Tumori, 97: 442-448, 2011
Disparity in the “time to patient access” to new
anti-cancer drugs in Italian regions. Results
of a survey conducted by the Italian Society
of Medical Oncology (AIOM)
Stefania Gori1, Massimo Di Maio2, Carmine Pinto3, Oscar Alabiso4,
Editta Baldini5, Enrico Barbato6, Giordano Domenico Beretta7, Stefano Bravi8,
Orazio Caffo9, Luciano Canobbio10, Francesco Carrozza11, Saverio Cinieri12,
Giorgio Cruciani13, Angelo Dinota14, Vittorio Gebbia15, Lucio Giustini16,
Claudio Graiff17, Annamaria Molino18, Antonio Muggiano19,
Giuliano Pandoli20, Fabio Puglisi21, Pierosandro Tagliaferri22, Silverio Tomao23,
and Marco Venturini24 on behalf of AIOM Working Group “Interaction with
Regional Sections” (2009-2011)
1Medical
Oncology, “SM della Misericordia” Hospital, Azienda Ospedaliera, Perugia;
Trials Unit, National Cancer Institute, “G Pascale” Foundation, Napoli; 3Medical Oncology
Unit, “S Orsola-Malpighi” Hospital, Bologna; 4Azienda Ospedaliero-Universitaria "Maggiore della
Carità", Università degli Studi del Piemonte Orientale "A Avogadro", Novara; 5Medical Oncology,
“Campo di Marte” Hospital, Lucca; 6Ospedale “SG Moscati”, ASL CE, UOSD, Oncologia, Aversa
(CE); 7Medical Oncology, Istituto Clinico Humanitas Gavazzeni, Bergamo; 8UO di Oncologia, Asl 1,
Città di Castello (Perugia); 9Medical Oncology Department, “S Chiara” Hospital, Trento;
10
Medical Oncology, PA Micone Hospital, ASL3 Genovese, Genova Sestri P; 11Medical Oncology,
"A Cardarelli" Hospital, Campobasso; 12Medical Oncology & Breast Unit, PO Senatore Antonio
Perrino ASL Brindisi, via Appia, Brindisi, and Medical Department, Istituto Europeo di Oncologia
(IRCCS) Milano; 13Medical Oncology, Umberto I Hospital, Lugo di Romagna (RA);
14
Medical Oncology, Azienda Ospedaliera S Carlo, Potenza; 15Medical Oncology, La Maddalena,
Palermo; 16Medical Oncology, Zona Territoriale 11 Fermo; 17Medical Oncology, Central Hospital
ASDAA/SABES, Bolzano/Bozen; 18Oncologia, Ospedale Civile Maggiore, Azienda Ospedaliera
Universitaria Integrata, Verona; 19Oncology Department, “A Businco” Hospital, ASL 8, Cagliari;
20
UO di Oncologia, ASL di Pescara, Pescara; 21Department of Clinical Oncology, University Hospital,
Udine; 22Medical Oncology Unit, Tommaso Campanella Cancer Center and Magna Graecia
University, Catanzaro; 23Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche, Università
degli Studi di Roma "Sapienza"; 24Medical Oncology, Ospedale Classificato Sacro Cuore Don
Calabria, Negrar, Verona, Italy
2Clinical
ABSTRACT
Aims and background. In 2009, the Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of regional pharmaceutical formularies on the
disparity of access to eight new drugs among cancer patients treated in Italian regions. The survey documented some regional restrictions for some anti-cancer drugs.
In the study, we analyzed the “time to patient access” to new anti-cancer drugs in Italian regions.
Key words: anticancer drugs, disparity, time to patient access.
Conflict of interest statement: The authors declare no conflict of interest
relevant to this work.
Methods. In March 2010, we analyzed the availability of 17 new anti-cancer drugs at
a regional level, specifically the coherence of regional authorizations compared with
national authorizations approved by the Italian Medicines Agency (AIFA). In the regions with pharmaceutical formularies, we analyzed the characteristics of technicalscientific committees for the evaluation of inclusion of hospital drugs in these formularies. We also analyzed the time from EMA (CMPH) authorization to AIFA marketing authorization, the time from AIFA marketing authorization to patient availability, and the total time from EMA (CMPH) authorization to patient availability of
the drugs in all Italian regions, for 11 of these drugs.
Correspondence to: Dr.ssa Stefania
Gori, Oncologia Medica, Ospedale
Santa Maria della Misericordia, Azienda Ospedaliera di Perugia, Via Dottori
1, 06122 Perugia, Italy.
Tel +39-075-5784212;
fax +39-075-5279082;
e-mail stefania.gori@tin.it
Results. Some drugs were included in all the regional pharmaceutical formularies,
without restrictions, whereas other drugs were not included in one and others were
Received November 5, 2010;
accepted January 17, 2011.
DISPARITY IN THE TIME TO PATIENT ACCESS TO NEW ANTICANCER DRUGS IN ITALY
not included in more than one formulary. Median time
from EMA to AIFA was 11.2 months (range, 2.9-17.1).
Median time from AIFA to patient availability was 1.4
months (range, 0.0-50.5) in regions with drug formularies versus 0.0 months in regions without drugs formularies. Median total time from EMA to patient availability was longer in regions with formularies (13.3 months;
range, 2.9-65.3) than in regions without formularies
(11.2 months; range, 2.9-24.0), where drugs are immediately available after AIFA marketing authorization.
Moreover, the interval was very long (range, 2.9-65.3) for
some drugs in regions with formularies.
Conclusions. The analysis confirmed that the presence
of multiple hierarchical levels of drug evaluation can
create disparity in drug availability for Italian citizens.
Introduction
As a general rule worldwide, new drugs obtain marketing authorization after an evaluation of scientific results obtained in clinical trials. Hospital drugs and thus
anti-tumor drugs have to complete a series of obstacles
before becoming available to Italian patients. Regarding
the Italian market, when a new drug is evaluated
through centralized European procedures, authorization is released by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMA). Italy, as a member state of the European
Community, automatically accepts drug marketing authorizations released by EMA. The implementation of
EMA decisions is performed by the “European Procedures” Subcommittee of the Technical-Scientific Committee of the Italian Medicines Agency (Agenzia Italiana
del Farmaco, AIFA). Before adding the approved product to the National Pharmaceutical Formulary, AIFA decides the supply regimen and negotiates the reimbursement price with the authorization holder.
After national marketing authorization by AIFA, a
drug for hospital use is not immediately available in
every hospital pharmacy. Its approval needs to undergo
further steps that may be quite different from one region to the next, and even within a single region these
steps may vary among the different health districts and
hospitals1. There can be several levels of regional and local technical-scientific committees, each having the
faculty of deciding the inclusion/exclusion of the drug
in the specific pharmaceutical formulary. Consequently,
the release of marketing authorization is performed at
high hierarchical levels (EMA/AIFA), but the actual
availability of the drug at each hospital is conditioned at
local and lower hierarchical levels. According to this
process, the number of drugs that are actually available
for patients can be restricted. A local committee cannot
insert in the local formulary a drug that is not included
in the National Pharmaceutical Formulary, but it may
decide to exclude from the local formulary a drug that
443
has been authorized by AIFA. Similarly, with a few exceptions, a hospital cannot include a drug in its formulary if the drug is not included in the regional pharmaceutical formulary, but may decide for exclusion of a
drug that has been approved at the regional level.
The existence of regional and local technical-scientific committees may cause disparities in the availability
of drugs for patients of different regions as well as for
patients treated at different hospitals within the same
region. The problem of drug availability is particularly
relevant in the oncology setting for two reasons: 1) patients want to receive the innovative drugs as part of
their treatment, if indicated; 2) these new anti-cancer
drugs most always have a very high price. In theory, the
decision regarding the inclusion of new drugs in local
formularies might be conditioned by the need for cost
control by regional and local administrations, which
can compromise the equality of treatment for Italian
patients treated in different contexts (Jommi C, Bartoli
S, Otto M. Analisi delle politiche regionali su accesso a
farmaci innovativi. Università Commerciale Luigi Bocconi – CERGAS [Centro di Ricerche sulla Gestione dell’Assistenza Sanitaria e Sociale], 2008). Disparity in access to anti-cancer treatments is a relevant problem, as
has been recently underlined by the American Society
of Clinical Oncology, although the social and health
context in the United States is profoundly different from
the Italian reality2.
In 2009, the Italian Society of Medical Oncology
(AIOM) conducted a survey to describe the impact of
the existence of regional pharmaceutical formularies on
the disparity of access to eight new drugs among cancer
patients treated in different Italian regions. Results of
the survey evidenced some regional restrictions for
some drugs3.
AIOM conducted the study in 2010 with the aim of
evaluate the differences in “time to patient access” of
the new anticancer drugs among Italian regions and any
possible disparity in the time to availability.
Methods
Information for this study was collected with the help
of coordinators of each regional section of AIOM. For
each region and for the two autonomous provinces that
form the Trentino-Alto Adige Special region, information was collected on the existence of a regional pharmaceutical formulary/provincial pharmaceutical formulary.
For regions where a regional/provincial pharmaceutical formulary was available, the most updated version
of the formulary at March 2010 was examined, in order
to verify the inclusion of the analyzed drugs, and the coherence with the national marketing authorization indication approved by AIFA. Moreover, the characteristics
of the technical-scientific committees for the evaluation
444
S GORI, M DI MAIO, C PINTO ET AL
of hospital drugs to be included in regional formularies
were analyed, both in terms of composition and the
scheduling of meetings.
We considered 17 drugs registered by AIFA from 2005
to 2009: bevacizumab, bortezomib, cetuximab, dasatinib, erlotinib, ibritumomab, imatinib, lapatinib, nilotinib, panitumumab, pemetrexed, rituximab, sorafenib,
sunitinib, temsirolimus, trabectedin, and trastuzumab.
We analyzed, in all Italian regions and autonomous
provinces, 3 time intervals: time from EMA (CMPH) authorization to AIFA marketing authorization (Time 1),
time from AIFA marketing authorization to regional
availability (Time 2), and the total time from EMA
(CMPH) authorization to regional availability (Time 3)
for the following drugs: bevacizumab, cetuximab, erlotinib, ibritumomab, lapatinib, nilotinib, pemetrexed,
sorafenib, sunitinib, trabectedin, and trastuzumab.
Results
As of March 2010, 15 Italian regions (Abruzzo, Basilicata, Calabria, Campania, Emilia Romagna, Lazio, Liguria,
Molise, Puglia, Tuscany, Sardinia, Sicily, Umbria, Valle
d’Aosta, and Veneto) and the autonomous province of
Trento had regional/provincial pharmaceutical formularies. Four regions (Piemonte, Lombardy, Friuli-Venezia
Giulia, Marche) and the autonomous province of Bolzano
did not have regional pharmaceutical formularies. The
same situation was observed in the previous analysis3.
In Italian regions and in the autonomous province with
regional formularies, there are technical-scientific committees for the evaluation of hospital drugs to be included in these formularies. The characteristics of these technical-scientific committees are reported in Table 1. Some
committees do not include a medical oncologist among
current members. Declared schedule of meetings was
different among the regions (ranging from monthly to
every 6 months), and the actual number of meetings during 2009 was very different, ranging from 0 and 11.
In Italian regions and in the autonomous province
with regional formularies, it was observed that in the
majority of cases the updated versions (at March 2010)
of regional pharmaceutical formularies used for the
present analysis included the 17 analyzed drugs, with
therapeutic indication coherent with national marketing authorization indications approved by AIFA (Table
2). However, eight of the 17 drugs (sorafenib, nilotinib,
dasatinib, ibritumomab, lapatinib, trabectedin, panitumumab and temsirolimus) were not included in some
of the existing regional pharmaceutical formularies. Six
drugs (cetuximab, bevacizumab, erlotinib, sunitinib,
pemetrexed and nilotinib) presented some restrictions
in some regions. In some regions, patient-specific requests were needed for some drugs.
In four Italian regions (Piemonte, Lombardy, FriuliVenezia Giulia, Marche) and in the autonomous
province of Bolzano (which did not have regional pharmaceutical formularies), national marketing authorizations were immediately applicable.
Table 1 - Technical-scientific committees for the evaluation of hospital drugs to be included in regional formularies (analysis
performed in February 2010)
Committee members
Region
Abruzzo
Basilicata
Calabria
Campania
Emilia-Romagna
Lazio
Liguria
Molise
Puglia
Sardinia
Sicily
Tuscany
(North-West
Wide-Area)
Trento Province
Umbria
Valle d’Aosta
Veneto
Pharmacist Pharmacologist
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
General
Medical Infectivologist Cardiologist Other Number of Meeting
practitioners oncologist
medical
schedule
oncologists
in the
Committee
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
2
0
0
0
2
1
5
1*
1
1
1
-**
Monthly
nr
Every 2 mo
Monthly
Monthly
Monthly
Every 6 mo
Every 6 mo
Monthly
Monthly
Monthly
Not regular
10
0
6
10
11
7
1
1
6
5
4
2
X
X
X
X
X
X
1
1
1
1
Monthly
Every 3 mo
Every 3 mo
Every 2 mo
10
3
4
7
X
X
X
X
X
X
X
X
X**
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
No. of
meetings
in 2009
*The number of medical oncologists varies according to the topics discussed at each meeting. **Presence of medical oncologist is on demand.
nr, not reported.
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
Limits
Yes
Limits
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
Limits
Yes
Limits
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
PSR
PSR
Yes
Yes
Yes
Yes
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Limits
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
PSR
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
NO
Yes
Yes
Yes
Yes
Limits
Yes
Yes
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
Yes
Yes
Yes
PSR
Yes
Limits
Yes
Yes
Yes
Yes
Limits
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
Yes
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
No
Yes
No
No
Yes
No
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Limits
Yes
PSR
Yes
Yes
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
Yes
No
No
No
No
PSR
No
No
Yes
Yes
No
Yes
Yes
No
Yes
Yes
No
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
No
No
Yes
No
No
Yes
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
PSR
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
No
No
No
Yes
Yes
Yes
No
Yes
Yes
Yes
No
Yes
Yes
PSR
Yes, drug included in the formulary; No, drug not included in the formulary; PSR, use of drug allowed by patient-specific request; Limits, drug included in the formulary, with limitations, A.P. Trento, autonomous province of Trento.
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Limits
Formulary Cetuximab Bevacizumab Trastuzumab Rituximab Erlotinib Sorafenib Sunitinib Pemetrexed Lapatinib Trabectedin Nilotinib Bortezomib Panitumumab Dasatinib Temsirolimus Imatinib Ibritumomab
analyzed
(date)
Abruzzo
02/2010
Basilicata
2008
Calabria
2008
Campania
2005
Emilia 02/2010
Romagna
Lazio
12/2008
Liguria
06/2008
Molise
10/2007
Puglia
09/2009
Sardinia
12/2009
Sicily
02/2009
Tuscany
06/2007
(North-West
Wide Area)
A.P. Trento 11/2009
Umbria
11/2009
Valle d’Aosta 01/2010
Veneto
02/2010
Region
Table 2 - Inclusion of selected drugs in Italian regional pharmaceutical formularies, as of March 2010
DISPARITY IN THE TIME TO PATIENT ACCESS TO NEW ANTICANCER DRUGS IN ITALY
445
446
Time to drug availability for neoplastic patients
in Italian regions
The time to drug availability for neoplastic patients in
Italian regions is shown in Figure 1. Tables 3 and 4 report
the time to drug availability in regions with and without
regional drug formularies, respectively. Both tables report the time from EMA (CMPH) authorization to AIFA
marketing authorization (Time 1), the time from the
AIFA marketing authorization to patient availability
(Time 2), and the total time from EMA (CMPH) authorization to patient availability of the drug (Time 3).
In the 15 regions and in the autonomous province of
Trento that have regional formularies, time elapsed before the availability of the drugs for the patients (Time 3)
is given by the sum of the two intervals: from the EMA
approval to AIFA marketing authorization (Time 1: 11.2
months; range, 2.9-17.1), and from AIFA marketing authorization to drug inclusion in the regional formulary
(Time 2: 1.4 months; range, 0.0-50.5) (Table 3). The overall median time required before patient access (Time 3)
in these regions was 13.3 months (range, 2.9-65.3) (Table
3). Moreover, the range of the values for Time 3 demonstrates that the interval can be very long for some drugs:
65.3 months for cetuximab in metastatic colorectal cancer, and 40.4 months for sorafenib in metastatic kidney
in the regions with regional drug formularies (Table 3).
In the 4 regions and in the autonomous province of
Bolzano that do not have regional formularies, Time 2 is
zero by definition and time of regional availability of
S GORI, M DI MAIO, C PINTO ET AL
drugs (Time 3) is dependent only on the time from EMA
approval to AIFA marketing authorization (Time 1: 11.2
months; range, 2.9-17.1) (Table 4). So, in these regions,
the overall median time required before patient access
(Time 3) was 11.2 months (range, 2.9-24.0), shorter than
in regions with regional formularies (13.3 months;
range, 2.9-65.3). Moreover, also the range of values for
Time 3 was more limited (range, 2.9-24.0) than for regions with regional formularies (range, 2.9-65.3).
Discussion
The present analysis, conducted as of March 2010,
was based on 17 new anti-neoplastic agents that were
registered by AIFA with indications for use in oncology
over the period 2005-2009. This series of drugs is larger
than the eight drugs considered in the previous publication3, and more adequately represents the increasing
number of agents that have been registered in recent
years for use in oncology.
In Italian regions with regional pharmaceutical formularies, all analyzed drugs were included in formularies
with therapeutic indication coherent with national marketing authorization indications approved by AIFA, but
eight of the 17 drugs were not included in some of the existing regional pharmaceutical formularies and six drugs
presented some regional restrictions. In some regions,
patient-specific requests were needed for some drugs.
Figure 1 - Median total time from the EMA (CHMP) authorization to regional availability of the drug (Time 3). EMA, European Medicines
Agency; CHMP, Committee for Medicinal Products for Human Use; HCC, hepatocellular carcinoma.
DISPARITY IN THE TIME TO PATIENT ACCESS TO NEW ANTICANCER DRUGS IN ITALY
Table 3 - Time to availability of anticancer drugs in Italian regions with regional drug formularies (March 2010)
Time 1
Interval
EMA-AIFA
Median
(range),
months
Time 2
Interval
AIFA-regional
availability
Median
(range),
months
Time 3
Interval
EMA-regional
availability
Median
(range),
months
2.9
(2.9-2.9)
0.0
(0-0)
2.9
(2.9-2.9)
16.9
(16.9-16.9)
5.1
(2.1-13.6)
22.0
(18.9-30.4)
SunitinibAIFA 2006
6.9
(6.9-6.9)
7.3
(1.9-19.3)
14.1
(8.7-26.1)
SorafenibAIFA 2006Kidney cancer
4.1
(4.1-4.1)
2.8
(0.3-36.3)
6.9
(4.4-40.4)
SorafenibAIFA 2008hepatocellular
carcinoma
9.1
(9.1-9.1)
Drug
Trastuzumabbreast cancer,
adjuvant
treatment
Trabectedin
Pemetrexed
AIFA 2009
NSCLC – First line
Table 4 - Time to availability of anticancer drugs in Italian regions without regional drug formularies (March 2010)
Drug
9.4
(9.4-26.4)
Time 1
Interval
EMA-AIFA
Median
(range),
months
Time 2
Time 3
Interval
Interval
AIFA-regional EMA-regional
availabilty
availability
Median
Median
(range),
(range),
months
months
2.9
(2.9-2.9)
0.0
(0-00)
2.9
(2.9-2.9)
16.9
(16.9-16.9)
0.0
(0.0-7.1)
20.4
(16.9-24)
Sunitinib-AIFA 2006
6.9
(6.9-6.9)
0.0
(0.0-0.0)
6.9
(6.9-6.9)
Sorafenib-AIFA 2006kidney cancer
4.1
(4.1-4.1)
0.0
(0.0-0.0)
4.1
(4.1-4.1)
Sorafenib-AIFA 2008hepatocellular
carcinoma
9.1
(9.1-9.1)
0.0
(0.0-0.0)
9.1
(9.1-9.1)
13.9
(13.9-13.9)
0.0
(0.0-0.0)
13.9
(13.9-13.9)
Nilotinib
8.6
(8.6-8.6)
0.0
(0.0-0.0)
8.6
(8.6-8.6)
Trastuzumabbreast cancer,
adjuvant treatment
Trabectedin
0.2
(0.2-17.2)
447
Pemetrexed
AIFA 2009
NSCLC – First line
13.9
(13.9-13.9)
0.4
(0.4-5.5)
14.3
(14.3-19.3)
Nilotinib
8.6
(8.6-8.6)
5.8
(0.8-17.8)
14.5
(9.4-26.4)
Lapatinib
11.3
(11.3-11.3)
0.0
(0.0-0.0)
11.3
(11.3-11.3)
Lapatinib
11.3
(11.3-11.3)
3.9
(1.4-8.5)
15.2
(12.7-19.7)
Ibritumomab
Ibritumomab
17.1
(17.1-17.1)
32.4
(15.4-45.4)
49.5
(32.5-62.5)
17.1
(17.1-17.1)
0.0
(0.0-0.0)
17.1
(17.1-17.1)
ErlotinibAIFA 2006- NSCLC
13.0
(13-13)
0.0
(0.0-7.7)
13.0
(13-20.7)
ErlotinibAIFA 2006-NSCLC
13.0
(13.0-13.0)
0.0
(0.0-0)
13.0
(13.0-13.0)
CetuximabAIFA 2005Colorectal cancer
14.8
(14.8-14.8)
11.4
(0-50.5)
26.3
(14.8-65.3)
Cetuximab-AIFA 2005colorectal cancer
14.8
(14.8-14.8)
0.0
(0.0-0.0)
14.8
(14.8-14.8)
Cetuximab-AIFA 2006Head and neck cancer
8.7
(8.7-8.7)
0.0
(0-0)
8.7
(8.7-8.7)
8.7
(8.7-8.7)
9.5
(0-22.7)
18.2
(8.7-31.4)
Cetuximab-AIFA 2009colorectal cancer
13.3
(13.3-13.3)
0.0
(0.0-0.0)
13.3
(13.3-13.3)
11.2
0.0
11.2
(11.2-11.2)
(0.0-0.0)
CetuximabAIFA 2006Head and neck
cancer
CetuximabAIFA 2009Colorectal cancer
13.3
(13.3-13.3)
Bevacizumab
AIFA 2005Colorectal cancer,
1st line
11.2
(11.2-11.2)
0.0
(0.0-19.1)
11.2
(11.2-30.3)
11.2 (2.9-17.1)
1.4 (0.0-50.5)
13.3 (2.9-65.3)
Total
0.0
(0-4.8)
13.3
(13.3-18.1)
Bevacizumab
AIFA 2005-colorectal
cancer, 1st line
Total
Time 1, the time from the EMA (CMPH) authorization to AIFA marketing authorization.
Time 2, the time from the AIFA marketing authorization to regional
availability of these drugs.
Time 3, the total time from the EMA (CMPH) authorization to regional availability of the drug.
These observations revealed that, in the majority of
cases, the regional technical-scientific committee (or
equivalent) confirmed the positive decision made at the
higher hierarchical level (AIFA). However, a significant
11.2 (2.9-17.1) 0.0 (0.0-7.1)
(11.2-11.2)
11.2 (2.9-24.0)
Time 1, the time from the EMA (CMPH) authorisation to AIFA marketing authorization.
Time 2, the time from the AIFA marketing authorisation to regional
availability of these drugs.
Time 3, the total time from the EMA (CMPH) authorisation to regional availability of the drug.
number of drugs had been excluded from the formularies in one or more regions: in these instances, the inferior hierarchical level (the lower level authority at the regional level) did not take into account the decision of
the higher authority (AIFA at the national level). This occurred despite, at a higher level, the scientific evidence
supporting the drug had been judged sufficient to warrant marketing authorization. On the contrary, in four
448
Italian regions and in the autonomous province of
Bolzano which did not have regional pharmaceutical
formularies, national marketing authorizations were
immediately applicable.
The presence of sub-national pharmaceutical formularies is a potential element of disparity in the access to
pharmacologic therapy for Italian patients. However, it
should be noted that regional formularies are made because they can be a tool for efficient allocation of resources and for appropriate prescription.
The analysis of time elapsed before the availability of
the drug for the neoplastic patient adds some relevant
elements to the issue of disparity between Italian regions. In the regions with regional formularies, the overall median time required before patient access (Time 3)
was 13.3 months (range, 2.9-65.3). Moreover, the range
of the values for Time 3 demonstrates that the interval
can be very long for some drugs: 65.3 months for cetuximab in metastatic colorectal cancer and 40.4 months
for sorafenib in metastatic kidney in the regions with regional drug formularies (Table 3).
In regions without regional formularies, the overall
median time required before patient access (Time 3) is
shorter: 11.2 months (range, 2.9-24.0), because this time
is dependent only on the time from EMA approval to
AIFA marketing authorization.
Furthermore, the total time to availability of anticancer drugs in Italian regions without regional drug
formularies is independent from other bureaucratic issues such as the difference in the frequency of technical-scientific regional commission meetings, which in
regions with drug formularies creates further disparity
between Italian patients. Currently, the declared schedule of meetings (ranging from monthly to every 6
months) and the actual number of meetings during
2009 was very different, ranging from 0 and 11. Such differences can also be a potential element of disparity in
the access to anti-neoplastic drugs for Italian patients
because they prolong the time already elapsed between
S GORI, M DI MAIO, C PINTO ET AL
the AIFA marketing authorization to regional availability of the drug.
In conclusion, the presence of multiple hierarchical
levels of drug evaluation necessary for inclusion in the
relative regional, provincial or wide-area formularies, as
well as those of local health authorities or hospitals, is a
potential element of disparity in the access to pharmacologic therapy for Italian neoplastic patients. Moreover, the regional/local processes create time delays
and discrepancies, and there is no guarantee that such
disparities will not continue to widen. In the ideal scenario, medical oncologists should be able to consider
and prescribe for their patients all drugs that have received national marketing authorizations. The commissions responsible for the territorial formularies have the
responsibility of evaluating and containing drug care
costs, but being at a lower hierarchical level they may
better achieve this objective through monitoring of the
appropriate use of authorized drugs.
References
1. Pammolli F, Integlia D: I farmaci ospedalieri tra Europa, Stato, Regioni e cittadini. Federalismo per i cittadini o federalismo di burocrazia? CERM – Competitività, Regolazione,
Mercati. Roma. Quaderno n. 1, 2009. Available at
http://www.cermlab.it/pub/group/q/item/102 (last accessed January 20, 2011).
2. Goss E, Lopez AM, Brown CL, Wollins DS, Brawley OW,
Raghavan D: American Society of Clinical Oncology Policy
Statement: Disparities in Cancer Care. J Clin Oncol, 27:
2881-2885, 2009.
3. Gori S, Di Maio M, Pinto C, Alabiso O, Baldini E, Beretta GD,
Caffo O, Caroti C, Crinò L, De Laurentiis M, Dinota A, Di Vito F, Gebbia V, Giustini L, Graiff C, Guida M, Lelli G, Lombardo M, Muggiano A, Puglisi F, Romito S, Salvagno L, Tagliaferri P, Terzoli E, Venturini M, on behalf of AIOM Working
Group “Interaction with Regional Sections” (2007-2009):
Differences in the availability of new anti-cancer drugs for
Italian patients treated in different regions. Results of analysis conducted by the Italian Society of Medical Oncology
(AIOM). Tumori, 96: 1010-1015, 2010.