RE: Reporting Modeling Results
Mark / James,
Just to clarify. The RCT performed on the back of the PKPD modeling papers
Steve highlighted showed decreased adverse events (bleeding) without loss in
effectiveness. So, I think we did show improved outcomes for an example
where there was a huge clinical need to do the work due to a less than
adequate drug label for the obese and renally impaired. Even with extremely
talented people in the industry and the regulatory authorities, dosing for
special populations with this drug was inadequately addressed to the extent
that many physicians were refusing to use the drug.
I also think that it is worth noting that many 'Clinical Pharmacists' are
employed specifically to dose individualize, and are often funded by medics
to do the job. I speak for the UK as that is my main experience, but I am
sure these services are offered worldwide. Specifically, warfarin, HIV,
lipid, heart failure clinics are commonly led by pharmacists to dose
optimize. Resources are available in hospitals in the UK as such
interventions have been shown to reduce readmission rates. In a typical UK
hospital about half the pharmacists are now funded from outside of the
'Pharmacy' budget.
Cheers
Bruce
----------------------------------------------------------------------------
--------------
Bruce Green, School of Pharmacy, University of Queensland, Australia
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On
Behalf Of Mark Sale - Next Level Solutions
Sent: Saturday, October 27, 2007 7:22 AM
Cc: 'nmusers'
Subject: RE: [NMusers] Reporting Modeling Results
Steve,
Thanks for the example, there are lots of examples like that, I now
realize, all you have to do is go to the annual meeting of ASCPT. and while
I certainly believe that good pk targeting is useful, I assume you didn't
actually show an improved outcome. But, there are examples of pk/pd clin
pharm studies that do show outcome, like Lou Cantellinas work with
terfenadine (and grapefruit juice/emycin).
I don't mean - at all - to suggest the pk work done in academics
(post-marketing, without industry or regulatory support), but I had to take
exception with the assertion:
>Regulatory and market! ing are minor shadows in the big picture of using
medicines to improve >health.
IMHO, there are a lot of very talented people in pharm companies and
regulatory agencies, working very hard to figure out the best way to use
drugs. I think that their contributions are not minor shadows in figuring
out how to use medicine. They are the front line in doing this, not just box
ticking exercises.
Mark Sale MD
Next Level Solutions, LLC
www.NextLevelSolns.com
919-846-9185
Quoted reply history
-------- Original Message --------
Subject: RE: [NMusers] Reporting Modeling Results
From: "Stephen Duffull" <[EMAIL PROTECTED]>
Date: Fri, October 26, 2007 2:56 pm
To: "'James G Wright'" <[EMAIL PROTECTED]>, "'Mark Sale - Next
Level Solutions'" <[EMAIL PROTECTED]>
Cc: "'nmusers'" <[email protected]>
James, Mark
I don't have time to go through all RCTs in this manner.
But I will provide a single recent example that I was involved with. For
Mark, the special population was obesity and renal impairment. In both
situations a continuous dosing scale was used rather than the recommended
"cut-off" value idea (i.e. change dose if CLCR < 30ml/min) ...
All studies were performed in academia, post-marketing, without industry
support
* Background study (model for LBM): Janmahasatian et al. Clin PK
2005;44:1051-1065
* PKPD studies: Green et al BJCP; 2002:54:96-103 & Green et al BJCP
2004;59:281-290
* Clinical study: (an RCT individualising dose to LBM) Barras, CPT 2007
[advance online publication 10 October 2007]
NNT: 4-8 (to reduce adverse outcomes)
Requirements, a dose calculator or nomogram to calculate LBM (see background
study), Cockcroft and Gault formula to calculate CLCR (based on LBM).
Otherwise limited impact on already busy clinical pharmacy services.
There are other examples (but I'm marking exams right now) but I'm sure
others can comment here too.
Steve
--
Professor Stephen Duffull
Chair of Clinical Pharmacy
School of Pharmacy
University of Otago
PO Box 913 Dunedin
New Zealand
E: [EMAIL PROTECTED]
http://email.secureserver.net/pcompose.php#Compose
P: +64 3 479 5044
F: +64 3 479 7034
Design software: www.winpopt.com
> -----Original Message-----
> From: James G Wright [mailto:[EMAIL PROTECTED]
http://email.secureserver.net/pcompose.php#Compose ]
> Sent: Friday, 26 October 2007 10:22 p.m.
> To: 'Stephen Duffull'; 'Mark Sale - Next Level Solutions'
> Cc: 'nmusers'
> Subject: RE: [NMusers] Reporting Modeling Results
>
> Hi Steve,
>
> I think it would be a good idea for you to cite the
> randomized studies that back up your points in order to move
> this discussion forward.
>
> When citing a number need to treat, we also need to consider
> the actually cost of doing so. It's not that the staff in
> hospitals around the world are not skilled, it's just that
> they are already very busy.
> I'm trying to imagine a world where every hospital has a
> specialist department for individually optimizing drug dosing
> for a wide variety of drugs. What staff and equipment would
> it require? Are these staff available? Would we require new
> procedures in the hospital to implement
> all of the different drug protocols? What are the actual numerical
> costs?
>
> I am not asking these question rhetorically, I just think
> that this is a very complex economic (rather than scientific)
> question and I would value additional insight.
>
> Best regards, James
>
> James G Wright PhD
> Scientist
> Wright Dose Ltd
> Tel: 44 (0) 772 5636914
> www.wright-dose.com
>
>
> -----Original Message-----
> From: [EMAIL PROTECTED]
http://email.secureserver.net/pcompose.php#Compose
> [mailto:[EMAIL PROTECTED]
http://email.secureserver.net/pcompose.php#Compose ]
> On Behalf Of Stephen Duffull
> Sent: 25 October 2007 23:53
> To: 'Mark Sale - Next Level Solutions'
> Cc: 'nmusers'
> Subject: RE: [NMusers] Reporting Modeling Results
>
>
> Mark, Nick
>
> I think there are two issues here.
>
> First,
>
> > I would, of course, have to disagree that regulatory
> and marketing
> > are minor shadows in the big picture - that is how new
> medicine come
> > to improve health. I would suggest that better use of existing
> > medicine is not much more than a minor shadow,
>
> I think we may have to agree to disagree here. There is
> mounting evidence in a variety of therapeutic areas that
> post-marketing optimization of existing drug treatments by
> skilled clinical staff can improve patient outcomes. Indeed,
> there is growing research that indicates that the numbered
> needed to treat (NNT) may be in the order of
> 10-15 patients (i.e. treat 10 patients with optimized care on
> existing drugs to save 1 additional event). This value of
> NNT is about as good as any new drug is usually able to claim
> (treating AFib with warfarin has an NNT of about 100).
>
> So - I think the pre-marketing and regulatory aspects are as
> important as the post-marketing clinical aspects. Clearly we
> need new drugs - but we also need to use them better. And I
> don't think we can hope to learn everything there is to know
> about a drug during the drug development process.
>
> Second,
>
> > and while I think you're almost certainly right (as usual), I can
> > think of only a couple of examples where this has been empirically
> > shown that pk/pd informed dosing insight GENERATED AFTER
> APPROVAL is
> > better.
>
> There are also a growing number of examples where dosing that
> has arisen out of PKPD studies, that were gained after
> marketing, has provided significant patient benefits. We
> have seen this in patients who are obese (and often not
> included in pre-marketing trials) and with a variety of
> disease pathologies.
>
> It is (for me) without question that industry, regulatory and
> academia all play equally important roles in improving patient care.
>
> Regards
>
> Steve
> --
> Professor Stephen Duffull
> Chair of Clinical Pharmacy
> School of Pharmacy
> University of Otago
> PO Box 913 Dunedin
> New Zealand
> E: [EMAIL PROTECTED]
http://email.secureserver.net/pcompose.php#Compose
> P: +64 3 479 5044
> F: +64 3 479 7034
>
> Design software: www.winpopt.com
>
>
<<image001.png>>