Doctoral Dissertation Research: New Therapies and the Multiplication of Disease Diagnoses

博士论文研究：新疗法和疾病诊断的倍增

• 批准号: 1602895
• 负责人: Gil Eyal
• 金额: $ 0.68万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1602895&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; New; Therapies

SES-1602895Gil EyalMoran LevyColumbia UniversityBetween 1950 and 1990 cancer research underwent a radical transformation. Drug screening programs in the 1950s tested single compounds on multiple cancers in heterogeneous patient samples. Yet in the decades that followed the first chemotherapy trials, researchers turned to studies of narrow subcategories of cancer (e.g. metastatic breast cancer in postmenopausal women) to test complex therapies involving surgery, radiotherapy and drug combinations. The shift between these research designs, that are practically mirror images of one another, poses puzzling questions: How has cancer research shifted its structure and orientation? How and when did 'cancer' stop being a meaningful clinical unit? How did multiple cancer diagnoses emerge and come to replace it?This project examines the structuring of cancer research to explain the multiplication of cancer diagnoses. The researchers hypothesize that the effort to improve anticancer drugs through clinical trials was a mechanism for creating new diagnoses. The introduction of statistical expertise pressured cancer scientists to homogenize patient samples so that they could compare treatment and control groups that were as similar as possible. This compelled researchers to narrow down trials' recruitment criteria and to transform diagnostic schemes. The study examines whether prognostic variables used in clinical trials to predict patients' responses to treatment turned into refined recruitment criteria in subsequent trials and were eventually translated into new diagnoses. The increasing specification of diagnosis limited patient pools and slowed down the recruitment of patients that met inclusion criteria. The researchers thus also hypothesize that diagnosis specification increased the collaboration between institutions that could recruit patients, reinforced the need for standardization and sophisticated statistical tools, allowing researchers to conduct multicenter trials and to work with small patient samples, and reinforced specialization in oncology. The researchers conduct comprehensive archival research and analyze materials from all major institutions involved in cancer research: The National Cancer Institute, The Food and Drug Administration, Medicare, Cooperative Research Groups from across the U.S, The U.S. National Library of Medicine and The Mary Lasker Paper Collection.This project offers an important contribution both to sociology of diagnosis and to sociology of standardization and evidence-based-medicine. Sociology of diagnosis asks how are new diagnoses created. The researchers suggest a novel mechanism that drives the creation of diagnoses. That is, medical drugs create opportunities and incentives to develop new diagnoses not only through pharmaceutical marketing and through medicalization of previously non-medical conditions, but also that drugs function to extract data that serve to split up patient populations and existing diagnoses. Sociology of evidence-based-medicine asks how clinical trials became the 'gold standard' of biomedicine. This project suggests that the endogenous effects of clinical trials acted to reinforce trials' golden status by fragmenting diagnosis clinical trials restructured cancer research and reinforced the need for standardization and statistical expertise. This study also offers a critical contribution to the understanding of how scientific procedures (homogenization) interact with exclusion and with disparities in the production of medical knowledge about different population groups.

1950年到1990年之间，癌症研究经历了一个根本性的转变。20世纪50年代的药物筛选计划在异质性患者样本中测试了多种癌症的单一化合物。然而，在第一次化疗试验之后的几十年里，研究人员转向研究狭窄的癌症亚类（例如绝经后妇女的转移性乳腺癌），以测试涉及手术，放疗和药物组合的复杂疗法。这些研究设计之间的转变，实际上是彼此的镜像，提出了令人困惑的问题：癌症研究如何改变其结构和方向？“癌症”是如何以及何时停止成为一个有意义的临床单位的？多种癌症诊断是如何出现并取代它的？这个项目检查癌症研究的结构，以解释癌症诊断的倍增。研究人员假设，通过临床试验改进抗癌药物的努力是创造新诊断的一种机制。统计学专业知识的引入迫使癌症科学家将患者样本同质化，以便他们可以比较尽可能相似的治疗组和对照组。这迫使研究人员缩小试验的招募标准，并改变诊断方案。该研究检查了临床试验中用于预测患者对治疗反应的预后变量是否在随后的试验中变成了精确的招募标准，并最终转化为新的诊断。越来越多的诊断规范限制了患者库，并减缓了符合入选标准的患者的招募。因此，研究人员还假设，诊断规范增加了可以招募患者的机构之间的合作，加强了对标准化和复杂统计工具的需求，允许研究人员进行多中心试验并使用小患者样本，并加强了肿瘤学的专业化。研究人员进行了全面的档案研究，并分析了所有参与癌症研究的主要机构的材料：国家癌症研究所，食品和药物管理局，医疗保险，来自美国各地的合作研究小组，美国国家医学图书馆和玛丽拉斯克论文集。该项目为诊断社会学和标准化和证据社会学做出了重要贡献。基础医学诊断社会学问的是新的诊断是如何产生的。研究人员提出了一种新的机制来驱动诊断的产生。也就是说，医疗药物不仅通过药品营销和通过以前非医疗条件的医疗化创造了开发新诊断的机会和激励，而且药物还可以提取用于分离患者人群和现有诊断的数据。循证医学社会学提出临床试验如何成为生物医学的“黄金标准”。该项目表明，临床试验的内生效应通过分割诊断临床试验、重组癌症研究和加强对标准化和统计专业知识的需求来加强试验的黄金地位。这项研究还为理解科学程序（同质化）如何与排斥和不同人口群体的医学知识生产差异相互作用做出了重要贡献。