Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: a critical overview.

An overview of the placebo-comparative articles retrieved by a literature search on Medline - Embase - Biosis data banks from 1972 to 1993 was performed to evaluate the therapeutic relevance of the medical treatment with S-carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in patients with otitis media with effusion (OME). Ten original published studies were reviewed by an independent physician who assessed their quality by standard nine-items methodology. A meta-analytical approach was used to compare outcomes across all qualifying studies. Because of the heterogeneity of clinical endpoints, a new outcome measure was defined, i.e. overall clinical improvement, which consisted of the number of patients with complete resolution of clinical signs and symptoms and no need for surgical intervention. The objective evaluation criteria of normalisation of tympanogram was an additional end-point. Potential confounding variables such as eligibility criteria, treatment protocol and study design of the six methodologically complying studies were statistically homogeneous. No association was found between treatment effect-size and publication date or patients' age. Outpatients with disease duration of < 6 months, not previously treated, with bilateral ear involvement were included in the studies; half of them presented hyperplasia or hypertrophy of the pharyngeal or the adenoid tissue. Out of 483 patients, 430 (89%) terminated studies and were evaluable. Results from this meta-analysis indicate that patients with OME receiving oral SCMC/-lys benefit from the medical treatment to the extent of avoiding surgical intervention approximately 2.31 times more often than similar patients receiving placebo (ratio of active drug to placebo-effect on overall clinical improvement: 2.31; C.I. 1.28-4.20, P < 0.01) and attain reversion to normal of the tympanogram at an extent close to statistical significance (odds ratio: 2.25, C.I. 0.97-5.22, P = 0.058). In conclusion, the use of this new methodology for the evaluation of the mucoactive drug effect in OME has shed light into methodological pitfalls of clinical trials to date and underlines the need for agreed outcome measures, which may modify medical policy, which addresses more and more often to symptomatic treatment.