Allergen immunotherapy for respiratory allergy: Quality appraisal of observational comparative effectiveness studies using the REal Life Evidence AssessmeNt Tool. An EAACI methodology committee analysis

Abstract

Background Observational comparative effectiveness studies in allergen immunotherapy (AIT) represent an important evidence source answering research questions that can be challenging to obtain from randomized controlled trials (RCTs), such as long‐term benefits of AIT, the effects on asthma prevention and the onset of new allergen sensitizations. However, observational studies are prone to several sources of bias, which limit their reliability. The REal Life Evidence AssessmeNt Tool (RELEVANT) was recently developed to assist in quality appraisal of observational comparative research to enable identification of useful nonrandomized studies to be considered within guideline development. Objective To systematically appraise the quality of published observational comparative AIT studies using RELEVANT. Methods Observational studies comparing AIT to pharmacotherapy for respiratory allergies, assessing as outcome measures reduction of symptoms and/or medication use reduction, were retrieved by computerized bibliographic searches. According to RELEVANT, a failure to meet any one of primary items (background, design, measures, analysis, results, discussion/interpretation, and conflict of interest) represents a critical flaw, significantly undermining the validity of the study results. Results The 14 studies identified supported the benefit of AIT in real‐life, which persists after treatment discontinuation. However, none of them met all the 7 primary RELEVANT criteria. The main defects were reported in the design (28.6% of studies), measures and analysis (64.3% of studies), and results (78.6% of studies) items, due to selection bias and lack of methods for adjusting controls. Half of the studies did not report on conflict of interest. Conclusion There is a need for more robust observational research in AIT. RELEVANT appears as an easy‐to‐use and sensitive tool for quality appraisal in AIT studies.

Efficacy and perceived satisfaction of 3-year SLIT in children with allergic rhinitis and asthma: A pilot study in real-life .

“…Looking specifically at RCTs performed in AIT, several issues could explain the inadequacy of RCTs in AIT. The studies generally have short duration and are limited to one pollen season, and it is well known that the potential of AIT in preventing new sensitization and onset of allergic diseases is strictly correlated with the duration treatment, and at least 3-year treatment course is recommended [29,30].…”

Comparison of evidence of treatment effects in randomized and nonrandomized studies on allergen immunotherapy

“…15,16 To address these issues, we systematically assessed published NRS on AIT and compared them with a selection of RCTs from published systematic reviews performed only on grass allergy AIT, as examples of evidence of treatment effect from AIT RCTs. 1,2,17 Evidence from RCTs on grass pollen is comparable with other allergens including house dust mites and other pollens, as shown by different studies. [2][3][4]18 Our results should inform clinicians, guideline developers, and other relevant stakeholders about how reliable NRS results are and whether they can complement or replace RCTs.…”

“…We updated three previous systematic reviews, one on NRS and two on RCTs on AIT (search strategy in Data S1; Figure S1). 1,2,17 We applied the following inclusion criteria for this analysis: (1) NRS and RCTs comparing AIT (both SCIT and SLIT) with standard pharmacological treatment (for NRS) or placebo (for RCTs); (2) RCTs using SCIT or SLIT, administered as tablet, for grass pollen allergy; (3) studies on adults and children with a diagnosis of rhinitis or rhino-conjunctivitis with or without mild to moderate allergic asthma; (4) rhinitis symptom score (SS) and medication score (MS) as outcome measures of the treatment effect, regardless of whether these were the primary end-points.…”

“…Regarding the NRS on AIT, previously identified in a recent systematic review (to which we refer for the detailed search strategy), we included in this analysis only those studies that provided data that could be included in a meta-analysis. 17 Different scoring systems and scales were used in the original studies to assess SS and MS and we, therefore, used standardized mean differences (SMDs), expressing the differences in the means between AIT and controls in terms of units of the pooled SDs. The overall SMD and 95% confidence interval (95% CI) among patients treated with AIT and controls were estimated using models based on fixed-effects and random effects assumptions, and data were combined using the method by DerSimonian and Laird.…”

Editorial: Pharmacotherapy and evidence based medicine

“…The updated methods to collect data on effectiveness and the new technological tools designed to increase treatment adherence are playing positively to improve the impact and outcome of randomized control trials (RCT) [8] and real-life studies (RLS) [9][10][11].…”