Table 4.
Analysis of methodological bias of the studies demonstrating the action of plant extracts in the bone repair process.
| Chow et al., 1982 [20] | Juma Ab, 2007 [21] | Sakakura et al., 2007 [22] | Oztürk et al., 2008 [23] | Huh et al., 2009 [24] | Kolios et al., 2009 [25] | Giavaresi et al., 2010 [26] | Kolios et al., 2010 [27] | Lacerda et al., 2010 [28] | Estai et al., 2011 [29] | Sharan et al., 2011 [30] | Ngueguim et al., 2012 [31] | Kumar et al., 2013 [32] | Ngueguim et al., 2013 [33] | He and Shen, 2014 [34] | Neto et al., 2015 [35] | Burim et al., 2016 [36] | Ezirganli et al., 2016 [37] | Selvakumar et al., 2016 [38] | Yang et al., 2016 [39] | Zhuang et al., 2016 [40] | Adhikary et al., 2017 [41] | Chen et al., 2017 [42] | Florence et al., 2017 [43] | Karvande et al., 2017 [44] | Khedgikar et al., 2017 [45] | Neto et al., 2017 [46] | Porwal et al., 2017 [47] | Giaze et al., 2018 [48] | Gurger et al., 2019 [49] | Pal et al., 2019 [50] | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | |||||||||||||||||||||||||||||||||
| Accurate and concise description of the article content | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 29 | 93.55% | ||
|
| |||||||||||||||||||||||||||||||||
| Abstract | |||||||||||||||||||||||||||||||||
| Background summary, research objectives, methods, principal findings, and conclusions | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 24 | 77.42% | |||||||
|
| |||||||||||||||||||||||||||||||||
| Introduction | |||||||||||||||||||||||||||||||||
| Sufficient scientific background | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 30 | 96.77% | |
| Explanation of the experimental approach and rationale | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 31 | 100% |
|
| |||||||||||||||||||||||||||||||||
| Objectives | |||||||||||||||||||||||||||||||||
| Clear primary and second objectives | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 24 | 77.42% | |||||||
|
| |||||||||||||||||||||||||||||||||
| Materials and methods | |||||||||||||||||||||||||||||||||
| Nature of the ethical review permissions, relevant licenses, and national or institutional guidelines for the care and use of animals | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 25 | 80.64% | ||||||
| Study design | |||||||||||||||||||||||||||||||||
| Number of animals per group | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 26 | 83.87% | |||||
| Information on whether the experiment was performed as a blind controlled study | X | X | X | X | X | X | X | X | X | X | 10 | 32.26% | |||||||||||||||||||||
| Experimental procedures | |||||||||||||||||||||||||||||||||
| Treatment description | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 28 | 90.32% | |||
| Treatment dosage | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 29 | 93.55% | ||
| Treatment duration | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 30 | 96.77% | |
| Time of day of treatment administration | X | X | 2 | 6.45% | |||||||||||||||||||||||||||||
| Experimental animals | |||||||||||||||||||||||||||||||||
| Information regarding animal species | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 31 | 100% |
| Animals' strain | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 29 | 93.55% | ||
| Animals' sex | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 27 | 87.09% | ||||
| Animals' weight range | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 30 | 96.77% | |
| Animals' age | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 19 | 61.29% | ||||||||||||
| Description of genetic modification status (knockout, transgenic, SPF) | 0 | 0% | |||||||||||||||||||||||||||||||
| Information related to previous procedures performed on the animals | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 14 | 45.16% | |||||||||||||||||
| Housing and husbandry | |||||||||||||||||||||||||||||||||
| Housing of experimental animals (facility type, cage or housing type, material, number of cage companions) | X | X | X | X | X | X | X | X | X | 9 | 29.03% | ||||||||||||||||||||||
| Husbandry conditions (breeding program, light/dark cycle, temperature, water) | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 15 | 48.39% | ||||||||||||||||
| Welfare-related assessments and interventions that were carried out before, during, or after the experiment | X | X | X | X | X | X | X | X | X | X | 10 | 32.26% | |||||||||||||||||||||
| Sample size | |||||||||||||||||||||||||||||||||
| Total number of animals used in each experimental group and the number of animals in each experimental group | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 23 | 74.19% | ||||||||
| Explanation regarding the decision of the number of animals and details of sample size calculation | X | 1 | 3.22% | ||||||||||||||||||||||||||||||
| Allocating animals to experimental groups | |||||||||||||||||||||||||||||||||
| Full details of how animals were allocated to experimental groups (including randomization or matching) | X | X | X | X | X | X | X | X | X | 9 | 29.03% | ||||||||||||||||||||||
| Order in which the animals in the different experimental groups were treated and assessed | 0 | 0% | |||||||||||||||||||||||||||||||
| Experimental outcomes | |||||||||||||||||||||||||||||||||
| Clear experimental outcomes assessed | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 28 | 90.32% | |||
| Statistical methods | |||||||||||||||||||||||||||||||||
| Statistical methods used for each analysis | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 28 | 90.32% | |||
| Unit of analysis specifications for each dataset | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 27 | 87.09% | ||||
| Methods used to assess whether the data met the assumptions of the statistical approach | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 28 | 90.32% | |||
|
| |||||||||||||||||||||||||||||||||
| Results | |||||||||||||||||||||||||||||||||
| Baseline data | |||||||||||||||||||||||||||||||||
| Description of animals' health status, for each experimental group, before treatment | 0 | 0% | |||||||||||||||||||||||||||||||
| Number analyzed | |||||||||||||||||||||||||||||||||
| Number of animals in each group included in each analysis (absolute numbers) | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 29 | 93.55% | ||
| Animals or data not included in the analysis (and explanation for the exclusion) | X | X | 2 | 6.45% | |||||||||||||||||||||||||||||
| Outcomes and estimation | |||||||||||||||||||||||||||||||||
| Information (mean = standard deviation) | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 28 | 90.32% | |||
| Adverse events | |||||||||||||||||||||||||||||||||
| Information regarding mortality of experimental animals (mean = standard deviation) | X | X | 2 | 6.45% | |||||||||||||||||||||||||||||
| Modifications to the experimental protocols made to reduce adverse events | 0 | 0% | |||||||||||||||||||||||||||||||
|
| |||||||||||||||||||||||||||||||||
| Discussion | |||||||||||||||||||||||||||||||||
| Interpretation/scientific implications | |||||||||||||||||||||||||||||||||
| Interpretation of the results, taking into account the study objectives and hypotheses, current theory, and relevant studies | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 31 | 100% |
| Comments on the study limitations (sources of bias, limitations of the animal model, imprecision associated with the results) | X | X | X | X | X | X | 6 | 19.35% | |||||||||||||||||||||||||
| Generalisability/translation | |||||||||||||||||||||||||||||||||
| Comments on how the findings are likely to translate to other species or systems, including relevance to human biology | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 14 | 45.16% | |||||||||||||||||
| Funding | |||||||||||||||||||||||||||||||||
| List of funding sources and the role of the funder(s) in the study | X | X | X | X | X | X | X | X | X | X | X | X | X | X | 14 | 45.16% | |||||||||||||||||
| Total results | 14 | 21 | 25 | 22 | 30 | 25 | 22 | 25 | 22 | 26 | 24 | 25 | 18 | 25 | 27 | 26 | 31 | 23 | 22 | 24 | 22 | 26 | 26 | 25 | 30 | 24 | 23 | 23 | 25 | 24 | 20 | ||
X: related; unmarked: not related.