Mark - your question is a good one. Our first conideration was at what
level of absolute CVD risk would the benefits of treatment outweigh any
harms wrt to major mordidity or mortality. As modern low dose drug therapy
doesn;t seem to have any important adverse effects, everyone is probably
likely to benefit from treatment although the lower the risk, the lower the
benefit.
We then considered the resource issue and clearly the most rational
approach would be to line up all therapies (and subgroups within therapy
groupings) by $/QALY suitably weighted by the public's priorities and the
go down the list until you run out of money. Clearly this wasn't available
so we ( a group including 4 GPs, 2 epidemiologists and a clinical
pharmacologist) discussed a number of patients who current get treatment
and don't get treatment, and we came up with a risk level of about 10-15%
as a level that seemed reasonable (don't ask me to define reasonable).
Subsequently I have modeleed the effect of different risk cutoffs using
risk data from representative population samples and have shown that at
about 15% 5 yr risk we would treat a similar net number of New Zealanders
but prevent an additional 30% events over 5 yrs because of better
targetting. We are currently writing this up. We have yet to get the
public involved at this level but our recommendations to doctors have been
that " a 5 year cvd risk of about 10% is a reasonable starting point for
discussion with patients about drug therapy." Many docs are now using the
cvd risk charts with individual patients.
Rod
>Rod
>
>Coming off the NNT debate slightly I was interested in your comments
>about the need to consider the 'best' use of scarce
>healthcare resources. In U.K this issue is part of wider discussion
>of 'prioritizing' or 'rationing' (depending on your
>politicial/ideological perspective) of healthcare and one which I
>think will again be raised once the full impact of Primary Care
>Group commissioning starts to become operational. In U.K many of
>these kind of decisions have been devolved to health authorities
>and/or individual clinicians. Partly as a result of this we have the
>well reported variations in access for services such as I.V.F for
>example. It seems to me by linking the issue to questions of
>resources it becomes much more than just a clinical one What I
>am interested in is how and by whom the figure of 10-15% 5 yr risk of
>CVD was decided upon did for example the public have any involvement
>and if so how was this achieved.
>
>
>mark
>
>
>
>
>Date: Tue, 09 Mar 1999 22:58:38 +1200
>From: Rod Jackson <[log in to unmask]>
>Subject: RE: What is a good number for NNT?
>To: "Djulbegovic, Benjamin" <[log in to unmask]>
>Cc: [log in to unmask]
>Reply-to: Rod Jackson <[log in to unmask]>
>
>Ben - while no one would argue that the treatment should be withheld if the
>risk of CVD is below AT using your terminology, the converse is not so
>clear cut. Evidence that a treatment results in more good than harm is a
>necessary but not sufficient reason for treatment. Alternative uses of
>scarce health resources need to be considered and this is very dependant on
>the wealth of the community in which you live. In New Zealand we suggest a
>10-15% 5 year risk of CVD is a reasonable level at which to discuss
>pharmacological treatment of raised blood pressure with patients. As it
>happens in NZ if we only treated people with a 15% 5 yr CVD risk, this
>would lead to little net change in numbers treated (although many would
>stop and many others would start) and we would inccrease the number of
>events prevented over 5 yrs by about 30%. We have a different threshold
>for lipid lowering treatment because despite a similar effect on risk, the
>drugs cost alot more in NZ. In the ideal world we would estimate $/QALY
>for all interventions and use these to help prioritise who should be
>treated with what.
>
>Rod
>
>
> >As I argued it at this group before and as we described it elsewhere (for
>>details see Cancer Control 1998;5:394-405; also at
>>http://www.moffitt.usf.edu/pubs/ccj/v5n5/article2.html , Med Decision
>>Making 1998;18:464
>>; Comp Biomed Res; or, see
>>http://www.hsc.usf.edu/~bdjulbeg/Programs/BR/br-java.htm ), normatively
>>highest (maximum) NNT at which treatment is worth administering in
>>prophylactic setting is equal to:
>> NNT<NNH or NNT<1/ R
>>where R is risk of the treatment .
>>For example, for a toxicity of 2%, the treatment NNT has to be at most 50 to
>>be worth administering the treatment, for a toxicity of 4%, the NNT has to
>>be at most 25, etc.
>>
>>If this condition is not satisfied, no NNT is "good NNT".
>>
>>In the setting of selection of Rx1 vs Rx2, in order to even consider the
>>treatment Rx1 as opposed to the alternative treatment Rx2, the following
>>inequality must be satisfied:
>>
>>NNT1 <= 1/(R1 - R2 + 1/NNT2)
>>
>>
>>This is not only normatively correct, but also makes sense intuitively: we
>>should not consider measures of treatment benefits without consideration of
>>other side of therapeutic coin (that is, treatment harm).Again, as I wrote
>>before, it is important to realize that same units of benefits and harms are
>>used when these calculations are performed.
>>
>>I am not aware of any normative model that successfully integrated patients
>>values with NNT, NNH or with any other EBM summary measures of therapeutic
>>effects (although, I should say that we are currently working on one such
>>model)
>>
>>Intertwined with this issue is the question of "action threshold". I will
>>try to illustrate it from perspective of ongoing discussion of CVD risk and
>>New Zealand tables for CVD. The tables use data from Framingham Heart study.
>>These tables suggest threshold for therapeutic action if risk of CVD is
>>10-15% at 5yrs (NNT=25 for 5 years) (see:
>>http://cebm.jr2.ox.ac.uk/docs/prognosis.html ) However, this treatment
>>threshold appears to be quite arbitrary. As I argued before, normatively
>>this action threshold (AT) is equal to
>>
>>AT= NNT/NNH or AT=risk of treatment*NNT=treatment
>>risk/(RRR*morbidity/mortality without Rx) (for details see references
>>provided above).
>>
>>We should treat if estimated risk of clinical event (in this case, CVD) is
>>above AT; conversely, we should withhold Rx if risk of CVD is below AT. For
>>example, package insert for pravastatin indicated that at median treatment
>>of 4.8 years, 0.10% of patients treated with pravastatin developed elevation
>>of AST as opposed to 0.03% of placebo treated patients. This would amount
>>roughly to NNH=1428. Using the action threshold equation this means that we
>>can consider treatment with statins if risk of CVD exceeds >1.7% at 5 years
>>(AT=25/1428). Even when I vary risk in sensitivity analysis, I still obtain
>>threshold for action, which is below recommended 2% or 3% per year. It is
>>not clear to me how current recommendations (for treatment actions) have
>>been derived. Can somebody care to comment? (Cardiovascular medicine is not
>>my field, and I am perhaps missing something here).
>>
>> (Incidentally, I developed a simple BASIC program that integrates this
>>threshold model with Framingham risk equations. If anybody is interested in
>>the program, I will be happy to send it to him/her.)
>>
>>
>>
>>hope this clarifies this issue
>>
>>ben d
>>
>>Benjamin Djulbegovic, MD
>>Associate Professor of Medicine
>>H. Lee Moffitt Cancer Center & Research Institute
>>at the University of South Florida
>>Division of Blood and Bone Marrow Transplant
>>12902 Magnolia Drive
>>Tampa, FL 33612
>>
>>e-mail:[log in to unmask]
>>http://www.hsc.usf.edu/~bdjulbeg/
>>phone:(813)979-7202
>>fax:(813)979-3071
>>
>>> -----Original Message-----
>>> From: Takeo Saio [SMTP:[log in to unmask]]
>>> Sent: Friday, March 05, 1999 5:32 PM
>>> To: Amit Ghosh
>>> Cc: [log in to unmask]
>>> Subject: RE: What is a good number for NNT?
>>>
>>> Hello! That's very good question.
>>>
>>> I think the NNTs of 2-4 are for therapeutic usage of drugs,and the NNTs
>>> over 20 are for preventitive usage of drugs.
>>> i.e. for acute condition,NNTs of 2-4:for chronic condition,NNTs of over
>>> 20.
>>>
>>>
>>> > A question I have , is what is a good number for NNT? Bandolier 12
>>> >indicated that a NNT of 2-4 is suggestive of good NNT ( i.e., ARR of
>>> >0.25-0.50). However most the the RCT reported in journal s NEJM, Annals
>>> >etc have statistical significance however their NNT are usually over 20,
>>> >ie, finasteride for BPH( NNT= 30). I reckon one of the disadvantages of
>>> >NNT maybe that despite the NNT being over 20 , these patients may have
>>> >significant improvement in quality of life and other subjective issues.
>>> >Or is the fact that NNT of 2-4 an over enthusiastic expectation when it
>>> >comes to a clinical response.I guess in the case of chronic diseases
>>> >with outcomes occurring over decades a NNT of 50 would be acceptable,
>>> >however in other more acute conditions one would consider a smaller
>>> >number for NNT as desirable. Could the members throw some additional
>>> >light in the defining what is a good number for NNT.
>>> **********************************************
>>> Saio,Takeo
>>> ///////////////CHIAKI hospital,JAPAN/////////
>>> e-mail;[log in to unmask]
>>> **********************************************
>>>
>>>
>>>
>
>
>Dr Rodney Jackson MBChB PhD FAFPHM
>Associate Professor of Epidemiology
>Head of Department
>Dpt of Community Health, School of Medicine
>University of Auckland
>(Grafton Mews, 52-54 Grafton Rd)
>Private Bag 92019, Auckland, New Zealand
>Phone: +64 (0)9-3737599 ext 6343
>Fax: +64 (0)9-3737503
>e-mail: [log in to unmask]
>
>
>Mark Newman
>Senior Lecturer:
>School of Health, Biological & Environmental Sciences (HeBES)
>Middlesex University &
>Chase Farm Hospital NHS Trust
>10 Highgate Hill
>London N19 3UA
>Tel: 0181 362 6627 or 0181 366 6600 ex 5775
>Fax: 0181 362 6299
>E-Mail: [log in to unmask]
Dr Rodney Jackson MBChB PhD FAFPHM
Associate Professor of Epidemiology
Head of Department
Dpt of Community Health, School of Medicine
University of Auckland
(Grafton Mews, 52-54 Grafton Rd)
Private Bag 92019, Auckland, New Zealand
Phone: +64 (0)9-3737599 ext 6343
Fax: +64 (0)9-3737503
e-mail: [log in to unmask]
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