Comparative Effectiveness and Cost Effectiveness of Cancer Chemotherapy

描述(申请人提供)：化疗已被证明能有效延长各种恶性肿瘤患者的生存时间。大量临床试验和综合分析的一个关键发现是，乳腺癌的化疗疗效已被证明随着年龄的增长而下降，从50岁以下女性10年死亡率按比例下降27%，50-59岁女性下降14%，60-69岁女性下降8%，而70岁或70岁以上的女性则没有任何益处。即使在1998年、2001年、2005年和2008年的较新试验中增加了更多的患者，对合并结果进行检查时，这些发现仍然保持不变。这些结果是惊人的，因为没有观察到卵巢癌女性患者以及肺癌和结肠癌患者的化疗效果随着年龄的增长而下降。许多临床试验表明，化疗对不同年龄段的肺癌和结肠癌男性和女性以及卵巢癌女性(包括70岁或以上的人群)同样有效。因此，美国国立卫生研究院(NIH)和其他卫生当局的循证化疗临床指南建议70岁以下的乳腺癌患者进行化疗，而对结肠癌、卵巢癌和肺癌患者没有年龄限制的建议。换句话说，强烈建议所有年龄段的结肠癌、卵巢癌和肺癌患者进行化疗。随机对照临床试验被认为是确定一种疗法疗效的金标准。然而，临床试验的参与者往往不能代表社区中不同阶层的患者，而老年患者在临床试验中的代表性明显不足。因此，基于人群的观察性研究可以作为随机对照试验的有益补充，以确定专科中心受控条件下的疗效是否转化为社区的真实有效性，并为社区实践中无法从临床试验中获得的治疗的好处提供有价值的洞察。此外，在某些情况下，由于伦理或后勤问题，随机试验是不可能的，良好的观察性研究可能有助于确定各种药物疗法的比较有效性。因此，迫切需要了解化疗的有效性是否仅对乳腺癌(如临床试验所示)随着年龄的增长而降低，还是对肺癌、结直肠癌和卵巢癌也随年龄的增长而降低，以及不同年龄组和不同肿瘤部位的化疗是否具有成本效益。本申请的具体目的是：1)确定在对照临床试验中观察到的化疗的阶段特异性疗效是否转化为延长65岁或65岁以上社区乳腺癌、卵巢癌、肺癌和结直肠癌患者生存的真实有效性；2)确定化疗有效性与年龄增长之间的关联(即，确定化疗对所有年龄组的这些肿瘤患者是否同样有效)；3)确定各种化疗药物或联合方案特定益处在延长生存期方面的比较有效性及其与年龄和肿瘤类型的关系；4)确定患者和肿瘤特征以及医院和医生因素是否以及在多大程度上影响化疗效果与年龄的关系；5)根据年龄和肿瘤类型确定化疗的成本-效果。我们的方法是从17个监测、流行病学和最终结果(SEER)登记中识别1991年至2005年超过55万名年龄在65岁或以上的乳腺癌、卵巢癌、肺癌和结直肠癌患者(2006年至2007年的癌症病例将从2011年初的新数据链接中增加)，这是一个基于人群的大型队列，占美国人口的25%以上。大量的患者将使我们能够检查化疗在许多亚群中的比较有效性。这项拟议的研究将检验在现实世界社区环境中，化疗与年龄增长有关的比较和成本效益，这是以前从未测试过的。拟议的创新使用全国和基于人群的医疗保险索赔数据，提供有关特定化疗药物或方案的信息，也将允许进行化疗特定效果分析。 与公共卫生相关：本项目的主要目标是确定不同化疗方案在延长65岁或以上社区乳腺癌、卵巢癌、肺癌和结直肠癌患者生存方面的比较效果和成本效益；并确定化疗对所有年龄段的这些肿瘤患者是否同样有效。

DESCRIPTION (provided by applicant): Chemotherapy has been documented to be efficacious in prolonging survival for patients with various malignancies. One critical finding from numerous clinical trials and pooled analyses is that the efficacy of chemotherapy for breast cancer has been shown to decrease with age, from a 27% proportional reduction in 10-year mortality for women less than 50 years of age to 14% for women ages 50-59 years and 8% for women ages 60-69 years, and no benefit for women 70 years or older. These findings have remained constant even when the pooled results were examined with the addition of more patients from more recent trials in 1998, 2001, 2005 and 2008. These results are striking because there has been no decreasing efficacy of chemotherapy observed with advancing age for women with ovarian cancer, and for men and women with lung cancer and colon cancer. Numerous clinical trials have shown that chemotherapy is equally efficacious across different age groups of men and women with lung and colon cancer as well as women with ovarian cancer, including populations 70 years or older. Therefore, evidence-based clinical guidelines on chemotherapy from the National Institutes of Health (NIH) and other health authorities recommend chemotherapy for women with breast cancer less than 70 years old, whereas there are no age-restricted recommendations for patients with colon, ovarian and lung cancer. In other words, chemotherapy is strongly recommended for patients of all age groups with colon, ovarian and lung cancer. Randomized controlled clinical trials are considered to be the gold standard for determining the efficacy of a therapy. However, participants in clinical trials often do not represent a cross-section of patients in the community, and older patients were significantly under-represented in clinical trials. Population-based observational studies can therefore be useful adjuncts to randomized controlled trials in determining whether efficacy under controlled conditions in specialty centers translates into real-world effectiveness in the community and provide valuable insight into the benefit of a therapy in community practices that cannot be obtained from the clinical trials. Furthermore, in some circumstances where the randomized trials are not possible due to ethical or logistical issues, well-conducted observational studies can potentially serve to determine the comparative effectiveness of various drug therapies. Therefore, there is a critical need for information on whether the effectiveness of chemotherapy decreases with age for breast cancer only (as shown in clinical trials), or also decreases with age for lung, colorectal, and ovarian cancer and on whether chemotherapy is cost effective by different age groups and by tumor site. The specific aims of this application are to: 1) determine whether the stage-specific efficacy of chemotherapy observed in controlled clinical trials is translated into real-world effectiveness in prolonging survival among community dwelling patients with breast, ovarian, lung and colorectal cancer at age 65 years or older; 2) determine the association between the effectiveness of chemotherapy and advancing age (i.e., to determine whether chemotherapy is equally effective for all age groups of patients with these tumors); 3) determine the comparative effectiveness of various chemotherapy agents or combination regimen-specific benefits in prolonging survival and their associations with age and tumor type; 4) determine whether and to what extent patient and tumor characteristics as well as hospital and physician factors affect the relationship between the effectiveness of chemotherapy and age; and 5) to determine the cost- effectiveness of chemotherapy by age and tumor type. Our approach is to identify a large nationwide, population-based cohort of over 550,000 patients diagnosed with breast, ovarian, lung and colorectal cancer at age 65 years or older in 1991 through 2005 (with more cancer cases in 2006- 2007 from the new data linkage in early 2011) from the 17 Surveillance, Epidemiology, and End Results (SEER) registries, accounting for over 25% of the U.S. population. The large numbers of patients will enable us to examine the comparative effectiveness of chemotherapy in many subpopulations. This proposed study will examine the comparative- and cost-effectiveness of chemotherapy in association with advancing age across four major tumors in the real world community setting, which has never been tested before. The proposed innovative use of the nationwide and population-based Medicare claims data, which provide information on specific chemotherapy drug or regimens, will also allow for chemotherapy-specific effectiveness analysis. PUBLIC HEALTH RELEVANCE: The main objectives of this project are to determine the comparative effectiveness and cost effectiveness of various chemotherapy regimens in prolonging survival among community dwelling patients with breast, ovarian, lung and colorectal cancer at age 65 or older; and to determine whether chemotherapy is equally effective for all age groups of patients with these tumors.