Author's response to reviews Title:Pharmaco-utilisation and related costs of drugs used to treat schizophrenia and bipolar disorder in Italy: the IBIS study Authors: Luca Degli Esposti (luca.degliesposti@clicon.it) Diego Sangiorgi (diego.sangiorgi@clicon.it) Claudio Mencacci (claudio.mencacci@gmail.com) Edoardo Spina (espina@unime.it) Carlotta Pasina (carlotta.pasina@astrazeneca.com) Marianna Alacqua (Marianna.Alacqua@astrazeneca.com) Flore la Tour (flore.latour@astrazeneca.com) Version:2Date:5 September 2014 Author's response to reviews: see over
Luca Degli Esposti CliCon Srl Via Salara 36 Ravenna, I-48121 Italy Tel: +39 054438393 Email: luca.degliesposti@clicon.it September 2014 Alice Murray BMC Psychiatry, BioMed Central 236 Gray's Inn Road London WC1X 8HB United Kingdom Dear Ms Murray, Response to reviewer comments on manuscript (MS: 1361729163131748) entitled Pharmacoutilisation and related costs of drugs used to treat schizophrenia and bipolar disorder in Italy: the IBIS study. Thank you for considering our manuscript for publication in BMC Psychiatry. We value the feedback provided and have produced a revised version of our manuscript incorporating the suggested alterations. We have produced a document with point-by-point responses to all of the reviewers comments and revisions are shown in tracked changes in the manuscript. We hope you agree with the changes and that the manuscript may now be considered suitable for publication. Thank you for your consideration. Yours sincerely, Luca Degli Esposti (Corresponding author)
Response to reviewers comments Reviewer 1: I think this is a good research, addressing a relevant issue and using a fair methodology. Nevertheless, several improvements are needed, as follows: Major revisions 1) In the Background, the references used do not seem updated. Please, the Authors should check if more updated bibliography exists. For instance, ref #8, should be replaced with an updated report by WHO. Response: The references cited in the background section have been updated where possible. However, the 2004 data on disability due to bipolar disorder are the most recent available, according to the WHO. 2) In the Background, Authors should introduce some data about the increasing use of psychiatric drugs in the last years, related to several factors such as the economic crisis and the reduced stigma of mental illness. International data confirm these increasing trends, for instance, about the use of antidepressants in Italy, a recently published work should be cited (Consumption of Antidepressants in Italy: Recent Trends and Their Significance for Public Health. Psychiatr Serv. 2014). Response: The Background section has been updated to include the following: The use of antipsychotic and antidepressant medication has increased in recent years [23] and this could be ascribed to a number of factors including the reduced stigma attached to mental health conditions, worsening economic conditions and the occurrence of natural disasters [23, 24]. 3) In the methods, the paragraph about the cost of illness and resources consumption should be improved. For instance, Authors should specify which costs they took into account (in the first sentence they should clarify which database they use, in the current version it is not very clear). Moreover, the Weiden method should be explained, while currently it is only cited in the text. In my opinion, it could be useful to the reader to know something more about it. Response: The cost of illness and resources consumption section in the Methods has been updated to include details of which databases were used to retrieve relevant costs. We believe that the costs that were taken into account have been already described in the subsequent paragraph, and this has been amended to provide further details of the Weiden method. The amended section now reads as follows: The costs to the health system were retrieved from the Mental Health Information System, the Medications Prescription Database, the Specialist Outpatient Services Database and the Hospital Discharge Database and were classified as either disease-related or unrelated to schizophrenia and BD. Disease-related costs considered all the services provided by Mental Health Departments, in particular residential access (nursing home, full day) and semi-residential access (nursing home, half day). Disease-related outpatient specialist services included functional assessment (global, segmental, monofunctional), graduated psycho-behavioural assessment, clinical psychological interviews, psychiatric evaluation, psychiatric evaluation for control, psychotherapy (individual, family, group) and psychodiagnostic examination. The approach proposed by Weiden et al [25], which takes into account a wide range of psychiatric diagnosis codes, was used to ensure all related hospitalisations were identified. Costs for hospitalisations were derived from the DRG codes and for outpatient services, costs were retrieved from regional tariffs.
4) In the results, the paragraph about the cost of illness and resources consumption should be enlarged and Table 1 and 2 should be made more understandable. For instance, I suggest to include the Monetary unit in Table 1 and 2. Response: Further details have been added to Tables 1 and 2 and the cost of illness and resource consumption section has been expanded to read as follows: The mean total disease-related cost per patient per annum was higher in patients with schizophrenia ( approximately 25% of total disease-related costs for patients with schizophrenia, with nursing home costs and hospitalisations contributing 43% and 27% of total costs, respectively. Similarly, the cost of antipsychotics accounted for approximately 27% of total disease-related costs of BD; however, nearly half of the total cost was due to hospitalisations (46.7%) whereas nursing home costs accounted for only 15% (Table 1). These costs are reflected in the resource consumption for each disease: a higher proportion of patients with schizophrenia (18%) had a stay in a nursing home as compared with only just 8% of patients with BD. Furthermore, 26% of patients with BD were hospitalised whereas fewer patients with schizophrenia (18%) spent time in hospital (Table 2). 5) In the Discussion, it should be interesting to introduce and discuss something about similar data and studies carried out in other Countries. It should be useful to make comparison with other context different from Italy. Response: Further details have been added to the discussion, along with several new references. Reviewer 2: Major compulsory revision 1) Data presented and discussed are not updated. Authors refer to a survey 2009-2010 and much is changed in this last 5 years both regarding therapeutic protocols and costs. Response: The limitations section of the discussion has been updated to acknowledge that the data are from 2009 10. In addition, similar recent studies have been discussed in the discussion section in response to comment no.5 from reviewer 1 above. 2) Methods are not clear. I cannot understand from which database Authors found cases and how they followed up them. The databases regarding drugs delivery in Italy are different region by Region. Which of them they used? Or they used the National AIFA register? If yes, how did they link patients? Response: The National AIFA register was not used. Patients were included from the administrative databases of 16 Local Health Units (LHU). The LHU, being a point of delivery for the National Health System (NHS), has an information system that routinely measures the volume of expenditure generated by the dispensing of medications to registered patients. In particular, this administrative/accounting type archive is used conventionally for recording the amounts that pharmacies are entitled to receive from the LHU by way of refund in respect of medications reimbursable by the public finance and dispensed free of charge. The prescriptions recorded are attributed in each case to the patient-recipient. The identification of the patient given by the personal health number, linked with the LHU registry office, the hospital database and the diagnostic tests and specialist visits database, allows the information on medication refills to be integrated with year of birth, gender, any record of hospitalisation, diagnostic test and specialist visit. Therefore, the data set is expected to include all patients data recorded in these databases.
Further details of which databases were used have been added to the Pharmaco-utilisation section and the Cost of illness and resources consumption section in the manuscript. The databases used and the linking of patients are also described in the methods section as follows: The databases used were: (i) the Health-assisted Subjects Database, containing patients demographic data; (ii) the Medications Prescription Database, providing information for each prescription such as the prescribing physician s number, the Anatomical-Therapeutic-Chemical (ATC) code of the drug purchased, the number of packs, the number of units per pack, the dosage, the unit cost per pack and the prescription date; (iii) the Hospital Discharge Database, which includes the date of the hospitalisation and discharge, admission and discharge wards, main and secondary discharge diagnosis, cost of the hospitalisation, based on Diagnosis Related Group (DRG) classification; (iv) the Mental Health Information System, which includes the diagnosis of the patient and nursing home accesses and psychiatric visits and related costs; (v) the Specialist Outpatient Services Database which includes information on outpatient services, dates and reimbursement costs, and (vi) the No Charges Database which includes information on free-of-charge services and dates. The personal health number permitted electronic linking between all databases, allowing information on medication refills to be integrated with the patients date of birth, gender, any record of hospitalisation, diagnostic test and specialist visit. 3) English needs a strong revision Response: The manuscript has been checked by a professional medical editor and amended where necessary. 4) As I do not understand methods I cannot assess results Response: The methods have been revised in response to several of the reviewer comments. We hope that this will enable the readers to better understand the manuscript.