Better science for safer medicines: the human imperative

Archibald, Kathy; Tsaioun, Katya; Kenna, J. Gerry; Pound, Pandora

doi:10.1177/0141076818812783

Cited by 14 publications

(19 citation statements)

References 49 publications

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“…The subsequent citing papers belonged to the following categories: in vitro research (1,239), resorting to the use of human biological material (789), laboratory animal biological material (373) or biological material from both sources (12); human research (978), of which 189 studies solely used human participants without concurrent use of in vitro-based research approaches; reviews (844); invasive animal research (464), of which 79 studies solely used live animals without concurrent use of in vitro-based research approaches; opinions (27); and in silico research (16). One hundred and fifty-four citing papers were not categorised due to being unavailable or written in a language other than English, Portuguese or Italian.…”

Section: Citation Analysismentioning

confidence: 99%

The Relevance ofIn Silico,In Vitroand Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder

et al. 2019

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Major depressive disorder (MDD) is the most severe form of depression and the leading cause of disability worldwide. When considering research approaches aimed at understanding MDD, it is important that their effectiveness is evaluated. Here, we assessed the effectiveness of original studies on MDD by rating their contributions to subsequent medical papers on the subject, and we compared the respective contribution of findings from non-human primate (NHP) studies and from human-based in vitro or in silico research approaches. For each publication, we conducted a quantitative citation analysis and a systematic qualitative analysis of the citations. In the majority of cases, human-based research approaches (both in silico and in vitro) received more citations in subsequent human research papers than did NHP studies. In addition, the human-based approaches were considered to be more relevant to the hypotheses and/or to the methods featured in the citing papers. The results of this study suggest that studies based on in silico and in vitro approaches are taken into account by medical researchers more often than are NHP-based approaches. In addition, these human-based approaches are usually cheaper and less ethically contentious than NHP studies. Therefore, we suggest that the traditional animal-based approach for testing medical hypotheses should be revised, and more opportunities created for further developing human-relevant innovative techniques.

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Section: Citation Analysismentioning

confidence: 99%

The Relevance ofIn Silico,In Vitroand Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder

et al. 2019

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“…In recent years, the shift toward a new human-biology-focused paradigm has been broadly encouraged in toxicology and regulatory testing [ 229 ], but also in other research fields, including immunology, human infectious diseases, and nutritional research [ 7 , 80 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 ].…”

Section: Discussionmentioning

confidence: 99%

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

et al. 2020

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The interaction between nutrition and human infectious diseases has always been recognized. With the emergence of molecular tools and post-genomics, high-resolution sequencing technologies, the gut microbiota has been emerging as a key moderator in the complex interplay between nutrients, human body, and infections. Much of the host–microbial and nutrition research is currently based on animals or simplistic in vitro models. Although traditional in vivo and in vitro models have helped to develop mechanistic hypotheses and assess the causality of the host–microbiota interactions, they often fail to faithfully recapitulate the complexity of the human nutrient–microbiome axis in gastrointestinal homeostasis and infections. Over the last decade, remarkable progress in tissue engineering, stem cell biology, microfluidics, sequencing technologies, and computing power has taken place, which has produced a new generation of human-focused, relevant, and predictive tools. These tools, which include patient-derived organoids, organs-on-a-chip, computational analyses, and models, together with multi-omics readouts, represent novel and exciting equipment to advance the research into microbiota, infectious diseases, and nutrition from a human-biology-based perspective. After considering some limitations of the conventional in vivo and in vitro approaches, in this review, we present the main novel available and emerging tools that are suitable for designing human-oriented research.

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“…In an ideal world, drug costs would be low(er) and success rates would be high(er), but even in a less-than-ideal world, it seems that there are shifts in the drug development and testing paradigm that could improve the cost-efficiency of this process and therefore enable a healthier return on investment [ 25 , 26 , 27 , 28 ]. There are well-recognized issues with high attrition rates for all drugs [ 26 , 29 , 30 ], and for oncology, the likelihood of success is estimated at less than 4% [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Patient-Derived Xenograft vs. Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014–2019

Marshall

Triunfol

Seidle

2020

Animals

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Cancer remains a major threat to mortality and morbidity globally, despite intense research and generous funding. Patient-derived xenograft (PDX) models—where tumor biopsies are injected into an animal—were developed to improve the predictive capacity of preclinical animal models. However, recent observations have called into question the clinical relevance, and therefore the translational accuracy, of these. Patient-derived organoids (PDO) use patient tumor samples to create in vitro models that maintain aspects of tumor structure and heterogeneity. We undertook a preliminary analysis of the number of breast, colorectal, and lung cancer research studies using PDX or PDO published worldwide between 2014–2019. We looked for evidence of impacts of this research on human health. The number of publications that focused on PDO is gradually increasing over time, but is still very low compared to publications using PDX models. Support for new research projects using PDO is gradually increasing, a promising indicator of a shift towards more human-relevant approaches to understanding human disease. Overall, increases in total funding for these three major cancer types does not appear to be translating to any consequential increase in outputs, defined for this purpose as publications associated with clinical trials. With increasing public discomfort in research using animals and demands for ‘alternative’ methods, it is timely to consider how to implement non-animal methods more effectively

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Better science for safer medicines: the human imperative

Cited by 14 publications

References 49 publications

The Relevance ofIn Silico,In Vitroand Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder

The Relevance ofIn Silico,In Vitroand Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

Patient-Derived Xenograft vs. Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014–2019

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