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Even though we focused on a single allergen source, there was high between-study heterogeneity for the treatment effect on symptoms, as seen in recent meta-analyses (9�C11). However, the SLIT natural allergen tablet modality (n?=?7) studies or dose levels within a study) showed the lowest between-study variability [tau2 and I2 (95% confidence intervals) for Hedges�� g: 0.016 (58.5% (4.3�C82%))], followed by SCIT with natural allergens (n?=?7) with 0.039 [44.6% (0�C76.7%)] and SLIT drops (n?=?10) with RhoC 0.045 [51.9% (1.1�C76.6%)]. The test was not applicable to SLIT with allergoid tablets and SCIT with allergoids, for which there were only one and two calculable studies, respectively. Meta-analysis and random effects meta-regression did not reveal a clear relationship between the treatment effect on one hand and SIT modality, dose or treatment duration on the other. Specifically designed clinical investigations are needed to address these precise questions, in the same way that optimal dosage has been determined in SLIT tablet trials. Data on study design and efficacy results for the five SIT modalities are summarized in Table?1. Data on safety and selleck chemical treatment compliance are presented in Table?2. Despite heterogeneity in the symptom scores (means, medians, area under the curve, challenge responses, etc.) and high variance, five of the seven trials showed significant efficacy for the active treatment in the first treatment season. The only large-scale, dose�Cresponse investigation was performed in a year-long trial on 410 randomized participants with two active dose levels (calculated cumulative dose: 207.6 and 20.76?��g, respectively) and a placebo group (20). There were dose-dependent reductions in the symptom score and (for the high dose only) this website the medication score (P?=?0.0007). The remaining trials featured low to middling population sizes (from 28 to 87 randomized subjects). The SCIT modality was the first to be investigated in terms of long-term efficacy, with up to 84?months of treatment in a trial comparing 3?years of treatment (discontinuation) with 6?years (i.e. continuation for an additional 3?years) in 47 randomized patients (22). Dolz et?al.��s (21) three-season study on 28 randomized patients reported significant (P?