Activity-based financing (T2A) reforms in France in 2004 led to the creation of a list of high-cost drugs reimbursed outside the hospital budget, the “liste-en-sus”. In 2013, this spending was over 2.8 billion Euro, with 7.5% growth Consequently, the French government has adopted multiple measures to control spending on “liste-en-sus” drugs. The most common measure taken is removal from the “liste-en-sus”. Patients and manufacturers have claimed that without such financing, removed drugs would not be prescribed, effectively denying access to certain products with marketing authorisation. We investigated the validity of this claim and the impact on spending.

1. Hospital spending in drugs (billions EUR) source CEPS2
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Liste-en-sus reform in France - what are the consequences?
Steven Flostrand1, Marcela Mitrano1
Objectives
Since 2004, French hospitals are funded through the tarification à l’activité (T2A) system, where patients are
classified based on their principal diagnostic and co-morbidities into Diagnostic Related Groups (DRG), for which
certain tariffs apply. Although DRG tariffs take into account most elements of care (e.g. diagnostics, treatments,
most drugs and devices), high-cost drugs are excluded. Due to their significant cost relative to the DRG tariff, as
well as access and equity concerns, such drugs are instead invoiced on top of the regular tariffs. Products financed
in this way feature on the ‘liste-en-sus’. In theory, new high-cost drugs are included on the ‘liste-en-sus’ for a
transitional period. When their usage becomes more standard or their price decreases, they are removed from the
list and their cost integrated into the regular GHS tariffs (which are adjusted accordingly).
Methodology
Results
Number of inclusions significantly reduced but not more exclusions
• Since 2013, there has been stricter application of the criteria at assessment,
resulting in fewer inclusions rather than increased exclusions
• Observed: fewer inclusions over time, while same number of exclusions.
More strict application of rules aim to limit growth of drug sales via the ‘liste-en-sus’. Analysis of the 21 products removed for insufficient clinical value shows that prescribing of
half of these products was maintained or increased, suggesting that removal did not deprive patients of authorized medicines. Sales fell after removal where alternatives were
available. For drug manufacturers, removal typically reduces sales, either through price discounts to achieve hospital DRG tariff levels, or a fall in prescribing.
The French ‘liste-en-sus’ is meant to offer temporary funding for innovation, yet the number of exclusions is low. Exclusion appears to have no negative consequences for
patients and little direct impact on sales for manufacturers. However; savings from such measures is very limited and unlikely to significantly reduce drug spending.
Conclusion
1 IMS Health, 5-7 place de la Pyramide, 92088 La Défense, France
PHP139
1) Sources: two main sources of information were used to perform this study: the ‘historique liste ucd en sus’ from ATIH website and IMS MIDAS data for France. Inclusions and
exclusions from the list within the period 2005-2015 YTD (September)* were analyzed and crossed with IMS MIDAS database. IMS MIDAS is a global pharmaceutical market
research service which provides sales data in 70 countries enabling quantitative and qualitative pharmaceutical sales analysis & assessment.
2) Product selection: The ATIH document covers 197 different brands and 145 different molecules. We looked at the inclusions and exclusions from the ‘liste-en-sus’ and
retained 66 brands that were excluded (55 molecules) to conduct the analysis.
3) Product qualification: the 66 excluded brands were classified in four categories based on the reason why they have been removed from the list:
• Market authorization withdrawal (n=4)
• Generic/biosimilar available after loss of exclusivity (LoE) lowered prices (n=37, of which n=20 were excluded since 2007)
• Switch of funding to retail sector (n=4)
• Other reason, likely insufficient clinical value based on SMR or ASMR scores. (n=21)
4) Analyses: number of inclusions and exclusions between 2007 and 2015, as well as individual product performance of the aforementioned categories over 4 years (16
quarters) before and after exclusion from the list, in volume. Products excluded from the list were aggregated and analyzed as a whole (1 line = 1 year of exclusion)
*Subsequent to abstract submission an additional eight products meeting criteria were identified and added to the analysis.
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Exclusions
Inclusions
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Fig 1. Liste-en-sus inclusions and exclusions (source: ATIH)
In February 2015 the conseil d’hospitalisation recommended that the existing inclusion criteria be retained but strictly respected. The main criteria are: an improvement in
medical benefit (ASMR) ≤III, or an ASMR of IV for exceptional cases, <80% of patients in the DRG needing it, and costs >30% price of the DRG tariff, though additional criteria
apply, such as the inscription of comparable products. Stricter application of the criteria is intended to slow the growth of drug costs.
Previous analysis1 of the list in 2014 showed that at least 36% of listed drugs have ASMR scores of V, suggesting that at least 47 products could potentially be removed from the
list en masse, if all comparable products were removed at once. In practice, removal from the list has been rare, and the impact of removal on usage unclear. The objective of
this analysis was to study the impact of removal on patients and manufacturers, who have claimed that without such financing, removed drugs would not be prescribed,
effectively denying access to certain products with marketing authorisation. We investigated the validity of this claim and the impact on drug spending.
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Hexvix ’12
Faslodex ’12
Navelbine ’10
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Exclusion 2014
Exclusion 2013
Exclusion 2011
Exclusion 2012
Exclusion 2007
Exclusion 2010
Fig 2. Impact of exclusion after LoE, N=20
Fig 3. Impact of exclusion after shift to retail sector, N=4 Fig 4. Impact of exclusion after clinical reevaluation, N=21
Exclusion from liste en sus
Exclusion from liste en susExclusion from liste en sus
Exclusion may not be definitive
• In 2012, Javlor (vinflunine) to treat bladder cancer was removed from the ‘liste-en-sus’ for economic reasons. It was reintegrated into the list in 2015 following appeal by the
manufacturer after the HAS acknowledged that due process was not respected and that economic reasons were not enough to justify exclusion. Vfend, and Alfalastin, both
excluded from the list for some indications were also re-included.
Re-evaluation of the clinical value does not change prescription rate
• Products may be excluded from the list after a re-evaluation; this is the most
common scenario, e.g. Vfend, Quadramet, Mabcampath, Revlimid
• Observed: prescriptions unchanged, and some increase of volumes over time, as
there are typically few alternatives to these products.
Prescribing shift to retail setting does not affect performance
• Use proven safe in the hospital setting is shifted to retail setting. The case is rare
as only four examples exist: Navelbine, Faslodex, Hexvix, Muphoran.
• Observed: No significant impact in the volumes sold for Faslodex and Hexvix;
Navelbine lost 25% market share after switch due to an IV alternative in the DRG.
Following loss of exclusivity there is little decline in usage
• Products after price decreases due to LoE, no longer meet criteria and are
excluded, e.g. Zometa, Taxotere, Gemzar, Mircera
• Observed: gradual decrease in usage as newer products replace old ones, trend
starts well before exclusion.
2.4 2.5 2.62 2.6 2.75 2.92 3.04
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1.96 2 2 1.82 1.4
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20142013
4.74
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Hors liste en sus
Liste en sus
1 Is the french ‘liste-en-sus’ still supporting access to innovative medicines? - Isabelle Ortiz, Caroline Conti, Jim Furniss (GfK London,UK), 2 CEPS activity report 2014-2015,
Muphoran ’15
Exclusion 2007
Exclusion 2012
Exclusion 2015
Exclusion 2013
The liste en sus is the driver for increasing expenditure on hospital drugs