Selecting process and results
21713 potentially relevant studies were selected initially. After excluding duplicates and those that is not fulfil the inclusion criteria, 4342 studies were included finally, in which there were 4925 animal experiments (some included multiple animal experiments). The selecting process and results are shown in Figure 1.
Epidemiological Characteristics
Frequency of citation of each inclusive study ranged from 0 to 12; more than 70% (73.03%, 3171/4342) had been cited lower than 5 times, of which nearly 50% (47.62%, 1510/3171) had not been cited. Only 29.04% (1261/4342) were published in journals of Chinese Science Citation Database. The highest proportion of the first authors were clinicians (45.07%, 1957/4342). (Table 1)
Table 1 Basic information of inclusive 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)
|
In 4925 inclusive animal experiments, the top three in the choice of animals are: rats (81.26%, 4002/4925), rabbits (15.07%, 742/4925), and dogs (1.91%, 94/4925). In the type of interventions, the top three are: 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 are: circulatory diseases (10.92%, 538/4925), digestive diseases (10.64%, 524/4925), and tumors (9.66%, 476/4925).
Reporting quality of inclusive studies (Table 2)
Table 2 Assessment of reporting quality of inclusive studies
Contact and Subject
|
Item
|
Description
|
Total
|
<2010 year
|
≥2010 year
|
χ2 value
|
P value
|
“Low risk” items
|
“Low risk” items
|
“Low risk” items
|
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. In terms of this, the "low risk" compliance rate of more than half of sub-items (51.28%, 20/39) is less than 50%, of which the "low risk" compliance rate of 90% (18/20) is less than 30%., even 65% (13/20) is less than 10%; only 28.21% (11/39) is higher than 90%.
In terms of 2 items (items 1-2) involved in the title and abstract, the "low risk" compliance rate of items 1 and 2 is higher than 90%. The "low risk" compliance rate of items 1 and 2 in studies published after 2010 is higher than that of studies published before 2010, and the difference between two groups in item 1 (P= 0.012) and 2 (P < 0.001) have statistical significance.
In terms of 3 items (items 3a-4) involved in abstract,the "low risk" compliance rate of items 3a and 4 is higher than 90%, and the "low risk" compliance rate of item 3b is only 37.06%. The "low risk" compliance rate of items 3a, 3b and 4 in studies published after 2010 is higher than that of studies published before 2010, and the difference between two groups in items 3a (P< 0.001), 3b (P< 0.001) and 4 (P= 0.003) have statistical significance.
In terms of 28 items (items 5-13c) involved in methods,the "low risk" compliance rate of items 6a, 6b, 6c, 7a, 8a, 8b, 10a, 11b, 12, 13A and 13b is more than 50%, of which the "low risk" compliance rate of items 6b, 6c, 7a, 8a, 11b and 12 is more than 90%; the "low risk" compliance rate of items 5, 6d, 7b, 7c, 7d, 9a, 9b, 9c, 10b、10c、11a and 13c is less than 50%, of which the other items except item 7d is less than 30%, and the "low risk" compliance rate of items 5, 6d, 7b, 9c, 10B and sub-item 10C is even less than 10%. The compliance rate of 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 is slightly higher than those before 2010. The difference between two groups in 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) have statistical significance, but the difference between two groups in 6c(P=0.890), 7a (P=0.242), 8a (P=0.268) and 10b (P=0.297) had none of statistical significance. However, the "low risk" compliance rate of items 7b, 7c, 9c and 10c in studies published after 2010 is even lower than those published before 2010. The difference between two groups in items 7b (P< 0.001) and 7C (P< 0.001) have statistical significance, but in item 9C (P=0.939) and 10C (P=0.474) have none of statistical significance.
In terms of the 6 items (items 14-17b) involved in results, the "low risk" compliance rate of items 15a, 15b and 16 is more than 50%, while items 14, 17a and 17b is less than 6%. The "low risk" compliance rate of items 14, 15a, 15b, 16 and 17a in studies published after 2010 is all higher than that of studies published after 2010. The differences between two groups in items 14 (P < 0.001), 16 (P < 0.001) and 17a (P = 0.002) have statistical significance, but in items 15a (P = 0.063) and 15b (P = 0.402) have none of statistical significance; whereas, the differences between two groups in item 17b (P = 0.337) have none of statistical significance.
In items of 5 items (items 18a-20) involved in discussion, except for the "low risk" compliance rate of items 18a is more than 90%, the "low risk" compliance rate of the other items is all less than 10%. The "low risk" compliance rate of 5 items in studies published after 2010 is all higher than that of studies published after 2010. The differences between two groups in items 18a (P= 0.001), 18B (P= 0.032), 18C (P= 0.048) and 20 (P= 0.005) have statistical significance, but the differences between two groups in item 19 (P= 0.128) have none of statistical significance.