Good morning from sunny Liverpool.
Brian, of course, has it right. The problem is this nirvana of design
hardly ever occurs and we end up analysing the implications of sub group
results on a case by case basis. I might, for example, take at least
some notice of a subgroup result if it was pre-specified, I could see
all of the pre-specified subgroups and the statistical test indicated a
highly significant difference, sometimes even if the primary outcome
wasn't significant. But its usually best to regard such results as
hypothesis generating than a result to guide clinical practice, at least
on its own. I can't recall ever seeing a 'check list' for subgroup
validity. (Perhaps this is because they are usually invalid?!)If there
is one, I agree with Gayle, it would be useful. If there isn't one,
perhaps one could be developed?
Best to all
Neal
Neal Maskrey. Director of Evidence Based Therapeutics, National
Prescribing Centre, 70 Pembroke Place, Liverpool L69 3GF. Tel: 0151 794
8135. e-mail: [log in to unmask]
-----Original Message-----
From: Evidence based health (EBH)
[mailto:[log in to unmask]] On Behalf Of Brian Alper
MD
Sent: 09 May 2007 11:35
To: [log in to unmask]
Subject: Re: Subgroup analyses - are they ever best evidence
I would suggest a pre-planned stratified randomization with analyses
within the stratified groups could provide level 1 evidence. This could
be called a "subgroup analysis" but would be the equivalent of
independent randomized trials being reported as a single trial.
All of the usual considerations for bias would have to be considered at
the level of the "subgroup" -- adequate sample size, adequate follow-up
rates, intention-to-treat analysis, etc.
In addition consider whether the effects of other trial activity
(including statistical evaluations) could in any way bias the chances of
finding and reporting significant differences in the "subgroup".
If the randomization was not stratified by the subgrouping, then the
clustering of confounding factors along with the "subgroup factor" could
nullify the initial reason for randomization. Adjusting for recognized
confounding factors cannot exclude bias from unrecognized confounding
factors.
--------------------------------------
Brian S. Alper, MD, MSPH
Editor-in-Chief, DynaMed (www.DynamicMedical.com) Medical Director,
EBSCO Publishing 10 Estes St.
Ipswich, MA 01938
office (978) 356-6500 extension 749
cell (978) 804-8719
fax (978) 356-6565
home (978) 356-3266
"It only takes a pebble to start an avalanche."
-----Original Message-----
From: Evidence based health (EBH)
[mailto:[log in to unmask]] On Behalf Of Olive Goddard
Sent: Wednesday, May 09, 2007 4:14 AM
To: [log in to unmask]
Subject: Re: Subgroup analyses - are they ever best evidence
Dear Colleagues,
Would anyone be prepared to respond to this query from Gayle Robins.
All good wishes,
Olive
>>> "Robins, Gayle" <[log in to unmask]> 09/05/2007 06:01
>>>
Hello Mrs Goddard
When I evaluate a clinical trial, I use the Oxford Centre for Evidence
Based Medicine's recommendation as a guideline for whether the
information provided by the trial could be considered as best evidence.
I note that individual randomised controlled trials with narrow
confidence intervals are considered as level 1b on your levels of
evidence chart. Please can you advise me where, if at all, subgroup
analyses of these level 1b randomised clinical trials would fall on the
best-evidence hierarchy.
I realise that there are many different types of subgroup analysis:
those that are defined apriori versus retrospectively or on an ad-hoc
basis; those that address the same outcome of interest that the
randomised controlled trial was designed to assess versus other
outcomes; and those that are part of a plethora of subgroup analyses of
the same trial and so require correction for multiplicity, to name a
few.
Are any subgroup analyses of level 1b randomised controlled trials ever
considered best evidence?
Thanks you for your time taken to read this email. I would appreciate
any advice that you can give me, or people that I could contact, in this
regard.
Gayle Robins
Team Leader
Clinical Trials Insight
Adis International
Wolters Kluwer Health
Ph: 09 4770700
Email: [log in to unmask]
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