factorial designs. background factorial designs are when different treatments are evaluated within...
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Background Factorial designs are when
different treatments are evaluated within the same randomised trial.
A factorial design has a number of important advantages.
Advantages Two trials for the price of one. Can test for an ‘interaction’
between treatments – does a treatment work even better in the presence of another therapy?
Disadvantages Can be more complicated to
undertake leading to a higher potential for error.
Interactions can mean some of the sample is lost, which will reduce power for main comparisons.
Example Waters et al. Examined the use of
HRT and antioxidant vitamins for treatment of coronary heart disease.
Observational data suggest a benefit of HRT and antioxidant vitamins.
Sensible to examine effects of both.
Factorial Design
HRT and Placebo Vitamins
HRT and Vitamins
Placebo HRT Vitamins
Vitamins + Placebo HRT
Analysis The analysis treats the study as
two separate trials. All women who got HRT would be compared with those who did not. Likewise all those given vitamins would be compared with who were not given vitamins.
HRT and Vitamin Trial Over 400 women randomise to the
4 treatment arms. Outcomes included surrogate
measures (lipid levels angiograms) plus ‘real’ outcomes – death MIs.
Results Both treatments INCREASED the
risk of MI and death. NO interaction with treatments
suggesting that the risk of death is additive.
RECORD TRIAL RECORD trial is a factorial trial of
calcium with or without vitamin D. Key question is whether vitamin D
is effective alone or NEEDS calcium to work.
Factorial design is specified to look for an interaction.
Record Trial The interaction is important because
there are biologically plausible reasons for both treatments to work better in the presence of each other (I.e a positive interaction).
Because vitamin D is so inexpensive it is important to know if this effective on its own.
More complications Basic factorial is 2 X 2 but can be
increased by infinite number of factors.
UK BEAM trial (backpain) uses a 3 x 2 factorial to test: exercise; GP care; manipulation; exercise plus manipulation.
Did include another factor making it a 3 x 2 x 2 design.
BEAM trial Factorial design enabled exercise
and manipulation questions to be answered in the same trial.
Also enables us to look for interactions between treatments.
Factorial Questionnaire Trial Puffer et al undertook a factorial
trial comparing single sided questionnaires vs double with one large questionnaire vs 3 separate questionnaires.
Outcome was response rates.
Underuse of Factorial trials Factorial trials could be more widely used
as they can answer two questions within the same trial, particularly if there is no reason to suspect an interaction.
Factorial trials also enable us to ‘tease’ out the different treatment effects. For example, fall prevention programmes are multifactorial and in standard trial we end up not knowing what produces the main effects.
Systematic Review of Factorial Trials
Are interactions common in factorial trials? A review of 44 trials found only 1 trial
where an interaction would have given the ‘wrong’ answer and 7 trials where there were indications of an interaction (only 2 were statistically significant).
Interactions are relatively unusual and therefore factorial trials are probably an efficient trial approach.
McAlister et al. JAMA 2003;289:2545.
Split plot design A split plot design is a special form
of factorial design, which mixes cluster and individual randomisation.
SAPPHIRE: example of a split plot design.
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Analysis of split plot The same as for a factorial. Will be
treated as two separate trials. Again giving us two trials for the price of one.
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