Academic response to improving value and reducing waste: A comprehensive framework for INcreasing QUality In patient-oriented academic clinical REsearch (INQUIRE)

Background
Compelling evidence has demonstrated that a large proportion of investment in biomedical research is wasted; this waste is avoidable. Academic institutions have, thus far, shown limited response to recommendations for increasing value and reducing waste. We formulated an academic response by (i) achieving consensus across a wide range of stakeholder groups on a comprehensive framework for quality of patient-oriented clinical research and (ii) highlighting first successful examples of its operationalization to facilitate waste-reducing strategies at academic institutions.
Methods and findings
Based on a systematic review of quality definitions, concepts, and criteria in the medical literature (systematic MEDLINE search up to February 15, 2015, with independent and in duplicate article selection) and on stakeholder websites from 13 countries (Australia, Austria, Canada, France, Germany, Italy, Japan, Norway, Spain, Sweden, Switzerland, United Kingdom, and United States), we systematically developed a comprehensive framework for the quality of clinical research. We identified websites through personal contacts with experts in clinical research or public health who also suggested, for each country, websites of the following 7 stakeholder groups: patient organizations; academic research infrastructures; governmental bodies; regulatory agencies; ethics committees; the pharmaceutical industry; and funding agencies. In addition, we searched websites of inter- or supranational bodies involved in clinical research until no further insights emerged. After consolidation of the identified definitions, concepts, and criteria of quality in a basic framework structure, we conducted 4 rounds of an adapted online Delphi process among the same 7 stakeholder groups from 16 countries. The Delphi process ultimately achieved consensus on structure and content. The framework addresses 5 study stages (concept, planning and feasibility, conduct, analysis and interpretation, and reporting and knowledge translation) and includes the following dimensions: (i) protection of patient safety and rights, (ii) relevance/patient centeredness and involvement, (iii) minimization of bias (internal validity), (iv) precision, (v) transparency/access to data, and (vi) generalizability (external validity) of study results. These dimensions interact with 2 promoters—infrastructure and sustainability through education—that include a set of factors that may enhance all listed quality dimensions. Each quality dimension contains specific questions and explanatory items that guide quality assessment at each research stage from conceptualization of the research question through reporting and knowledge translation of study results. In the last survey round, Delphi participants from 9 countries (Austria, Australia, Canada, Germany, Italy, the Netherlands, Switzerland, UK, and US) agreed on the structure, content, and wording of the research stages, quality dimensions, specific questions, and descriptive examples of the final framework. In Switzerland, INQUIRE has resulted in a roadmap that guides initiatives to increase value within the Swiss Clinical Trial Organization network and through affiliated researchers.
Conclusions
We present a framework based on a consensus of different stakeholder groups guiding the practical assessment of clinical research quality at all stages of a research project. Operationalization of this common structure will support the increase of value by guiding academic institutions and researchers in developing quality enhancement initiatives, from posing the right research question to the transparent publication of results.

背景
确凿证据表明，生物医学研究中有大量投入被浪费，且此类浪费本可避免。迄今为止，学术机构对提升研究价值、减少浪费的相关建议响应寥寥。为此我们提出了一套学术应对方案：其一，联合多类利益相关方（stakeholder）就以患者为导向的临床研究质量综合框架达成共识；其二，展示该框架落地应用的首批成功案例，以助力学术机构推行减少研究浪费的策略。

方法与结果
本研究通过对医学文献中有关质量的定义、概念与标准开展系统综述（系统检索MEDLINE数据库至2015年2月15日，采用双人独立、重复筛选文献的方式），并梳理了13个国家（澳大利亚、奥地利、加拿大、法国、德国、意大利、日本、挪威、西班牙、瑞典、瑞士、英国、美国）的利益相关方网站，系统性构建了临床研究质量综合框架。
本研究通过与临床研究或公共卫生领域专家的私人联系获取相关网站，这些专家同时为每个国家推荐了以下7类利益相关方的网站：患者组织、学术研究基础设施、政府机构、监管机构、伦理委员会、制药行业以及资助机构。此外，本研究还检索了参与临床研究的国际或超国家机构网站，直至未再获得新的有效信息。
在将筛选得到的质量定义、概念与标准整合至基础框架结构后，我们面向来自16个国家的上述7类利益相关方开展了4轮改良版线上德尔菲（Delphi）调查。本次德尔菲调查最终就框架的结构与内容达成共识。
该框架涵盖5个研究阶段（概念构思、规划与可行性评估、研究实施、分析与解读、成果报告与知识转化），并包含以下质量维度：（1）患者安全与权益保护；（2）研究相关性/以患者为中心与患者参与；（3）偏倚控制（内部效度（internal validity））；（4）研究精准性；（5）数据透明度与可及性；（6）研究结果的外推性（外部效度（external validity））。上述质量维度与两大推动要素相互作用——基础设施建设与通过教育实现的可持续性，这两大要素包含一系列可强化所有前述质量维度的影响因素。
每个质量维度均包含具体问题与说明条目，可指导从研究问题构思到成果报告与知识转化的全研究阶段的质量评估。在最后一轮调查中，来自9个国家（奥地利、澳大利亚、加拿大、德国、意大利、荷兰、瑞士、英国、美国）的德尔菲调查参与者就最终框架的研究阶段、质量维度、具体问题与描述性示例的结构、内容及措辞达成一致。在瑞士，INQUIRE项目已形成一份路线图，用于指导瑞士临床试验组织网络及其附属研究人员开展提升研究价值的相关工作。

结论
本研究提出了一套基于多类利益相关方共识的框架，用于指导研究项目全阶段临床研究质量的实操性评估。该通用框架的落地应用，将通过指导学术机构与研究人员制定质量提升举措（从提出恰当的研究问题到成果的透明发表），助力提升研究价值。