Sommario

Introduction 

As a result of a global reassessment of the Italian National formulary, the Italian Ministry of Health excluded from reimbursement all antihistaminics from January 2003 up to March 2004, except for patients with moderate or severe chronic allergic rhinitis and urticaria (Nota 89B2). At present no datais available to describe the impact of the exclusion of a full class of drugs for a limited time period on the use of such drugs, its outcome and resource utilisation. This was the objective of a request for proposal from Schering Pluogh US to whom the proposal is addresse 
Proposal 
This study aims at evaluating the impact of the exclusion (January 2003 - March 2004) from reimbursement of all antihistaminic drugs for respiratory allergic disease in Italian children (0-14 years) in terms of clinical outcomes and resource use (including prescriptions, hospitalisations, emergency room visits, lab test etc. 

Methods 

Study design 

Retrospective cohort study 

Source population 

The source population for this study (PEDIANET July 2005 drawn down) comprised 180,096 children aged 0-14 years who were registered for at least one year (or were newborns) with one of the 109 pediatricians during the period 2002-2005 

Cohorts 

In this source population we identified children who had asthma or wheezing and/or allergic rhinitis. The underlying source population is dynamic as children may transfer out and be newly registered but we conducted analyses using a dynamic approach and a fixed cohort approach. 
Asthma 

For the dynamic approach children were considered to be asthmatic if they had a diagnosis for asthma and had at least two prescriptions for asthmadrugs within one year. If one of these criteria was fulfilled the subsequent persontime of that child was considered to asthmatic persontime, in total 28,447 attributed persontime to the asthma cohort. 

To be eligible for the fixed cohort approach children needed to have an asthma diagnosis prior to the start of the study (01/01/2002) or treatment with at least two asthma drugs occurred before the start of the study, 13,874 persons were part of the fixed asthma cohort. 
Allergic rhinitis 

For the dynamic approach children were considered to be suffering from allergic rhinitis if they had a diagnosis for allergic rhinitis or had one or more prescriptions for nasal steroids. If one of these criteria was fulfilled the subsequent persontime of that child was considered to be allergic rhinitis persontime, 22,529 children attributed persontime to the allergic rhinitis cohort. 

To be eligible for the fixed allergic rhinitis cohort approach children needed to have a diagnosis of allergic rhinitis prior to the start of the study (01/01/2002) or treatment with nasal steroids or antihistamines before the start of the study, 20,410 children contributed to the fixed cohort. 

Children contributed persontime to the asthma+AR cohort if both conditions were fulfilled: 10,481 children contributed persontime. Children were in the fixed asthma+AR cohort if they had both condition prior to start of the study period, these conditions were fulfilled for 6871 children. 


Statistical analysis 

To assess whether rates for hospitalizations emergency visits and other resource use changed between the before, during and after policy periods the following analyses were conducted 


1. Descriptive: 

Rates were calculated per month and aggregated for 2002 (before), 2003-march 2004 (during) and for April 2004-Marzo 2005. Tables with monthly counts, rates and aggregated rates plus confidence intervals are provided. For each item a graph was produced. 


2. Analytic: 

Crude incidence rate ratios were calculated and multivariate Poisson regression was used for estimation of adjusted rate ratios. Two comparisons were made, the rate in the period during the policy was compared with before and the rate after the policy control was compared with the rate before. For comparison of rates with a frequent outcome we adjusted for all potential confounders: age, gender, monthly (average of weeks) counts for pollen, socio-economic status (gross income for an area), number of other visits, epilepsy, diabetes, sinusitis, otitis, pneumonia, influenza, varicella, hospitalization for asthma (year prior), number or oral corticosteroid prescriptions in year prior, number of SABA prescriptions in year prior. For pollen we obtained per week, year and region the absolute counts from the following site: www.pollinieallergia.net. Since the counts were inferred from graphs they may not be exact. To calculate monthly counts we calculated the average over the weeks. 

Socio-economic status was classified by the mean income rate per household in the area of the physician. Low socio-economic status: income< 25.000 euro’s (25th percent), 25-30 medium socio-economic status and > 30000 euro’s per household (75th percent) : high socioeconomic status. 

Hospitalizations and emergency room visits were rare and the full model did not converge. These rates were compared while adjusting for age, gender, socio-economic status (gross income for an area), hospitalization for asthma (year prior), number or oral corticosteroid prescriptions in year prior, number of SABA prescriptions in year prior. In some subanalyses only crude rate ratios could be calculated. 

For all Poisson and other rate analyses the unit of analysis was a month, this means that the confounder status was assessed per month and therefore was time-varying. 
Results 

About 25,000 children with Allergic Rhinitis and asthma were enclosed in analysis. 5900 were evaluated prior of the study period, 8600 during the study period (Jan 2003-March 2004) and 9700 after the period. A total of more than 3.000.000 person/days of follow up were considered. 

No significant difference was found in the hospitalisation rates and consumption of resources between the different study period.

Partecipanti e Collaborazioni

Coordinatori

Miriam CJM Sturkenboom 
Department of Epidemiology and Buiostatistics and medical informatics, Erasmus University Medical Centre, Rotterdam 
Carlo Giaquinto 
Dipartimento di Pediatria, Padova 
Luigi Cantarutti 
Coordinamento Pedianet, PLS, Padova 
David Battleman 
Valuemedics Reserach, Arlington, VA, USA 
Jonatan Tierce 
Valuemedics Reserach, Arlington, VA, USA 
Patrizia Berto 
PBE consulting, Verona 
Walter Giorgio Canonica 
Clinica di Malattie dell'Apparato Respiratorio e Allergologia DIMI - Dipartimento di Medicina Interna Università degli Studi Genova

Partecipanti

Abruzzo 
Bonfigli Emanuela, Collacciani Giuseppe, Ferretti Michele, Forcina Paolo. 
Campania 
Basile Paola, Bratto Massimo, Castaldo Annunziata, Conte Ugo Alfredo, Costanzo Nicola, Di Santo Giuseppe, Falco Pietro, Ferraiuolo Maurizio, Mariniello, Petrazzuoli Giovanni, Speranza Francesco, Sticco Maura, Tambaro Paolo. 
Emilia Romagna 
Alberti Arturo, Barone Roberto, Biondi Claudio, Casalboni Rita, Faedi Clara Maria, Hamameh Marwan, Lucchi Elide, Mazzini Franco, Ponti Roberto, Trebbi Miro, Varni Pierfiorenzo. 
Friuli Venezia Giulia 
De Clara Roberto, Lorusso Giuseppe, Masotti Sergio, Muzzolini Carmen, Nicolosio Flavia, Ulliana Antonella. 
Lombardia 
Battilana Maria Pia, Clerici Schoeller Mariangela, Curto Salvatore, Elio Giuseppe, Frattini Claudio, Lietti Giuseppe, Mauri Laura, Picco Patrizia, Pirola Ambrogina, Ragazzon Ferdinando, Rosignoli Rino, Russo Annarita, Terenghi Albino, Tusa Antonino, Vannini Paola, Vertua Guido. 
Marche 
Bollettini Stefano, Budassi Roberto, Dolci Marco, Galvagno Andrea, Gentili Alberta, Gentilucci Pierfrancesco, Gobbi Costantino, Grelloni Mauro, Olimpi Laura, Senesi Paolo, Tonelli Gabriele. 
Piemonte 
Mirabelli Maria Cristina, Sciolla Nico Maria, Valpreda Andrea. 
Sardegna 
Basoccu Pietro, Cera Giuseppe Egidio, Cuboni Giancarlo, Lazzari Maura, Mulas Anna, Rosas Paolo. 
Sicilia 
Alongi Angelo, Avarello Giovanni, Barberi Frandanisa Maria, Petrotto Giuseppe, Puma Antonino, Salamone Pietro, Speciale Sergio, Volpe Concetta. 
Toscana 
Storelli Francesco 
Veneto 
Barbieri Patrizia, Bucolo Carmelo, Cantarutti Luigi, Cozzani Sandra, D’Amanti Vito Francesco, De Marchi Annamaria, Doria Mattia, Drago Stefano, Ferrara Enrico, Fusco Fabrizio, Giancola Giuseppe, Girotto Silvia, Grillone Giuseppe, Katende Charles Mulopo, Lista Cinzia, Macropodio Nadia, Milano Massimo, Pasinato Angela, Passarella Andrea, Ruffato Bruno, Sambugaro Daniela, Saretta Luigi, Schievano Paolo, Semenzato Flavio, Spanevello Walter, Tamassia Gianni, Toffol Giacomo.

Collaborazioni

Data Monitor

Antonio Scamarcia 
Società Servizi Telematici, Padova

Assistenza informatica

Alessandro Zandarin 
Società Servizi Telematici, Padova

Pubblicazioni

Finanziamenti

Lo studio è stato parzialmente finanziato da Schering, US.