Foreword: Special Topics in Clinical Monitoring (sponsor DoD Hearing Center of Excellence; Pharmaceutical Interventions for Hearing Loss Group)

This supplemental edition of the International Journal of Audiology (IJA), “Ototoxicity – Special Topics in Clinical Monitoring,” came about via a working group established by the United States Department of Defense (DoD) Hearing Center of Excellence (HCE). The HCE is dedicated to focussing on initiatives regarding the prevention, diagnosis, mitigation, treatment, and rehabilitation of hearing loss and auditory-vestibular system injury for Service members and Veterans. The HCE formed the Pharmaceutical Interventions for Hearing Loss (PIHL) Working Group so that interests from the DoD, Department of Veterans Affairs (VA), the National Institute on Deafness and Communication Disorders (NIDCD), and other federal agencies could be joined with those of academia and industry. An Ototoxicity Monitoring Subcommittee was formed after recognising the need for more standardisation in ototoxicity monitoring protocols and programmes in the DoD and VA, as well as in the private sector. The Ototoxicity Monitoring Subcommittee, a subset of the PIHL Ototoxicity Committee, focuses primarily on clinical issues and solutions to ototoxicity caused by pharmaceuticals and/or ionising radiation.

The audiology community has long known that monitoring for medication-induced ototoxicity is helpful in improving or addressing patients auditory and vestibular outcomes subsequent to therapeutic treatment protocols. Though guidance exists to inform monitoring protocols (ASHA 1994; AAA 2009), these documents align more with specific testing and reporting protocols than with strategies to develop successful programmes. Factors related to design of ototoxicity monitoring programmes (OMP) logistics, promotion of the value and importance of audiologic monitoring to stakeholders, as well as communication of significant findings and recommendations to the patient and patient care team may make it difficult to get a programme off the ground if these issues are not considered in the planning stages.

In order for audiologists to appreciate their role in the treatment care team, it is important to recognise how other care providers view ototoxicity and OMPs. In this supplement, through interviews with four treatment care providers (one oncologist and three pulmonologists) in the United States, Garinis et al. shed light on the physician viewpoint regarding ototoxicity monitoring. Although there was an understanding that ototoxicity is a potential problem and monitoring is important, the approaches to ototoxicity monitoring varied by provider and institution. Maru and Al-Malky developed a questionnaire, presented in this issue, for healthcare providers in the United Kingdom’s National Health Service. Responses from 134 providers indicate that referral methods, testing protocols, and post-treatment follow-up vary widely by treatment centre and provider. These results highlight both the need for national and international protocols for the management and monitoring of ototoxicity, as well as the importance of promoting the services audiologists are able to provide in this arena.

Barriers to implementation of OMPs for adults exist even for some of the premier programmes in the private sector, VA, and DoD clinics. In this issue, Konrad-Martin et al. discuss these obstacles and conclude that audiology participation in oncology multi-disciplinary team clinics; referrals generated by pharmacy departments; and dedicated appointment slots, personnel, and test-rooms can all enhance the success of a programme. Further solutions can be found in the use of new technology in clinical settings, as outlined in this supplement by Brungart et al. By making test equipment portable and boothless via methods such as tablet-based testing, patients can be easily and reliably tested at their bedside, reducing the burden on patients and providers, while freeing up space in the audiology clinic.

The importance of and approach to ototoxicity monitoring in paediatric patients is addressed by two articles in the supplemental edition. Brooks and Knight remind us that the risk for cisplatin ototoxicity in paediatric patients is higher than in adults. This is of considerable concern in infants and children for whom even a slight hearing loss can have a detrimental impact on speech and language development, literacy, and educational success. Pediatric ototoxicity monitoring approaches vary with patient age, attention, and ability to complete examinations, making it important that a priori strategies are in place to ensure that the most important audiometric information is obtained first. Unlike in older children, for whom cisplatin is the most commonly used ototoxic drug, neonates receive aminoglycosides most often. Garinis et al. point out in this issue that the ototoxic impact of aminoglycosides may be exacerbated by concurrent medications, inflammatory status, genetics, and noise levels in the Neonatal Intensive Care Unit. Because there are no widely accepted protocols for monitoring ototoxicity in neonates, we have come to rely on newborn hearing screening methods that focus on the speech frequencies and not the higher frequencies that are the most common ototoxic target of aminoglycosides.

King and Brewer, in this supplemental edition, cover and demystify the various scales by which ototoxicity can be classified for the purpose of clinical trials and clinical ototoxicity monitoring protocols. These grading scales differ in many aspects of how hearing loss is defined or deemed actionable, age range covered, and testing required. Knowledge of the types of scales and their applicability to the clinician’s patient populations is imperative in being able to select the most suitable scale. Similarly, for those participating in clinical trials, fully understanding the requirements of an ototoxicity grading scale will ensure consistent and accurate collection and interpretation of hearing data shared with researchers, regulatory agencies, and other stakeholders.

Vestibulotoxicity is often overlooked in OMPs. Vestibular issues can be difficult to quantify, as the typical battery of tests may be complex and require more attention and endurance than an ailing patient may have. In this supplement, Handelsman describes the vestibulotoxicity evaluation methods, which may include both subjective questionnaires and objective bedside and formal laboratory tests. When used in concert for baseline metrics, these tests can be sensitive to changes in vestibular function regardless of the patient’s ability to return to the clinic or perform an entire battery of tests.

The existing literature on treatment modalities for head and neck squamous cell carcinoma indicates the treatment for this type of tumour typically includes cisplatin and radiation therapy, with possible resection of the tumour. Schmitt and Page give insight into the detrimental effects that the combination, known as “chemoradiation”, may have on the auditory system in this issue. Due to the proximity of the radiation to the cochlea, middle ear, and eustachian tube, standard protocols for cisplatin chemotherapy and radiation, in combination, may have more ototoxic effects than either in isolation. Newer treatment paradigms with more frequent, lower doses of cisplatin, other medications, or newer therapeutic delivery models may reduce ototoxic effects, but more research is needed in this area.

As we glimpse into the future of ototoxicity monitoring, in this supplemental edition Hammill and Campbell review the recent research in otoprotection. Studies on the prevention of ototoxicity-induced hearing loss indicate that, particularly in animal models, concurrent administration of vitamins and antioxidants for management of intracochlear oxidative stress has been successful. Other methods being studied are use of steroids and salicylates, and a reduction in the required dosage of cisplatin by concurrently administering agents that sensitise tumour cells to the therapeutic drug. This suggests that the prevention and mitigation of ototoxicity-induced hearing loss in humans may be on the horizon. Proof of otoprotection will require clinical trials and patient recruitment; however, it can be difficult to pinpoint an at-risk population and generate interest in study participation. In their article, Sanchez et al. examine the success of various recruitment methods for concurrent clinical trials of pharmaceutical interventions for hearing related disorders in the US and UK. Results indicate that the most efficient method in both locations was through printed material in hearing-related publications for both patients and providers. Even in this day and age of e-communication, investigators running clinical trials for ototoxicity protection should consider print media in trade journals targeting treatment care providers to bolster recruitment.

We hope this effort provides a practical resource for clinicians to implement and enhance clinical monitoring programmes for ototoxicity. Further, it is our hope that this supplemental edition provides some forward-thinking for what lies ahead in our profession. We thank the DoD HCE for sponsoring this supplemental edition and all authors for their time and expertise. A special thanks to Marilyn Dille, PhD, Kelly King, AuD, PhD, and Dawn Konrad-Martin PhD, who were instrumental in the planning and development of this supplemental edition.

The information presented and the opinions expressed herein are those of the author(s) and do not necessarily reflect the position or policy of the Department of Defense (DoD), or the United States government. No financial conflicts of interest exist. Reference herein to any specific commercial products, process, or service by trade name, trademark, manufacturer, or otherwise, does not constitute or imply its endorsement, recommendation, or favoring by the United States Government, and shall not be used for advertising or product endorsement purposes.