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Problems with boceprevir data?

13 Responses
137025 tn?1217768341
This is not Scherings first time with charges of data manipulations....more like just one more time they got caught.


Avatar universal
Saw my specialist today-he is at the leading edge of new drug development.
He knew about the drop in the Vertex share price in the light of the Boceprevir data.
Said that the Boceprevir data had been presented in an 'incomprehensible' manner.
Also said the compound caused a complication (don't remember the name) causing undesirable increase in white cells.Remains convinced Telaprevir is the great hope.
I am hoping to get in the relapsers trial end of the year.
137025 tn?1217768341
As a relapser, I am hoping for early approval for all of us non-responders.   The data is so very good from Vertex, I'm praying for a big dose of common sense to whack the FDA upside the head and let all of us that need the medication have it.  I can always hope.  Good luck on your trial....the combo treatment is the best chance any of us have right now.  

158241 tn?1237723123
there is one blog of a memebr from the VERTEX board and you are already sure there is manipulation from Schering? There is share price business from many sides. Relax and wait for the company's answers before you decide what is true and what is ffake.
137025 tn?1217768341
Well, I have read more than one blog...there are Dr. reports online also, asking about the numbers...plus the previous information on Scherings difficulties with trial data.  The share price business is kind of irrelevant to me anyway.  These things go back and forth, on somebodys whim.  

All I really care about, in a relaxed way, is that one or the other of these drugs is available to all of us very very soon.  I would prefer it was the best PI too, not the one supported by the biggest pharma and I'm sure all the bugs will get worked out in the end.  I really do "hope for the best", after all we have been thru, we deserve it.  That and the truth.

Avatar universal
As I recall there have been studies in the past that were exclusively designed for blacks, as is another part of these trials which these long time anti-S-P  hooligans are complaining about.   Given the unique differences in treatment response  of blacks compared to whites it makes very good scientific and trial performance sense to separate the two groups for research/clinical trial  purposes which allows for a more focused and more successful approach to the treatment of HCV infected persons of African decent.  That is good.

The alternative of inclusion would mean that black patients would not receive that special focus with specific concern for the distinct characteristics related to their  lower response rates, so it would not be a good deal at all for those individuals to be mixed in with the non-black group.  On the contrary this separate clinical trial would allow for a closer study of the treatment needs and best protocols for the black population.   There is no racist issue  here, Willow.  

There is also no 'manipulation of data' here  in the sense that false infomation is given to the medical and scientific communities,  but rather there is a lack of understanding and comprehension by some  and also those fanatics who will contrive  any conceivable issue in their waste of energy war against S-P.  It started over a decade ago with the bundling of Ribavirin, but the law of the land allowed them to do that.  

There is always manipulative sales propaganda from these leading corporations but that is part of  the nature of the beast.

The essence of the problem is the whole political and economic system, not just this corporation or that corporation.  

I'm too tired to write clearer thoughts about this but my advice to you is to not be lured in  and don't pay  attention to these anti S-P fanatics.  If you have been around long enough you should know their agendas like I do.  I personally don't have the time nor the energy for all of that mostly contrived inflammatory nonsense.  What good is that going to do for me or you?

I'd rather be sitting outside watching the wind in the trees, while hoping for a new medicine that will work for me but for now I am going to get some sleep



Avatar universal
I would think that members on this board would want to know factual information about the leading HCV drugs in trial.  So, posting clear inforamtion about problems in the data for one of the candidates would be important news and not simply labeled as Schering bashing.  

At any rate, the information on the problems in the boceprevir data is out there.  So, caveat emptor.

158241 tn?1237723123
QUOTE Willows:
"The share price business is kind of irrelevant to me anyway."

Profile Willows:
"Interests: the stock market,"

Avatar universal
thanks for posting. I agree that all information is worth looking at, but as best I can tell there's no serious discrepancy between the Aug 4 press release and the Milan EASL presentation by Kwo, either as summarized in the abstract on the EASL site or in the (more complete) slides from that presentation as archived at hivandheaptitis.com.

From the slide 8 , SVR rates reported at EASL for the 28-wek arm were 57( lead in) and 55 (no lead in); in the 8/4 press report they are given as 56 and 55. In April, SVR-12 data was only available for the 28w arm, now that the 48w arm numbers are out, we know that 76 of the 103 originally assigned to the 48w  arm, or 74%, reached SVR-12. This is an ITT statistic so is not affected by discontinuations. The actual SVR rate among those who actually completed tx out of that 103 is presumably better.

Total discontinuation rates( slide 12)  as released at EASL were 28% with 11% due  to adverse effects . Slide 13 gives the breakdown it's the all too familiar list of complaints,  but the only category where they did worse than SOC seemed to be  hair  loss (34% vs 26% SOC)

Agreed that Schering's press release is a bit flimsy, for  example as noted  earlier, it says nothing about the low RBV arm. However, my take is  that press releases come out of marketing and thus are intrinsically spin-modulated. The actual data, as presented at EASL, with full results presumably to be released at AASLD'08 seems sound.  The final check should be what gets filed wih the FDA.
Avatar universal
Thanks for the intelligent reply.  

After reviewing the EASL presentations and the various press releases and info on a number of websites, I've identified three problems witht the boceprevir data.

The first is a design issue.  The boceprevir trial was open-label and thus is not as reliable as double-blind and would probably in this case lead to higher SVRs for the experimental arms and greater spreads between the control and experimental.  I say this becuase those in the experemental arms would have a significant incentive to struggle through a/e's, while the control would not.

The second is probably the most important and deals with the two 48 week arms.  I hope you would bear with me and if I am missing something, please point it out. Slide 12 that you mentioned above shows an average 27% dropouts for the two 28 week arms.  So, what would you expect for the experimental 48 week arms?  At least the same! And likely more!  But, the recent pr doesn't give the total drop out rates, it just gives a range of discontinuations from a/e's across the four experimental arms - 9 to 19%.   The two 48 week arms had SVR 12s of 66 and 74%.  If we just added the average total dropout rate of 27% from the 28 week arms, we would get 93 and 101%.  But each arm should have three groups - discontinuations; SVR; and failures.  But the 93% would allow for only 7% failures and the 101% for no failures.  So, something seems goofy to me, as I would expect failures to be 15% or more.

The third issue has to do with 16 missing patients in the no lead-in arms.  Basically all of the data up until the recent PR had 226 patients in the no lead in arms.  But, the PR has only 210.  (Coicindentally the 28 week arms also add to 210, but that is not relevant.) The relevant issue is that all of a sudden we go from 226 to 210 in the no lead-in arms.  As you point out this is ITT, so there is no excuse for dropping out patients, which were there as of the EASL abstract.  Since Schering is decreasing the denominator,the impact of dropping out 16 patients is to increase the SVR rates in the press release for the no lead-in groups.

Feel free to logically and rationally point out the errors of my ways and calculations.
Avatar universal
agreed it's frustrating the release of data is so incomplete, however this seems to be a feature of all clinical trials. My preference would be to make  release of the underlying (anonymous) data a condition for journal publication. One could then calculate whatever summaries seemed relevant.

WRT the points you raise

- yes, double blinding would have been preferable, but in fact , at least in the 28w arms, the total discontinuation rate in the PI arms is about twice  the 14% of the control arm(slide 12). So it seems frequent bailout in the control group was not an issue

- agreed that the total discontinuation rate in the 48w arms  would be expected be   at least 28%, but that's only an assumption, I don't see how it can be used to show their reported stats are invalid. We don't yet know what the disc. numbers are in those two arms, and small unexpected variations are not unusual (eg the number of breakthroughs is lower in the control arm!)

- the 226 vs 210 is a puzzle. The EASL abstract (from the EASL site)  references 595 patients divided into 206 lead, 226 no lead, 59 low RBV and 104 control. Kwo's slides also reference 104 control, and repeatedly identify the 28w lead in at 103 and no lead at 107. Combining the two sources would imply 48w lead in arms as 103 and no lead as 226-107=119, however the press release only references 103 for the 48w no lead-in.  Thus the 74% ITT for the 48w lead-in arm is consistent, but for the no-lead in arm the SVR rate would be 68/119=57% rather than the reported 68/103=66%.  I expect they will clear this up those missing 16 no lead in patients by AASLD; maybe they found some (valid?) rationale for eliminating them from ITT.
137025 tn?1217768341
Wow, you read my profile.  I'm kind of creeped out in a way.  If I invested too much energy in the fluctuations of the stock market...I would be curled up in the fetal position in the corner.  Having Hep C does that to me sometimes, but i work hard against it.  

I DO invest a lot of good time and energy around researching both new drugs, (also on my profile), the stock market AND my grand kids photos (also on my profile).  Next time, please make a comment about how cute my grand kids are.  It is so much healthier and friendlier too.  

I'm feeling the need to make a comment about being an anti-SGP "hooligan" but I kind of like the name.....I'm a hooligan.  An acceptable accomplishment at 55+!  


Avatar universal
Yes, I recognize those assumptions can bite you in uncomfortable places.  And partially for that reason I wouldn't be too comfortable with the data from an open-label study.  One can assume that all is OK because there is a spread of 2x.  But, that is an assumption.  I suspect that due to the open-label nature the SVR in the experimental arms is significantly lower than the  advertised number in the PR.  Is that a suspicion or an assumption.  -:)

As far as the discontinuation rates in the 48 week arms, if the discontinuation rates end up being significantly lower than the 28 week arms, what competent researcher would put any real faith in the study?  But, if the 48 week rates aren't lower than the 28 week ones, the numbers for the 48 week simply won't compute.  So, on the face of the published evidence and not resorting to assumptions, I contend there is something wrong with the 48 week data in the PR.

P.S.  I suspect if we put trust and suspicion on two ends of a pole, you would gravitate toward the trust end.

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