BCPT policy for experimental and clinical studies

Inconsistencies in the reproducibility of research findings are of pertinent concern throughout the scientific community. The disclosure of an apparent and low degree of reproducibility has fuelled investigations of causal factors, ranging from behavioural preferences in decision-making/“human nature” and conviction bias to experimental constituents.1-3 The increased awareness has identified several aspects in data collection, analysis and subsequent interpretation to be carefully considered, and a range of preventive measures and considerations has been proposed to improve reproducibility. In this, research transparency has been highlighted as instrumental.2, 4 Enhancing transparency enables independent replication of published findings, and for findings to be reviewed in greater detail, including comparisons of methodology, statistical applications and experimental protocols, raising the credibility and reducing the risk of unnecessary multiplications of performed studies. Basic and Clinical Pharmacology and Toxicology receives an increasing number of manuscript submissions each year. Through the efforts of reviewers assisted by the editorial team, the submitted manuscripts are scrutinized as part of the selection process prior to a putative acceptance for publication. Despite the high quality of many of the submitted manuscripts, the editorial team is frequently faced with rejecting submissions due to insufficient disclosure of experimental details and/or failure to comply with generally accepted standards of experimental design and data analysis. The editorial team has therefore decided to revise the BCPT guidelines for authors in order to ensure that research transparency and standards are uniformly communicated for both experimental/non-clinical and for clinical studies. Extensive efforts have been made to implement an increased focus on the validity of pre-clinical and clinical studies, and to comply with ethical principles, such as the 3R principles for animals applied in research.5, 6 This has resulted in several initiatives outlining good research practice, for example ARRIVE guidelines7; CIOMS-ICLAS principles (https://council.science/member/iclas-international-council-for-laboratory-animal-science/- accessed August 2020) and the experimental design assistant (EDA).8 Recommendations propose several measures to improve reliability during all phases of experimentation starting in the early planning phase. This includes generating a hypothesis prior to designing the experiment, determining statistical power and group sizes based on pre-experimental considerations and diminishing sources of bias (e.g. blinding and randomization) to reduce the risk of flawed statistical analysis and the overestimation of a hypothesized effect (Table 1). In addition, upholding methodological measures to ensure reproducibility and diminish bias in data analyses is crucial. This applies to all methodological aspects and includes randomization and blinding of samples, the identification and use of proper controls and adequate sample sizes (Table 1). Specifically regarding antibody-based analyses such as immunoblotting and immunohistochemistry, used to identify protein expression, for example reflecting therapeutic targets, intracellular signalling and treatment responses. This emphasizes the need for validation of antibody specificity and selectivity, and necessitates clear guidance for the application of these techniques, the need for controls (both positive and negative9) and the most appropriate methods for quantification (Table 2). BCPT supports the five alternative validation pillars as laid out by the International Working Group for Antibody Validation (IWGAV),10 and if an antibody has been evaluated previously, the citation for this work must be included. Stringent methodology regarding quantification of results should be transparent to readers; for example, images of blotting results are included with controls and molecular markers to determine target size. BCPT supports the Resource Identification Initiative (https://www.force11.org/group/resource-identification-initiative, accessed August 2020), which aims to promote research resource identification, discovery and reuse. This initiative, led by the Neuroscience Information Framework and the Oregon Health & Science University Library (https://neuinfo.org/ and https://www.ohsu.edu/library), provides unique identifiers for antibodies, model organisms, cell lines and tools including software and databases. These IDs, called Research Resource Identifiers (RRIDs), can be used to search for all papers where a particular resource was used and to increase access to critical data to help researchers identify suitable reagents and tools. For studies including experimental animals, considerations of animal welfare, such as husbandry, pain management and humane endpoints, are crucial in preserving animal health, hereby complying with welfare legislations and ensuring reproducibility of in vivo studies (Table 3). Sex of the animals is also an issue requiring careful consideration and rationale.11 BCPT endorses the use of reporting guidelines for studies with human participants (clinical studies). The EQUATOR network (Enhancing the QUAlity and Transparency Of health Research) is an international initiative that seeks to promote accurate reporting of health science globally. The network has gathered knowledge and links to guidelines for main study types such as randomized trials (CONSORT), observational studies (STROBE), systematic reviews (PRISMA), study protocols (SPIRIT) and clinical practice guidelines (AGREE). The EQUATOR website (available at http://www.equator-network.org/—accessed June 2020) currently links to approximately 400 reporting guidelines (Table 4). The website gives general information on how to choose an appropriate guideline. In some situations, more than one guideline is relevant. In such cases, authors should combine the guidelines and make sure to manage all the items adequately. When using any guideline, the article should as a minimum report the content addressed by each item on the identified checklist, or state that the item was not considered in the study (Table 4). www.agreetrust.org https://www.equator-network.org/reporting-guidelines/stard/ Compliance with these basic reporting requirements will greatly improve the value of the manuscript and will facilitate the peer-review process. This replaces the previous version of BCPT guidelines.12