Discussion
We performed a pilot, monocenter, retrospective cohort study to evaluate the efficacy and perceived satisfaction of 3-year SLIT inreal-life , measured by a validated questionnaire, in a population of mono- or poly-sensitized patients with allergic rhinitis and/or asthma. As expected, the SLIT significantly contributed in modifying the disease course in patients suffering from allergic rhinitis and asthma as well asthma with rhinitis. The positive impact of treatment has been assessed by significant changes in perceived efficacy in patients, rescue medication use; perceived satisfaction in patients; disease control and impact on quality of life; and number of disease exacerbations. Significant changes have also been recorded in the frequency of symptoms of patients suffering from asthma and asthma with allergic rhinitis; however, no changes were reported in the allergic rhinitis group. The absence of significant changes has been related to the small sample size: only six patients were suffering from allergic rhinitis.
Confirming the efficacy of SLIT, the perceived satisfaction for all enrolled patients was high, and it is reasonable to hypothesize that these data were related to the improvement in clinical outcome. Sparse studies investigated the efficacy/perceived satisfaction ratio, which is crucial in obtaining a high treatment adherence [13-15]. Moreover, when this issue was investigated, several biases were affecting the results, such as conflict of interests [13, 14]. In our study, all patients reported a high rate of satisfaction, more probably as a consequence of efficacy treatment. It has been reported that the reasons for premature cessation of AIT are the inability to reach the clinical centre, the ineffectiveness of therapy, and the long course of treatment [16]. Herein, the nature study allowed us to enrol patients that were highly motivated to start treatment as well as to participate in a study in the absence of a strict protocol. All these factors resulted in high treatment adherence as 60/70 (85.7%) of all enrolled patients declared themselves very satisfied, 6/70 (8.57%) much satisfied, and 4/60 (5.71%) satisfied. Adherence is the key to ensure SLIT effectiveness, as poor adherence is a potential factor affecting negatively the efficacy of AIT. In line with this finding, all enrolled patients completed at least three years of treatment, showing 100% spontaneous adherence to the prescribed treatment. Contrary to other studies in which a high treatment adherence was obtained thanks to the help of nurse interventions, frequent scheduled visits and telephone calls [17-19], herein, our patients showed 100% spontaneousadherence to the prescribed treatment. In this regard, we believe that patients were obtaining real benefit from the treatment probably since the first year of the therapy; thus, a good efficacy achieved during the first year of treatment could be considered as a favourable prognostic factor for treatment adherence for the next two years with long-lasting positive effects in real-practice. Also, only a continuous AIT for a period of at least 3 years modifies the course of the disease and ensures the long-term remission of symptoms for several years [20-23]. RCTs and observational studies on treatment adherence reported that the discontinuation rate for SCIT is approximately 22%, 34%, and 26% from one to three treatment years, respectively; and, for SLIT is 42%, 29%, and 27% from one to three treatment years [24, 25]. Herein, we firstly reported that the treatment adherence for SLIT was 100% troughtout the study duration. Similar to other chronic conditions, allergic diseases require ongoing care to minimize their impact, improve health outcomes, prevent clinical worsening and comorbidities, and reduce healthcare costs [26]. Nevertheless, it has been estimated that only the half of patients with chronic conditions take their medications as prescribed; since several factors affect the patients’ability to follow treatment recommendations correctly [26, 27]. We strongly believe that the complete treatment adherence in our population can primarily be attributed to the study design. In RCTs, patients are strictly selected and monitored over time to limit bias; and, when patients differ from that set out, they are excluded from the final study results. Conversely, more reliable data can be derived from real-life studies, since a combination of strategies, such as educational plans and regular assessments, can be more easy applicable [28].
Moreover, the novelty and strength of our study were also to show the efficacy and perceived satisfaction of 3-year SLIT via areal-life design. Although the health sciences community selects RCTs as the main tool able to investigate and evaluate clinical interventions with the lowest risk of bias, the obtained data does not ever fit with the general population; thus, the translation and the use of data obtained from RCTs in real-practice can be questionable. 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].
The RCTs are designed to test if the selected treatment is working, but they do not evaluate if the treatment works in real-life. Aiming to limit  any factor that could potentially influence final results, RCTs are designed in compliance with a rigid and strictprotocol; however, the latter is not the same adopted by all RCTs; thus, a “within-study” and “between-study” heterogeneity is extensively reported among different trials [6]. Moreover, the RCTs are investigating an experimental treatment in a selected group of patients who must respect the study’s inclusion criteria [6]. Any protocol modification is foreseen for patients who do not strictly meet the inclusion criteria or unforeseen events [6].  Thus, it can happen that, due to several reasons (e.g., age, disease severity, comorbidities, use of concomitant medications, etc), a cluster of patients, from which it could be possible to extract potential and interesting data, must be excluded from the study with a gap in knowledge  of the investigated treatment in real-practice.
Whether on one hand the “one-size-fits-all” approach can provide the opportunity to apply a treatment for a large population; on the other hand, it does not work for everyone. A treatment defined as “effective” in an ideal clinical setting can not give specific quantifiable answers under individual cases in a routine clinical setting. Tailor healthcare approach and treatment to meet the specific needs of each patient. is urgently needed as only a “sartorial” approach can provide an individual’s unique molecular, lifestyle, and clinical information.
We strongly believe that real-world studies, using data collected in everyday clinical settings, can hold the promise of providingreal data to maximize the applicability and generalizability of an intervention. Nevertheless, we do not aim to fule a war between a “wrong” and “right” research approach rather we want to shift form adichotomous to an integrated perspective, able to combine the strengths of each research method -the prospective, randomized, and analytical design of the RCTs with more representative and generalizable data of real-life studies- and exceed the limits of restrictive inclusion and exclusion criteria of RCTs and the risk of low-quality control of the surrounding data collection and susceptibility to multiple sources of bias occurring in real-life studies.