Agree Roy.
Don’t think we can assume, based on these case-series in highly selected populations, that the “eradication” rate is >=90% or that SVR is a good surrogate. Also, although the studies were registered with SVR24 as primary outcome the FDA let them give SVR12 as part of the “breakthrough” designation so we don’t even have a particularly good surrogate.
Virtually all of the subjects in published studies had very positive treatment prognosis anyway. Over half of subjects had HCV genotype 2 which is the easiest to treat no matter what drug used. And there is certainly more than a hint in several of the studies of substantial relapse rates after SVR24 achieved (e.g. ~9% in NUTRINO.) I honestly think that most people are listening to the marketing drumbeat on this drug and not reading the papers for themselves. I’d be happy to have these drugs be the breakthrough that most people seem to think that they are, but in my opinion, currently there are a lack of data to support that position.
Cheers,
Valerie
Valerie J. King, MD, MPH
Professor of Family Medicine, and
Public Health & Preventive Medicine
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Center for Evidence-based Policy
Oregon Health & Science University
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From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of Poses, Roy
Sent: Thursday, July 24, 2014 07:08
But it is not clear that SVR is a good surrogate marker.
See: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961025-4/fulltext
and the Cochrane review it references:
http://www.ncbi.nlm.nih.gov/pubmed/24585509As an aside, given that hep C infection is a chronic problem and bad effects from it occur long after original infection, it is extremely strange that no one has ever thought to do a good RCT with long term follow up to assess clinical outcomes of ANY hepatitis C treatment.
On Wed, Jul 23, 2014 at 4:54 PM, Djulbegovic, Benjamin <[log in to unmask]> wrote:
But, if eradication of viral load is greater than 90% ( and we accept viral load as a good surrogate marker), would then single arm study be justified?
Ben
Sent from my iPhone(Please excuse typos & brevity)
On Jul 23, 2014, at 4:50 PM, "Poses, Roy" <[log in to unmask]> wrote:That seems reasonable, but certainly does not apply to this particular clinical situation and article.
On Wed, Jul 23, 2014 at 4:47 PM, Steve Simon, P.Mean Consulting <[log in to unmask]> wrote:
On 7/23/2014 9:39 AM, Poses, Roy wrote:
> I still don't see why case-series without any control groups are now
> regarded as credible ways to evaluate efficacy of therapy???I cannot comment on this particular example, but in general you can safely dispense with a control group when there is close to 100% morbidity or mortality in that control group. In such a setting, any improvement is painfully obvious and does not need a rigorous design or fancy statistical analysis. Also, it is pretty difficult and probably unethical to randomly assign half your patients to be in a group that has 100% morbidity or mortality.
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Roy M. Poses MD FACP
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