Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study

Table 2 Characteristics of published, superiority, randomized, pivotal trials of novel drugs first approved by the FDA between 2005 and 2012 based on trials using surrogate markers of disease as primary endpoints with at least one postapproval match

	Pivotal trials	Postapproval trials
Characteristics			P value^a
Total studies	43 (100.0)	43 (100.0)
Allocation
Double or triple blind	39 (90.7)	31 (72.1)	0.008
Single blinded or open label	4 (9.3)	12 (27.9)
Number of arms
Median (interquartile range)	3 (2, 4)	2 (2, 4)	0.14^b
Comparator options
Active only	9 (20.9)	17 (39.5)	0.04
Placebo only or active and placebo	34 (79.1)	26 (61.5)
Center status
Multicenter	43 (100.0)	40 (93.0)	0.25
Single center	0	3 (7.0)
Funder type
Industry or mixed funding that includes industry	40 (93.0)	38 (88.4)	0.69
All others (non-profit, government, mixed non-industry, none, not specified)	3 (7.0)	5 (11.6)
Sample size
Total ITT or mITT, median (interquartile range)	672 (390, 822)	395 (154, 735)	0.02^b
Study duration
Duration in weeks, median (interquartile range)	24 (10, 26)	24 (12, 26)	0.57^b

^aAnalyses based on McNemar’s exact test
^bAnalyses based on Wilcoxon signed-rank test
ITT intention to treat (when available, all subjects randomized), mITT modified intention to treat (all subjects randomized that received at least one treatment)

ISSN: 1741-7015