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VA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（随机化后长达3年）目标。VA肿瘤学国家领导层认识到耳毒性是癌症患者的一个重要问题，但耳毒性监测计划充其量是利用不足，而且在VA中几乎不存在。因此，很少有退伍军人能够在治疗期间从听力变化的早期检测中受益，这可以为在听力损失成为残疾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，以减少听力损失的影响作为治疗的必要后果。阻碍将耳毒性监测纳入以患者为中心的VA护理的障碍包括缺乏设备和无法获得基于证据的、时间效率高的方案，这些方案对有限的人力资源施加了不必要的压力。此外，我们的数据表明，即使早期发现，护理方面的重要差距仍然与康复有关。患有癌症的退伍军人可能需要额外的支持来获得这些服务，以及在整个过程中跟踪他们的系统。具体目标1是开发和验证用于顺铂耳毒性监测的一体化椅侧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，以增加功能，包括i）基于退伍军人和治疗因素的高度准确的听力变化预测工具，ii）畸变产物耳声发射（DPOAE）监测，对于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学报告模板，并提供干预和解释建议。最低程序性能标准包括听力变化预测模型精度在5 dB以内的语音频率和标称DPOAE假阳性识别率（5%）。具体目标2是实施COMP-VA并将其与当前护理标准（SOC）进行对比，即，不一致的监测，在一个平行的两组随机试验。推荐COMP-VA上级于当前SOC的证据包括：i）随机分配至COMP-VA组的退伍军人获得治疗后听力学服务的比率更高，ii）肿瘤学家在考虑剂量调整时使用COMP-VA预测和教育工具，他们认为耳毒性事件是治疗调整的动机，比率更高，和iii）随机分配至COMP-VA的患者在随机分配后1-3年具有相似的无复发存活率，更高的健康相关生活质量结果，与随机分配至SOC的患者相比，耳毒性相关听力损失进展较少。每个临床试验组的有效性将由独立人员使用听力测量进行评估（项目评价，PE）在随机化前和随机化后5周和1年进行。PE将包括耳镜检查、鼓室检查和通过20 kHz的行为气导纯音听力测试。将分别在PE #1和#3以及PE #3时提供询问听力障碍（HHIE、HHIA）和总体健康相关生活质量（FACT-GP）的标准化问卷。PE听力学家将从以下时间开始每隔3个月联系受试者： T=随机化后90天，以确保在此期间遵守听力保护，并促进参与随机化后最终1年的测量。此外，120名对照受试者将以类似于化疗治疗间隔的间隔进行听力测试和DPOAE测量，以建立DPOAE复检参考限值，从中可以检测早期耳蜗损伤。结果将大大增加对接受耳毒性药物治疗的患者进行耳毒性监测的重要性的知识基础，并将告知有关肿瘤护理和听力学首选实践程序的国家政策。结果还将用于确定如何最好地将COMP-VA过渡到全国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.