Within a given controlled (Class II) study, the authors describe the therapeutic effect of thymectomy by comparing the rate myasthenia gravis patients receiving thymectomy achieved desirable outcomes with the rate myasthenia gravis patients not receiving thymectomy achieved desirable outcomes. The nonrandomized nature of Class II studies often introduces differences in the baseline characteristics of the thymectomy and non-thymectomy patient groups that can effect myasthenia gravis outcomes independent of thymectomy. To the extent possible, the authors adjust for these confounding differences in baseline prognostic characteristics. In the absence of randomized controlled trials, such adjustments are critical for estimating the actual therapeutic effect, if any, of thymectomy. (Note: Class III studies were excluded from consideration.)
From the controlled studies describing outcomes, the following characteristics were abstracted: method and setting of cohort assembly, years during which patients were enrolled in the cohort, number of subjects assembled, duration of follow-up, proportion of subjects lost to follow-up, and the thymectomy techniques employed.
Because of reported associations with myasthenia gravis outcomes, the authors also extracted the following study population characteristics: proportion of patients younger than 50 years at the time of diagnosis of myasthenia gravis, proportion of female patients with more severe myasthenia gravis at the time of diagnosis (defined by Osserman's grade 2b, 3, or 4), and the proportion of patients with strictly ocular myasthenia at the time of diagnosis.
Thymectomy in patients with thymoma has benefits other than myasthenia gravis treatment. Therefore, patients with thymoma were excluded from the analysis.
In reviewing each study the authors considered the following myasthenia gravis outcomes: survival (taking into account perioperative mortality), improvement since diagnosis, asymptomatic on or off medication, and asymptomatic off medication (i.e., medication-free remission).
Ideally, controlled studies of thymectomy in myasthenia gravis patients report outcomes using time-to-outcome (survival) techniques. Survival techniques account for the differences in the duration of follow-up and changes in outcomes over time. Unfortunately, most controlled studies of thymectomy in myasthenia gravis simply report the proportion, or crude rate, of patients achieving an outcome over the study’s follow-up period. Crude outcome rates vary with the duration of follow-up of the study. Within a given study, however, crude outcome rates of the thymectomy and nonthymectomy patient groups can be compared when the patient groups have similar follow-up durations.
To compare the crude rates within a given controlled study, the authors calculated the relative rate by dividing the thymectomy patient group’s crude rate of achieving the outcome by the nonthymectomy patient group’s crude rate of achieving the outcome using the formula presented in table 1 of the guideline document.
The authors also calculated the 95% confidence interval of these relative rates. Calculation of the relative outcome rates in this manner compensates for differences in follow-up duration between controlled studies, and allows the analysis of the results of all controlled thymectomy myasthenia gravis studies.
In studies providing sufficient information, the authors re-calculated the relative rates of outcomes after controlling for potential confounding variables of age, gender, and severity of myasthenia. The authors used Wilcoxon’s test to determine significance of the changes in relative rates measured after controlling for these variables.