Does the low prevalence affect the sample size of interventional clinical trials of rare diseases? An analysis of data from the aggregate analysis of clinicaltrials.gov

Table 3 Fitted mean of sample size and 95% confidence interval (CI) back transformed from logarithmic values, type III F statistic and the corresponding p value of the effect of the covariate on sample size adjusted by class of prevalence, phase of trial and interaction between prevalence and phase

Characteristics	No. of trials, m	Fitted mean	95% CI	F test	p value
Inclusion criteria
Gender	1148			10.61	<.0001
Both		49.30	(41.85–58.08)
Female		58.12	(44.23–76.38)
Male		21.09	(14.04–31.69)
Age categories ^a	1148			4.52	0.0004
Children only		36.29	(28.03–46.99)
Adults only		58.49	(45.34–75.45)
Elderly only		89.17	(58.86–135.08)
Children and adults		51.94	(39.74–67.87)
Children to elderly		44.98	(36.88–54.85)
Adults to elderly		50.93	(42.66–60.80)
Study designs
Has DMC? ^b	963			9.94	0.0017
No		42.95	(35.92–51.36)
Yes		52.43	(44.06–62.38)
FDA regulated intervention? ^c	1076			4.09	0.0433
No		52.30	(43.72–62.56)
Yes		46.20	(38.77–55.06)
Intervention model	1114			56.55	<.0001
Crossover assignment		28.63	(21.84–37.53)
Factorial assignment		139.83	(56.36–346.91)
Parallel assignment		71.38	(60.45–84.28)
Single group assignment		34.28	(29.05–40.46)
Interventions, facilities and authorities
Lead sponsor	1148			1.53	0.2041
US Federal		68.43	(30.81–151.99)
Industry		46.20	(38.50–55.43)
NIH		65.80	(44.80–96.65)
Other		49.20	(41.46–58.38)
Trial location	1148			7.68	<.0001
US only		42.50	(35.57–50.79)
EU only		71.63	(55.99–91.64)
US and EU		46.29	(35.40–60.53)
Single European country		49.77	(41.55–59.62)
No. of countries involved in the trial	1148	1.07 ^d	(1.04–1.11)	16.07	<.0001
Year that enrolment to the protocol begins	1141			3.14	0.0081
<1990		131.48	(34.06–507.57)
1990–1999		57.83	(41.44–80.69)
2000–2004		63.10	(50.12–79.44)
2005–2009		44.61	(37.31–53.34)
2010–2014		48.72	(40.92–58.01)
2015 and after		49.89	(35.70–69.71)
No. of arms	1085	1.39 ^d	(1.30–1.49)	83.75	<.0001

^a Minimum and maximum age groups are mutually exclusive. Children, term new born infants to adolescents up to 18 years; adults, 18–64 years old; and elderly, 65 years or older
^b Indicate whether or not a data monitoring committee (DMC) has been appointed for this study
^c Indicate whether or not the trial includes an intervention subject to US Food and Drug Administration regulation under section 351 of the Public Health Service Act or any of the following sections of the Federal Food, Drug and Cosmetic Act: 505, 510(k), 515, 520(m), and 522
^d Estimated coefficient, the estimated increase of sample size for every unit increase of the covariate

ISSN: 1750-1172