rescue drugs and trials

[Andiamo1]

Earlier this week, I had a message from the research coordinator that my Hgb had dropped to 9.5 and that I should decrease Riba to 800 mg per day.  I have done that and withing two days I am out of bed and taking short walks -- on level ground - LOL.

The bad news here is that I have increased the probability of relapse by lowering one of the important drugs.

I once posted that I thought rescue drugs were banned in the trial strictly based on the cost to Vertex, and many people disagreed.  I still believe that is the case: the purpose of the trial is to determine how the trial drug will perform in the environment in which it will be used; clearly, procrit will be part of the environment once the FDA approves the drug.

Vertex has given the trial participants a long list of drugs that interact with Telepravir and should not be taken; Procrit is not on the list.  I know people want a pure environment, but there is no such thing.  We humans live in a polluted environment and we take many other drugs, so why pick on Procrit?

I think the answer is money: Procrit is so expensive that Vertex would have no choice but to provide it to trial participants in order to have a level playing field.  If they did not do that, people with good health insurance would get the drug, rich people would pay out of their pocket and poor people would not get the drug.  This would not fly with the FDA, since the trial is biased against poor unemployed people.

I am curious about what you all think.

[Andiamo1]

I agree with you and if this had happened early in treatment, I would probably have found a source of Procrit.  As it is, I am at week 23 now, so I will tough it out until I can have procrit.

In this trial, you run the risk of Vertex discovering that you took it and bouncing you out.  I am sure the change in Hgb levels would get their attention.

[sfbaygirl]

I always had a problem with no rescue drugs on the trials, wouldn't do it knowing this is the case. As a relapser, I KNOW I needed them on tx, and wouldn't expect the next tx to be different. I agree with those who say 'it's your body and you should look after yourself'.  Yes, I know it's going to skew the data for the trial, but it were me and I needed a rescue drug to finish tx after many, many weeks of hell, I would find a hemotologist to give them to me.  Boosting blood counts doesn't have an effect on the VX.  Perhaps it's dishonest, but frankly it's my body, my tx and potential SVR. Why put yourself through this only to have to quit b/c the trial won't allow rescue drugs?  My life, my chance at SVR.  I know others have done this on trials....okay maybe I'm bad,  but that is the main reason I doubt I will go into a trial.  

[Andiamo1]

Interesting - this was the last product I built for Broadview Networks.  My partner did the provisioning and network management and I did the billing system.

[APKhaos]

This whole discussion seems to be ignoring the possibility that HGB drop is entirely due to SOC drugs, particularly Riba. As I said above, my HGB dropped rapidly after starting SOC + VX-950 and bounced along between 9.8 and 10.2 the entire 24 weeks of treatment. The last 12 weeks were SOC ONLY. Stopping VX-950 at 12 weeks had absolutely no impact of HGB levels. In fact, they tended lower in teh last 12 weeks WITHOUT VX-950. That's just one sample, but the point is obvious.

As for the 'no rescue drugs' trial design, the anwer probably lies in keeping the trial data free of potential interactions caused by additional drugs. Its flat out not fair to the subjects, and anyone in Andiamo's position has every right to be pi$$ed, but I suspect its nothing more sinister than protecting the integrity of the trial data.

[geterdone]

Startups are very had even with the best product on the block. For a distraction, read up on this company in your spare time, hehehe, no pun intended. Opsware Inc. great story and will be for some time to come but it all came down to marketing and networking.

jasper

[Willy50]

Whoops, hit the wrong key and it "sent".  I'm off to work but no worries you came across fine.  

Willy

[Andiamo1]

Whew!!!!!!!!!!!!  THANK YOU.

[geterdone]

After reading the thread I understand what you’re saying about the two rescue drugs. It has nothing to do with the trial directly or FDA at this point, it is business and a marketing thing right now. The vx telepravir has to stand on its own right now to find the lowest possible tolerance and it seems that the hemoglobin is one of the stumbling blocks at this point of the trial phases. The people in the trial will suffer the most because of it but after the approval of telepravir, if it should happen, I am sure these two will be the rescue drugs of choice. Just my take on the thread.

jasper
  
LOL... different language

[Andiamo1]

I hope that last comment didn't sound cross.  I appreciate that you took the time to think about the issues.  My problem is TX and lack of sleep, so that I feel very inarticulate these days.  

It feels to me that I am speaking a different language than everyone else. I spent a lot of my career managing whacked out computer scientists and mediating design disputes over topics much more complex than this, yet I can't influence any thinking on this topic.

I think that I can easily be wrong on this and Flguy provided a link that made me believe that part of my theory was wrong.  But no one addresses the main issue of why these two drugs are treated separately from ALL  other drugs.

[Andiamo1]

I am going to give up on this, since I must be very inarticulate not to be able to describe a simple problem.

But I can't resist one last try:  Evaluating the compound can't be the reason these drugs are not allowed.  They are singled out over all other drugs.  Many drugs are advised not to be used, since they interfere with evaluating the compound; systemic steroids for example.  There is a long list of these drugs and procrit and neupogen are not on the list.

Again, these two drugs are unrelated chemically, so why these two?  the only thing they have in common is price.

The FDA does not dictate the details of the trial.  They only look to see if it is structured in a way to give an accurate picture of how the drug will perform in the real world.  Since Procrit and Neupogen will be used after FDA approval there is no reason to exclude them from the trial.  I participated in the earlier trials of Pegasys, and Procrit was allowed; I took it!

[Willy50]

Let me start by saying I know nothing.  : )

I think the issue is about clearly evaluating the compound.  I don't know how much say Vertex has in trial design.  Maybe lots or maybe they follow what the FDA recommends.

It may be that for drugs that are already approved the FDA won't insist on certain protocols.  In this case however Telaprevir hasn't gone through umpteen trials; this is the first time thru the blocks.

I think this could be about statistical certainty.  Think of a few classes you've had in school.  A class where everyone passes with A's and B's does not really have the tests set up well; likewise with a class in which all flunk.  If the tests the grading is set up well in the end there will be a spread of results.  

You are correct that if all rescue drugs were permitted that there would be some sense of how effective the treatment was.  The point of the trial however is to gain as much clarity about the exact efficacy and exact toxicity of the compound when taken in certain doses with (perhaps in this case) interferon and ribiviren.  Each drug and compound added to the mix tends to muddy the meaning of the results.  The results are the actual purpose of the trial.  Curing people along the way is a happy byproduct of the testing.  Restated then, they could cure more people but the results and meanings of the trials would be less clear.  

It may be that in Phase 3 other new changes may come into play.  The use of rescue drugs could become one of them if sufficient information has already been gathered.  That will be up to the FDA and Vertex.  You are correct that information can be gleaned either way.  I'm simply guessing that if for instance you were trying to discern; does TVR cause anemia...... the use of procrit would muddy the meanings of a trial.  

A final point to make is that if you google any of the rescue drugs you'll see that they can all provide their laundry list of symptoms.  (remember the black box warnings for TX; it's endless  : ) )

The FDA not only has to track the trials and ongoing symptoms but any complaints which can arise FOLLOWING the trials.  If you are an FDA official you have to be concerned about what happens about both.  

By the way..... have you noticed how many threads there are about anemia right now?  It's a very common ailment in people who treat.

APK, interesting to read about your background.  We are a diverse group.

best,
Willy

[Andiamo1]

and by the way, procrit was not banned in the earlier trials - I took it in the phase III pegasys trial.

[Andiamo1]

Hypothetically, you are the manager of vertex; what advantage is it to the company to ban rescue drugs?

Does that make the trial scientifically more accurate? If so, why just these two drugs that have nothing in common except high cost?

Level the field (what ever that means)?

Why not ban topical cream that treats the Vertex rash (it uses steroids and could influence the immune response)?

Why is it bad to include J&J in the trial and end up with approval for treating HCV with Procrit and increase the SVR rate with better compliance?

I don't have the answers, but nothing anyone has said provides a logical explanation IMHO.

[Andiamo1]

I feel much better.  I was only getting out of bed a few hours a day and now I am up most of the day.  I can take slow walks and enjoy it.  Not running any marathons, but definitely feeling better.

My starting Hgb was over 16 and last week was 9.5.

Eric

[geterdone]

I have a question, do you feel better since reducing the dosage of Riba from 1200mg to 1000mg? I ask this because I did just that six weeks ago, reduced the riba to 1000mg and it took about a week and a half to start feeling normal, well as close to it a possible. I had set a date to increase it back up to 1200mg next week and have a doc’s appointment next Wed. I had gotten a letter from the doc that said my enzymes are in the normal range and blood count is 42.3 and am happy about that but he did not send the lab work and will find out on the next visit. I am hoping that the ths are also back in the normal range as well and will confirm that it has bounced back. I hope what ever you decide is good for you.

jasper

[APKhaos]

I'm in the DC area. Even though I'm SVR, my drinking is extremely moderate.

I've led a couple of startups, and now I'm on the boards of several. There are major bear traps to be avoided as a startup. Having BTDT makes it possible for me to help these companies navigate their way through without falling into them. The scars of battle are vaulable after all.

[Andiamo1]

Are you in the NY area?  Perhaps if I reach SVR I can drink again!

I am in week 22 now and don't have another blood test until week 24.  I am going to raise the Riba dose back up to 1200 tomorrow.  I have more than enough drug to carry me until the next trip to the research coordinator.

Are you involved in a startup?  It was certainly an eye opener for me to see the negative impact banks and VCs can have on your business.  It is like doing business with the devil.

[APKhaos]

We should have a few beers and share VC war stories one day, ideally leaning against the pushpit on a nice broad reach :-).

FWIW, my HGB dropped from 15.9 to 10.1 in quick time, and bounced along the bottom between 9.8 and 10.low for the remainder of tx in Prove 1. Whenever it turned up <10.0, the trial coordinator called me in for a second CBC to confirm before dropping the Riba dosage. In every case, my HGB clawed its way back to a flat 10.0, so no Riba reduction. You should ask you clinic to do a second CBC before accepting the riba reduction. Also, there were other P1 lab rats who were given a Riba reduction but still achieved SVR, so all is not lost.

Also FWIW, there was absolutely no change in my HGB between the first 12 weeks of SOC + Telaprevir and the second 12 weeks of SOC only.

[NYgirl]

Please hang in there.  Once the virus is killed off it's killed off and if you were SVR at the time of the decrease it shouldn't matter that you did decrease.

I've never thought it was right that trial participants aren't allowed to take Procrit - especially if the insurance company will pay for it - but I do believe that Jim is right in this case, it's not just the money.  It is still in the "trial" stage.  When it is approved by the FDA and becomes a SOC drug - then there won't be any problem allowing the different rescue drugs because it will be out of the trial environment.  

I'm sorry your hemo dropped so low - many of us know what that feels like.  Lately I feel for some reason like I am very anemic...same exact signs and symptoms...but Im not on any meds so it's confusing.  But it reminded me how totally much it SUCKS and my heart breaks for you trying so hard and having to feel SO weak.

You are so lucky to have Mafalda there to love you and give you strength.  She must be a constant source of compassion, you are blessed.

Your friend, Debby

[Andiamo1]

The link provided by flguy convinced me that it isn't money, since Vertex has partnered with J&J and they make procrit.

I participated in the phase III trial for peg and riba.  It allowed Procrit.  Since Telepravir itself adds to anemia, the FDA might have made them keep it out in order to see the total riba/vx impact on Hgb.  It will be interesting if they allow it in phase III.

In the post to you about money I was trying to explain the way VCs and banks prevent you from spending money even when the ultimate prize is many billion dollars, sometimes in ways that make no business sense at all.  I was surmising that this might be the reason.

Eric

[jmjm530]

I think you're making my case in your above post. If you were to get Procrit outside of the study -- such as the other drugs approved on the list -- Vertex would not be paying for those drugs. They would be either paid by your insurance company or out of pocket.

In this light -- and others -- the  fact that Vertex specifically forbids Procrit and Neupogen, again leads me to believe that it has nothing to do with money but the way the trial was set up for FDA approval. Again, Vertex has to show that their drug combo at least equals or is better than SOC. The SOC FDA trials did not have those helper drugs. Another reason -- or perhaps related --  may have to do with getting a better handle on the side effect profile of these newer drugs.

I'm sure you will see follow-up trials allowing more liberal use of both Procrit and Neupogen.

[dointime]

Remember that you will have more information on how your virus is responding to tx when you get your VL results at the unblinding.  The earlier you went UND and stayed that way, the better your outlook for SVR.      
dt.    

[Andiamo1]

Those of us in prove 3 have been given a detailed paper on drugs to avoid, and those that can be used with caution.  Procrit is not mentioned in this list and it and Nupogen are the only drugs that are specifically forbidden under any circumstances.  This is not up to the administering medical center, it is part of the agreement with Vertex.

The only thing that is obviously in common between these two drugs is the high cost.

The coordinator told me that it is not that critical if I need to reduce the Riba dose at this  point.  She said that I am saturated now and a couple of weeks at a reduced dose will not be that critical.  I believe that no one can know that for sure and I don't want to take any chances.

thanks again for all the data and support.

Eric

[ladywhy]

ybonfield at earthlink dot net