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Table 1 Characteristics of the HPV vaccine industry study programmes and non-industry funded clinical studies

From: Index of the human papillomavirus (HPV) vaccine industry clinical study programmes and non-industry funded studies: a necessary basis to address reporting bias in a systematic review

Study characteristics Industry HPV vaccine studies Non-industry funded HPV vaccine studies P valuek
Total: N = 145 GSK (Cervarix): N = 69 Merck (Gardasil and Gardasil 9): N = 66 Otherj: N = 10 Total: N = 61 Cervarix: N = 6 Gardasil and Gardasil 9: N = 48 Other: N = 7
Type of study
 Randomized clinical trial 96 (67%) 43 (62%) 45 (68%) 8 (80%) 40 (65%) 4 (67%) 33 (69%) 3 (43%) 1.00
 - “Placebo”a comparison 5 of 96
(5%)
0 of 43
(0%)
3 of 45
(7%)
2 of 8
(25%)
12 of 40
(30%)
0 of 4
(0%)
11 of 33
(33%)
1 of 3
(33%)
0.0002
 - Adjuvantb comparison 36 of 96
(39%)
15 of 43
(35%)
19 of 45
(42%)
2 of 8
(25%)
0 of 40
(0%)
0 of 4
(0%)
0 of 33
(0%)
0 of 3
(0%)
<0.0001
 - Vaccinec comparison 51 of 96
(51%)
28 of 43
(65%)
19 of 45
(42%)
4 of 8
(50%)
24 of 40
(60%)
3 of 4
(75%)
19 of 33
(58%)
2 of 3
(67%)
0.57
 - No intervention in control arm 0 of 96
(0%)
0 of 43
(0%)
0 of 45
(0%)
0 of 8
(0%)
3 of 40
(8%)
1 of 4
(25%)
2 of 33
(6%)
0 of 3
(0%)
0.027
 - Unclear 4 of 96
(5%)
0 of 43
(0%)
4 of 45
(9%)
0 of 8
(0%)
1 of 40
(2%)
0 of 4
(0%)
1 of 33
(3%)
0 of 3
(0%)
1.00
 Follow-up to randomized clinical trial 23 (16%) 18 (26%) 5 (8%) 0 (0%) 3 (5%) 0 (0%) 0 (0%) 3 (43%) 0.037
 Non-randomized 24 (16%) 8 (12%) 14 (21%) 2 (20%) 18 (30%) 2 (33%) 15 (31%) 1 (14%) 0.039
 Unclear 2 (1%) 0 (0%) 2 (3%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1.00
Phase of studyd
 I 8 (5%) 2 (3%) 4 (6%) 2 (20%) 6 (10%) 0 (0%) 2 (4%) 4 (57%) 0.36
 II 32 (22%) 14 (20%) 14 (21%) 4 (40%) 7 (11%) 0 (0%) 6 (13%) 1 (14%) 0.081
 III 79 (55%) 44 (64%) 31 (47%) 4 (40%) 10 (16%) 1 (17%) 9 (19%) 0 (0%) <0.0001
 IV 9 (6%) 4 (6%) 5 (8%) 0 (0%) 22 (37%) 5 (83%) 17 (35%) 0 (0%) <0.0001
 Unclear 17 (12%) 5 (7%) 12 (18%) 0 (0%) 16 (26%) 0 (0%) 14 (29%) 2 (29%) 0.013
Type of HPV vaccine used
 Monovalent 5 (3%) 0 (0%) 5 (8%) 0 (0%) 4 (7%) 0 (0%) 0 (0%) 4 (57%) 0.45
 Bivalent (e.g., Cervarix) 76 (52%) 65 (94%) 2 (3%) 9 (90%) 7 (11%) 6 (100%) 0 (0%) 1 (14%) <0.0001
 Quadrivalent (e.g., Gardasil) 43 (30%) 4 (6%) 38 (57%) 1 (10%) 44 (72%) 0 (0%) 44 (92%) 0 (0%) <0.0001
 Octavalent 3 (2%) 0 (0%) 3 (5%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0.56
 Ninevalent (e.g., Gardasil 9) 17 (12%) 0 (0%) 17 (25%) 0 (0%) 4 (7%) 0 (0%) 4 (8%) 0 (0%) 0.45
 Unclear 1 (1%) 0 (0%) 1 (2%) 0 (0%) 2 (3%) 0 (0%) 0 (0%) 2 (29%) 0.21
Funding
 Industry funded study 128
(88%)
69
(100%)
49
(75%)
10
(100%)
0
(0%)
0
(0%)
0
(0%)
0
(0%)
<0.0001
 Industry co-funded study 17 (12%) 0 (0%) 17 (25%)i 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0.004
 Non-industry funded study 0 (0%) 0 (0%) 0 (0%) 0 (0%) 61 (100%) 6 (100%) 48 (100%) 7 (100%) <0.0001
Study completion status
 Completed 110
(76%)
57
(83%)
49
(75%)
4
(40%)
39
(64%)
3
(50%)
29
(60%)
7
(100%)
0.090
 - Mean study time in monthse 36.9
[2; 140]
34.2
[2; 97]
42.1
[8; 140]
15.8
[8; 30]
42.2
[5; 143]
45
[12; 81]
32.6
[6; 66]
56
[5; 143]
NAl
 On going 27 (19%) 7 (10%) 14 (20%) 6 (60%) 19 (31%) 2 (33%) 17 (36%) 0 (0%) 0.066
 Terminated prematurely 5 (3%) 4 (6%) 1 (2%) 0 (0%) 2 (3%) 1 (17%) 1 (2%) 0 (0%) 1.00
 Unclear 3 (2%) 1 (1%) 2 (3%) 0 (0%) 1 (2%) 0 (0%) 1 (2%) 0 (0%) 1.00
Study centre statusf
 Single centre 27 of 106
(25%)
9 of 60
(15%)
11 of 37
(30%)
7 of 9
(78%)
40 of 53
(75%)
6 of 6
(100%)
28 of 41
(68%)
6 of 6
(100%)
<0.0001
 Multicentre 79 of 106 (75%) 51 of 60
(85%)
26 of 37
(70%)
2 of 9
(22%)
13 of 53
(25%)
0 of 6
(0%)
13 of 41
(32%)
0 of 6
(0%)
<0.0001
 - Mean centres per multicentre study 36.5
[2; 105]
35.3
[2; 135]
39.9
[2; 105]
6.0
[2; 10]
21.5
[2; 134]
NA 21.5
[2; 134]
NA NA
 Unclear 39 (27%) 9 (13%) 29 (44%) 1 (10%) 8 (13%) 0 (0%) 7 (15%) 1 (14%) 0.044
Participants
 Both females and males 22 (16%) 4 (5%) 16 (24%) 2 (20%) 19 (31%) 0 (0%) 14 (29%) 5 (71%) 0.013
 Only females 113
(78%)
64
(93%)
41
(62%)
8
(80%)
38
(62%)
6
(100%)
30
(63%)
2
(29%)
0.025
 Only males 5 (3%) 1 (2%) 4 (6%) 0 (0%) 4 (7%) 0 (0%) 4 (8%) 0 (0%) 0.45
Unclear 5 (3%) 0 (0%) 5 (8%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0.32
 Total number of enrolled participantsg 522,298 122,323 376,643 23,332 100,707 42,801 47,452 10,454 <0.0001
 - Mean participants per studyg 3602 [2; 189,629] 1773 [2; 34,206] 6726 [24; 189,629] 2592 [90; 12,000] 1767 [12; 24,000] 8560 [200; 24,000] 1054
[12; 20,000]
1493 [45; 10,000] NA
 - Mean participants per multicentre studyf,g 2388 [20; 34,206] 2073 [20; 34,206] 2692 [67; 14,840] 6450 [900; 12,000] 2745 [75; 20,000] NA 2745 [75; 20,000] NA NA
 - Mean participants per centre in multicentre studiesf,g 66
[2; 1513]
59
[2; 1513]
67
[10; 240]
1075 [450; 1200] 128
[5; 2222]
NA 128
[5; 2222]
NA NA
 Studies with > 1000 participantsg 51 (35%) 22 (32%) 26 (39%) 3 (30%) 10 (16%) 2 (33%) 7 (15%) 1 (14%) 0.007
 Studies with participants under age 18h 77 (53%) 23 (33%) 49 (75%) 5 (50%) 28 (46%) 4 (67%) 23 (48%) 1 (14%) 0.36
  1. aIf a study reported that it used a ‘placebo’ comparator, but the study did not describe the “placebo” (i.e., as saline), we noted the comparator as ‘placebo’
  2. bAdjuvant comparisons contained, for example, the aluminum adjuvants used in Cervarix and Gardasil/Gardasil 9, i.e., aluminum hydroxide (Al[OH]3) and amorphous aluminum hydroxyphosphate sulfate (AAHS), respectively
  3. cVaccine comparisons included: Adacel, Boostrix, Cervarix (compared with Gardasil or Gardasil 9), Dengvaxia, Engerix, Gardasil (compared with Cervarix or Gardasil 9), Gardasil 9 (compared with Cervarix or Gardasil), Havrix, Infanrix, Menactra, Priorix, Repevax, and Twinrix
  4. dIf a study was both a phase I and a phase II study, we noted the study as the uppermost phase (i.e., phase II)
  5. e105 of the 110 completed industry studies and 33 of the 39 completed non-industry studies had information for mean study time
  6. fThe exact number of study centers could be assessed in 106 of the 145 industry studies and 53 of the 61 non-industry studies
  7. gThe number of participants could be assessed in 140 of 145 industry studies and 57 of 61 non-industry studies (studies that were terminated prematurely were not included)
  8. hThe number of participants under age 18 could be assessed in 140 of the 145 industry studies and 59 of the 61 non-industry studies
  9. i10 Merck studies were co-funded with universities, four with hospitals and three with governmental healthcare institutions
  10. jOther HPV vaccine manufacturers were Shanghai Zerun Biotechnology Co., Ltd. and Xiamen Innovax Biotech Co., Ltd
  11. kP values were calculated for total industry studies vs. total non-industry studies with Fisher’s exact test (http://www.langsrud.com/fisher.htm)
  12. lNot applicable