Author Affiliations: Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri.
Idiopathic sudden sensorineural hearing loss, or sudden deafness, is the acute onset of hearing loss of at least 30 dB in 3 connected frequencies occurring instantaneously or over a period of up to 3 days.1 Sudden hearing loss is thought to be relatively rare,2 occurs mainly in patients between the ages of 30 and 60 years, and can be devastating for the patient. Therefore, sudden hearing loss should be treated as a medical emergency. The natural course is characterized by spontaneous recovery among approximately 50% of patients.3,4 Accurate estimates of incidence are difficult to obtain because a significant number of patients who spontaneously recover do not seek medical attention.5 As the term idiopathic implies, the etiology and pathophysiology of hearing loss are unknown. Possible causes include infections (especially viruses), autoimmune disease, circulatory problems, and neurological disease, including multiple sclerosis. Treatment options include oral steroids, intratympanic steroid injections, oral antivirals, vasodilators, diuretics, hyperbaric oxygen therapy, and vitamins.6 As a result of the high rate of spontaneous resolution, multiple potential causes, and absence of validated tests for etiological identification, the evaluation of treatment effectiveness is difficult.
In this issue of JAMA, Rauch and colleagues7 describe the findings from the first multi-institutional study of oral vs intratympanic corticosteroid therapy for hearing loss. In this study, 2443 adult patients were assessed for eligibility at 16 different academic and community-based otology practices. Of these patients, 250 (10%) agreed to participation and were randomized to receive either 60 mg/d oral prednisone for 14 days with a 5-day taper (n = 121) or four 1-mL doses of 40 mg/mL of methylprednisolone injected into the middle ear over a 2-week period (n = 129). Audiometry and safety monitoring were performed at screening, and after 1 week, 2 weeks, 2 months, and 6 months of treatment. The primary study hypothesis was that intratympanic methylprednisolone is inferior to oral prednisone for the treatment of hearing loss. The investigators established an average of more than 10 dB as the clinically significant amount of audiometric difference between the 2 study groups. Subgroup analyses of patients based on the amount of hearing loss (<90-dB or ≥90-dB pure-tone average [PTA]) were specified a priori.
The primary finding of the study was a 2.0-dB difference in PTA between the 2 treatment groups at 2 months with a maximum difference (upper limit of the confidence interval) of 6.6 dB. This value of 6.6 dB was below the required value of 10 dB to demonstrate clinical significance and reject the null hypothesis of noninferiority (ie, intratympanic treatment is worse than oral prednisone). Among the patients who presented with hearing loss of 90 dB or greater and dizziness, came for treatment in fewer than 7 days from onset, or had no prior steroid use, the possibility of a clinically meaningful difference in hearing recovery between the 2 groups could not be ruled out. Overall, the 2 treatments were well tolerated, and the number and severity of serious adverse events and adverse events were similar between groups, as had been anticipated from prior studies. However, of the patients randomized to receive intratympanic steroids, 3.1% had persistent tympanic membrane perforation and 4.7% had persistent otitis media vs 0% and 0.8% in the oral group, respectively.
At present, the emergency administration of a tapering dose of systemic steroids after hearing loss onset is widely considered standard treatment. Several uncontrolled studies suggested that intratympanic steroids have equivalent efficacy as oral steroids,8,9 while minimizing the potential adverse systemic effects of oral steroids. The practice of prescribing a tapering dose of oral steroids is largely based on the results of 1 randomized clinical study3 and a retrospective study.10 In the study by Wilson et al,3 patients in the steroid group had a recovery rate (61%) that was similar (65%) to untreated patients reported by Mattox and Simmons.4 Furthermore, a Cochrane Review11 based largely on 2 systematic reviews12,13 concluded that there exists insufficient evidence of benefit of oral steroids over placebo. Nevertheless, based on current practice and clinical beliefs, it is unlikely that equipoise could be claimed in a trial of oral steroids vs a no-treatment control. Until the study by Rauch et al, no controlled trials had compared oral and intratympanic steroids for hearing loss management.
The investigators chose to use a noninferiority trial design to compare the effectiveness and safety of oral vs intratympanic steroid for treatment of hearing loss because similar efficacy but unique advantages of intratympanic over oral steroids had been suggested.8,9 A traditional active-controlled superiority trial would have required a substantially larger sample size to achieve sufficient power to detect a clinically meaningful difference in hearing between oral and intratympanic steroids. Noninferiority trials are designed to demonstrate that the experimental treatment is not clinically worse than the active comparator by more than a prespecified small amount, known as the noninferiority criterion or margin.14 Unlike the traditional superiority trials, noninferiority trials do not require large sample sizes to detect a clinically meaningful difference. As part of the research protocol and determined before patient enrollment began, the investigators specified the noninferiority criterion used to declare intratympanic inferior—mean posttreatment change in PTA of the oral group exceeded that of the intratympanic group by higher than 10 dB. The investigators also identified a sample size of 127 per study group to obtain a power of 90% to detect a noninferiority margin of 10 dB or greater. The upper limit of the confidence interval, based on the α or type I error level of 5%, was reported for the various statistical comparisons between treatment groups and predefined subgroups to assess whether the observed dB difference could include the noninferiority criterion value of 10 dB.
The study by Rauch et al7 presents important treatment information for the primary care physician evaluating a patient reporting acute-onset hearing loss with aural fullness and suspected sudden hearing loss. Once cerumen or congestion from upper respiratory infection has been ruled out, the need to rapidly diagnose sudden hearing loss is imperative because it is believed that a delay in diagnosis can lead to permanent hearing loss. There are a variety of relatively simple ways, including softly whispering simple words and using tuning forks, to assess hearing function in a patient with suspected sudden hearing loss.15 Once a diagnosis of sudden hearing loss is suspected or made, rapid specialty referral and administration of steroids should be initiated.
The finding of noninferiority of intratympanic steroids when compared to oral steroids now provides a new therapeutic option for patients with sudden hearing loss for whom oral steroids are contraindicated. The use of intratympanic steroids is moderately uncomfortable, inconvenient, and more costly than oral steroids and is associated with several relatively minor adverse effects. Nevertheless, for patients with sudden hearing loss who are thought to be at too high a risk for systemic steroid usage, this study suggests a reasonable alternative in the setting of rapid specialty referral. Additional research should focus on identifying subgroups of patients for whom steroid treatment seems especially helpful and whether combination oral and intratympanic is better than single modality alone. However, the study by Rauch et al7 did not answer the lingering question of whether there is any benefit of steroids for the patient with sudden sensorineural hearing loss. A better understanding of the pathophysiology of hearing loss, identification of unique prognostic subgroups, and adherence to rigorous clinical research methods are required for the proper assessment of the therapeutic benefits of existing treatments and discovery of new treatments for this disorder.
Corresponding Author: Jay F. Piccirillo, MD, Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8115, St Louis, MO 63110 (firstname.lastname@example.org).
Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association.
Piccirillo JF. Steroids for Idiopathic Sudden Sensorineural Hearing LossSome Questions Answered, Others Remain. JAMA. 2011;305(20):2114-2115. doi:10.1001/jama.2011.696