Applying U.S. national guidelines for ototoxicity monitoring in adult patients: perspectives on patient populations, service gaps, barriers and solutions

Figures & data

Table 1. Characteristics of the clinical ototoxicity monitoring programmes (OMPs) examined.

	Oregon Health & Science University (OHSU)CF Clinic	Yale University	Mayo Clinic Rochester, MN	Veteran’s Affairs Portland Health Care System(VA Portland)	Walter Reed
OMP Stage	Planning	Implementation	Implementation	Established	Established
Facility Type	Civilian (Clinic Effort)	Civilian (Clinic Effort)	Civilian (Clinic & Research Effort)	Government (Clinic Effort)	Government (Clinic Effort)
Primary Patient Population
Outpatient	Yes	Yes	Yes	Yes	Yes
Inpatient	No	No	No	No	No
Treatments Targeted
Cisplatin (including chemoradiation)	No	Yes	Yes	Yes	Yes
Carboplatin (including chemoradiation)	No	Yes	Yes	Yes	Yes
Radiation Alone	No	No	Yes (primarily H/N)	No	Yes (primarily H/N)
AMGs	Yes (IV and inhaled)	No	Yes (IV and inhaled)	Yes (IV)	Yes (IV and inhaled)
Mode of Access to Patients
Audiologist staffs MTD, TB and/or oncology clinics	Never	Never	Usually	Never^a	Never
Oncology Referral prior to first treatment	Rarely	Rarely	Usually	Usually for cisplatin^a	Always
Oncology Referral during treatment	Rarely	Sometimes	Usually	Sometimes	Always
Patient Referral during treatment	Rarely	Rarely	Rarely	Rarely	Rarely
Scheduling
Audiology clinic responsible	Yes	Yes	Shared with Oncology	Yes	Shared with Oncology
Locations Used for Monitor Tests
Sound treated booth	Sometimes	Usually	Usually	Usually	Usually
Portable equipment	Usually	Sometimes	Rarely	Rarely	Sometimes

Information is provided regarding the stage of OMP, facility type, aspects of the patient population, how patients are accessed and scheduled and where they are tested. The OMPs ranged from planning and implementation stages, to well-established programmes. Three facilities were civilian health care settings, whereas two were government hospitals. All programmes provided monitoring for any patient by request; however, patients rarely self-referred. Additionally, most sites had only occasional referrals from their physician providers of ototoxic drugs (i.e. from oncology, infections disease or pulmonary medicine). Only one site, Walter Reed, reported consistently obtaining referrals from physician providers in a schedule that supported optimal monitoring. Most facilities targeted only certain patient populations through specific outreach activities [e.g. creating consult templates for use in the medical record, cross-specialty inservices, in some cases, staffing tumour boards, multidisciplinary clinics (MTD) and/or treatment units].

AMG, Aminoglycoside antibiotics; H/N, head and neck cancer; OMP, Ototoxicity Monitoring Program; IV, Intravenous; MTD, Multidisciplinary clinics; TB, Tumour Board Meetings.

^aThe number of referrals at this site increased substantially when MTD and TB clinics began to be staffed as part of an ongoing clinical trial at the VA Portland site (described in Table 4). This is not a task performed by the clinical audiologists at this site.

Table 2. Ototoxicity Monitoring Program (OMP) Objectives, Protocols and Hearing Change Criteria.

	Oregon Health & Science University (OHSU) CF Clinic	Yale University	Mayo Clinic Rochester, MN	Veteran’s Affairs Portland Health Care System(VA Portland)	Walter Reed
OMP objectives	Patient and provider education on ototoxicityFor inhaled AMGs:Consistent monitoring throughout treatment;No specific timeline for testsFor IV-AMGs: Inpatient: baseline, Day 1, 7, 14 and 1-month postOutpatient: bi-annual hearing tests to monitor for hearing shifts.Counseling and Rehabilitation services	Patient and provider education on ototoxicityConsistent monitoring throughout treatmentCounseling and Rehabilitation services	Patient and provider education on ototoxicityBaseline prior to or w/in 24 h of first treatmentMonitor prior to each dose for platin drugs; prior to each cycle for AMGs or radiation alonePost-treatment follow upCounseling and Rehabilitation services	Patient and provider education on ototoxicityPatient-driven monitoring schedule during and after treatmentCounseling and Rehabilitation services	Patient and provider education on ototoxicityBaseline prior to or w/in 24 h of first treatmentMonitor prior to each dose for platin drugs; prior to each cycle for AMGs or radiation alonePost-treatment follow upCounseling and Rehabilitation services
OMP protocol
Recommended baseline	Comprehensive evalTinnitus and dizziness questions	Comprehensive evalTinnitus and dizziness questions	Comprehensive eval + ultra-high frequencies + DPOAEsTinnitus and dizziness questions	Comprehensive eval + ultra-high frequencies 9–12 kHz; Optional DPOAEsTinnitus and dizziness questions	Comprehensive eval + SRO + DPOAEsTinnitus and dizziness questions
Monitor	AC only 0.25–16 kHz + Tympanometry;DPOAEsIf changes detected Comprehensive evalTinnitus and dizziness questions	Comprehensive eval preferred, however, testing abbreviated if time or equipment, or patient tolerance for testing or constrains eval (e.g., no bone conduction, no available high-frequency audiometer)Tinnitus and dizziness questions	AC only 0.25–16 kHz + Tympanometry;DPOAEsIf changes detected Comprehensive evalTinnitus and dizziness questions	Comprehensive if patient schedule permits or if rehabilitation is a focusOtherwise, AC only 0.25–12 kHz + Tympanometry; Additional tests as neededIf changes retest within 24–48 hTinnitus and dizziness questions	AC only SRO frequencies;Tympanometry;DPOAEsIf changes detected Comprehensive evalTinnitus and dizziness questions
Post-treatment	Comprehensive evalTinnitus and dizziness questions	Comprehensive evalTinnitus and dizziness questions	Comprehensive evalTinnitus and dizziness questions	Done only if patient and clinician decide further rehabilitative intervention is necessary; Testing typically is comprehensive eval	Comprehensive evalTinnitus and dizziness questions
Hearing Change Criteria
ASHA	Yes	Yes	Yes	Yes	Yes
CTCAE	No	No	Yes	No	Yes

Facilities had similar OMP objectives, aside from the planned OMP in the Oregon Health & Science University (OHSU) cystic fibrosis (CF) clinic which was solely focussed on monitoring for aminoglycoside (AMG)-induced ototoxicity. Each site recommended obtaining a comprehensive audiometric evaluation at baseline, but all five sites routinely abbreviated monitoring tests. Yale University and VA Portland often attempted comprehensive monitoring tests, but reported having to shorten testing to accommodate patients and adapt to equipment available (i.e. when patient time was limited, testing occurred on the treatment unit or at satellite clinics without sound booths or extensive equipment). All sites reported using American Speech-Language-Hearing (ASHA) 1994 criteria to identify ototoxic hearing shifts. Walter Reed and Mayo Clinic reported also providing oncologists with an indication of whether a hearing shift met Common Terminology Criteria for Adverse Events (CTCAE v4.03, 2010) criteria for an ototoxic adverse event.

AC: Air Conduction Thresholds; AMG: Aminoglycosides; ASHA: American Speech Language Hearing Association; BC: Bone Conduction Thresholds; CTCAE: Common Terminology Criteria for Adverse Events.

Table 3. Randomised clinical trial contrasting two ototoxicity monitoring approaches at the Portland VA.

	Ototoxicity Monitoring Randomised Clinical Trial at VA Portland
	Usual Care Arm^a	Experimental (OtoID) Arm
Primary Patient Population
Outpatient	Yes	Yes
Inpatient	No	No
Treatments Targeted
Cisplatin (including chemoradiation)	Yes	Yes
Mode of Access to Patients
Audiologist staffs MTD, TB and/or  oncology clinics	Never^b	Usually
Oncology Referral prior to first treatment	Usually^c	Always
Oncology Referral during treatment	Sometimes, tends to rely on patient compliance with testing	Rarely, patients are managed as part of the OMP
Patient self-referral during treatment	Never for patients in this trial	Never
Scheduling
	Audiology clinic	Research team, in coordination with oncology nurses
Locations used for monitor tests
Sound booth	Usually	Rarely (follow-up/verification tests only)
Portable equipment	Rarely	Usually
OMP protocol
Monitor	Comprehensive if patient schedule permits or if rehabilitation is a focusOtherwise, AC only 0.25–12 kHz + Tympanometry; Additional tests as neededIf changes retest within 24–48 hTinnitus and dizziness questions	Patient Self-test includes AC in SRO frequencies only with results forwarded to audiologist for review;If ASHA shift is detected: Otoscopy, tympanometry, Clinician retests hearing to confirm change and may test the speech frequencies for functional hearing shifts and/or DPOAEsHearing Handicap Inventory for adults (HHIA) or for the Elderly (HHIE), Tinnitus Functional Index (TFI), Functional Assessment of Cancer Therapy (FACT) QOL questionnaire
Post-treatment	Done only if patient and clinician decide further rehabilitative intervention is necessary; Testing typically is comprehensive eval	AC only 0.5–20 kHz + SRO, Tympanometry, DPOAEs, TFI, HHIA/E, TFI questionnaire, FACTRouted to clinic for additional testing to serve rehabilitive needs
Hearing Change Criteria	ASHA	ASHA + CTCAE

A description of the two arms of the trial are provided. Format of the table is the same as for Table 1. Patients receiving chemotherapy with cisplatin were eligible to take part in the clinical trial. Exclusions included being cognitively or physically unable to participate, having Meniere's disease or active/recent middle ear disorder. Willing participants not excluded were randomised to one of two arms: usual care as provided in the audiology clinic versus monitoring conducted by the research team primarily in the oncology unit using a portable high-frequency audiometer with store and forward capabilities (Oto-ID, experimental arm). For the usual care arm, ototoxicity monitoring services were accessed by patient self-referral and/or treatment provider referral. For the experimental arm, the study team tracked each patient’s treatments using the electronic medical record and sent reminders to the oncology nurses prompting them to provide Oto-ID to patients on each day of treatment with the appropriate baseline comparison test loaded on the device. By comparing protocols for the two arms, it can be seen that testing was more comprehensive for the usual care arm. However, testing occurred far less frequently for the usual care arm (see Table 4 and accompanying text).

AMG, Aminoglycoside antibiotics; H/N, head and neck cancer; IV, Intravenous; MTD, Multidisciplinary clinics; Oto-ID, portable ultra-high frequency audiometer with store and forward telehealth capability; TB, Tumour Board Meetings.

^a Usual Care Arm protocol is the VA Portland audiology clinic protocol, replotted from Table 2. Individuals who decline participation in the research study may still obtain usual care ototoxic monitoring in the audiology clinic.

^b The number of referrals at this site increased substantially when MTD and TB clinics began to be staffed as part of an ongoing clinical trial at the VA Portland site (described in Tables 3 and 4).

^c The research audiologists associated with the trial staff the MTD and TB clinics (i.e., this is not a task performed by the clinical audiologists) at this site.

Table 4. Clinical trial study arm comparison: numbers of hearing evaluations by patient and cisplatin dose.

	Study arm
	Usual care (Arm n = 19)	Oto-ID (Arm n = 21)
Total (N)
Doses of cisplatin administered	109	103
Baseline hearing tests obtained	9	21
Monitor hearing tests obtained	13	103
Average (range)
Doses of cisplatin per patient	5.7 (2–20)	4.9 (1–8)
Monitor hearing tests per patient	0.7 (0–3)	4.9 (1–8)

A baseline hearing evaluation is defined as a hearing test that occurs prior to or within 24 h of the first dose of cisplatin. A monitor evaluation is defined a hearing test that is completed during treatment, after first dose and before last dose of cisplatin. Table shows the number of patients that received a baseline or monitor hearing evaluation by study arm in relation to the number of administered cisplatin doses by study arm for those individuals who had concluded cancer treatment. Less than 50% (9/19) of patients randomized to usual care obtained a baseline prior to treatment. Monitor tests occurred in 47% (9/19) of these patients. Most received just one monitor test during treatment (6 patients) and only 11% (2/19) patients completed a hearing monitor prior to each dose. All 21 patients randomized to the Oto-ID arm had a baseline and a monitor tests prior to each dose. This was facilitated by patient self-testing using the Oto-ID while receiving pre-treatment hydration on the oncology unit.

American Speech-Language-Hearing Association (ASHA). 1994. “Guidelines for the Audiologic Management of Individuals Receiving Cochleotoxic Drug Therapy.” ASHA 36: 11–19.

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Common Terminology Criteria for Adverse Events (CTCAE v4.03). 2010. “National Institutes of Health.” Accessed 27 January 2017. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf

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