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.

Public Health Relevance

Prevention and rehabilitation of hearing loss and tinnitus, the two most commonly awarded service-connected disabilities, are high priority initiatives in VA. In the last decade, over 33,00 Veterans were treated with cisplatin chemotherapy at VA Medical Centers nationally. If trends continue, over 4000 Veterans will receive cisplatin this year with over half sustaining a permanent hearing shift and nearly 40% developing new tinnitus. Furthermore, most of these Veterans begin treatment with significant hearing loss such that minor hearing shifts substantially influence communication. With improved survivability following cancer treatment, Veterans treated with cisplatin should be approached with the dual goals of effective treatment and preserved quality of life. The proposed study is designed to establish that ototoxicity monitoring when introduced as a comprehensive program of evidence-based protocols will improve Veteran hearing outcomes and quality of life by influencing therapeutic planning and improving access to timely audiological rehabilitation services.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01RX000239-07
Application #
9261388
Study Section
Sensory Systems/Communication Disorders (RRD3)
Project Start
2014-04-01
Project End
2018-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Portland VA Medical Center
Department
Type
Independent Hospitals
DUNS #
089461255
City
Portland
State
OR
Country
United States
Zip Code
97239
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Brungart, Douglas; Schurman, Jaclyn; Konrad-Martin, Dawn et al. (2018) Using tablet-based technology to deliver time-efficient ototoxicity monitoring. Int J Audiol 57:S25-S33
Garinis, Angela C; Cornell, Alexandra; Allada, Gopal et al. (2018) Ototoxicity monitoring through the eyes of the treating physician: Perspectives from pulmonology and medical oncology. Int J Audiol 57:S19-S24
Konrad-Martin, Dawn; Knight, Kristin; McMillan, Garnett P et al. (2017) Long-Term Variability of Distortion-Product Otoacoustic Emissions in Infants and Children and Its Relation to Pediatric Ototoxicity Monitoring. Ear Hear :
Konrad-Martin, Dawn; Poling, Gayla L; Dreisbach, Laura E et al. (2016) Serial Monitoring of Otoacoustic Emissions in Clinical Trials. Otol Neurotol 37:e286-94
Reavis, Kelly M; McMillan, Garnett P; Dille, Marilyn F et al. (2015) Meta-Analysis of Distortion Product Otoacoustic Emission Retest Variability for Serial Monitoring of Cochlear Function in Adults. Ear Hear 36:e251-60
Dille, Marilyn F; McMillan, Garnett P; Helt, Wendy J et al. (2015) A Store-and-Forward Tele-Audiology Solution to Promote Efficient Screenings for Ototoxicity during Cisplatin Cancer Treatment. J Am Acad Audiol 26:750-60
Konrad-Martin, Dawn; Reavis, Kelly M; McMillan, Garnett et al. (2014) Proposed comprehensive ototoxicity monitoring program for VA healthcare (COMP-VA). J Rehabil Res Dev 51:81-100
Konrad-Martin, Dawn; Reavis, Kelly M; McMillan, Garnett P et al. (2012) Multivariate DPOAE metrics for identifying changes in hearing: perspectives from ototoxicity monitoring. Int J Audiol 51 Suppl 1:S51-62
Dille, Marilyn F; Wilmington, Debra; McMillan, Garnett P et al. (2012) Development and validation of a cisplatin dose-ototoxicity model. J Am Acad Audiol 23:510-21