The Women's Health Study: Addition of New Data to Maximize its Research Impact

描述(由申请人提供)：本申请涉及广泛的挑战领域(04)临床研究，以及特定的挑战主题04-HL-104：对现有数据进行二次分析，以回答重要的临床和预防医学研究问题。我们请求资金支持对女性健康研究(WHS)参与者进行额外一个周期的观察性随访，以确定和验证队列受试者中的心血管疾病(CVD)和癌症终点，以保留工作，支持初级教员的研究，并增加继续和发起临床重要问题评估的能力。WHS始于1992年，最初是一项阿司匹林和维生素E在心血管疾病和癌症一级预防中的随机试验，对象为39,876名年龄为45岁的女性卫生专业人员。经过平均10年的治疗和随访，于2004年完成，现在对参与者进行观察跟踪，返回每年的终点和风险因素问卷。发病率随访率远高于90%；死亡率随访率几乎为100%；完成了对自我报告的心血管疾病和癌症终点约90%的医疗记录的审查。因此，WHS是女性研究的非凡资源，因为它不仅拥有广泛的人口统计、生活方式和病史风险因素数据以及平均15年间每年收集的39,000多名女性的心血管疾病和癌症结局数据，而且还拥有超过28,000名参与者的全面的基于血浆的生物标记物和基因数据(包括全基因组扫描)。然而，我们目前的NIH资金支持心血管和癌症终点的确定和验证(女性健康研究：继续随访-CA047988)，将于2009年6月30日结束(我们目前的NHLBI资助(HL080467)仅为基因分析提供支持，而不支持任何终点确定)。虽然这笔资金将使我们能够如期在5月发出2009年的后续调查问卷，但我们没有资金来处理这些问卷、获得参与者对自我报告的终端的医疗记录审查的同意、获取医疗记录或通过我们的终端医生委员会进行验证。我们的竞争续签申请得到了肯定的审查，但没有收到可资助的分数，我们将在2009年7月重新提交申请。然而，由于重新提交的时间和随后的开始日期，我们将无法为整个2009年的终点周期提供资金，而且由于这一缺口，我们将无法继续维持世界卫生组织目前的人员配置和职能。这一缺口的财务影响是巨大的：如果没有额外的资金，我们将需要解雇5名全职WHS工作人员(研究协调员、程序员、数据经理和两名研究助理)，而对3名WHS研究人员的FTE支持将大幅减少。此外，WHS的研究影响在很大程度上是由可用于支持依赖其资源的研究的经过验证的端点的数量推动的。如果没有额外的后续行动，由此导致的有效终点数量的减少将严重影响WHS调查人员正在进行的许多研究的成功，以及辅助研究和NIH赞助的与其他心血管疾病、癌症和基因组研究人员的合作。由于队列的老龄化，这一额外的跟踪周期将增加来自医疗记录审查的新数据，涉及大约171个有效的CVD和327个有效的癌症终点，增加了许多研究人员可用的统计能力，以充分评估与女性特别相关的特定研究假设。目前有超过29笔资助的辅助赠款和10笔赠款已提交，并正在接受国家卫生研究院的审查，需要这些更新的端点。12名有代表性的调查人员的支持信包括在内，他们的研究依赖于世界卫生组织的这些终点。到目前为止，WHS终点的确定和验证的影响是巨大的，发表了230多份出版物，完成了35项辅助研究。除了促进科学知识，这项提案的资金还将实现美国复苏和再投资法案(ARRA)的目标，即创造和保留就业机会并提振经济。如果得到资助，这项提议将保留预防医学部、布里格姆和妇女医院的5个工作人员职位，并为世界卫生组织的3名教员提供部分支助。产生的数据将支持40多名研究人员的研究努力，他们资助的、提交的或即将提交的辅助研究研究依赖于这些WHS数据。毫无疑问，更多的后续行动(以及由此增加的感兴趣的终点)将最大限度地发挥妇女健康研究的影响，继续促进研究不足的妇女群体中关于心血管疾病和癌症预防的知识状况。妇女健康研究是一项正在进行的(自1992年以来)对一项已完成试验的近40,000名参与者进行的观察性后续研究，旨在增加有关预防妇女心血管疾病和癌症的知识。资金将允许确定和验证一个周期的终点，从而增加评估假设的能力、保留5名工作人员的能力，以及该研究继续成为40多名教师正在进行和计划中的研究的数据来源的能力。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04) Clinical Research, and specific Challenge Topic 04-HL-104: Perform secondary analyses of existing data to answer important clinical and preventive medicine research questions. We request funding to support one additional cycle of observational follow-up of Women's Health Study (WHS) participants, to ascertain and validate cardiovascular disease (CVD) and cancer endpoints among cohort subjects, in order to retain jobs, support the research of junior faculty, and have increased power to both continue and initiate the evaluation of clinically important questions. The WHS began in 1992 as a randomized trial of aspirin and vitamin E in the primary prevention of CVD and cancer among 39,876 female health professionals aged e45 years. Completed in 2004 after an average of 10 years of treatment and follow-up, the participants are now followed observationally, returning yearly endpoint and risk factor questionnaires. Morbidity follow-up is well over 90%; mortality follow-up virtually 100%; and review completed of about 90% of medical records for self-reported CVD and cancer endpoints. Thus, the WHS is an extraordinary resource for research in women, in that not only does it have extensive demographic, lifestyle and medical history risk factor data as well as CVD and cancer outcome data for over 39,000 women collected yearly over an average of 15 years, but it also has comprehensive plasma-based biomarker and genetic data (including whole genome scans) available on over 28,000 participants. However, our current NIH funding supporting the ascertainment and validation of both the cardiovascular and cancer endpoints (Women's Health Study: Continued Follow-up - CA047988), ends on 6/30/09 (our current NHLBI funding (HL080467) provides support only for genetic analyses, not for any endpoint ascertainment). While this funding will allow us to mail out the 2009 follow-up questionnaires in May as scheduled, we have NO funding to process these questionnaires, obtain participant consent for medical record review of self-reported endpoints, obtain medical records, or validate through our Endpoints Committee of physicians. Our competing renewal application was positively reviewed but did not receive a fundable score, and we are resubmitting the application in July, 2009. However, because of the timing of this resubmission and subsequent start date, we will have no funding for the entire 2009 cycle of endpoints, and because of this gap, we will not be able to continue the current WHS staffing and functions. The financial impact of this gap is substantial: without additional funding, we will need to lay off 5 FTE WHS staff members (the study coordinator, programmer, data manager, and two research assistants) and FTE support for three WHS research faculty will be substantially reduced. Moreover, the research impact of the WHS is substantially driven by the number of validated endpoints available to power the studies which depend upon its resources. Without additional follow-up, the resultant decrease in the number of validated endpoints will critically adversely impact the success of many ongoing investigations by WHS investigators, as well as ancillary studies and NIH-sponsored collaborations with other CVD, cancer and genomic investigators. Because of the aging of the cohort, this one additional cycle of follow-up will add new data from medical record review for an estimated 171 validated CVD and 327 validated cancer endpoints, increasing the statistical power available for many investigators to adequately evaluate specific research hypotheses of particular relevance to women. There are currently over 29 currently funded ancillary grants and 10 grants submitted and under NIH review requiring these updated endpoints. Letters of Support from 12 representative investigators whose studies are dependent on these endpoints from the WHS are included. The impact of the ascertainment and validation of WHS endpoints to date has been substantial, with over 230 publications and 35 completed ancillary studies. In addition to furthering scientific knowledge, funding of this proposal will fulfill the goal of the American Recovery and Reinvestment Act (ARRA) to create and retain jobs and boost the economy. If funded, this proposal will retain 5 staff positions in the Division of Preventive Medicine, Brigham and Women's Hospital, as well as partial support for three WHS faculty. The data generated will support the research efforts of more than 40 research faculty whose funded, submitted or about to be submitted ancillary research studies are dependent on these WHS data. Additional follow-up (and the resulting increase in the endpoints of interest) will, without question, maximize the impact of the Women's Health Study in continuing to contribute to the state of knowledge concerning CVD and cancer prevention in the understudied population of women. The Women's Health Study is an ongoing (since 1992) observational follow-up study of almost 40,000 participants from a completed trial, designed to add knowledge concerning prevention of cardiovascular disease and cancer in women. Funding will allow the ascertainment and validation of one cycle of endpoints, allowing increased power to evaluate hypotheses, the ability to retain 5 staff members, and the ability for the study to continue to be a source of data for ongoing and planned research of over 40 faculty.