The clinical impact of high-profile animal-based research reported in the UK national press: a detailed discussion of articles from 1995, and full search results from the Nexis database

Objectives: We evaluated animal-based biomedical ‘breakthroughs’ reported in the UK national press in 1995 (25 years prior to the conclusion of this study). Based on evidence of over-speculative reporting of biomedical research in other areas (e.g. press releases and scientific papers), we specifically examined animal research in the media, asking, “In a given year, what proportion of animal research ‘breakthroughs’ published in the UK national press had translated, more than 20 years later, to approved interventions?”

Methods: We searched the Nexis media database (LexisNexis.com) for animal-based biomedical reports in the UK national press. The only restrictions were that the intervention should be specific, such as a named drug, gene, biomedical pathway, to facilitate follow-up, and that there should be claims of some clinical promise. 

Main Outcome Measures: Were any interventions approved for human use? If so, when and by which agency? If not, why, and how far did development proceed? Were any other, directly related interventions approved? Did any of the reports over-state human relevance?

Results: Over-speculation and exaggeration of human relevance was evident in all the articles examined. Of 27 unique published ‘breakthroughs’, only one had clearly resulted in human benefit. Twenty were classified as failures, three were inconclusive, and three were partially successful.

Conclusions: The results of animal-based pre-clinical research studies are commonly over-stated in media reports, to prematurely imply often-imminent ‘breakthroughs’ relevant to human medicine.

Methods
The “Nexis” database is an archive of more than 40,000 information sources of various types, including news content, provided by the international company, LexisNexis (lexisnexis.com). Media sources were selected to include ‘UK national newspapers’, in the calendar year 1995. The search strategy involved selecting the ‘Medical research’ index term, then adding the following animal terms to identify news items based on animal research: ‘animal OR mouse OR mice OR rodent OR rat OR dog OR cat OR monkey OR primate OR guinea pig OR rabbit’. Articles that did not describe a clear, direct clinical promise, or that described a non-clinical application (e.g. agricultural or veterinary), or that described onlymechanisms of action, pathophysiology, or diagnosis, or in which the intervention was not of a specific named procedure or compound, or was not speculated to be associated with a specific gene/molecule/pathway, were excluded. For each report, the associated academic publication(s) were obtained, where available, and as much of the following data that were available were extracted: title, news media source, publishing journal, date of publication, author name(s), PubMed ID and links, animal species and numbers used, intervention, preventive/therapeutic in nature, expected clinical benefit and years to expected benefit, relevant text and summary of findings, disease in question, institution, funding body, harms to animals, any salient quotes from authors, any obvious related material, etc.

To investigate whether clinical benefit transpired within 20-plus years, the following websites and sources were consulted: PubMed, the European Medicines Agency (EMA), the UK Medicines and Healthcare Regulatory Agency (MHRA), the US Food and Drug Administration (FDA), clinicaltrials.gov, Medscape.com, the National Institute for Health and Care Excellence (NICE), the British National Formulary (BNF), Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), and the US National Library of Medicine’s TOXNET. Data obtained from thorough searches of these sources were collated, and used to determine the outcome of each ‘breakthrough’ with regard to any further studies that were conducted; whether these were human, animal or both; if clinical trials were conducted, and what the results of these were with respect to efficacy and adverse drug reactions (ADRs); if the drug/intervention reached the market, and if so, if it had been relabelled or recalled. Based on the above, a decision was made, in consultation with colleagues, about whether the 1995 media report had been accurate in reporting the research as a ‘breakthrough’. For clarity: if the intervention in question had not been approved at the time of writing, more than 20 years after the media report, it was classified as ‘Failed’. Some were classified as a ‘Partial success’, if, for example: use was restricted clinically and/or geographically; any use was specific to particular, rather than general, circumstances (i.e. a narrower use than had been claimed); an approved therapy was of questionable efficacy; evidence from other, non-animal research data (including human data) suggested the animal data were not crucial to the ‘breakthrough’; there was an indirect relation between the ‘breakthrough’ and the successful intervention; there was questionable clinical relevance of the animal data, and so on.

研究目标：本研究评估了1995年（即本研究结题前25年）英国全国性媒体报道的基于动物的生物医学「突破性进展」。鉴于其他领域（如新闻稿和学术论文）存在对生物医学研究的过度推测性报道现象，我们专门针对媒体中的动物研究展开调查，旨在探究：在某一给定年份，英国全国性媒体报道的动物研究「突破性进展」中，有多大比例在20余年后成功转化为获批的干预手段？

研究方法：我们通过Nexis媒体数据库（LexisNexis.com，LexisNexis）检索英国全国性媒体报道的基于动物的生物医学相关内容。本次检索仅设置两项限制：其一，干预手段需明确具体，例如命名药物、基因或生物医学通路，以方便后续追踪；其二，报道需宣称该研究具备一定临床前景。

主要结局指标：①相关干预手段是否获批用于人类临床使用？若获批，获批时间及审批机构为何？②若未获批，未获批的原因是什么？其研发推进至何种阶段？③是否有其他直接相关的干预手段获批？④相关报道是否存在夸大人类适用性的情况？

研究结果：所有被分析的报道均存在对人类适用性的过度推测与夸大。在27项独立发表的「突破性进展」中，仅有1项明确实现了人类获益；20项被归类为失败，3项结果不明确，3项为部分成功。

研究结论：基于动物的临床前研究成果常被媒体报道过度夸大，过早宣称其即将成为与人类医学相关的「突破性进展」。

补充研究方法：
Nexis数据库是国际企业LexisNexis（lexisnexis.com）提供的归档资源，涵盖超4万个各类信息源，包含新闻内容。本次研究选取1995日历年的英国全国性报纸作为媒体检索源。检索策略为：首先选取「医学研究」索引词，随后添加以下动物相关检索词以筛选基于动物研究的新闻条目：「动物（animal）、小鼠（mouse/mice）、啮齿类（rodent）、大鼠（rat）、犬（dog）、猫（cat）、猴（monkey）、灵长类（primate）、豚鼠（guinea pig）、兔（rabbit）」。
排除标准如下：未明确提及直接临床前景的报道；涉及非临床应用（如农业或兽医领域）的报道；仅描述作用机制、病理生理学或诊断方法的报道；干预手段未明确为特定命名程序或化合物的报道；未被推测与特定基因/分子/通路相关的报道。
对于每篇报道，尽可能获取其关联的学术出版物（如有），并提取以下可用数据：报道标题、新闻媒体来源、发表期刊、出版日期、作者姓名、PubMed（美国国家医学图书馆PubMed数据库）ID及链接、使用的动物物种及数量、干预手段、干预类型（预防性/治疗性）、预期临床获益及预期获益实现年限、相关文本及研究发现摘要、所针对的疾病、研究机构、资助机构、动物遭受的伤害、作者的相关引述、任何显著关联材料等。

为探究临床获益是否在20余年内实现，本研究查阅了以下网站及数据源：PubMed（美国国家医学图书馆PubMed数据库）、欧洲药品管理局（European Medicines Agency, EMA）、英国药品与医疗保健产品监管局（Medicines and Healthcare Regulatory Agency, MHRA）、美国食品药品监督管理局（Food and Drug Administration, FDA）、clinicaltrials.gov（美国临床试验注册平台）、Medscape.com、英国国家卫生与临床优化研究所（National Institute for Health and Care Excellence, NICE）、英国国家处方集（British National Formulary, BNF）、美国疾病控制与预防中心（Centers for Disease Control and Prevention, CDC）、世界卫生组织（World Health Organization, WHO）以及美国国家医学图书馆的TOXNET数据库。
对上述数据源进行全面检索后，将获取的数据进行整理，以此判定每项「突破性进展」的后续研究进展：包括是否开展了人类研究、动物研究或两者兼具；是否开展临床试验，以及试验在有效性和药品不良反应（adverse drug reactions, ADRs）方面的结果；相关药物/干预手段是否上市，若上市是否存在重新标签或召回情况。
基于上述信息，并与同事协商后，我们判定1995年的媒体报道是否准确将该研究称为「突破性进展」。需明确说明：若在媒体报道发布20余年后的本研究撰写时，相关干预手段仍未获批，则将其归类为「失败」。若出现以下情况，则归类为「部分成功」：例如，临床应用或地理范围受限；仅适用于特定而非通用场景（即应用范围窄于报道宣称的情况）；获批疗法的有效性存疑；其他非动物研究数据（包括人类数据）表明动物数据并非该「突破性进展」的关键依据；「突破性进展」与成功获批的干预手段仅存在间接关联；动物数据的临床相关性存疑，等等。