A survey to assess animal methods bias in scientific publishing.

Publication of scientific findings is fundamental for research, pushing innovation and generating interventions that benefit society, but it is not without biases. Publication bias is generally recognized as a journal's preference for publishing studies based on the direction and magnitude of results. However, early evidence of a newly recognized type of publication bias has emerged in which journal policy, peer reviewers, or editors request that animal data be provided to validate studies produced using nonanimal-based approaches. We describe herein "animal methods bias" in publishing: a preference for animal-based methods where they may not be necessary or where nonanimal-based methods may be suitable, which affects the likelihood of a manuscript being accepted for publication. To gather evidence of animal methods bias, we set out to collect the experiences and perceptions of scientists and reviewers related to animal- and nonanimal-based experiments during peer review. We created a cross-sectional survey with 33 questions that was completed by 90 respondents working in various biological fields. Twenty-one survey respondents indicated that they have carried out animal-based experiments for the sole purpose of anticipating reviewer requests. Thirty-one survey respondents indicated that they have been asked by peer reviewers to add animal experimental data to their nonanimal study; 14 of these felt the request was sometimes justified, and 11 did not think it was justified. The data presented provide preliminary evidence of animal methods bias and indicate that status quo and conservatism biases may explain such attitudes by peer reviewers and editors.

Author Guide for Addressing Animal Methods Bias in Publishing.

There is growing recognition that animal methods bias, a preference for animal-based methods where they are not necessary or where nonanimal-based methods may already be suitable, can impact the likelihood or timeliness of a manuscript being accepted for publication. Following April 2022 workshop about animal methods bias in scientific publishing, a coalition of scientists and advocates formed a Coalition to Illuminate and Address Animal Methods Bias (COLAAB). The COLAAB has developed this guide to be used by authors who use nonanimal methods to avoid and respond to animal methods bias from manuscript reviewers. It contains information that researchers may use during 1) study design, including how to find and select appropriate nonanimal methods and preregister a research plan, 2) manuscript preparation and submission, including tips for discussing methods and choosing journals and reviewers that may be more receptive to nonanimal methods, and 3) the peer review process, providing suggested language and literature to aid authors in responding to biased reviews. The author's guide for addressing animal methods bias in publishing is a living resource also available online at animalmethodsbias.org, which aims to help ensure fair dissemination of research that uses nonanimal methods and prevent unnecessary experiments on animals.

Increasing the availability of quality human tissue for research.

Advances in 3D and other in vitro tissue model platforms have led to fundamental improvements in research on human disease, development of novel therapies, and safety testing. In addition, histological and cellular investigations of human tissues continue to serve as keystones in understanding disease and health processes. In recognition of the importance of human tissues in research, the Physicians Committee for Responsible Medicine held a workshop. Working closely with key stakeholders from the research community, regulatory agencies, and organ procurement organizations, the goal was to explore, understand, and address the barriers to increased use of human organs, tissues, and cells in research. Workshop participants were tasked with identifying the challenges of accessing and qualifying tissues for research purposes and creating a strategy to help meet the needs of the research communities to increase the availability and quality of human tissues in biomedical and translational research. Break-out groups identified significant challenges in the areas of policy, scientific development, and public engagement with respect to the provision and application of tissues and cells for scientific advancement. Following working group recommendations, stakeholders concluded that there is a need to facilitate the availability and quality of human tissues for the research community, as well as provide a framework for education of the public, medical professionals, and researchers to foster donation and utilization for research in place of animal models. The success of these new initiatives will facilitate greater access to high-quality human tissues for biomedical and translational research and help ensure the transition away from the dependence on animal models.

Alzheimer's Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research.

Dementia and cancer are becoming increasingly prevalent in Western countries. In the last two decades, research focused on Alzheimer's disease (AD) and cancer, in particular, breast cancer (BC) and prostate cancer (PC), has been substantially funded both in Europe and worldwide. While scientific research outcomes have contributed to increase our understanding of the disease etiopathology, still the prevalence of these chronic degenerative conditions remains very high across the globe. By definition, no model is perfect. In particular, animal models of AD, BC, and PC have been and still are traditionally used in basic/fundamental, translational, and preclinical research to study human disease mechanisms, identify new therapeutic targets, and develop new drugs. However, animals do not adequately model some essential features of human disease; therefore, they are often unable to pave the way to the development of drugs effective in human patients. The rise of new technological tools and models in life science, and the increasing need for multidisciplinary approaches have encouraged many interdisciplinary research initiatives. With considerable funds being invested in biomedical research, it is becoming pivotal to define and apply indicators to monitor the contribution to innovation and impact of funded research. Here, we discuss some of the issues underlying translational failure in AD, BC, and PC research, and describe how indicators could be applied to retrospectively measure outputs and impact of funded biomedical research.

A stable producer cell line for the manufacture of a lentiviral vector for gene therapy of Parkinson's disease.

ProSavin is an equine infectious anemia virus vector-based gene therapy for Parkinson's disease for which inducible HEK293T-based producer cell lines (PCLs) have been developed. These cell lines demonstrate stringent tetracycline-regulated expression of the packaging components and yield titers comparable to the established transient production system. A prerequisite for the use of PCL-derived lentiviral vectors (LVs) in clinical applications is the thorough characterization of both the LV and respective PCL with regard to identity and genetic stability. We describe the detailed characterization of two ProSavin PCLs (PS5.8 and PS46.2) and resultant ProSavin vector. The two cell lines demonstrate stable production of vector over a time period sufficient to allow generation of master and working cell banks, and subsequent large-scale vector production. ProSavin generated from the PCLs performs comparably in vivo to that produced by the standard transient transfection process with respect to transduction efficiency and immunogenicity. The development of ProSavin PCLs, and the detailed characterization described here, will aid the advancement of ProSavin for clinical application.