Comprehensive Ototoxicity Monitoring Program for VA: A Randomized Trial

描述(由申请人提供)： 本研究的目标是开发、验证和实施退伍军人医疗保健(COMP-VA)的综合耳毒性监测计划，包括短期(治疗期间)和长期(随机后长达3年)两个目标。退伍军人管理局肿瘤学国家领导层认识到耳毒性是癌症患者面临的一个重要问题，但退伍军人管理局的耳毒性监测项目充其量也只是没有得到充分利用，几乎不存在。因此，能够从治疗期间及早发现听力变化中受益的退伍军人太少，这可以为在听力损失变得无效之前重新考虑药物治疗计划提供一个窗口，并可以导致及时提供听力康复，以减少由于治疗的必要结果而造成的听力损失的影响。阻碍耳毒性监测纳入退伍军人管理局以患者为中心的护理的障碍包括缺乏设备和无法获得以证据为基础的、省时的方案，这对有限的人力资源造成了不必要的压力。此外，我们的数据显示，即使是在早期发现的情况下，与康复有关的护理方面的重要差距仍然存在。患有癌症的退伍军人可能需要额外的支持才能获得这些服务，并需要一个系统在整个过程中跟踪他们。具体目标1是开发和验证用于顺铂耳毒性监测的一体式椅侧COMP-VA。为了实现这一目标，我们的便携式OtoID听力计系统将进行进一步的工程设计，以增强功能，包括i)基于退伍军人和治疗因素的高精度听力变化预测工具，ii)失真产物耳声发射(DPOAE)监测，对无法进行行为测试的危重退伍军人尤为重要，iii)包括节省时间的可定制听力报告模板，以及干预和解释建议。最低程序性能标准包括听力变化预测模型在语音频率内的准确度在5分贝以内，以及标称DPOAE假阳性识别率(5%)。具体目标2是在一项平行的两组随机试验中，实施COMP-VA与当前护理标准(SOC)的对比，即不一致的监测。推荐COMP-VA优于目前SOC的证据将包括：i)退伍军人随机接受COMP-VA治疗后听力服务的比率更高，ii)肿瘤学家在考虑剂量调整时使用COMP-VA预测和教育工具，他们将耳毒性事件视为在更高比率下修改治疗的动机，以及iii)与随机接受SOC治疗的患者相比，随机接受COMP-VA治疗的患者在1-3年内的无复发生存率相似，健康相关的生活质量结果更高，耳毒性相关的听力损失进展更少。每个临床试验组的有效性将由独立人员使用随机化前以及随机化后5周和1年后进行的听力测量(计划评估，PE)进行评估。PE将包括耳镜、鼓室导纳和20 kHz的行为气导纯音听力测试。询问听力障碍(HHIE，HHIA)和全球健康相关生活质量(FACT-GP)的标准化问卷将分别在1号和3号体育课和3号体育课发放。受试者将由体育听力专家每隔3个月联系一次，从 T=随机化后90天，以确保在此期间遵守听力保护，并促进参与最终的随机化后1年测量。此外，120名对照受试者将接受听力测试和DPOAE测量，时间间隔类似于化疗间隔，以建立DPOAE重新测试参考限值，从中可以检测到早期的耳蜗损伤。结果将大大增加监测接受耳毒性药物的患者耳毒性的重要性的知识基础，并将为有关肿瘤学护理和听力学首选实践程序的国家政策提供信息。结果还将用于确定如何最好地在全国范围内将Comp-VA过渡到VA医疗保健。

DESCRIPTION (provided by applicant): The goal of this research is to develop, validate and implement a comprehensive ototoxicity monitoring program for VA healthcare (COMP-VA) with both short term (during treatment) and long term (up to 3 years following randomization) objectives. VA oncology national leadership recognizes ototoxicity as an important problem for cancer patients, yet ototoxicity monitoring programs are at best under-utilized and mostly non- existent in VA. As a result, too few Veterans are able to benefit from early detection of hearing shifts during treatment, which can provide a window for the drug treatment plan to be reconsidered before hearing loss becomes disabling, and can lead to timely provision of aural rehabilitation to reduce the impacts of hearing loss incurred as a necessary consequence of treatment. Barriers that prevent the inclusion of ototoxicity monitoring into VA patient-centered care include lack of equipment and lack of access to evidence-based, time-efficient protocols exerting unwarranted pressure on limited staffing resources. Further, our data show that even with early detection, important gaps in care remain pertaining to rehabilitation. Veterans with cancer may need extra support to access these services, and a system to follow them throughout the process. Specific Aim 1 is to develop and validate an all-in-one chair side COMP-VA for cisplatin ototoxicity monitoring. To accomplish this aim, our portable OtoID audiometer system will undergo further engineering for increased functionality to include i) a highly accurate hearing change prediction tool based on Veteran and treatment factors, ii) distortion-product otoacoustic emission (DPOAE) monitoring, particularly important for critically-ill Veterans unable to be tested behaviorally and iii) incluson of time saving customizable audiological report templates with intervention and interpretation suggestions. Minimum program performance standards include hearing change prediction model accuracy to within 5 dB in the speech frequencies and nominal DPOAE false positive identification rates (5%). Specific Aim 2 is to implement and contrast COMP-VA with the current standard of care (SOC), i.e., inconsistent monitoring, in a parallel two-group randomized trial. Evidence to recommend COMP-VA as superior to the current SOC would include that i) Veterans randomized to COMP-VA access post-treatment Audiology Services at higher rates, ii) Oncologists use COMP-VA prediction and education tools when considering dose modification and they view ototoxic events as motivation for treatment modification at higher rates, and iii) Patients randomized to COMP-VA have similar relapse-free survival rates 1-3 yrs post-randomization, higher health-related quality of life outcomes, and less ototoxic- related hearing loss progression than patients randomized to SOC. The effectiveness of each clinical trial arm will be evaluated by independent personnel using audiometric measures (Program Evaluations, PE) performed prior to randomization and at 5-weeks and 1-year post-randomization. PE will include otoscopy, tympanometry, and behavioral air-conduction pure-tone hearing testing through 20 kHz. Standardized questionnaires that inquire about hearing handicap (HHIE, HHIA) and global health-related of quality of life (FACT-GP) will be given at PE #1 and #3 and at PE #3, respectively. Subjects will be contacted by the PE Audiologist at 3-month intervals starting at T=90 days post-randomization to ensure compliance with hearing protection during this period and to promote participation in the final 1-year post-randomization measurement. In addition, 120 control subjects will have hearing testing and DPOAE measures done at intervals similar to chemotherapy treatment intervals to establish DPOAE retest reference limits from which early cochlear damage can be detected. Results will considerably increase the knowledge base of the importance of monitoring ototoxicity in patients receiving ototoxic medications and will inform national policy pertaining to oncologic care and audiological preferred practice procedures. Results will also be used to determine how best to transition COMP-VA into VA healthcare nationally.