Download ricerca finalizzata 2009

RICERCA FINALIZZATA 2009
Ministero della Salute – Direzione Generale della Ricerca Scientifica e Tecnologica
Application resume
Title: OBSERVANT - OBservational Study of Effectiveness of avR-taVi procedures
for severe Aortic steNosis Treatment
Code
RF-2009-1470920
Institution:
Istituto Superiore di Sanita'
Type of research:
Clinical
Length (months)
36
Total budget of the project
€ 919.000,00
Funding required to Ministry of
Health
€ 600.000,00
Total amount of co-financings
€ 200.000,00
Institutional resources
€ 119.000,00
NIH primary classification
IRG: Healthcare Delivery and Methodologies
Study section: Health Services Organization and Delivery - HSOD
Keyword: HDM-HSOD-0675 - Healthcare quality, effectiveness, and outcomes; clinical practice guidelines; treatment and
prevention outcomes; patient and provider satisfaction; health status and outcomes assessment; evidence-based practice; health-related quality of life; medical decision-making.
NIH secondary classification
IRG (2): Cardiovascular and Respiratory Sciences
Study section (2): Clinical and Integrative Cardiovascular Sciences - CICS
Keyword (2): CVRS-CICS-0363 - Clinical, population, or translational studies of the responses of the cardiovascular system
to trauma or surgery: arrhythmias associated with cardiac surgery or cardiopulmonary bypass, cardiac sudden death, resuscitation, stenting, pacemakers;,cardiovascular injury and repair, and myocardial ischemia/reperfusion injury.
IRG (3): N/A
Study section (3): N/A
Keyword (3): N/A
Principal Investigator
Name: Seccareccia Fulvia
Role: Senior Researcher
Date and place of birth : 05/07/1956 , Roma (RM)
Address: Camillo Pilotto, 79, 00139 Roma (RM)
Phone number 1: 06/49904234
Phone number 2: 339/3795783
E-mail: [email protected]
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RICERCA FINALIZZATA 2009
Current employment and institution: Senior Researcher. Department of Cardiac and Cerebrovascular Diseases, National
Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy
Profile of the principal investigator
EDUCATION
1. Lyceum "Archimede", Rome, Italy; Graduated at Scientific High School, July 27, 1975
2. University of Rome "La Sapienza", School of Biology, Rome, Italy; Graduated with honour in Biological Sciences, December 3, 1979.
POSITION HELD
Member of Research Group.
- The Rome Project of CHD Prevention (WHO European Collaborative Trial): (1980-1996).
- The Seven Countries Study (1980-2003)
- The ECCIS Project (Epidemiology and Clinics of Silent Ischemic Heart Disease): Member of the Research Group
(Responsible of data analysis) (1989-1995)
- The RIFLE Project (RIsk Factors and Life Expectancy) (1990-2003)
- The Rome UTP Study (Urban Traffic Pollution) (1994-1996)
- The RIMA Project (Ventricular Remodelling after Acute Myocardial Infarction): Member of the Research Group
(Responsible of data analysis) (1994-1999)
- Progetto MATISS: Malattie cardiovascolari ATerosclerotiche (Cardiovascular Atherosclerotic Diseases) (1998 -2003)
- OEC: Epidemiologic Cardiovascular Observatory (ISS-ANMCO) (1998-2003)
- EUROCISS: EUROpean Cardiovascular Indicator Surveillance Set (2000-2003)
- "Il Progetto CUORE" (Epidemiology and Prevention of Ischaemic Heart Diseases of the Italian Ministry of Health)
(1998-2003)
Project Leader
- NFR (New cardiovascular Risk Factors)(1999-2002)
- Diet and health: diet and cardiovascular health association ecologic study (CNR-ISS (2000-2003)
- Short term outcome study of Coronary Artery By-pass Graft (CABG) interventions in the Italian Cardiac Surgery Centers
(Ministry of Health - ISS)(2002-2004)
- "Valutazione di Esito" nell'ambito della "Ricerca Finalizzata 2003" del Progetto strategico "Il Progetto Cuore II: risk assessment individuale, di struttura e dei percorsi prognostico terapeutici per le malattie cardiovascolari". Operative Unit 2.
(2003-2006)
- EUPHORIC - European Public Health Outcome Research and Indicators Collection (EU Commission - SANCO)
(2004-2007)
- Progetto Mattoni del Ministero della Salute - Mattone "Misura dell'Outcome" (Ministero della Salute - ISS)(2004-2008)
- Sperimentazioni Mattoni (Stenting - Angioplastica)
- Valutazione degli esiti per promuovere il miglioramento dell'efficacia nell'erogazione delle prestazioni ricomprese nei LEA
(Convenzione Ministero della Salute/Dip. Qualità - ISS)(2008-2009)
- Sviluppo e produzione degli indicatori di esito per SIVeAS (Convenzione Ministero della Salute/Dip. Qualità - ISS)
(2008-2009)
- Valutazione della performance: programma di valutazione delle decisioni e delle attività delle strutture sanitarie - Operative
Unit 2. (convenzione CCM del Ministero della Salute - ISS) (2010-2011)
- Studio osservazionale per la valutazione di appropriatezza, efficienza ed efficacia delle procedure AVR-TAVI per il trattamento della Stenosi Aortica (Convenzione Ministero della Salute/Dip. Innovazione - ISS) ( 2010-2012)
Member of the Steering Committe and Responsible for the Istituto Superiore di Sanità
- Registro Italiano Stenting Carotideo - RISC2 ISS - Università degli Studi di Milano-Bicocca (2006-2008)
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RICERCA FINALIZZATA 2009
- Progetto "OSCAR per la Qualità" - Outcome Survey sui Centri che eseguono Angioplastiche coronariche: Risultati a 6 mesi
per valutare la Qualità. ISS - Società Italiana di Cardiologia Invasiva (GISE) (2005-2007)
- Italian Network on Acute Coronary Syndromes (IN-ACS) Outcome. ISS - ANMCO - Heart Care Foundation (2006-2008)
- Progetto "Mattone Outcome - BYPASS" ISS - Dipartimento di Epidemiologia, ASL RME (2006-2008)
EXPERIENCE
From 1980: epidemiology and prevention of cardiovascular disease, cardiovascular risk factors, statistical analysis of predictive models.
From 2002 to date: outcome research
TEACHING ACTIVITIES
From 1995 to 2003: Teacher in several institutional courses concerning the epidemiology and prevention of cardiovascular
disease
From 2004 to date: Course Director and Teacher in annually institutional courses concerning outcome research.
Summary and collaborations
Transcatheter aortic valve implantation (TAVI), a new interventional procedure for treating severe symptomatic aortic stenosis (SSAS), is less invasive compared to a conventional approach (surgical aortic valve replacement, AVR) and designed to
treat high-risk patients. The TAVI procedure was introduced into clinical practice in the absence of comparative efficacy studies. In spite of the relative newness of the approach (first performed in humans in 2002), it very quickly became of interest
for patients who had previously attempted medical treatment and for patients eligible for AVR. For this latter subpopulation,
the effectiveness of TAVI vs. AVR in terms of medium- and long-term outcomes has not been demonstrated. Since 2007,
TAVI procedures have regularly been performed in Italy.
The first observational outcome study on the comparative effectiveness of TAVI, AVR, and medical therapy for the treatment
of SSAS in the Italian population is being proposed, involving all Italian hospitals where TAVI and/or AVR are provided.
Clinical and procedural information will be collected for each enrolled SSAS patient.
This study aims to
-evaluate and compare short-, medium-, and long-term outcome in patients undergoing the three SSAS treatments (AVR, TAVI, or medical treatment), in terms of both survival and major adverse cardiac and cerebrovascular events (MACCE);
-verify the use, appropriateness, and economic and organizational impact of TAVI and AVR procedures;
-define specific "indication criteria" to guarantee future appropriate patient selection for AVR or TAVI;
-build a new pre-procedure risk score, specific for the elderly Italian population; and
-build guidelines on TAVI procedure coding and a system of administrative follow-up to be proposed to the regional health
systems for future management of the use of AVR and TAVI.
The study outputs will represent concrete support for cardiologists and cardiac surgeons to properly identify the TAVI target
population and to make evidence-based decisions that allow reducing re-interventions, controlling direct costs, and enhancing
patient quality of life and life expectancy. This study will also supply the National and Regional Health Systems with appropriate tools and methodologies to monitor economic and organizational aspects linked to the introduction of TAVI into the
health system.
COLLABORATIONS
RECRUITED HOSPITALS. Clinical and follow-up data collection; support of clinical monitoring procedures.
REGIONAL HEALTH AUTORITIES (RHAs) - LOMBARDIA, FRIULI, VENETO, EMILIA ROMAGNA, TOSCANA,CAMPANIA, CALABRIA, SICILIA. Check for completeness of study cohort enrollment; follow-up data collection within the Regional Administrative Health Informative System and Regional Mortality Registry. Dissemination of a) clinical
guide lines for appropriate patients' selection to AVR or TAVI and analysis of the related organizing problems, b) indication
for TAVI procedure coding for administrative control (ASP LAZIO).
OPERATIVE UNIT (OU) 1 - DEPARTMENT OF EPIDEMIOLOGY OF THE REGIONAL HEALTH SYSTEM, LAZIO.
Participation in study protocol writing and minimal dataset definition; contribution to data management and analysis; cooperation in drafting the intermediate and final reports.
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RICERCA FINALIZZATA 2009
OU2 - CLINICAL MONITORING UNIT. Setting up of standardized operating procedures (SOPs) for clinical monitoring;
periodical revision of hospital discharge diagnoses and identification of SSAS suspected ICD-9-CM codes; original clinical
chart revision; drafting of clinical monitoring reports.
OU3 - SOFTWARE PROVIDER. Implementation of a dedicated web site; building database structure for data recording;
creation of a document-sharing section for information exchange.
OTHER COLLABORATIONS
Italian Ministry of Health
AGENAS (National Agency of Regional Health Services)
FIC - Italian Federation of Cardiology
SICI -GISE - Italian Society of Interventional Cardiology
SICCH - Italian Society of Cardiac Surgery
ITACTA - Italian Association of Cardiothoracic Anaesthesiologists
Teaching hospitals, scientific institutes for research, hospitalization, and health care
Rational purpose, and specific impacts on the subject
Aortic stenosis is the most common acquired valvular heart disease in the western world, and its prevalence is strongly linked
to the phenomenon of population ageing. The prevalence of severe symptomatic aortic stenosis (SSAS) is around 3% among
people over age 75 years, but this percentage rises steeply with increasing age. After symptom onset, patients with SSAS, if
untreated, show very poor prognoses, unavoidably reaching complete disability status with a significant reduction in survival.
Aortic valve replacement (AVR) is the definitive therapy for patients with SSAS who have symptoms or objective consequences such as left ventricular dysfunction. With proper selection, operative mortality is quite low, even in elderly patients,
and long-term results have proved satisfactory. However, elderly people with SSAS often have also significant associated comorbidities such as reduced left ventricular function, impaired renal function, pulmonary hypertension, liver cirrhosis, and
coronary artery disease, and the risk of open heart surgery is therefore elevated. In addition, several registries show that referring physicians often do not propose surgery, as was the case in the Euro Heart Survey with 33% of patients not being considered for surgery despite severe valve disease and severe symptoms.
Palliative balloon aortic valvuloplasty is now rarely used, mainly due to its limited long-term efficacy; thus, despite good results with valve surgery, a new, less-invasive alternative like transcatheter aortic valve implantation (TAVI) has been considered, at least for a large proportion of patients with very high or prohibitive operative risk. Seven years after its first use in
humans, TAVI for the treatment of SSAS currently represents a dynamic field of research and development.
The two manufacturers leading the development of transcatheter aortic bioprosthesis valve implantation technology are Edwards Life Sciences (Edwards SAPIEN Transcatheter Heart Valve; second generation) and CoreValve Corporation
(CoreValve Percutaneous Revalving System; second generation). Although lacking official approval from the US Food and
Drug Administration (FDA), both systems have been CE-marked and are currently used in Europe. Other commercial manufacturers and improvements in valve technology are expected.
Currently, there are two routes for transcatheter valve replacement for aortic stenosis. These are retrograde via the femoral artery or via transapical access directly through the left ventricle wall. The choice of technique is influenced by calcification
and tortuosity of the femoro-iliac access route.
TAVI technology has been applied primarily in very old patients with a high number of comorbidities. Operative risk score
calculators (i.e., logistic EuroSCORE, Parsonett score, Society of Thoracic Surgeons Predicted Risk of Mortality
[STS-PROM] score) that take into consideration the most important patient comorbidities have been used to determine which
patients are at very high or prohibitive surgical risk. However, many elderly patients are deemed inoperable on the basis of
comorbidities not included in surgical risk calculators. Therefore, a high proportion of patients have been refused AVR and
have undergone TAVI on the basis of risk factors such as porcelain aorta or frailty, neither of which is included in the surgical risk calculators.
Since 2007, TAVI procedures have commonly been performed in Italy. Over three years, this procedure originally was used
in a specific subgroup of pre-operative high-risk patients but has spread dramatically, increasing from 30 procedures performed in 2007 to about 700 in 2009. Moreover, as documented in some official reports, this increasing trend is associated with
the involvement of younger and younger patients who lack the hard contraindications to the conventional surgical approach
(AVR).
The introduction of a new technology into clinical practice furthermore has a strong structural, organizational, and economic
effect on the health system. In Italy, because of current device costs, an unplanned use of TAVI will lead to unavoidable direct cost increases (2000 euro for each device employed in the AVR procedure vs. 28,000 euro for each bio-prosthesis used
in the TAVI procedure). Thus, taking into account the current trend, an outlay of 28 million euro for about 1000 TAVI against 20 million euro for the estimated 10,000 AVR is expected in Italy in 2010. Moreover, a further expenditure increase for capital equipment investment (i.e., hybrid theaters), facilities, and personnel training is expected in the health providers' balance
sheet. Finally, as reported in national and international consensus documents, because TAVI procedures must be performed
by multidisciplinary teams in surgical or hybrid theaters, a deep hospital internal reorganization is expected. Although the
AVR-TAVI issue arouses lively interest at the international level, data are from only a few registries conducted by the companies developing the devices, and few post-market studies are currently available.
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RICERCA FINALIZZATA 2009
To date, the safety and efficacy of TAVI procedures have been measured by comparing the procedural and 30-day results with predicted operative mortality as calculated by questionable and outdated surgical risk calculators, but (a) no RCTs have determined results either comparing the transfemoral/percutaneous and transapical routes for TAVI against routine palliative
care or TAVI against AVR; (b) no studies have yielded reliable information on medium- and long-term TAVI effectiveness
or cost-effectiveness profiles; and (c) no studies have determined the results of TAVI in patients with porcelain aorta or frailty, two of the most frequent comorbidities in elderly patients with severe aortic stenosis not included in the surgical risk scores.
The new phenomenon of systematic control based on current administrative data, i.e., hospital discharge records (HDRs), is
not feasible because shared consensus guidelines on TAVI procedures coding are lacking. Regional systems seem to suggest
different options, and sometimes an ICD-9-CM code used to record a TAVI procedure in one hospital is not the same as that
used in other institutes or hospitals in the same region. Moreover, the lack of data recording of some crucial clinical parameters in administrative databases prevents an accurate severity description of patients undergoing TAVI or AVR.
The just now approved New National Program for Comparative-Effectiveness Research (CER) in the USA asserts that, for
each selected "research question" the most appropriate research method that can fill gaps in the evidence has to be identified.
Regarding non-pharmacological treatments, because of the organizational conditions of health treatment supply, the speedy
development of health technologies can often prevent their experimental evaluation of efficacy in accordance with the rigorous scientific protocol of RCTs.
In these cases, observational outcome studies (OOSs) represent a valid scientific alternative to the experimental approach
(i.e., RCT). Their implementation allows evaluation of the comparative effectiveness of standard approaches with new treatments or health technologies, included and supplied by the National Health System, for which no valid efficacy proofs exist.
Moreover, being observational and not pre-defined, these studies can allow monitoring of the evolution of the new technologies and the aspects and consequences linked to their introduction into the health system.
In this regard, a recently published document on the CER program states: "Some questions will require a definitive RCT,
whereas well-designed cohort studies may answer some questions with sufficient certainty for decision makers and may be
more applicable to real-world setting" (NEJM 2010; 362(11):970-3).
Because an OOS is not experimental, the allocation of patients to a particular treatment/exposure category is not random. In
this regard, estimates are computed taking into account all known confounding factors and possible effect modifiers. This
specific methodology is known as "risk adjustment".
The proposed study will be observational. It will not define eligibility criteria and, being intended to observe and record what
happens in clinical practice, will not interfere in local decision processes. The study starts from the hypothesis that the three
compared treatments (AVR, TAVI, or medical treatment) should be offered to SSAS patients with different demographic and
severity characteristics. The rapid spread of TAVI has involved not only patients previously eligible for medical treatment, as
expected, but also patients eligible for AVR. For this latter subpopulation, the effectiveness of TAVI vs. AVR in terms of
medium- and long-term outcomes has not been demonstrated.
This proposal describes the first observational multicenter perspective study on the comparative effectiveness of TAVI, AVR,
and medical therapy in the Italian population with SSAS.
The collection of some clinical and procedural information on SSAS patients admitted to one of the Italian hospitals where
TAVI and/or AVR are provided, will allow researchers to
- evaluate and compare short-, medium-, and long-term outcome in patients undergoing one of the three SSAS treatments
(AVR, TAVI, or medical treatment) in terms of both survival and major adverse cardiac and cerebrovascular events
(MACCE), after adjusting for pre-treatment patient characteristics;
- verify use, appropriateness, and economic and organizational impact of TAVI and AVR procedures;
- define specific "indication criteria" to guarantee appropriate patient selection for AVR or TAVI;
- determine results of TAVI in patients deemed inoperable because of either porcelain aorta or frailty;
- build a new pre-procedure risk score, specific for the elderly Italian population; and
- build guidelines on TAVI procedure coding and a system of administrative follow-up to be proposed to the regional health
systems for managing the use of the AVR or TAVI procedures.
In February 2010, a preliminary plenary assembly was held in cooperation with the Italian Ministry of Health, National Health Institution, and the National Agency for Regional Health Services, Italian Regions, Italian scientific societies and federations representing professionals involved in this topic and hospitals, individual cardiologists, and cardiac surgeons. The meeting sealed an alliance between all the involved main partners. A general consensus, together with a strong interest to participate in the proposed study and realize its objectives, was recorded on that occasion.
Bibliography
-ACC/AHA Task Force on Practice Guidelines. ACC/AHA 2006 guidelines for the management of patients with valvular
heart disease: a report of the ACC/AHA Task Force on Practice Guidelines. Circulation. 2006 Aug 1;114(5):e84-231. Review.
-Vahanian A, Alfieri OR, Al-Attar N, et al. TAVI for patients with aortic stenosis: a position statement from the EACTS and
the ESC, in collaboration with the EAPCI. Eur J Cardiothorac Surg. 2008 Jul;34(1):1-8.
-Sethi S. Daniel T, Howell J, Griffen C. A commissioning framework for TAVI for SSAS. 2009 March. Available from:
www.bcis.org.uk/resources/documents/TAVI%20National%20Commissioning%20Framework%20FINAL%20160309.pdf
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RICERCA FINALIZZATA 2009
-Rodés-Cabau J, Webb JG, Cheung A, et al. TAVI for the Treatment of SSAS in Patients at Very High or Prohibitive Surgical Risk Acute and Late Outcomes of the Multicenter Canadian Experience. J Am Coll Cardiol. 2010 Jan 13. [Epub ahead of
print]
-Santoro G, Vitali E, Tamburino C, et al. Impianto transcatetere di protesi valvolare aortica in pazienti con stenosi valvolare
severa sintomatica. Documento di Consenso FIC - SICCH. G Ital Cardiol (Rome). 2010. [in press]
Up to 5 of the best scientific work of the applicant, indicating the impact factor in
the year of publication, the number of citations since the publication until request
for financing and the h-index.
Qizilbash, N; Lewington, S; Duffy, S; et al. Cholesterol, diastolic blood pressure, and stroke: 13000 strokes in 450000 people
in 45 prospective cohorts. LANCET, 346 (8991-2): 1647-1653 DEC 23 1995
IF =10.2; N. Cit. = 526
Greco, CA; Salustri, A; Seccareccia, F; et al. Prognostic value of dobutamine echocardiography early after uncomplicated
acute myocardial infarction: A comparison with exercise electrocardiography. JOURNAL OF THE AMERICAN COLLEGE
OF CARDIOLOGY, 29 (2): 261-267 FEB 1997
IF = 7.37; N.Cit. = 42
Salustri, A; Ciavatti, M; Seccareccia, F; et al. Prediction of cardiac events after uncomplicated acute myocardial infarction by
clinical variables and dobutamine stress test. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 34 (2):
435-440 AUG 1999
IF= 7.37; N.Cit = 23
Menotti, A; Lanti, M; Seccareccia, F; et al. Multivariate prediction of the 1st major cerebrovascular event in an Italian population-sample of middle-aged men followed up for 25 years. STROKE, 24 (1): 42-48 JAN 1993
IF = 5.53; N. Cit = 13
Seccareccia, F; Pannozzo, F; Dima, F; et al.Heart rate as a predictor of mortality: The MATISS Project. AMERICAN JOURNAL OF PUBLIC HEALTH, 91 (8): 1258-1263 AUG 2001
IF = 3.03; N. Cit. = 57
H-INDEX = 5
Up to 5 of the scientific work of the applicant on the subject of the request, indicating the impact factor in the year of publication, the number of citations since the
publication until request for financing and the h-index
Seccareccia, F; Perucci, CA; D'Errigo, P; et al. The Italian CABG Outcome Study: short-term outcomes in patients with coronary artery bypass graft surgery. EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 29 (1): 56-62 JAN 2006
IF = 2.1; N.Cit. =15
D'Errigo, P; Seccareccia, F; Rosato, S; et al. Comparison between an empirically derived model and the EuroSCORE system
in the evaluation of hospital performance: the example of the Italian CABG outcome project. EUROPEAN JOURNAL OF
CARDIO-THORACIC SURGERY, 33 (3): 325-333 MAR 2008
IF = 2.2; N. Cit. = 9
D'Errigo, P; Tosti, ME; Fusco, D; et al. Use of hierarchical models to evaluate performance of cardiac surgery centres in the
Italian CABG outcome study. BMC MEDICAL RESEARCH METHODOLOGY, 7: Art. No. 29 JUL 3 2007
IF = 2.8; N. Cit. = 2
Rosato S, Seccareccia F, D'Errigo P, Fusco D, Maraschini A, Badoni G, Perucci CA. Thirty-day mortality after AMI: effect
modification by gender in outcome studies. Eur J Public Health. 2009 Nov 27.
IF = 2.18; N. Cit. = 0
Rosato S, D'Errigo P, Badoni G, Fusco D, Perucci CA, Seccareccia F. Comparison between administrative and clinical databases in the evaluation of cardiac surgery performance. G Ital Cardiol (Rome). 2008 Aug;9(8):569-78. (Italian).
H-INDEX = 2
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RICERCA FINALIZZATA 2009
Up to 5 of the recent scientific work of the applicant, indicating the impact factor
in the year of publication, the number of citations since the publication until request for financing and the h-index
Seccareccia, F; Perucci, CA; D'Errigo, P; et al. The Italian CABG Outcome Study: short-term outcomes in patients with coronary artery bypass graft surgery. EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 29 (1): 56-62 JAN 2006
IF = 2.1; N.Cit. =15
D'Errigo, P; Seccareccia, F; Rosato, S; et al. Comparison between an empirically derived model and the EuroSCORE system
in the evaluation of hospital performance: the example of the Italian CABG outcome project. EUROPEAN JOURNAL OF
CARDIO-THORACIC SURGERY, 33 (3): 325-333 MAR 2008
IF = 2.2; N. Cit. = 9
Massari, M; Freeman, KM; Seccareccia, F; et al. An index to measure the association between dietary patterns and coronary
heart disease risk factors: findings from two Italian studies . PREVENTIVE MEDICINE, 39 (4): 841-847 OCT 2004
IF = 2.3; N. Cit. = 5
D'Errigo, P; Tosti, ME; Fusco, D; et al. Use of hierarchical models to evaluate performance of cardiac surgery centres in the
Italian CABG outcome study. BMC MEDICAL RESEARCH METHODOLOGY, 7: Art. No. 29 JUL 3 2007
IF = 2.8; N. Cit. = 2
Rosato S, Seccareccia F, D'Errigo P, Fusco D, Maraschini A, Badoni G, Perucci CA. Thirty-day mortality after AMI: effect
modification by gender in outcome studies. Eur J Public Health. 2009 Nov 27.
IF = 2.18; N. Cit. = 0
H-INDEX = 3
Originality of the project
This study addresses a new interventional procedure (transcatheter aortic valve implantation, TAVI) for the treatment of severe symptomatic aortic stenosis (SSAS) that has been introduced into clinical practice without comparative efficacy studies.
This proposal describes the first OOS to address the comparative effectiveness of TAVI, AVR, and medical therapy for the
treatment of SSAS in an Italian population.
The main originality of the proposed project is that it represents the first national example of cooperation among national and
regional institutions, scientific societies, hospitals, and individual specialists, all of them involved and driven by a professional interest in the topic and a strong desire to have evidence-based information to address doubts and questions about the use
of TAVI vs. AVR. In addition, this work will mark the first European attempt of contemporary data collection on the three
possible treatments (AVR, TAVI, or medical) in a cohort of SSAS hospitalized patients performed at the national level.
To address comparative effectiveness evaluations, OOSs are increasingly used. They represent a valid approach to evaluating
comparative treatment effectiveness in real populations, mainly when experimental studies are difficult to set up. OOSs can
easily be described as an alternative/complement to experimental studies, making the most of tools and methodologies suitable to achieving the same aims of RCTs, but avoiding some known problems related to trial organization. To this extent, a
further originality lies in the study organization and methodology. In fact, this is the first time in Italy that an OOS is being
used at national level to evaluate the clinical effectiveness of a procedure that was systematically introduced into the National
Health System without evidence of efficacy. Moreover, given that the spread of a new methodology in clinical practice has a
strong structural, organizational, and economic impact on the system, this project will allow monitoring of all aspects and
consequences linked to the introduction of TAVI into the health system. In particular, concerning the TAVI procedure, this
study marks the first effort to estimate the direct cost increase in Italy.
The TAVI technique was originally designed to treat SSAS patients at very high-risk for an open surgical approach. The currently used operative risk score calculators (i.e., logistic EuroSCORE) have definitively been judged as outdated and overestimating the real individual risk without considering some important elderly related risk factors such as frailty and porcelain
aorta. Although this problem has been defined worldwide, this study represents the first attempt in Europe to elaborate a new
risk score, comprising new recognized risk factors and tailored to an elderly population of SSAS patients.
In Italy, any systematic control concerning the introduction of TAVI into clinical practice using current administrative data is
not feasible because consensus guidelines on TAVI procedure coding are not available. This study offers the possibility of a
standardized fit into the coding system by drawing up shared coding guidelines to be proposed to the regional health offices,
with the aim of establishing systematic administrative control.
Finally, one of the strengths of this study is the establishment of a clinical monitoring system aimed at controlling the quality
of recorded data. To this aim, independent observers, following specific standardized operating procedures (SOPs), will visit
each participating hospital and compare data from the transmitted records to those reported in the original clinical charts.
These procedures will allow assessment of the reliability and completeness of the database and help maintain a consistent
quality control. Moreover, the analyses of "suspected ICD-9-CM codes" from hospital discharge records and the subsequent
original clinical chart control will guarantee the completeness of the SSAS cohort enrollment.
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RICERCA FINALIZZATA 2009
Development strategy of the project, methodology, preliminary data and bibliographic references
The rapid growth of health technology and medical devices can often make it difficult to conduct the rigorously scientific
protocols of RCTs. Observational outcome studies can provide prompt results and scientific evidence to support medical decisions. Implementing this type of study is easier than implementing RCTs to yield answers from real clinical practice while
avoiding some experimental constraints such as "eligibility and/or exclusion criteria." This feature is particularly appropriate
for monitoring the current situation in its ongoing evolution.
OOSs, while non-experimental, are being increasingly used to assess and compare treatments. Their main peculiarity is the
implicit lack of randomization. Methods of study design and analysis implemented to balance this characteristic are generally
called "risk adjustment." These methods compensate for the lack of randomization, controlling for all known factors associated with the outcome and heterogeneously distributed among the categories of exposure under study.
The project will be conducted in the following four phases:
The FIRST PHASE will last 6 months (0-6). A further peer review of the scientific literature on severe SSAS treatments will
be performed. The project operative protocol and the set of patient characteristics and risk factors to collect will be developed. All Italian hospitals offering medical and procedural (AVR and/or TAVI) treatment to SSAS patients will be identified
and invited to participate in the study.
The SECOND PHASE will last 6 months (6-12). Data collection will be started. Using the SAS statistical package, routines
aimed at linking regional hospital discharge records (RHDRs) from the same patient within the clinical registry will be developed. Clinical monitoring activities and procedures leading to the completeness assessment will be set up.
The THIRD PHASE will last 18 months (12-30). Data collection will continue. Follow-up data within RHDRs and regional
mortality registries (RMRs) will be collected. Clinical monitoring will become operative. Interim epidemiological and statistical analysis of the collected data will be performed. A report dealing with all of the intermediate objectives will be generated.
The FOURTH PHASE will be completed between months 30 and 36. Epidemiological and statistical analysis of collected data will be performed. All scientific findings concerning the declared objectives will be summarized in a scientific report and
disseminated during a final workshop.
METHODOLOGY
Study design and data collection
An observational prospective multicenter cohort study is being proposed; it includes even those patients for whom a randomized comparison of treatment alternatives is not feasible. Hospitals invited to participate are those where a medical and procedural (AVR and/or TAVI) treatment can be offered to SSAS patients.
In the participating hospitals, to define the patient risk profile for each patient with SSAS, data on demographic characteristics, health status prior to intervention and presence of comorbidities will be collected. Moreover, complete information on
the type of intervention will be gathered. Data collection will be carried out with standardized online data entry on a password-protected website. In each center, data collection will be carried out under the oversight of a coordinator. Collected data will be stored at the central management unit at the National Institute of Health; each center will be able to check and download their own data at all times.
In each hospital, a survey will be carried out to record the characteristics of each operative unit and to monitor their possible
time changes linked to dissemination of new technologies. A structured questionnaire investigating available human resources, training courses, operative and hybrid theaters, etc., will be distributed for completion to all participant centers at the beginning of the study and at least 12 months later.
Study population
The study will include all adult patients first admitted to hospitals with a diagnosis of SSAS and requiring medical or interventional treatment. SSAS is defined as an aortic valve area <1 cm2, maximum aortic velocity >4 m/s, or mean pressure gradient >40 mmHg together with a NYHA class >2 (at least one of the following symptoms: syncope, exercise-induced angina,
dyspnea on exertion, congestive heart failure).
End-point and follow-up
Mortality within 30 days from intervention is the primary adverse outcome. In addition, data on mortality within 6 months
will be collected. Each enrolled center will be requested to gather this information. Secondary outcomes include mortality within 12 and 24 months and the incidence of in-hospital major adverse cardiac and cerebrovascular events (MACCE). For this
purpose, an administrative follow-up will be set up through a record linkage between the first and later admissions recorded
in the RHDRs. Long-term outcome information will be integrated through a record linkage with RMRs.
Data quality assessment
1.Clinical monitoring: For each participating center, a sample of records will be randomly selected from the electronic archive. Independent observers, following specific SOPs, will visit each center and compare the contents of transmitted records to
those reported in the original clinical charts. These procedures will allow assessment of the reliability and completeness of
the database and help maintain constant quality control.
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RICERCA FINALIZZATA 2009
2.Completeness assessment: The completeness of enrollment in each center will be evaluated using hospital discharge records supplied by hospital and regional health information systems. For patients with a suspected SSAS diagnosis
(ICD-9-CM 424.1) but not enrolled in the study, the clinical chart content will be evaluated. If the SSAS diagnosis has been
verified and confirmed, the patient will be included in the study database. Clinical and procedural information will be extracted from clinical charts. This procedure will assure the continuous cohort completeness control.
Data analysis
To compare the effectiveness of AVR, TAVI, and medical treatment in terms of medium- and long-term outcomes, accounting for possible differences in patient case-mix among the three treatment groups, risk adjustment techniques will be applied.
These will involve construction of a measure of patient severity by applying multivariate regression models to the enrolled
SSAS population (predictive models). The severity measure will be used to obtain adjusted outcome measures for valid comparison between treatments. To account for possible time-dependent risk factors, time trend analysis will be evaluated.
INTERNATIONAL PRELIMINARY DATA
Aortic stenosis is a common condition in all western countries with a clear increase in prevalence with age: 1.3% in patients
aged 65-75 years, 2.4% in those aged 75-85 years, and 4% in patients older than 85 years(1). Untreated symptomatic severe
disease shows a very poor prognosis progressively evolving towards complete disability. The mean survival rates are 40-50%
and 20% at 2 and 5 years, respectively(2-3).
To prevent irreversible damage to the cardiac muscle, aortic stenosis requires surgical intervention. With this indication, approximately 50,000 AVRs take place in Europe annually(4) and about as many are performed in the USA(5). AVR has a significant survival benefit with 1, 2, and 5-year survival rates of 87%, 78%, and 68%, respectively, vs. 52%, 40%, and 22% in
those without AVR (p < 0.001)(2). Over time, even the early outcome improves: currently, operative mortality of isolated
AVR is 2-5% in patients <70 years and 5-15% in older adults(6-7). Nevertheless, in a study conducted by Iung in the Euro
Heart Survey, 33% of elderly patients with severe symptomatic aortic stenosis were denied surgery(8). In recent years, a new
therapeutic approach is available for this kind of patient, feasible in hemodynamic laboratories from interventional cardiologists. Seven years after the first clinical use, over 6000 patients have been treated by TAVI. The immediate risk of the procedure seems to be related to the experience level of centers performing the technique and patient clinical condition. Long-term
results appear to depend more on comorbidities than on cardiac status(7).
TAVI can be performed by two different approaches, the trans-apical or trans-femoral . A recent study shows a TAVI procedural success rate of 93.3% and 30-day mortality rate of 10.4% (TF: 9.5%, TA: 11.3%). Moreover, survival rates for the entire study population at 1 and 2-year follow-up were 76% and 64%, respectively, with 75% and 65%, respectively, for the TF
group and 78% and 64%, respectively, for the TA group. Patients free of MACCE at 1- and 2-year follow-up were 72% and
60%, respectively, with 73% and 63% for the TF group and 72% and 59% for the TA group(9).
Finally, the outdated operative risk score calculators (i.e., logistic EuroSCORE) currently used for pre-treatment patient risk
estimation are not suitable for innovative procedures and emerging technologies such as the TAVI(10-11).
ITALIAN PRELIMINARY RESULTS
A national preliminary analysis has been performed on national hospital discharge records (HDR 2007) and on data from the
Interventional Cardiology Register (GISE 2008). In 2007, a total of 62,567 hospital admissions with a 424.1 ICD-9-CM code
(Aortic Stenosis Disorders, ASDs) were recorded. The 30-day in-hospital mortality rate (HMR) was 3.46%. Because the
424.1 code is very poor in terms of specificity and a SSAS is highly improbable among young patients, the analysis was focused on patients 70 years and older to better identify the target population. In this case, a total of 44,633 admissions were recorded, with an HMR of 4.35% (22,558 >=80 years, HMR 6.18%).
To estimate the number of medically treated patients (without associated procedures), admissions with AVR ICD-9-CM codes (35.20, 35.21, and 35.22) were excluded; the result was 54,515 records with an HMR of 3.41. Considering only patients
>=70 years old, the number of admissions was 40,091 with an HMR of 4.27% (21,488 >=80 years, HMR 6.16%).
Considering only hospitals with a cardiac surgery department, admissions of medically treated patients >=70 years with ASD
numbered 10,351. Among these, about 20% underwent an AVR intervention in the following 6 months.
In 2007, 9582 AVR procedures associated with the 424.1 ICD-9-CM code were recorded (HMR: 3.24%). Considering patients >=70 years, the number of admissions was 5458 with an HMR of 4.29% (1302 >=80 years, HMR 5.38%). To identify
isolated AVR procedures, all the admissions with a coronary artery bypass code (ICD-9-CM 36.1) were excluded, resulting
in a database of 6613 admissions (HMR: 2.68%). For patients >=70 years, 3464 admissions with isolated AVR were found
(HMR 3.67%; 790 >=80 years, HMR 4.43%).
Because TAVI is a relatively new procedure, any investigation of administrative data (available up to 2007) is not feasible.
The Italian Society of Interventional Cardiology (GISE) maintains a register of activity of hemodynamic laboratories. Some
results are published on their website (www.gise.it)(12). In 2008, 450 TAVIs were performed in Italy, 322 with Corevalve
and 128 with the Edward's valve. Campania, Emilia Romagna, Lazio, Liguria, Lombardia, Piemonte, Puglia, Sicilia, Toscana, and Veneto are the Italian regions where TAVI was performed.
Finally, as Tamburino et al.(13) report in an as-yet-unpublished paper, a total of 663 consecutive patients undergoing TAVI
in one of the 14 enrolled centers from June 2007 to December 2009 were followed up. Procedural success and intraprocedural mortality were 98% and 0.9%, respectively. Mortality rates were 5.4% at 30 days, 10.5% at 6 months, 13.3% at 1 year,
and 14.6% at 2 years. MACCE rates were 6.4% at 30 days, 12.9% at 6 months, 15.2% at 1 year, and 15.8% at 2 years.
In the international scientific literature, no results concerning the comparative effectiveness of AVR vs. TAVI in SSAS patients have been published.
9
Bibliography
1.Carabello B A, Paulus W J; Aortic stenosis; Lancet 2009; 373: 956-66
2.Varadarajan P, Kapoor N, Bansal R C, Pai R G; Survival in elderly patients with severe aortic stenosis is dramatically improved by aortic valve replacement: results from a cohort of 277 patients aged >= 80 years; European Journal of Cardio-thoracic Surgery 30 (2006) 722-727
3.Carabello BA; Aortic stenosis; N Engl J Med, Vol. 346, No. 9: 677-682
4.Butcahrt E G et al.; Recommendations for the management of patients after heart valve surgerY. European Heart Journal
(2005) 26, 2463-2471
5.Tardif J C; New Treatment For Aortic Valve Stenosis May Let Patients Avoid Open Heart Surgery, Animal Study Suggests; Science Daily, 2008; available on line:
http://www.sciencedaily.com/releases/2008/04/080418115022.htm (12/03/2010)
6.Hannan E L et al.; Aortic Valve Replacement for Patients With Severe Aortic Stenosis: Risk Factors and Their Impact on
30-Month Mortality; Ann Thorac Surg 2009;87:1741-50
7.Vahanian A et al.; Risk stratification of patients with aortic stenosis; European Heart Journal (2010) 31, 416-423
8.Iung B et al.; A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular
Heart Disease; European Heart Journal (2003) 24, 1231-1243
9.Rodés-Cabau J et al.; TAVI for the Treatment of SSAS in Patients at Very High or Prohibitive Surgical Risk - Acute and
Late Outcomes of the Multicenter Canadian Experience; (Article in press) Journal of the American College of Cardiology
10.Osswald B R et al.; Overestimation of aortic valve replacement risk by EuroSCORE: implications for percutaneous valve
replacement; European Heart Journal 2009 30(1):74-80
11.Piazza N et al.; Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of
Mortality score in patients implanted with the CoreValve ReValving System-A Bern-Rotterdam Study; Am Heart J
2010;159:323-9
12.Register of the hemodynamic laboratories activity: http://www.gise.it/attivita_2008.xls (12/03/2010)
13.Tamburino C, Capodanno D et al.; Incidence and Predictors of Early and Late Mortality after TAVI in 663 Patients with
Severe Aortic Stenosis; (Under revision); Circulation
Structure and equipment available for research and collaborations
The coordinating center (Istituto Superiore di Sanità) will make use of the cooperation of all hospitals performing AVR and/
or TAVI that agree to participate in the project. All regional health authorities (RHAs) where the hospitals performing the
studied procedures are located will be asked to participate. Their main task will be to support some project activities, like the
complete enrollment of the study cohort, easing contact and recruitment of the selected hospitals, and establishing administrative follow-up.
Finally, three operative units (OUs) will be directly involved in the study: one independent OU will cooperate with the coordinating center to set up and realize all the clinical monitoring activities; one OU will cooperate with the coordinating center
in all scientific activity and workshop organizations; and the third OU will be responsible for all informatics activities and
software management.
A detailed description of the activities follows.
COORDINATING CENTER - ISTITUTO SUPERIORE DI SANITÀ
Study protocol writing and minimal data set definition. All activities related to the building and set up of a dedicated website
for data collection and information diffusion. Periodical data collection control and drawing up of intermediate reports. Participation in periodic meetings for information sharing. Participation in the writing of all scientific papers representing official
outputs of the project. The coordinating center will also perform all other activities not listed as OU activities.
For fulfillment of all listed activities, five PCs, three printers, a fax, and a share of consumables and supplies will be put at
Project disposal. Moreover, a dedicated portion of a local server for the storage of data from the hospitals will be created. The
SAS and STATA statistical packages will be used for data analysis.
RECRUITED HO750.0 (stenosi0 (stenhe) -250.0 (stenhe) -2SpnT2(st -316.7yIe) -282.125 (activities,) i1study) -850.0 (protoc,dy) -850.0 (drawing) -
RICERCA FINALIZZATA 2009
Cooperation in activities related to the check of the complete enrollment of the study cohort (periodic control of SSASsuspected ICD-9-CM codes from hospital discharge records); follow-up data collection within the Regional Administrative
Health Informative System (retrieval of subsequent in-hospital major adverse cardiac and cerebrovascular events for each enrolled patient), and the RMRs (patient life status). Participation in periodic meetings for information sharing. Dissemination
of a) clinical guide lines for appropriate patients' selection to AVR or TAVI and analysis of the related organizing problems;
b) indication for TAVI procedures coding in administrative control (ASP LAZIO). In each RHA, a PC for data management,
a printer, and a fax will be put at Project disposal.
OU 1 - DEPARTMENT OF EPIDEMIOLOGY OF THE REGIONAL HEALTH SYSTEM, LAZIO
Participation in study protocol writing and minimal data set definition; contribution to data management and analysis; participation in periodic meetings for results interpretation. Cooperation in the drafting of the intermediate and final reports. Sharing of all project scientific activities and workshop organizations. Two PCs, a printer, and a fax will be put at Project disposal. The SAS statistical package will be used for data analysis.
OU2 - CLINICAL MONITORING UNIT
Setting up of standardized operating procedures (SOPs) to be followed in each participating hospital to compare information
recorded in the project and that reported in the original clinical charts. Periodic revision of each hospital discharge diagnosis,
identification of SSAS-suspected ICD-9-CM codes, original clinical chart revision for patients not recorded, and inclusion of
newly identified SSAS patients in the project database. Cooperation in the drafting of the intermediate and final reports for
the clinical monitoring section. Four dedicated specialists will be employed to fulfill activities provided for the clinical monitoring procedures. Four notebooks, a PC, a printer, and a fax will be put at Project disposal.
OU3 - SOFTWARE PROVIDER
Implementation of a dedicated password-protected web site accessible by each participating hospital. Building of a database
structure for data recording. Creation of a document-sharing section on the web site aimed at implementing information exchange among all the parties involved in the Project (national and regional institutions, hospitals, professionals, etc.). Creation and management of a local server section dedicated for the storage of data from hospitals. Two PC, a storage block for
data manteinance will be put at Project disposal.
OTHER COLLABORATIONS
Italian Ministry of Health
AGENAS (National Agency of Regional Health Services)
FIC - Italian Federation of Cardiology
SICI -GISE - Italian Society of Interventional Cardiology
SICCH - Italian Society of Cardiac Surgery
ITACTA - Italian Association of Cardiothoracic Anaesthesiologists
Teaching hospitals, scientific institutes for research, hospitalization, and health care
Relevance of the project for the National Health Service (on basis of rapid trasferibility on assistance)
TAVI is a new interventional procedure for the treatment of severe symptomatic aortic stenosis (SSAS) that is less invasive
compared to a conventional approach (surgical aortic valve replacement, AVR) and designed to treat high-risk patients. The
TAVI procedure has been introduced into clinical practice without results from comparative efficacy studies. Some consensus documents drawn up by scientific societies and aimed at identifying a set of criteria shared by cardiologists and cardiac
surgeons for SSAS patient management have appeared in the international scientific literature during the last 3 years. As results from RCTs on the comparative efficacy are not yet available, all the suggested criteria are not evidence derived from
RCT results but from clinical experience and common sense.
The primary criterion is the pre-treatment patient risk score. This score is currently estimated by the use of outdated risk score
calculators (i.e., logistic EuroSCORE), which overestimate the real individual risk and do not consider some important elderly risk factors like frailty and porcelain aorta.
The proposed study will yield comparative evaluations of short-, medium-, and long-term outcomes in patients with SSAS
undergoing AVR, TAVI, or medical treatment, adjusting for the individual pre-treatment risk factors. A direct consequence
of this evaluation will be the possibility of elaborating a new risk score calculator, comprising newly recognized risk factors
and tailored to the Italian elderly population of SSAS patients.
Concerning the relevance for the National Health System in terms of transferability of knowledge about assistance, the proposed study will allow identification of the relative performance of the different procedures, elaboration of new "TAVI indications criteria" based on the effectiveness of this procedure in a real population, and, finally, modulation of the different therapeutic approaches used, taking into account population features.
A relevant effect deriving from this study will be its benefits to National Health System management. In fact, the dissemination of a new methodology in clinical practice has a strong structural, organizational, and economic effect on the system. In
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RICERCA FINALIZZATA 2009
Italy, because of current device costs, the use of the TAVI procedure is expected to result in an unavoidable direct cost increase. A further expenditure increase for capital equipment investment (i.e., hybrid theaters), facilities, and personnel training is expected in the health provider balance sheet. Indeed, because of the requirement that TAVI procedures must be performed by multidisciplinary teams in surgical or hybrid theaters, a deep hospital internal reorganization is expected. Cost data
have not been systematically collected, and the cost effectiveness of TAVI is still unknown. This study will supply the national and regional health systems with appropriate tools and methodologies to monitor economic and organizational aspects
linked to the introduction of TAVI into the health system.
Moreover, the shift observed during the past 3 years towards performing TAVI on younger and younger patients represents a
clear trend to extending the TAVI technology to a more extensive group of patients, younger than before and without clear
contraindications to the conventional surgical approach (AVR). Before further increased application, TAVI needs to prove its
cost effectiveness as compared to the AVR procedure, which remains the gold standard treatment for SSAS patients.
Given that "TAVI indication criteria" is one of the expected study outputs, another relevant effect of this project will be providing concrete support to professionals for properly identifying the target population for TAVI and for making appropriate
management choices, thus avoiding re-interventions, controlling direct costs, and enhancing patient quality of life and life expectancy.
Another important issue concerns the possibility of using current administrative data to monitor the spread of TAVI into clinical practice. In Italy, this systematic procedure is not yet feasible because consensus guidelines on TAVI procedure coding
are not available. Regional systems seem to suggest different options and sometimes an ICD-9-CM code used to record a TAVI procedure in one hospital is not the same as that used in other institutes or hospitals belonging to the same region. This
study will offer the possibility of standardizing the coding system by drawing up shared coding guidelines to be proposed to
the regional health offices, with the aim of establishing systematic administrative control.
In conclusion, in its form as an observational outcome study, this project will allow comparison of the effectiveness of TAVI
with other therapeutic approaches available for SSAS patients in clinical practice. RCTs are carried out under experimental
conditions, and the researcher plays a determinant role in establishing rules and outlining the population under study, i.e., by
defining a list of patient exclusion and eligibility criteria. In this way, investigators determine the selection of an "ideal population" for study, limiting the transfer or extrapolation of results to the real population. An OOS differs from RCTs because it
lacks this direct intervention of the researcher, and results are derived from the "real population."
For this reason, the complete knowledge base derived from this study will be directly transferable to (a) professionals, giving
them the tools to manage the different aspects of the decision and to make evidence-based choices for the good of patients
and (b) policy makers, giving them evidence-based results for use in their decision-making process regarding management of
the national and regional health systems.
Compliance to call
YES
Co-financings
Co-funding institutions
Institution
Available from
Amount
Italian Ministry of Health - Department
Innovation
30/09/2010
€ 200.000,00
Overall costs of the project
Costs items and brief description
Part covered by MoH funds
[a]
Total
1. Permanent staff
€ 93.000,00
None
1 senior researcher, 1 administrative assistant
2. Project Staff (ad hoc contracts/consultants/fellowship)
€ 206.000,00
€ 206.000,00
3. Travel Costs and Subsistence Allowances
€ 55.000,00
€ 55.000,00
4. Equipment
€ 70.000,00
€ 19.000,00
2 researchers; 1 technical assistant
10 PC, 4 Notebooks, 5 printers, 3 fax, a storage block for data manteinance will be put at project disposal for coordinating and clinical monitoring activities. In addition, 1 PC, 1
printer and 1 fax will be put at project disposal by each recruited hospital and RHA.
12
RICERCA FINALIZZATA 2009
Costs items and brief description
Part covered by MoH funds
[a]
Total
5. Consumables and Supplies directly linked to the Project
€ 70.000,00
€ 25.000,00
€ 65.000,00
€ 35.000,00
€ 300.000,00
€ 200.000,00
€ 60.000,00
€ 60.000,00
€ 919.000,00
€ 600.000,00
Stationery articles, reams, folders, toner cartridges. 2 user licenses for SAS and STATA statistical packages
6. Dissemination of results (publications, meetings/
workshops etc.)
Scientific publications, meetings and workshops organizations
7. Data handling and analysis (specify)
Clinical monitoring procedures, web site implementation, data management and analysis
8. Overheads for all Institutions involved (specify)
coordinating center (ISS) and OU 1
Totale
TOTAL BUDGET OF THE
PROJECT:
€ 919.000,00
TOTAL AMOUNT OF COFINANCINGS:
€ 200.000,00
FUNDING REQUIRED TO
THE MINISTRY OF
HEALTH:
€ 600.000,00
INSTITUTIONAL RESOURCES:
€ 119.000,00
a: MoH - Ministry of Health
13