Roy and all evidencers.

The scientific method of Galileo has been subverted before our very eyes.

Galileo observed, described and then produced a hypothesis or theory which he then proceeded to test with an experiment. This model has served us well in the last 400 years with a few exceptions (the already cited penicillin for example).

What we now witness is a fundamental subversion of the order (I am not going to call it a paradigm shift) of things. Observations are fact, case-controls, case series, cohorts (even retrospective and datalinked ones) are being held out as proof. Trials are for regulators, they say.

The origin of all this is complex and partly known. In the Tamiflu story as we began uncovering the extent of reporting bias affecting the clinical trials that had been used to make policy and justify stockpiling, decision makers turned to observational evidence (of universally recognised poor quality) as props for their unchangeable policies.

It is a sad parable of the world we live in.

Best wishes,

Tom.

On 24 July 2014 16:33, Valerie King <[log in to unmask]> wrote:

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

Director of Research

Center for Evidence-based Policy

Oregon Health & Science University

Mailstop MDYCEBP

Suite 250

3030 SW Moody Ave.

Portland, OR 97201

Voice: 503-494-8694

Fax: 503-494-3807

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www.ohsu.edu/policycenter/

Twitter: @drvalking

 

 

 

From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of Poses, Roy
Sent: Thursday, July 24, 2014 07:08

To: [log in to unmask]
Subject: Re: Since when did case series become acceptable to prove efficacy?

 

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/24585509

As 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.

Steve Simon, [log in to unmask], Standard Disclaimer.
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dares to call itself average at www.pmean.com/news

 

--
Dr Tom Jefferson
Medico Chirurgo
GMC # 2527527
www.attentiallebufale.it