Table 1.

Comparison of methodologies for testing of bronchodilator efficacy.

Methodology	Reference*	Population	Advantages	Disadvantages	Nominal rating
Spirometry – FEV1	13	Mild to moderate reversible airways disease	Simple technique	Plateau effect	+
			Single dose comparison
Spirometry – FEV1	21	Mild to moderate reversible airways disease	Simple technique	Variability of disease (baseline and responsiveness)	++++
Separate day dose–response comparison			No carry over effects
				Increased number of study days required
Spirometry – FEV1	24	Mild to moderate reversible airways disease	Simple technique	Plateau effect	++
Cumulative dose–response comparison			Single study day	Carry over effects
Spirometry – FEV1	30,32	More severe reversible airways disease	Simple technique	Carry over effects	+++
Cumulative dose–response comparison			Clinically relevant population
			Reduced chance of plateau effect
Plethsymography – sGaw	34	Healthy volunteers	No variability due to disease state	Specialized equipment requirement	+
			Potentially larger response	Not tested in target population
Challenge – PC20/PD20	46,47	Mild to moderate reversible airways disease	Dose–reponse more easily demonstrated	Complex technique requiring experience	++++
				Clinical relevance of model
			Smaller number of patients than FEV1	Patient safety
Pharmacokinetic – drug levels in blood	60	Healthy volunteers and mild to moderate reversible airways disease	Early levels indicate relative lung dose	Invasive	+
			Simple, requires no specialized lung function testing	Indirect measure of efficacy
			Small number of subjects
Pharmacokinetic – drug levels in urine	64,65	Healthy volunteers and mild to moderate reversible airways disease	Early levels indicate relative lung dose	Indirect measure of efficacy	+
			Simple, requires no specialized lung function testing	No information on lung distribution
			Non–invasive
			Small number of subjects
Gamma scintigraphy	67	Healthy volunteers and mild to moderate reversible airways disease	Lung distribution information (confounded by 2 dimensional images)	Complex technique requiring experience	+
				Specialized equipment requirement
			Small numbers of subject	Indirect measure of efficacy
Long term clinical studies	68	Mild to moderate reversible airways disease	Clinically relevant population and treatment period	Variability issues	+++

^*Reference to an example of a study using such a design/methodology.