|Year : 2021 | Volume
| Issue : 3 | Page : 211-217
Reporting of Animal Research Studies in Concordance with ARRIVE Guidelines in Indian Medical Journals: A Retrospective Study
Kavita Sawachia1, Shubha Singhal2, Ankita Mishra3, Bhupinder Singh Kalra2
1 Department of Pharmacology, Dr Baba Saheb Ambedkar Medical College, New Delhi, India
2 Department of Pharmacology, Maulana Azad Medical College, New Delhi, India
3 Department of Pharmacology, Vardhman Mahavir Medical College, New Delhi, India
|Date of Submission||08-Jul-2021|
|Date of Decision||11-Aug-2021|
|Date of Acceptance||24-Aug-2021|
|Date of Web Publication||24-Dec-2021|
Dr. Bhupinder Singh Kalra
Department of Pharmacology, Maulana Azad Medical College, New Delhi-110002
Source of Support: None, Conflict of Interest: None
Background: Inappropriate reporting of animal studies has been a serious issue. The Animals in Research: Reporting in Vivo Experiments (ARRIVE) guidelines were published to improve design, analysis, and reporting of animal studies. Methods: The present study is a retrospective observational study of published original research using small laboratory animals. Studies published between the year 2015 and 2020 in Indian Journal of Medical Research (IJMR), Indian Journal of Pharmacology (IJP), Indian Journal of Experimental Biology (IJEB), and Journal of Pharmacology and Pharmacotherapeutics (JPP) were reviewed in accordance with ARRIVE guidelines. Results: Three hundred and seventy-seven studies (JPP n = 15, IJMR n = 37, IJEB n = 157, IJP n = 167) were analyzed. A statement regarding ethics approval was reported in 90.2% of studies. Information regarding randomization and blinding was reported in 20.4% and 0.53% of studies, respectively. Only nine studies mentioned sample-size calculation. Macroenvironmental information such as room temperature/humidity were detailed in 87.5% and light/dark cycle in 96.5% of studies. Concerning microenvironmental conditions, access to food and water was reported in 75% of studies. Only 6.3% studies mentioned the details of adverse events. Information regarding humane endpoint was missing in all studies. Conclusion: Inappropriate and inadequate reporting in some areas of animal research need to be curbed by adhering to ARRIVE guidelines.
Keywords: Animal ethics, animal research, ARRIVE guidelines, preclinical studies
|How to cite this article:|
Sawachia K, Singhal S, Mishra A, Kalra BS. Reporting of Animal Research Studies in Concordance with ARRIVE Guidelines in Indian Medical Journals: A Retrospective Study. MAMC J Med Sci 2021;7:211-7
|How to cite this URL:|
Sawachia K, Singhal S, Mishra A, Kalra BS. Reporting of Animal Research Studies in Concordance with ARRIVE Guidelines in Indian Medical Journals: A Retrospective Study. MAMC J Med Sci [serial online] 2021 [cited 2022 May 29];7:211-7. Available from: https://www.mamcjms.in/text.asp?2021/7/3/211/333606
| Introduction|| |
Preclinical studies provide the preliminary validation of the safety and efficacy of interventions. These studies are also important in determining the entry of new interventions into the clinical research phase. The validation of animal studies must be based on design of the study, standardized experimental procedures, and transparent reporting. Several studies have been conducted which highlighted the issue of poor reporting of animal studies published in different journals.,,
Systematic survey carried out by the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) to assess the quality of experimental design, statistical analysis, and reporting of animal research highlighted various quality issues related to the reporting of animal studies. Developing reporting standard specifically for animal research was also stressed for credibility of animal research and welfare of laboratory animals.
It was also stressed on the importance of improving the quality of reporting, in 2010, The Animals in Research: Reporting in Vivo Experiments (ARRIVE) guidelines were released. These guidelines were drawn up by NC3Rs based at United Kingdom with main objective to improve the design, analysis, and reporting of research. The ARRIVE guideline is a 20-item checklist that was intended to improve the reporting of animal research. This checklist is analogous to CONSORT guidelines for reporting of clinical trials. This checklist includes all the vital information that can also act as a guide in planning and conduct of the study.
The ARRIVE guidelines that were developed to improve the design, analysis, and reporting of research are partially being adhered to.,,, A complete and systematic description of objectives, methodology, statistical analysis, etc., may avoid unnecessary repetition and facilitate data integration from different studies. The problem of poor quality of reporting of preclinical studies is not limited to one region; it has become a global issue. Reporting of animal studies in leading Indian medical journals has been inconsistent and nonuniform as no guidelines were being followed with regard to standard pattern of reporting a research study. It is pertinent not only to conduct the research ethically but also to present the research systematically so as to maximize the output from that research possible.
The quality of reporting animal research studies in the Indian subcontinent on the basis of ARRIVE guideline so far has not been studied. Hence, we thought of taking up this study where we can comment upon quality of publications with regard to animal studies in Indian medical journals.
| Materials and Methods|| |
The present study was a retrospective observational study carried out in the Department of Pharmacology, Maulana Azad Medical College, New Delhi.
Screening and selection of animal studies
Animal studies using small laboratory animals were retrieved from four selected leading journals such as Indian Journal of Medical Research (IJMR), Indian Journal of Pharmacology (IJP), Indian Journal of Experimental Biology (IJEB), and Journal of Pharmacology and Pharmacotherapeutics (JPP).
Inclusion criteria were (1) Animal studies published during the period 2015 to 2020 in selected four Indian journals, and (2) original research studies. Exclusion criteria were (1) papers categorized as in vitro studies, (2) review studies, (3) correspondence, and (4) short communications. Studies were retrieved using search engines such as PubMed, ERMED, Google scholar, journal’s website, etc. Two independent reviewers screened and reviewed a total of 409 studies. Subsequently, authors performed critical review of all publications to determine the eligibility of each of the studies [Figure 1].
|Figure 1 Flow chart depicting number of articles included in the study for analysis. IJEB, Indian Journal of Experimental Biology; IJMR, Indian Journal of Medical Research; IJP, Indian Journal of Pharmacology; JPP, Journal of Pharmacology and Pharmacotherapeutics.|
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Analysis of concordance with ARRIVE guidelines
Selected studies were rated according to the checklist of 20 items mentioned in the ARRIVE guidelines using a dichotomous scale (described = 0, not described = 1). Subitems were added to the checklist that we felt deserved specific attention.
List of subitems added is as follows:
- Item 2 of checklist (abstract): background, research objective, details of species, and strain of animal used were considered as separate subitems.
- Item 6b (study design): randomization and blinding were considered as separate subitems.
- Item 7 (experimental procedures): method of euthanasia considered as separate point.
- Item 8 (experimental animals): species, strain, sex, development stage, and weight were considered as separate subitems.
Descriptive statistics were performed and data were expressed as number (percentage). Each study was assessed against the 20 items of the ARRIVE guidelines, generating percentages of fully reported items. Mean percentages of items were calculated for each journal.
| Results|| |
Among the total 409 studies screened, 377 studies were included in the study [Figure 1].
Reporting of title and abstract section
Concise and accurate title was observed in 91.2% of the reviewed studies. We observed that in abstract of the assessed studies, research objective (99.2%), key methods (98.9%), principal findings (98.4%), and conclusion (95.7%) were adequately reported. However, background (58.3%) and details of animal species and model used (77.9%) were missing [Table 1].
|Table 1 Assessment of title and abstract on the basis of ARRIVE guidelines|
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Reporting of introduction section
Study background, including primary and secondary objectives, were well reported. However, only 19.2% of the studies clearly described rationale for specific animal model used and how that model can address the scientific objectives of the study [Figure 2].
|Figure 2 Assessment of introduction of articles on the basis of ARRIVE guidelines. IJEB, Indian Journal of Experimental Biology; IJMR, Indian Journal of Medical Research; IJP, Indian Journal of Pharmacology; JPP, Journal of Pharmacology and Pharmacotherapeutics.|
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Reporting of methods section
A statement regarding ethics approval was reported in 92.7% of the reviewed publications. There were several key items in study design that were poorly reported. Information regarding randomization was mentioned only in 20.4% of reviewed studies. Blinding was reported in only two publications. Details of sample size calculation were given in 2.3% of the studies. Information regarding how animals were allocated to experimental groups was detailed in 9.7% of the studies. Two-third of the reviewed studies failed to mention euthanasia methods (37.9%) [Table 2]. Basic details about the animals used such as species (96%), strain (88.5%), age (85.9%), weight (67.6%), and source of animals (99.2%) were mentioned in most of the studies [Table 2].
|Table 2 Evaluation of reporting of methods on the basis of ARRIVE guidelines|
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Macroenvironmental information such as room temperature and humidity were detailed in 87.5% of studies and light and dark cycle in 96.5% of studies. Concerning microenvironmental conditions, access to food and water (mostly ad libitum) was reported in 75% in published studies. Housing conditions were mentioned in most of the reviewed studies but information with regard to type of cage, bedding material, and number of animals in each cage was not properly addressed. Details of statistical method used for each analysis and unit of analysis were mentioned in 96% of studies [Table 2].
Assessment of reporting of result and discussion sections
Baseline data were mentioned in 80.6% of assessed studies (57.8% IJMR, 71.3% IJEB, 92.6% IJMR, and 100% JPP). Only in 6.3% of studies, details of all important adverse events were mentioned [Table 3]. Only 14% of the studies commented on the limitation of their study. Implication of the 3Rs was mentioned only in six studies of IJMR out of all 377 studies that were included in the present study [Table 4]. List of funding sources was mentioned in 75% studies [Table 4].
|Table 3 Assessment of reporting of results on the basis of ARRIVE guidelines|
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| Discussion|| |
In our study, we observed inadequacies in reporting of animal studies predominantly with regard to method section. Many studies failed to report complete methodology, results, and other vital information that is important for effective communication.,,
Several steps have been taken to standardize the reporting of in vivo experiments; one such step is ARRIVE guidelines. Studies were conducted globally to measure the impact of ARRIVE guidelines but the results were not very encouraging., In India, the information regarding the quality of published animal studies is inadequate and there is paucity of data about the impact of ARRIVE guidelines.
We observed inadequacies in abstract section, as information with regard to background and animal species and strain used were missing in more than 50% of the studies. The information regarding the animal species or strain used for a particular study was available in 77% of studies. Our study results are in contrast to previous published study, where none of the studies reviewed mentioned the animal strain or species. In our point of view, information about animal species and strain is vital in assessing suitability of animal model to address the research question.
Animal models play a critical role in finding new drug targets, exploration of disease pathophysiology, and in testing of new chemical entities. Validity of animal model opted for research is crucial because an animal model should measure what it purports to measure. Genetic variations within each species or between closely related genetic species can alter the study results. For example, some mouse strains are fully resistant to Ebola virus, others die without specific symptoms and others develop fatal hemorrhagic fever.
Statement regarding ethics approval was mentioned in 90% of the studies which was comparable with the study published in the IJP which reported it to be 97%. Another study compared the reporting of ethics statement in two Indian medical journals in comparison with British Journal of Pharmacology (BJP). In this study, 79% of animal studies published in the Indian journals included ethics committee approval statement. In contrast, it was reported only in 62% of animals studies published in BJP. Similarly, in a systematic review, it was observed that 78% of studies included the approval from Animal Ethic Committee statement.
We also observed that there was insufficient information in the methodology section. The two important indicators of good study design, that is, randomization and blinding, were reported in 20.4% and 0.53% (two studies), respectively. In a study, where quality of reporting of intervention animal studies were assessed using the ARRIVE guidelines, randomization and blinding were reported in 17.1% and 29.3%, respectively. Another retrospective study, also revealed poor reporting of study design in animal studies. The poor reporting of methodologies is one area which needs maximum focus. Inadequate reporting of methodology will make it impossible for researchers to reproduce the model in a new study. Preregistration of animal studies can be more effective tool in solving the problem of poor reporting of methodology, it can tackle the issue at early stage of planning of any animal study. Preregistration as being undertaken for clinical trials (clinical trial registry of India) could improve quality of protocol making as researcher has to register the study and describe all the statistical test/experimental procedure before starting any study.
We also observed that details of the anesthesia, analgesia, or the schedule of drug administration along with route of drug administration were reported inadequately. In a systematic review accessing quality of reporting of published international animal studies, detailed information regarding anesthesia was mentioned only in 33% and information regarding preanesthetic medication was mentioned in 24.9% and postinterventional analgesia in 12.2% of studies. Animal welfare guidelines recommend minimal harm to be inflicted to animals during research. As a result, adequate anesthesia and analgesia should be administered if not contraindicated. Postintervention analgesia is also recommended after completion of intervention to prevent postoperative pain.
Different methods of euthanasia for killing animals may affect outcomes of the study. It was observed in a study that use of different method of euthanasia in rodent models influences the level of inflammatory mediators. It was observed that information regarding method of euthanasia was mentioned in 61.4% of studies published in Indian journals in comparison with 44.4% of BJP studies. In our study, information regarding method of euthanasia was mentioned only in 37.9% of the studies. In ARRIVE guidelines, euthanasia is a part of experimental procedure and not a separate item. We suggest that method of euthanasia must be a separate item in checklist to improve the quality of reporting.
Although information about species, strain and weight of the animal were mentioned in majority of studies, only half of the studies mentioned the developmental stage (age) of the animals (53.8%). Some investigators believe that age of the rodent can be calculated from the bodyweight curves. The correlation of bodyweight and age is highly dependent on life stage, stock, and stage of animal. Moreover, nutritional and environmental factors also affect the weight of the animal. Thus, reporting age of animals in a particular research is important. Diseases such as Alzheimer and osteoarthritis are age related, and testing or screening new drug in young animals can give misleading result. Information regarding health or immune status of the animal was missing in most of the studies. The findings of present study echoed with other studies where the relevant characteristics of animal were inadequate and incomplete in most of the studies.,
A study was conducted to find out the effect of physical and social environmental enrichment on growth and behavior of adolescent male rats. The results revealed that physiologic and behavioral differences are evident soon after differential housing of the rats. We observed that details of husbandry conditions were mentioned in most of the assessed studies but failed to mention information regarding enrichment (1.3%) and welfare-related assessment (10.8%).
We found that only few studies (1.5%) provided a statement regarding the implication of 3R procedures in animal welfare. These 3Rs are being globally practiced to replace animal models with other in vivo alternatives, refine the techniques to minimize pain/suffering and reducing the number of animals in research study to the extent of statistical significance only. This can only be improved by appropriate training of researchers. Education and training are needed to raise awareness and courses in laboratory animal sciences can be helpful in improving the present scenario.
In our study, sample size was not uniform across four journals, we opted for descriptive analysis. In addition, our objective was to bring out quality of reporting with regard to ARRIVE guidelines. We restrained from commenting on editorial process of a journal.
| Conclusion|| |
Overall analysis of studies revealed inadequate and nonuniform reporting of the animal experiments in all four Indian journals. Studies failed to elaborate study design, experimental procedures, and details of husbandry conditions. To standardize the reporting of animal studies and to improve the quality: ARRIVE guidelines are an important tool. It gives a basic frame work for better planning of animal experiments and also for effective communication to solve the issue of reproducibility and transparency. Every journal should implement these guidelines for appraisal and publication of manuscript. Preregistration of animal studies such as clinical trial registry may be a helpful tool in improving the standard of reporting of animal studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]