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，以及具体的挑战主题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妇女健康研究（WHS）参与者进行一个额外周期的观察性随访，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，并增强继续和启动临床重要问题评估的能力。WHS开始于1992年，是一项针对39,876名年龄在45岁之间的女性卫生专业人员的阿司匹林和维生素E初级预防心血管疾病和癌症的随机试验。在平均10年的治疗和随访后于2004年完成，现在对参与者进行观察性随访，每年返回终点和风险因素问卷。发病率随访超过90%；死亡率随访几乎100%；并完成了约90%的自我报告的心血管疾病和癌症终点的医疗记录的审查。因此，WHS是一个非凡的妇女研究资源，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年每年收集的39000多名妇女的心血管疾病和癌症结果数据，而且还拥有综合的基于血浆的生物标志物和遗传数据（包括全基因组扫描），可用于28000多名参与者。然而，我们目前的NIH资助支持心血管和癌症终点的确定和验证（妇女健康研究：持续随访- CA047988），于2009年6月30日结束（我们目前的NHLBI资助（HL080467）仅支持遗传分析，不支持任何终点的确定）。虽然这笔资金将允许我们在5月份如期邮寄2009年的后续调查问卷，但我们没有资金来处理这些调查问卷，获得参与者同意对自我报告的终点进行医疗记录审查，获取医疗记录，或通过我们的终点医生委员会进行验证。我们的竞争续期申请得到了积极的审查，但没有收到一个可资助的分数，我们将在2009年7月重新提交申请。然而，由于这次重新提交的时间和随后的开始日期，我们将没有资金用于整个2009年周期的端点，并且由于这一缺口，我们将无法继续目前的WHS人员配备和职能。这一缺口的财政影响是巨大的：如果没有额外的资金，我们将需要解雇5名全职工作人员（研究协调员、程序员、数据经理和两名研究助理），而全职工作人员对三名全职工作人员的支持将大大减少。此外，WHS的研究影响在很大程度上取决于可用于支持依赖其资源的研究的验证终点的数量。如果没有额外的随访，验证终点数量的减少将严重影响WHS研究者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、癌症和基因组研究者的合作。由于队列的老龄化，这一个额外的随访周期将增加来自医疗记录审查的新数据，估计有171个证实的心血管疾病和327个证实的癌症终点，增加了许多研究人员充分评估与女性特别相关的特定研究假设的统计能力。目前有超过29项资助的辅助拨款和10项提交和正在NIH审查的拨款需要这些更新的终点。包括了12位代表性研究者的支持信，他们的研究依赖于WHS的这些终点。迄今为止，WHS终点的确定和验证的影响是巨大的，有超过230篇出版物和35项完成的辅助研究。除了促进科学知识之外，该提案的资金将实现《美国复苏和再投资法案》（ARRA）的目标，即创造和保留就业机会，促进经济发展。如果获得资助，该提案将保留布莱根妇女医院预防医学部的5个工作人员职位，并为WHS的3名教员提供部分支持。所产生的数据将支持40多个研究学院的研究工作，这些研究学院的资助、提交或即将提交的辅助研究都依赖于这些WHS数据。毫无疑问，更多的随访（以及由此产生的兴趣终点的增加）将最大限度地发挥妇女健康研究的影响，继续为未充分研究的妇女人群中心血管疾病和癌症预防的知识状态做出贡献。妇女健康研究是一项正在进行的（自1992年以来）观察性随访研究，来自一项已完成的试验的近4万名参与者，旨在增加有关预防妇女心血管疾病和癌症的知识。资金将用于确定和验证一个终点周期，从而增加评估假设的能力，保留5名工作人员的能力，以及使该研究继续成为40多名教员正在进行和计划进行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.