Determinants of Participation in an Anal Cancer Prevention Trial

参与肛门癌预防试验的决定因素

• 批准号: 7815335
• 负责人: JOEL Michael PALEFSKY
• 金额: $ 50万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7815335
• 关键词: Address; African American; Anal Intraepithelial Neoplasia; Anti-Retroviral Agents; Anus; Area; Biopsy; Cancer Prevention Trial; Caring; Cervical; Cervical Intraepithelial Neoplasia; Characteristics; Child Care; Cities; Classification; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Control Groups; Cytology; Data; Data Analyses; Education; Employment; Ensure; Epidemic; Ethnic Origin; Ethnic group; Focus Groups; Funding; Gender; General Population; Guidelines; HIV; HIV Seropositivity; Health Services Accessibility; Health Status; Human Papillomavirus; Incentives; Incidence; Individual; Intervention; Intraepithelial Neoplasia; Latino; Light; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Measures; Medical; Medical Research; Methods; Minority; Minority Groups; Molecular; Motivation; Observational Study; Participant; Patients; Performance; Physicians; Population; Population Heterogeneity; Premalignant; Preparation; Prevention; Preventive; Procedures; Provider; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recommendation; Recruitment Activity; Research; Research Design; Resolution; Risk; Sample Size; Sampling; Screening for cancer; Screening procedure; Series; Specimen; Surveys; Testing; Time; Transportation; Underrepresented Minority; United States; United States Public Health Service; Upper arm; Venous blood sampling; Viral Load result; Woman; base; biobank; cervical and anal cancer; comparative effectiveness; demographics; design; digital; effectiveness research; eligible participant; ethnic minority population; experience; health disparity; high risk; men; men who have sex with men; prevent; racial and ethnic; rectal; socioeconomics; standard of care; treatment program; willingness

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (05) Comparative effectiveness research (CER) and specific Challenge Topic, 05-CA-102* Comparative Effectiveness Research on Cancer Screening. The project, "Determinants of participation in an anal cancer prevention trial" is designed to provide information that will be critical to the performance of a pivotal randomized clinical trial of screening and treatment of anal intraepithelial neoplasia (AIN) to prevent anal cancer. Anal cancer is a growing problem in the United States. Increasing by approximately 2 percent per year among both men and women in the general population, it is particularly common among certain high-risk groups such as HIV-positive men and women. Among HIV-positive individuals, the incidence of anal cancer has continued to increase despite the availability of effective anti-retroviral therapy (ART). The current incidence of anal cancer among HIV-positive men who have sex with men (MSM) may be as high as 137/100,000, or more than 10 times the current incidence of cervical cancer in the screened population of women in the U.S., and is higher than the highest incidence of cervical cancer in unscreened populations of women world-wide. The incidence of anal cancer is almost 7-fold higher among HIV-positive women compared with the general population. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) and is preceded by a series of precancerous changes known as anal intraepithelial neoplasia (AIN). The incidence of cervical cancer has been sharply reduced by screening with cervical cytology to identify women with high-grade cervical intraepithelial neoplasia (CIN), which is then treated to prevent progression to cancer. Like cervical cancer anal cancer may be preventable through treatment of the anal equivalent, high-grade AIN (HGAIN). The combination of an unacceptably high incidence of anal cancer with the likelihood that anal cancer is preventable calls for urgent intervention. At this time however, there are no formal guidelines recommending anal screening and treatment of HGAIN. This is because no studies have yet been done to demonstrate that screening for and treatment of HGAIN reduced the incidence of anal cancer. The USPHS guidelines for the care of HIV-positive individuals currently state that "anal cytology screening of HIV-seropositive MSM and of women may be useful preventive measures. However, studies of screening and treatment programs for AIN 2 or 3 need to be implemented before definitive recommendations for anal cytology screening can be made". This application will provide critical information that will support the conduct of such a study, namely determinants of participation in a randomized clinical trial in which 50 percent of participants with HGAIN will be screened and treated, and 50 percent will be observed without treatment. At the end of a 5-year period, the number of anal cancer cases will be compared in both arms. Given the complexities of the underlying clinical issues that might govern willingness to participate, the increasing proportion of underrepresented minorities that comprise the HIV epidemic and the varying issues around participation that each of these racial/ethnic groups might have, a rigorous study to measure these determinants in geographically and racially/ethnically diverse groups that comprise the HIV epidemic in the U.S. is critical. The specific aims of this application are therefore to: 1. To identify and assess the determinants of provider willingness to refer eligible participants; 2. To identify and assess the determinants of patient willingness and motivation to participate in the RCT; and 3. To determine the optimum study design and sample size, and recruitment strategies based on the analysis of data from Aims 1 and 2. This application is responsive to this challenge topic in which data from earlier observational studies would be augmented with physician and patient acceptability data to permit the pivotal RCT to proceed. Although the results of the RCT will set standard of care for HIV-positive men and women, they will also have wide implications beyond that of the HIV-positive population. The results will guide screening and treatment for HIV-negative populations as well, and the study will provide a biobank of clinical specimens that will be invaluable to understanding molecular determinants of progression from anal intraepithelial neoplasia to anal cancer. These results will also be applicable to understanding the factors underlying progression to cervical cancer, and will be particularly important since assembly of such as biobank of women at risk for cervical cancer would be currently impossible given that the standard of care is to treat high-grade CIN to prevent cervical cancer. Finally, this study will have broad influence by informing strategies to enhance participation in clinical studies by underrepresented minority groups. 7. Project Narrative (for lay audience) The incidence of anal cancer among people with HIV is higher than cervical cancer was before routine cervical cytology screening was introduced, but unlike cervical cancer, there are currently no screening recommendations in place for anal cancer. The proposed focus group/survey study will be essential to planning a large definitive randomized controlled trial (RCT) in HIV-positive men and women to test whether treatment of anal cancer precursors identified through anal cytology screening can prevent anal cancer. The RCT planned with the assistance of this proposed study will set the standard of care for HIV- positive men and women, but will also have wide implications for screening and treatment for HIV- negative populations, as well as understanding the factors underlying progression to cervical and anal cancer.

描述（由申请人提供）：本申请涉及广泛的挑战领域（05）比较有效性研究（CER）和特定的挑战主题，05-CA-102* 癌症筛查比较有效性研究。该项目“参与肛门癌预防试验的决定因素”旨在提供对筛查和治疗肛门上皮内瘤变（AIN）以预防肛门癌的关键随机临床试验至关重要的信息。肛门癌在美国是一个日益严重的问题。在一般人群中，男性和女性的发病率每年都以大约2%的速度增长，在某些高危群体中特别常见，如艾滋病毒阳性的男性和女性。在艾滋病毒阳性者中，尽管有有效的抗逆转录病毒疗法，肛门癌的发病率仍在继续增加。目前，艾滋病毒阳性的男男性行为者（MSM）中肛门癌的发病率可能高达137/100，000，是美国筛查的女性人群中宫颈癌发病率的10倍以上，并且高于全世界未经筛查的妇女群体中宫颈癌的最高发病率。艾滋病毒阳性妇女的肛门癌发病率几乎是普通人群的7倍。与宫颈癌一样，肛门癌与人乳头瘤病毒（HPV）有关，并且在此之前会出现一系列癌前病变，称为肛门上皮内瘤变（AIN）。宫颈癌的发病率已大幅下降，通过宫颈细胞学筛查，以确定妇女与高度宫颈上皮内瘤变（CIN），然后治疗，以防止进展为癌症。与宫颈癌一样，肛门癌可以通过治疗肛门等效的高级别AIN（HGAIN）来预防。肛门癌的高发病率与肛门癌是可以预防的可能性相结合，需要紧急干预。然而，目前还没有正式的指南推荐肛门筛查和治疗HGAIN。这是因为还没有研究证明HGAIN的筛查和治疗可以降低肛门癌的发病率。美国公共卫生署关于艾滋病毒阳性者护理的指导方针目前指出，“对艾滋病毒血清阳性的男男性行为者和妇女进行肛门细胞学筛查可能是有用的预防措施。然而，在对肛门细胞学筛查提出明确建议之前，需要对AIN 2或3的筛查和治疗方案进行研究。该应用程序将提供关键信息，以支持此类研究的开展，即参与随机临床试验的决定因素，其中50%的HGAIN参与者将接受筛选和治疗，50%将在不接受治疗的情况下进行观察。在5年期结束时，将比较两组的肛门癌病例数。考虑到潜在的临床问题的复杂性，可能会影响参与的意愿，越来越多的代表性不足的少数民族，包括艾滋病毒流行病和不同的参与问题，这些种族/民族群体可能有，严格的研究，以衡量这些决定因素在地理和种族/民族多样化的群体，包括艾滋病毒流行病在美国是至关重要的。因此，本申请的具体目的是：1.确定和评估提供者愿意转介合格参与者的决定因素; 2.识别和评估患者参与RCT的意愿和动机的决定因素; 3.根据目标1和2的数据分析，确定最佳研究设计和样本量以及招募策略。本申请是对这一挑战主题的回应，其中来自早期观察性研究的数据将用医生和患者可接受性数据进行补充，以允许关键RCT继续进行。虽然随机对照试验的结果将为艾滋病毒阳性男女确定护理标准，但它们也将产生超出艾滋病毒阳性人口的广泛影响。研究结果也将指导HIV阴性人群的筛查和治疗，该研究将提供一个临床标本的生物库，这对于了解从肛门上皮内瘤变进展到肛门癌的分子决定因素非常宝贵。这些结果也将适用于了解宫颈癌进展的潜在因素，并且将特别重要，因为考虑到护理标准是治疗高级别CIN以预防宫颈癌，目前不可能组装诸如宫颈癌风险妇女生物库的组件。最后，这项研究将通过提供战略来提高代表性不足的少数群体对临床研究的参与，从而产生广泛的影响。7.艾滋病毒感染者中肛门癌的发病率高于常规宫颈细胞学筛查引入之前的宫颈癌，但与宫颈癌不同，目前没有针对肛门癌的筛查建议。拟议的焦点小组/调查研究对于计划在HIV阳性男性和女性中进行大型确定性随机对照试验（RCT）以测试通过肛门细胞学筛查确定的肛门癌前体治疗是否可以预防肛门癌至关重要。在这项拟议研究的协助下计划的随机对照试验将为艾滋病毒阳性男性和女性制定护理标准，但也将对艾滋病毒阴性人群的筛查和治疗以及了解宫颈癌和肛门癌进展的潜在因素产生广泛影响。