Minimum sample size estimates for trials in inflammatory bowel disease: A systematic review of a support resource

Table 1 Overall summary of power calculations and sample size deficits

	Total studies	Studies with power calculation	Studies with difference of 10% and less1	How many studies didn’t achieve target sample size	Mean sample size underpowered (range)	Mean sample size needed	How many studies are underpowered2
CD induction	39	26	12	6	28 (2-70)	231	11
CD maintenance	25	19	9	3	52 (7-79)	300	10
UC induction	27	19	8	3	22 (1-55)	219	4
UC maintenance	16	10	0	1 + 1 didn’t report	21	196	7

¹Those studies were not included in analysis.

²Either didn’t achieve their target sample size, or their achieved sample size is less than mean sample size needed.

UC: Ulcerative colitis; CD: Crohn’s disease.

Table 2 Proposals for minimum clinically important difference and associated power calculations for future studies

Ulcerative colitis-comparison	Ulcerative colitis-difference achieved (Group 1–Placebo)	Ulcerative colitis-Minimum sample size needed based on data	Crohn’s disease-comparison	Crohn’s disease-difference achieved (Group 1–Placebo)	Crohn’s disease-Minimum sample size needed based on data
Induction studies
Outcome–clinical remission			Outcome–clinical remission
Vedolizumab vs Placebo	14.8%	190	Glutamine-enriched diet vs Placebo	-11.1	634
			Azathioprine vs Placebo	-3.6%	NA
			6-MP vs Placebo	5%	NA
Fecal Transplant vs Control	20.3%	150	6-MP vs Placebo	5%	NA
Budesonide vs Placebo	6.5%	NA	Interventional diet vs Control diet	20.9%	160
Type 1 IFNs vs Placebo	5.9%	NA	Elemental diet vs Non elemental diet	1.6%	NA
Etrolizumab vs Placebo	13.4%	140	N6/N9 rich feeds vs non N6/N9 rich food	-1.1%	NA
			Low dose naltrexone vs Placebo	9%	NA
5-ASA vs Placebo	11.8%	422	GM-CSF vs Placebo	7.8%	NA
Outcome–endoscopic remission			Brakinumab vs Placebo	8.5%	NA
Vedolizumab vs Placebo	37.7%	182	Ustekinumab vs Placebo	8.6%	NA
			Natalizumab vs Placebo	14.8%	310
Fecal Transplant vs Control	26.4%	160	Methotrexate vs Placebo	-14.8%	350
Budesonide vs Placebo	13.9%	NA	Antibiotics vs Placebo	10%	780
Methotrexate vs Placebo	46.7%	NA	Outcome–endoscopic remission
Etrolizumab vs Placebo	7.7%	NA	Low dose naltrexone vs Placebo	22.2%	60
5-ASA vs Placebo	53.7%	306
Maintenance studies
Outcome–clinical relapse			Outcome–clinical relapse
5-ASA vs Placebo	-16.4%	290	5-ASA vs Placebo, medically induced	3.1%	NA
Vedolizumab vs Placebo	-27.4	84	5-ASA vs Placebo, surgically induced	-5.4%	NA
Interventional diet vs Control diet	-3.6%	NA	Anti-TB vs Placebo	-23%	130
Probiotics vs Control	-16.7	154	Azathioprine vs Placebo, medically induced	-9.9%	NA
Azathioprine vs Placebo	-22.4	154	Azathioprine vs Placebo, surgically induced	-17.3%	254
Methotrexate vs Placebo	19.9%	194	6-MP vs Placebo, surgically induced	-10.9%	646
Rectal 5-ASA vs Placebo	-29%	90	Omega -3 fatty acids diet vs Control diet	-8.5%	NA
Curcumin vs Placebo	-9.6%	NA	Elemental diet vs No supplemets	-29.4%	88
Outcome–endoscopic relapse			Interventional diet vs Control diet	-2.5%	NA
Vedolizumab vs Placebo	-34	60	Antibiotics vs Placebo	-14.6%	360
			Methotrexate vs Placebo	-24.2%	128
5-ASA vs Placebo	-16.4%	290	Methotrexate vs Placebo	-24.2%	128
			Outcome–endoscopic relapse
			5-ASA vs Placebo	2.7%	NA
			Azathioprine vs Placebo	-23%	130
			6-MP vs Placebo	-3.8%	NA
			Antibiotics vs Placebo	6.6%	NA
Induction studies
Outcome–clinical remission			Outcome–clinical remission
Vedolizumab vs Placebo	14.8%	190	Glutamine-enriched diet vs Placebo	-11.1	634
			Azathioprine vs Placebo	-3.6%	NA
			6-MP vs Placebo	5%	NA
Fecal Transplant vs Control	20.3%	150	6-MP vs Placebo	5%	NA
Budesonide vs Placebo	6.5%	NA	Interventional diet vs Control diet	20.9%	160
Type 1 IFNs vs Placebo	5.9%	NA	Elemental diet vs Non elemental diet	1.6%	NA
Etrolizumab vs Placebo	13.4%	140	N6/N9 rich feeds vs non N6/N9 rich food	-1.1%	NA
			Low dose naltrexone vs Placebo	9%	NA
5-ASA vs Placebo	11.8%	422	GM-CSF vs Placebo	7.8%	NA
Outcome–endoscopic remission			Brakinumab vs Placebo	8.5%	NA
Vedolizumab vs Placebo	37.7%	182	Ustekinumab vs Placebo	8.6%	NA
			Natalizumab vs Placebo	14.8%	310
Fecal Transplant vs Control	26.4%	160	Methotrexate vs Placebo	-14.8%	350
Budesonide vs Placebo	13.9%	NA	Antibiotics vs Placebo	10%	780
Methotrexate vs Placebo	46.7%	NA	Outcome–endoscopic remission
Etrolizumab vs Placebo	7.7%	NA	Low dose naltrexone vs Placebo	22.2%	60
5-ASA vs Placebo	53.7%	306
Maintenance studies
Outcome–clinical relapse			Outcome–clinical relapse
5-ASA vs Placebo	-16.4%	290	5-ASA vs Placebo, medically induced	3.1%	NA
Vedolizumab vs Placebo	-27.4	84	5-ASA vs Placebo, surgically induced	-5.4%	NA
Interventional diet vs Control diet	-3.6%	NA	Anti-TB vs Placebo	-23%	130
Probiotics vs Control	-16.7	154	Azathioprine vs Placebo, medically induced	-9.9%	NA
Azathioprine vs Placebo	-22.4	154	Azathioprine vs Placebo, surgically induced	-17.3%	254
Methotrexate vs Placebo	19.9%	194	6-MP vs Placebo, surgically induced	-10.9%	646
Rectal 5-ASA vs Placebo	-29%	90	Omega -3 fatty acids diet vs Control diet	-8.5%	NA
Curcumin vs Placebo	-9.6%	NA	Elemental diet vs No supplemets	-29.4%	88
Outcome–endoscopic relapse			Interventional diet vs Control diet	-2.5%	NA
Vedolizumab vs Placebo	-34	60	Antibiotics vs Placebo	-14.6%	360
			Methotrexate vs Placebo	-24.2%	128
5-ASA vs Placebo	-16.4%	290	Methotrexate vs Placebo	-24.2%	128
			Outcome–endoscopic relapse
			5-ASA vs Placebo	2.7%	NA
			Azathioprine vs Placebo	-23%	130
			6-MP vs Placebo	-3.8%	NA
			Antibiotics vs Placebo	6.6%	NA

NA is put when the difference achieved is less than 10% (which is the least Minimal Clinically Important Difference used by the studies).