure in the support of all the great people in this forum, which makes all the difference in these tricky confrontations with the medical profession. Reading all these warm and generous replies I felt again that wonderful feeling of belonging that I felt when I joined the forum a year ago, a feeling so nourishing that it's surely the best of all therapies.

I also want to thank especially Denise, Jim, Marcie, Trin, Willy, Trish, and MerryB for remembering me with such kind words. Being remembered like that is awfully nice, and flattering. I may have to revise my image of myself; maybe I'm not such a &%$# after all...

Now for the trial. It's a phase II, double-blind, placebo-controlled trial of Boehringer-Ingelheim's protease inhibitor BI201335. There are five arms (I personally prefer "legs" but appreciate the correction) designed to test dosage and timing, quite similar to other protease inhibitor trials.

They gave me the trial prospectus which I have now read, for whatever it's worth (not much, as it's pretty confusing).

I don't know if they will give me a copy of the consent form prior to signing it. Doesn't really matter, actually (see below).

They weren't very forthcoming with answers to my questions. They did tell me that all blood samples go to Germany for analysis, but that leaves a lot of holes, for example: who will do the weekly exams?, who will monitor my side-effects?. Stuff like that. And when I asked about rescue drugs, they seemed reluctant to commit. They suggested maybe I could get them from my regular hospital where I'm a health plan member, which is ridiculous. When I put pressure on, they admitted they had the rescue drugs there at the study hospital, but I had to twist their arm to get them to say they would give them to me. And when I asked if having anemia or other adverse reactions would curtail the trial or result in dose reduction, they wouldn't answer except by saying that "Boehringer makes all the decisions".

Needless to say, I was not happy with the interview. I had the feeling they were participating in the trial strictly for the money (Boehringer pays the "fees" of the doctors conducting it), and that their attention to patients would be minimal. It certainly was in this first interview. They made appointments for me and fourteen others at the same hour, and we had to wait in a room with no windows, no air conditioning (it's summer here), no telephone, and no water!

Furthermore, I now suspect that the reason this public hospital initially refused me antiviral therapy was so that they could get me into one of these trials. When I left the clinic yesterday I chatted outside with a patient who's on therapy for the third time, no problem getting the meds (I accompanied her to the hospital pharmacy where she collected her weekly doses of Pegasys and Copegus!). She said she knew lots of people getting treatment there and couldn't understand why they had refused me.

By the way, this is the hospital that asked to borrow the biopsy specimen taken at my health plan hospital in order to do their own pathology of it, and then didn't return it, thereby getting me into trouble with my own hospital. Apparently something untoward happened to the specimen in their hands and they don't want anyone to see it. They may even have thrown it out. So If I need to have a second biopsy in a couple of years, my hospital's pathology department may refuse to do it because I never returned the original one. So as you can imagine (and even given that I am a cynic and long-time hater of doctors) I was not exactly well-disposed towards these people to begin with.

As a final red flag, I found the following in an online news item (http://www.hivandhepatitis.com/2008icr/aasld/docs/111108_c.html):
"Investigational HCV Protease Inhibitor BI 201335
• A majority of patients in all dose groups experienced viral load rebound during the first 14 days of monotherapy"
Cheery, huh?

So, all things considered, I'm not going to do the trial. I'd rather wait until my regular hospital decides to give me tx, even if it means waiting another couple of years for approval of a good med combination. I've got analyses coming up in April, so I should have a better idea how the disease is progressing then. And I might even be able to convince the people in Sevilla to do follow-up FibroTCs, which are much less invasive than biopsies. (If someone can tell me how to post a .pdf file to the forum, I will post the results (images) of my FibroTC, which is a very interesting alternative diagnostic for fibrosis.)

Thanks again to everyone for your help with this. You guys make all the difference. I love ya.


475555 tn?1469304339
Hi, GreatBird! Thanks for the suggestions. I hope you are feeling less shot today.

475555 tn?1469304339
Hi, Annie. I hope your trial is going okay.  What's the study drug?

I was interested that you have an option to add the study drug later. I never heard of that before. What's the rationale for adding the study drug if you have a 2log drop but not if you're UND? Do you know?


475555 tn?1469304339
Denise!, my favorite GSDgirl (whatever that means), how the heck are ya?

I thank you sincerely for your wishes of luck, Deni. As a matter of fact I do seem to have a lot of luck. Unfortunately, it's mostly not of the good variety. However, as my shrink says, it's all my own fault. (I accept that. I am making progress. My shrink likes me. I pay the bills on time and never argue. How can you argue with a shrink?)

Tell me, Denise, what's it like in Pittsburg these days? After being disindustrialized, the last thing that city needs is an economic collapse. Do you still get running water and electricity? Is there garbage disposal? Can you go out at night?

I may decide some day to return to the States, so your replies to these important questions will be studied carefully.


475555 tn?1469304339
Hiya, Jim! So, you remembered my crazy story about going to Bs As for my teeth and getting dioagnosed HCV+ as a sort of "side benefit" of the trip? I feel kinda embarrassed by the whole thing, frankly, and will appreciate it if you wouldn't bring it up again  because the lovely demoiselles in the forum who seem to like me for some reason might decide, realizing how coocoo I am, that it's dangerous to have anything to do with me.

Kidding aside (?), I did finally have a biopsy. The pathologist gave it the following:
IAH: A:2, B:0, C:2, D:3 = 7/18
Estado 2/6
Metavir: A:2, F:1

Not sure what all these sawbones hieroglyphics mean, but my hep MD said I had light to moderate fibrosis and moderate inflammation. How bad is that? Your guess is as good as mine.

Thanks for all the suggestions and info.

Mike (Guinea Pig XR49T00825)
475555 tn?1469304339
Marcie, my dear, how goes it in Copenhagen? Or are you back in the tropics?

You never answered my last note, you naughty girl. I know, I know, your social life is just sooo busy...

475555 tn?1469304339
Hiya, Trin. How's tricks? (That´s a suggestive salutation from the netherworld of my mis-spent youth.)

I don't know why the ladies here are so friendly to me, Trin. Do you think it could be that they sense I need mothering?

475555 tn?1469304339
Hi, Port. Now, just exactly what do you mean by saying that you may not be a lady? Tsk-tsk. Would you care to enlarge on that? Details would be helpful.

475555 tn?1469304339
Hello, Willy. Thanks for the good words.

You have put the fear of g*d into me with your tale of mayhem in Great Britain.

Any idea where I can get info on the effects of failing a protease inhibitor trial, especially as regards drug-resistant viral variants? These protease and polymerase inhibitors haven't been around very long, but there must be some studies of the consequences. I wonder if they don't make your infection a whole lot more intractable if you happen to not clear the virus. I think something of the sort happened with HIV, didn´t it?

"Sometimes it's good to get the placebo..." I hear ya.


Avatar universal
I have not tested these individuals sites but I think you can upload files for public viewing for free.


475555 tn?1469304339
Trish, you sweetie-pie, have you reclaimed life yet? For that matter, is life truly reclaimable? It would be good to have some clear evidence of that, if you have any.

My own experience (admittedly a particularly sad case) has been that no claims at all can be made on life, and that the so-called human species is in itself a horrendous epidemic. But we would have to question the frogs and dandelions about this.

Arms? Not legs? Why?

Your admonitions about rescue drugs are well taken. Thanks. All your explanations are a big help in sorting out so many preoccupattions, whether I do a trial or wait for approval.

If there's nothing in the trial particulars about rolling over into SOC if you fail, does that mean they won't do it? Or should I query them on every point? (Even if I don't do this trial, I want to make up a list of all necessary questions, for the future.)

I don't know how to post the trial details except to scan the document they gave me, and I don´t have a scanner. Anyway, it's in Spanish (translated by the usual aphasics).


475555 tn?1469304339
Hi, Merry! I have decided to run not walk away from this phase 2 trial, as you suggest. I am good at running away.

Still, it would be nice to get revenge on them for the shoddy way they treated me at the interview. So I may not so much run as zig-zag, fake to the side, and dart over the line to kick their captain in the shin before speeding out of their grasp.

I considered blowing the whistle on them to the Boehringer boys in Berlin, but they have my address and I fear retaliation from the Argentine Medical Hit Squad.

So, a quick one to the shins and I'm away.


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