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Table 2 Characteristics of rare disease trials conducted in the United States (US) and/or European Union (EU) by class of prevalencea. Data are number of trials, m (%), or mean (standard deviation, SD)

From: 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

 

Class of prevalence

<1/1,000,000 (m = 19)

1–9/1,000,000

(m = 126)

1–9/100,000

(m = 791)

1–5/10,000

(m = 631)

Unknown

(m = 37)

m

(%)

m

(%)

m

(%)

m

(%)

m

(%)

Inclusion criteria

 *Gender

  Both

17

(89)

119

(94)

772

(97)

505

(80)

33

(89)

  Female

.

.

5

(3)

6

(<1)

111

(17)

1

(2)

  Male

2

(10)

2

(1)

13

(1)

15

(2)

3

(8)

Accepts healthy volunteers?

  Yes

1

(5)

2

(1)

11

(1)

7

(1)

.

.

  No

18

(94)

124

(98)

778

(98)

620

(98)

37

(100)

  Missing

.

.

.

.

2

(<1)

4

(<1)

.

.

*Age categories b

 Children only

2

(10)

11

(8)

65

(8)

42

(6)

2

(5)

 Adults only

1

(5)

3

(2)

45

(5)

68

(10)

1

(2)

 Elderly only

.

.

.

.

24

(3)

9

(1)

.

.

 Children to elderly

9

(47)

36

(28)

107

(13)

69

(10)

11

(29)

 Children and adults

2

(10)

16

(12)

42

(5)

31

(4)

.

.

 Adults to elderly

5

(26)

60

(47)

508

(64)

412

(65)

23

(62)

Study designs

Phase of investigation c

 Phase 2

16

(84)

92

(73)

602

(76)

450

(71)

28

(75)

 Phase 2/3

3

(15)

6

(4)

30

(3)

23

(3)

4

(10)

 Phase 3

.

.

28

(22)

159

(20)

158

(25)

5

(13)

*Has DMC? d

 Yes

7

(36)

51

(40)

401

(50)

258

(40)

17

(45)

 No

11

(57)

37

(29)

224

(28)

207

(32)

11

(29)

 Missing

1

(5)

38

(30)

166

(20)

166

(26)

9

(24)

*FDA regulated intervention? e

 Yes

10

(52)

67

(53)

438

(55)

246

(38)

19

(51)

 No

9

(47)

39

(30)

271

(34)

275

(43)

13

(35)

 Missing

.

.

20

(15)

82

(10)

110

(17)

5

(13)

Is Section 801? f

 Yes

10

(52)

59

(46)

389

(49)

213

(33)

14

(37)

 No

.

.

8

(6)

45

(5)

28

(4)

3

(8)

 Missing

9

(47)

59

(46)

357

(45)

390

(61)

20

(54)

*Intervention model

 Crossover assignment

.

.

7

(5)

43

(5)

27

(4)

1

(2)

 Factorial assignment

.

.

.

.

5

(<1)

4

(<1)

.

.

 Parallel assignment

7

(36)

32

(25)

284

(35)

264

(41)

7

(18)

 Single group assignment

12

(63)

79

(62)

425

(53)

276

(43)

28

(75)

 Missing

.

.

8

(6)

34

(4)

60

(9)

1

(2)

Masking

 Double blind

5

(26)

19

(15)

153

(19)

139

(22)

7

(18)

 Single blind

1

(5)

1

(<1)

12

(1)

11

(1)

1

(2)

 Open label

13

(68)

99

(78)

601

(75)

430

(68)

28

(75)

 Missing

.

.

7

(5)

25

(3)

51

(8)

1

(2)

Allocation

 Randomized

7

(36)

35

(27)

320

(40)

319

(50)

9

(24)

 Non-randomized

.

.

37

(29)

183

(23)

108

(17)

11

(29)

 Missing

12

(63)

54

(42)

288

(36)

204

(32)

17

(45)

Endpoint classification

 Efficacy study

3

(15)

30

(23)

199

(25)

151

(23)

9

(24)

 Safety/efficacy study

14

(73)

77

(61)

467

(59)

366

(58)

27

(72)

 Safety study

1

(5)

4

(3)

39

(4)

16

(2)

.

.

 Bio-equivalence study

.

.

.

.

3

(<1)

1

(<1)

.

.

 Pharmacodynamics study

.

.

.

.

.

.

3

(<1)

.

.

 Pharmacokinetics study

.

.

1

(<1)

3

(<1)

1

(<1)

.

.

 Pharmacokinetics/dynamics study

.

.

1

(<1)

.

.

2

(<1)

.

.

 Missing

1

(5)

13

(10)

80

(10)

91

(14)

1

(2)

Interventions, facilities and authorities

*Lead sponsor

 US Federal

.

.

2

(1)

.

.

6

(<1)

.

.

 Industry

10

(52)

35

(27)

208

(26)

185

(29)

9

(24)

 NIH

.

.

12

(9)

47

(5)

21

(3)

3

(8)

 Other

9

(47)

77

(61)

536

(67)

419

(66)

25

(67)

*Trial location

 US only

6

(31)

77

(61)

485

(61)

255

(40)

17

(45)

 EU only

3

(15)

7

(5)

28

(3)

86

(13)

2

(5)

 US and EU

4

(21)

6

(4)

38

(4)

34

(5)

2

(5)

 Single European country

6

(31)

36

(28)

240

(30)

256

(40)

16

(43)

*No. of countries where trials run

  m

19

126

791

631

37

 Mean

1.53

1.43

1.25

1.70

1.35

 Standard deviation, SD

0.77

1.52

1.10

2.06

1.27

*No. of arms

  m

19

106

700

523

29

 Mean

1.53

1.42

1.60

1.66

1.38

 SD

0.84

0.69

0.85

0.72

0.68

*Year that enrolment to the protocol begins

 <1990

.

.

1

(<1)

2

(<1)

1

(<1)

1

(2)

 1990–1999

.

.

6

(4)

40

(5)

47

(7)

2

(5)

 2000–2004

1

(5)

27

(21)

117

(14)

90

(14)

4

(10)

 2005–2009

5

(26)

42

(33)

266

(33)

263

(41)

15

(40)

 2010–2014

11

(57)

49

(38)

328

(41)

210

(33)

14

(37)

 2015 and after

2

(10)

.

.

25

(3)

14

(2)

1

(2)

 Missing

.

.

1

(<1)

13

(1)

6

(<1)

.

.

Overall recruitment status

 Active, not recruiting

2

(10)

17

(13)

131

(16)

103

(16)

3

(8)

 Completed

7

(36)

44

(34)

308

(38)

258

(40)

14

(37)

 Enrolling by invitation

.

.

3

(2)

8

(1)

3

(<1)

.

.

 Not yet recruiting

2

(10)

6

(4)

26

(3)

22

(3)

3

(8)

 Recruiting

8

(42)

35

(27)

209

(26)

152

(24)

12

(32)

 Suspended

.

.

2

(1)

1

(<1)

7

(1)

.

.

 Terminated

.

.

13

(10)

84

(10)

66

(10)

4

(10)

 Withdrawn

.

.

6

(4)

24

(3)

20

(3)

1

(2)

Primary completion duration (years) g

  m

19

110

713

534

30

 Mean

2.95

4.16

3.81

3.46

3.27

 SD

2.7

3.35

2.88

2.33

1.75

  1. * Covariates considered in the ANOVA/linear regression model as described in Section Statistical analyses
  2. a Member states of the EU and associated countries
  3. b 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
  4. c As defined by the US FDA for trials involving investigational new drugs
  5. d Indicate whether or not a data monitoring committee (DMC) has been appointed for this study
  6. e 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
  7. f Whether the FDA regulated intervention is an “applicable clinical trial” as defined in US Public Law 110–85, Title VIII, Section 801
  8. g The difference between enrolment date and the actual primary completion date where the final subject was examined or received the intervention for the purpose of data collection for the primary outcome or anticipated date where trials were ongoing
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172