Selection process and results
A total of 21713 potentially relevant studies were initially selected. After excluding duplicates and those that did not fulfill the inclusion criteria, 4342 studies were finally included, in which 4925 animal experiments were conducted (as some included multiple animal experiments). The selection process and results are shown in Figure 1.
Basic information of the studies included in the review
The number of citations for each included study ranged from 0 to 12. More than 70% (73.03%, 3171/4342) had been cited fewer than 5 times, of which nearly 50% (47.62%, 1510/3171) had not been cited at all. Only 29.04% (1261/4342) had been published in journals included in the Chinese Science Citation Database. The greatest proportion of first authors were clinicians (45.07%, 1957/4342) (Table 1).
Table 1 Basic information of included studies
Category
|
Feature
|
Total N (%)
|
Citation
|
0
|
1510 (34.78)
|
1—5
|
1661 (38.25)
|
>5
|
1171 (26.97)
|
Categories of journals
|
Professional journals
|
1991 (45.86)
|
Comprehensive journals
|
1654 (38.09)
|
Others
|
697 (16.05)
|
Identities of the first author
|
Clinical doctors
|
1957 (45.07)
|
Postgraduate students
|
740 (17.04)
|
Researchers
|
1645 (37.89)
|
Of the 4925 animal experiments included in the review, the most frequently-used species of animal was the rat (81.26%, 4002/4925), then rabbits (15.07%, 742/4925), and dogs (1.91%, 94/4925). Of the type of intervention, the top three were drugs (82.23%, 4050/4925), surgery (7.39%, 364/4925), and acupuncture (3.70%, 182/4925) (Figure 2). In coverage and classification of related diseases, the top three were circulatory diseases (10.92%, 538/4925), digestive diseases (10.64%, 524/4925), and tumors (9.66%, 476/4925).
Reporting quality of inclusive studies (Figure 3, Table 2)
Table 2 Assessment of reporting quality of included studies
Contact and Subject
|
Item
|
Description
|
Total
|
pre-ARRIVE
|
post-ARRIVE
|
χ2 value
|
P value
|
items assessed as "low risk"
|
items assessed as "low risk"
|
items assessed as "low risk"
|
N
|
%
|
N
|
%
|
N
|
%
|
TITLE
|
|
1
|
Provide as accurate and concise a description of the content of the article as possible.
|
4241
|
97.67
|
2196
|
97.13
|
2045
|
98.27
|
6.25
|
0.012
|
ABSTRACT
|
|
2
|
Provide an accurate summary of the background, research objectives (including details of the species or strain of animal used), key methods, principal findings, and conclusions of the study
|
4117
|
94.82
|
2084
|
92.17
|
2033
|
97.69
|
67.25
|
<0.001
|
INTRODUCTION
|
Background
|
3a
|
Include sufficient scientific background (including relevant references to previous work) to understand the motivation and context for the study, and explain the experimental approach and rationale.
|
4071
|
93.76
|
2057
|
90.98
|
2014
|
96.78
|
62.36
|
<0.001
|
3b
|
Explain how and why the animal species and model being used can address the scientific objectives and, where appropriate, the study’s relevance to human biology.
|
1609
|
37.06
|
737
|
32.60
|
872
|
41.90
|
40.24
|
<0.001
|
Objectives
|
4
|
Clearly describe the primary and any secondary objectives of the study, or specific hypotheses being tested.
|
4248
|
97.84
|
2198
|
97.21
|
2050
|
98.51
|
8.60
|
0.003
|
METHODS
|
Ethical statement
|
5
|
Indicate the nature of the ethical review permissions, relevant licenses (e.g. Animal [Scientific Procedures] Act 1986), and national or institutional guidelines for the care and use of animals, that cover the research.
|
286
|
6.59
|
125
|
5.53
|
161
|
7.74
|
8.59
|
0.003
|
Study design
|
6a
|
For each experiment, give brief details of the study design, including: the number of experimental and control groups.
|
3741
|
86.16
|
1893
|
83.72
|
1848
|
88.80
|
23.44
|
<0.001
|
6b
|
For each experiment, give brief details of the study design, including: any steps taken to minimise the effects of subjective bias when allocating animals to treatment (e.g., randomisation procedure) and when assessing results (e.g., if done, describe who was blinded and when).
|
3961
|
91.23
|
2034
|
89.96
|
1927
|
92.60
|
9.43
|
0.002
|
6c
|
For each experiment, give brief details of the study design, including: the experimental unit (e.g. a single animal, group, or cage of animals).
|
4312
|
99.31
|
2245
|
99.26
|
2067
|
99.33
|
0.02
|
0.890
|
6d
|
For each experiment, give brief details of the study design, including: A time-line diagram or flow chart can be useful to illustrate how complex study designs were carried out.
|
63
|
1.45
|
15
|
0.66
|
48
|
2.31
|
20.46
|
<0.001
|
Experimental procedures
|
7a
|
For each experiment and each experimental group, including controls, provide precise details of all procedures carried out. For example: How (e.g., drug formulation and dose, site and route of administration, anaesthesia and analgesia used [including monitoring], surgical procedure, method of euthanasia). Provide details of any specialist equipment used, including supplier(s).
|
4172
|
96.08
|
2165
|
95.75
|
2007
|
96.44
|
1.37
|
0.242
|
7b
|
For each experiment and each experimental group, including controls, provide precise details of all procedures carried out. For example: When (e.g., time of day).
|
269
|
6.20
|
214
|
9.46
|
55
|
2.64
|
86.78
|
<0.001
|
7c
|
For each experiment and each experimental group, including controls, provide precise details of all procedures carried out. For example: Where (e.g., home cage, laboratory, water maze).
|
513
|
11.81
|
309
|
13.67
|
204
|
9.80
|
15.53
|
<0.001
|
7d
|
For each experiment and each experimental group, including controls, provide precise details of all procedures carried out. For example: Why (e.g., rationale for choice of specific anaesthetic, route of administration, drug dose used).
|
1631
|
37.56
|
806
|
35.65
|
825
|
39.64
|
7.38
|
0.007
|
Experimental animals
|
8a
|
Provide details of the animals used, including species, strain, sex, developmental stage (e.g., mean or median age plus age range), and weight (e.g., mean or median weight plus weight range).
|
4162
|
95.85
|
2160
|
95.53
|
2002
|
96.20
|
1.23
|
0.268
|
8b
|
Provide further relevant information such as the source of animals, international strain nomenclature, genetic modification status (e.g. knock-out or transgenic), genotype, health/immune status, drug- or testnaive, previous procedures, etc.
|
3785
|
87.17
|
1909
|
84.43
|
1876
|
90.15
|
31.68
|
<0.001
|
Housing and husbandry
|
9a
|
Housing (e.g., type of facility, specific pathogen free (SPF); type of cage or housing; bedding material; number of cage companions; tank shape and material etc. for fish).
|
1022
|
23.54
|
409
|
18.09
|
613
|
29.46
|
77.81
|
<0.001
|
9b
|
Husbandry conditions (e.g., breeding programme, light/dark cycle, temperature, quality of water etc. for fish, type of food, access to food and water, environmental enrichment).
|
928
|
21.37
|
338
|
14.98
|
590
|
28.35
|
115.83
|
<0.001
|
9c
|
Welfare-related assessments and interventions that were carried out before, during, or after the experiment.
|
147
|
3.39
|
77
|
3.41
|
70
|
3.36
|
0.01
|
0.939
|
Sample size
|
10a
|
Specify the total number of animals used in each experiment and the number of animals in each experimental group.
|
3440
|
79.23
|
1728
|
76.43
|
1712
|
82.27
|
22.47
|
<0.001
|
10b
|
Explain how the number of animals was decided. Provide details of any sample size calculation used.
|
1
|
0.02
|
0
|
0.00
|
1
|
0.05
|
1.09
|
0.297
|
10c
|
Indicate the number of independent replications of each experiment, if relevant.
|
6
|
0.14
|
4
|
0.18
|
2
|
0.10
|
0.51
|
0.474
|
Allocating animals to
experimental groups
|
11a
|
Give full details of how animals were allocated to experimental groups, including randomization or matching if done.
|
522
|
12.02
|
208
|
9.20
|
314
|
15.09
|
35.54
|
<0.001
|
11b
|
Describe the order in which the animals in the different experimental groups were treated and assessed.
|
4070
|
93.74
|
2100
|
92.88
|
1970
|
94.67
|
5.89
|
0.015
|
Experimental outcomes
|
12
|
Clearly define the primary and secondary experimental outcomes assessed (e.g., cell death, molecular markers, behavioral changes).
|
4071
|
93.76
|
2098
|
92.79
|
1973
|
94.81
|
7.55
|
0.006
|
Statistical methods
|
13a
|
Provide details of the statistical methods used for each analysis.
|
3585
|
82.57
|
1677
|
74.17
|
1908
|
91.69
|
230.97
|
<0.001
|
13b
|
Specify the unit of analysis for each dataset (e.g. single animal, group of animals, single neuron).
|
2840
|
65.41
|
1287
|
56.92
|
1553
|
74.63
|
150.14
|
<0.001
|
13c
|
Describe any methods used to assess whether the data met the assumptions of the statistical approach.
|
662
|
15.25
|
284
|
12.56
|
378
|
18.16
|
26.33
|
<0.001
|
RESULTS
|
Baseline data
|
14
|
For each experimental group, report relevant characteristics and health status of animals (e.g., weight, microbiological status, and drug- or test-naı¨ve) before treatment or testing (this information can often be tabulated).
|
223
|
5.14
|
87
|
3.85
|
136
|
6.54
|
16.06
|
<0.001
|
Numbers analysed
|
15a
|
Report the number of animals in each group included in each analysis. Report absolute numbers (e.g.10/20, not 50%)
|
3023
|
69.62
|
1546
|
68.38
|
1477
|
70.98
|
3.46
|
0.063
|
15b
|
If any animals or data were not included in the analysis, explain why.
|
3213
|
74.00
|
1661
|
73.46
|
1552
|
74.58
|
0.70
|
0.402
|
Outcomes and estimation
|
16
|
Report the results for each analysis carried out, with a measure of precision (e.g, standard error or confidence interval).
|
3811
|
87.77
|
1918
|
84.83
|
1893
|
90.97
|
38.01
|
<0.001
|
Adverse events
|
17a
|
Give details of all important adverse events in each experimental group.
|
64
|
1.47
|
21
|
0.93
|
43
|
2.07
|
9.66
|
0.002
|
17b
|
Describe any modifications to the experimental protocols made to reduce adverse events.
|
1
|
0.02
|
1
|
0.04
|
0
|
0.00
|
0.92
|
0.337
|
DISCUSSION
|
Interpretation
/scientific
implications
|
18a
|
Interpret the results, taking into account the study objectives and hypotheses, current theory, and other relevant studies in the literature.
|
4157
|
95.74
|
2143
|
94.78
|
2014
|
96.78
|
10.62
|
0.001
|
18b
|
Comment on the study limitations including any potential sources of bias, any limitations of the animal model, and the imprecision associated with the results.
|
228
|
5.25
|
103
|
4.56
|
125
|
6.01
|
4.59
|
0.032
|
18c
|
Describe any implications of your experimental methods or findings for the replacement, refinement, or reduction (the 3Rs) of the use of animals in research.
|
15
|
0.35
|
4
|
0.18
|
11
|
0.53
|
3.89
|
0.048
|
Generalisability/translation
|
19
|
Comment on whether, and how, the findings of this study are likely to translate to other species or systems, including any relevance to human biology.
|
281
|
6.47
|
134
|
5.93
|
147
|
7.06
|
2.32
|
0.128
|
Funding
|
20
|
List all funding sources (including grant number) and the role of the funder(s) in the study.
|
47
|
1.08
|
15
|
0.66
|
32
|
1.54
|
7.74
|
0.005
|
The ARRIVE guidelines have 6 sections with 20 items and 39 sub-items. The "low risk" compliance rate of around half of the sub-items (51.28%, 20/39) was less than 50%, of which a "low risk" compliance rate of 90% (18/20) was less than 30%, even 65% (13/20) was less than 10 % and only 28.21% (11/39) was higher than 90%.
① Items relating to the title, abstract, and introduction
For items 1-2, involving the title and abstract, the "low risk" compliance rate was higher than 90%. The "low risk" compliance rate of items 1 and 2 in studies published after 2010 was higher than that of studies published before 2010. The differences between the two groups for both items 1 (P= 0.012) and 2 (P < 0.001) were statistically significant.
For items 3a-4, which involved the abstract, the "low risk" compliance rate was higher than 90%, although the "low risk" compliance rate of item 3b was only 37.06%. The "low risk" compliance rate of items 3a, 3b and 4 in studies published after 2010 was higher than that of studies published before 2010, and the differences between the two years of publication were statistically significant, for item 3a (P< 0.001), 3b (P< 0.001) and 4 (P= 0.003).
② Items relating to methodology
For 28 items (items 5-13c) involving methodology, a "low risk" rate of compliance for items 6a, 6b, 6c, 7a, 8a, 8b, 10a, 11b, 12, 13a and 13b was greater than 50%. A "low risk" compliance rate of items 6b, 6c, 7a, 8a, 11b and 12 was greater than 90%, but less than 50% for items 5, 6d, 7b, 7c, 7d, 9a, 9b, 9c, 10b, 10c, 11a and 13c. Except for item 7d, the "low risk" rate of compliance in the latter group was less than 30%, and for items 5, 6d, 7b, 9c, 10b and sub-item 10c it was even less than 10%. The compliance rate for items 5, 6a, 6b, 6c, 6d, 7a, 7d, 8a, 8b, 9a, 9b, 10a, 10b, 11a, 11b, 12, 13a, 13b and 13c in studies published after 2010 was slightly higher than those before 2010. The differences between the two publication year groups were significantly different for items 5 (P= 0.003), 6a (P< 0.001), 6b (P= 0.002), 6d (P< 0.001), and 6d (P< 0.001), (P< 0.001), 7d (P= 0.007), 8a (P< 0.001), 9a (P< 0.001), 9b (P< 0.001), 10a (P< 0.001), 11a (P< 0.001), 11b (P< 0.015), 12 (P< 0.006), 13a (P< 0.001), 13b (P< 0.001) and 13c (P< 0.001), but not for 6c (P=0.890), 7a (P=0.242), 8a (P=0.268) or 10b (P=0.297). However, the "low risk" compliance rate for items 7b, 7c, 9c and 10c in studies published after 2010 was even lower than in reports published before 2010. The difference between the two publication year groups for items 7b (P< 0.001) and 7c (P< 0.001) was significant, but not for items 9c (P=0.939) or 10c (P=0.474).
③ Items relating to the results and discussion
For items 14-17b involving the results, the "low risk" compliance rate of items 15a, 15b, and 16 was greater than 50%, while for items 14, 17a, and 17b it was less than 6%. The "low risk" compliance rate for items 14, 15a, 15b, 16 and 17a for studies published after 2010 were higher than in studies published after 2010. The differences between the two publication year groups for items 14 (P < 0.001), 16 (P < 0.001) and 17a (P = 0.002) were significant, but not for items 15a (P = 0.063), 15b (P = 0.402) or 17b (P = 0.337).
For items 18a-20 involving the discussion, except for the "low risk" compliance rate of item 18a, which was greater than 90%, that of the other items was lower than 10%. The "low risk" compliance rate of the 5 items in studies published after 2010 was higher than those of studies published prior to 2010. For items 18a (P= 0.001), 18b (P= 0.032), 18c (P= 0.048), and 20 (P= 0.005), the differences between the two publication year groups were significant but not for item 19 (P= 0.128).