This is a question for the biostatisticians on the list.
I'm thinking of formulating a commentary on accepted research
procedures in my area that I think could be improved by observing basic
statistical arguments presented to researchers by biostatisticians.
It has been suggested that in a randomized clinical trial design with
baseline (B) and followup (F) test measures comparing a control and
treatment group (G), performing an ANOVA on the ratio pre/post is the
worst choice of the 4 ways to deal with baseline differences:
(1) post: analyze F by G
(2) difference: analyze F-B by G
(3) ratio: analyze F/B by G
(4) ancova: analyze F = constant + b1*B + b2*G, for G differences
In light of biostatisticians' suggestion (e.g., Vickers, BMC Medical
Research Methodology (2001) 1:6,
http://www.biomedcentral.com/1471-2288/1/6) that method (4) above is
preferred most and method (3) is least preferred, does it apply to
"prepulse inhibition" literature?
In an area of schizophrenia research, subjects show a deficit in basic
sensorimotor gating, as measured by prepulse inhibition of the acoustic
startle response. The startle response is simply startle to a loud
noise. Prepulse inhibition is simply inhibition of that startle
response by preceding the loud noise with a soft noise. In both
non-schizophrenics and schizophrenics, startle is comparable, but
prepulse inhibition is _less_ in schizophrenics. That is, both groups
startle comparably to a loud noise, but schizophrenics startle less
when a startling noise is preceded by a soft noise. So, there are two
brain circuits underlying this behavior and the prepulse inhibition
circuit is compromised in schizophrenics.
Across the board, prepulse inhibition papers generally employ method
(3). That is, each subject is measured with trials for startle, and
also (at the same testing session) with trials for prepulse inhibition,
and then a ratio is formed for that subject
100*(startle-prepulse)/(startle) to represent the percent prepulse
inhibition relative to startle. That percent (%PPI) is then analyzed as
the response measure. I'm thinking the baseline measure discuss at the
top of this email is analogous to the startle trial response, and the
followup is analogous to the prepulse trial response. A difference is
that both trial types are given pre and post to any (e.g., drug)
intervention. An additional complication is that the %PPI ratio is
analyzed in the context of both between-subject designs and
within-subject designs.
Is method (4) applicable to prepulse inhibition studies, and is it
applicable to both between and within designs?
By way of example, let's suppose we have the following between-subjects
data:
group, startle, prepulse, ppi
where group indicates a between-subjects design where one group had a
placebo and another group had the drug. Then, method (4) says to
analyze group difference by the regression (ANCOVA) model, prepulse =
constant + b1*startle + b2*group, and in Stata, this would be "anova
prepulse group startle, continuous(startle)". The usual ANOVA on %PPI
by method (3) would be "anova ppi group".
Next we could have the same question but using within-subjects data:
subject, startle, prepulse, ppi, treatment
where treatment indicates that each subject is exposed to the placebo
and drug at different times in random order. Is it also possible to use
a within-subjects design with the advantages of method (4)
incorporated? Usually, one would do "anova ppi subject treatment" on
%PPI. Does the model "anova prepulse subject treatment startle,
continuous(startle)" make sense?
