Table 2.

Advantages and disadvantages of various designs.

Design	Situations where design should be considered	Advantages	Disadvantages
Dose finding [7,68,93,134]	Dosages that are expected to be safe, tolerated, and efficacious are unknown for the condition of interest	May increase the probability of finding an analgesic effect at safe and tolerated dosages in subsequent studies For adaptive dose finding designs, see adaptive designs row	For adaptive dose finding designs, see adaptive designs row
Single dose	Limited resources Treatment is known to have prompt onset of analgesic effect	Lower probability of missing data Decreased costs because of single dose of treatment and short duration of follow up	Only applicable to treatments with prompt onset of analgesic effect Single dose and short duration of observation may preclude identification of many adverse events Predictive value for long-term efficacy is not clear
Parallel group	Limitations of other designs make them unsuitable for the treatment and objective of interest	Relatively straightforward design, execution, analysis and interpretation Potentially increased generalizability	Requires larger sample sizes than several other designs
Cross-over [54,109]	Limited resources and patient numbers	Increased power, reduced sample size requirements	Potential for unforeseen treatment-by-period interaction (e.g., carryover) Longer duration and patient burden Greater impact of missing data
Adaptive designs [6,38,116,124]	Trials with a large learning component, for example, sample size estimates, dosage selection, safety	Appreciably increased efficiency Highly informative for planning subsequent studies	Careful and extensive planning is needed to preserve the validity and integrity of the trial Requires unique statistical expertise Several logistical and procedural issues need to be considered in the planning and execution of the trial
Sequential parallel comparison design (SPCD) [32]	Placebo effects are anticipated to be relatively large, possibly decreasing the assay sensitivity of the trial	May decrease the placebo effect in the second stage [33,91], and thus increase power compared to traditional parallel group design	Longer duration of follow-up than in a conventional parallel group design If placebo non-responders are refractory patients who also do not respond to treatment, SPCD could have less power than conventional parallel group designs SPCD is patented and investigators must pay to use it.