Accountability and the Role of the Principal Investigator in Multicenter Trials

描述(申请人提供)：制药、生物技术和设备行业为大多数临床试验提供资金。然而，此类试验的责任问题令人担忧，部分原因是有证据表明，此类试验往往有利于该公司的产品，人们担心低估不良事件，以及最近披露的关于代写的情况。对行业赞助的研究负责的一个主要机制是有一名学术首席调查员(PI)，期刊、临床医生和公众认为他是试验的担保人。然而，没有关于PI扮演的角色或他们对主要任务和决策的控制程度的数据。因此，很难知道将私人投资机构视为其审判的担保人是否合理。此外，关于PI的作用还没有详细的公布标准。本建议的目的是：1)根据主要利益攸关方的意见，阐明多中心随机对照试验(RCT)中总体PI应发挥的作用的详细的规范性概念；2)描述主要期刊上发表的多中心随机对照试验的PI对PI的适当角色和责任的态度；3)描述PI在特定试验中所起的实际作用；以及4)检验行业赞助的多中心随机对照试验中的PI与非行业赞助的试验中的PI所扮演的不同角色的假设。为了实现这些目标，我们将与不同利益相关者群体(NIH临床研究负责人；临床试验合作小组和网络主席；PI；行业临床研究负责人；杂志编辑；FDA官员)的代表组成6个德尔福小组。在这些小组之后，将对发表在主要普通、肿瘤学、心血管和精神病学期刊上的多中心随机对照试验的PI进行平行调查，以评估他们对PI角色的规范观点(调查1)和他们作为PI的实际做法(调查2)。这些小组和调查将考虑到主要利益攸关方群体的意见，对多中心试验中总体绩效指标的责任和期望进行第一次详细说明。此外，他们还将提供有关PI在一系列不同试验中的实际作用和责任的数据，为临床研究中关于PI责任的问题提供第一个系统的答案。 公共卫生相关性：本提案涉及的问题对医学和公共卫生具有深远影响。通过医生、患者和监管机构的决定，多中心试验对医学产生了重大影响。鉴于这些审判的根本重要性，必须确认目前保障这些审判的道德操守和廉正的机制。这项提案的结果要么将重申对这些试验的信任，要么将刺激加强临床研究责任制度的发展。

DESCRIPTION (provided by applicant): The pharmaceutical, biotechnology and device industries fund most clinical trials. However, accountability in such trials is the subject of concern, due in part to evidence that such trials tend to favor the company's product, to worries about underreporting of adverse events, and to recent disclosures about ghostwriting. One major mechanism of accountability for industry-sponsored research is the presence of an academic Principal Investigator (PI), whom journals, clinicians and the public view as the trial's guarantor. However, no data are available regarding the roles that PIs play or the degree of control they exercise over major tasks and decisions. Consequently, it is difficult to know whether it is reasonable to view PIs as guarantors of their trials. Furthermore, there are no detailed published standards regarding the PI's role. The Aims of the present proposal are: 1) to articulate a detailed normative conception, based on major stakeholders' views, of the roles that overall PIs in multicenter randomized controlled trials (RCTs) should play; 2) to describe attitudes among PIs of multicenter RCTs published in major journals towards the appropriate roles and responsibilities of the PI; 3) to describe the actual roles that PIs played in particular trials; and 4) to test the hypothesis that PIs in industry-sponsored multicenter RCTs play different roles than do PIs in non-industry sponsored trials. To achieve these Aims, we will conduct 6 Delphi panels with representatives of diverse stakeholder groups (NIH clinical research leaders; clinical trial cooperative-group and network chairs; PIs; industry clinical research leaders; journal editors; FDA officials). These panels will be followed by parallel surveys of PIs of multicenter RCTs published in major general, oncology, cardiovascular and psychiatry journals to assess both their normative views of the PI role (survey 1) and their actual practices as PIs (survey 2). These panels and surveys will provide the first detailed description, taking into account the views of key stakeholder groups, of the responsibilities and expectations of overall PIs in multicenter trials. In addition, they will provide data regarding the actual roles and responsibilities of PIs in a diverse set of trials, providing the first systematic answers to questions about PI accountability in clinical research. PUBLIC HEALTH RELEVANCE: The questions addressed by the present proposal have profound implications for medicine and public health. Through decisions by physicians, patients and regulators, multicenter trials have a major impact on medicine. Given their fundamental importance, it is essential to validate the current mechanisms for guaranteeing the ethics and integrity of these trials. The findings of this proposal will either reaffirm trust in these trials, or will stimulate the development of enhanced systems of accountability for clinical research