Access to care: towards better use of resources by taking ......Access to care: towards better use...
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Access to care: towards better use of resources by
taking into consideration clinical benefit
Alexandru ENIU, MD, PhDCancer Institute Ion Chiricuţă
Cluj-Napoca, Romania
Coordinator, ESO Eastern Europe and Balkan Region programme (EEBR)
Chair, ESMO Global Policy CommitteeESMO Executive Board Member
We are currently experiencing a cancer epidemic
Global Cancer Trends (IARC)Human Development Index (2008-2030)
Some punching statements:(which are VERY REAL!)
“Globally, more people die of cancer than of tuberculosis, malaria, and HIV/AIDS combined”
“The majority of the estimated 13 million cancer deaths in 2030 will occur in limited-resource countries, with higher case fatality”
“21.6 million new cases per year: how can we find resources for that?”
Atun et al, Lancet Oncol 2015; 16: 1153–86
Pillar one: pathology
WITHOUT PATHOLOGY:
How to treat cancer ?
How to report cancer incidence?
How to plan cancer control?
Adesina et al, Lancet Oncol, 14(4), 2013
Figure 9. Coverage of radiotherapy services according to country as determined by global equipment databases, an activity-basedoperations model, cancer incidence, and evidence-based estimates of radiotherapy needEstimates depend on the nature of equipment use...
Pillar two: Radiotherapy
90% of the population in LMICs lacks access to radiotherapy
Radiotherapy access in Europe
Rosenblatt E, et al. Lancet Oncol 2013;14:e79–86
“only 5% of patients in LIC and 20% in MICs have access to safe,
affordable, and timely cancer surgery”
Some evident challenges with limited resources?
Significantly limited health care resources pose unique challenges
Unavailable parameters prohibit the use of guidelines
Because of lack of resources, we are forced sometimes to make decisions against our best medical knowledge
Clinician= manager of scarce resourcesWith the current trend of meaningful advances that
come at a high cost, even traditionally “wealthy” systems struggle
Resource-stratified guidelines: BHGIIncremental allocation & implementation
Eniu A et al, Cancer: 113 (8 suppl), 2008
*** If the costs associated with trastuzumabwere substantially lower, trastuzumab would be used as a limited-level therapy.
Basic level: Core resources or fundamental services necessary for any breast health care system to function.
Limited level: Second-tier resources or services that produce major improvements in outcome such as survival.
Enhanced level: Third-tier resources or services that are optional but important, because they increase the number and quality of therapeutic options and patient choice.
Maximal level: Highest-level resources or services used in some high resource countries with lower priority on the basis of extreme cost
Anderson et al, The Breast J: 12 (1), 2006
NCCN Framework for Resource Stratification
Disparities in cancer outcomes (survival ) across Europe
De Angelis, et al: Cancer survival in Europe 1999–2007 by country and age: EUROCARE-5Lancet Oncol, 2013
Factors accounting for cancer outcomes disparities
Disparities in cancer care
General population health and
lifestyle
Cancer “workforce”
Patient Access & Availability of
Cancer Medication
(Late) Stage at diagnosisHealth
systeminfrastructure
Cancer care infrastructure
(priority devices?)
Lancet Oncol 2014
Access to cancer medication:What are the obvious problems?
Health professionals
PharmaNational bodies
Not enough quality/benefit obtained with new strategies/drugs
Dramatically increasedpricing
Incoherentreimbursement strategy
PatientAccess to
Cancer Medication
ESMO Anti-Neoplastic Medicines Surveys
Perception survey to map access to cancer medicines, including WHO Essential Medicines, reporting on:
Approval status ( yes/no) across Europe and the world Informative for new drugs
Reimbursement ( yes/no) Highlight differences in cancer policies Residual (out of pocket) cost to patients Delays in access due to special authorization
Actual availability Drug shortage for old drugs Unavailability in the pharmacy (parallel export) for expensive drugs
Cherny, Sullivan, Torode, Saar, Eniu Ann Oncol. 2017 Nov;28(11):2633–2647Cherny, Sullivan, Torode, Saar, Eniu Ann Oncol. 2016 Aug;27(8):1423-43
Adjuvant breast cancer: : formulary inclusion and availability : TAMOXIFEN
AvailabilityFormulary and cost to patients
Availability
Drug shortages affect several essential, old and inexpensive drugs (tamoxifen, doxorubicin, cisplatin, 5-FU, bleomycin…)
Not an issue of resources!Cherny, Sullivan, Torode, Saar, Eniu Ann Oncol. 2016 Aug;27(8):1423-43
WHO ESSENTIAL MEDICINES LIST 2015Solid Tumors
Cytotoxics Cytotoxics Cytotoxics Hormones
bleomycin docetaxel irinotecan anastrozole
calcium folinate doxorubicin methotrexate bicalutamide
capecitabine etoposide oxaliplatin dexamethasone
carboplatin fluorouracil paclitaxel leuprorelin
cisplatin filgrastim rituximab tamoxifen
cyclophosphamide gemcitabine trastuzumab
dacarbazine Ifosfamide+mesna vinblastine
dactinomycin imatinib vincristine
vinorelbine
• UICC Task Force on EML: UICC, Dana Farber Cancer Institute, ESMO, ASCO, SIOP, US NCI, NCCN International & others• New drugs, tumor-specific indications
http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf
Adjuvant breast cancer:Cost & availability - Tamoxifen
Free
<25% cost
25-50% cost
Discount >50% and <100%
Full cost
Not available
Missing data
High
Upper Middle
Low Middle
Low
Multi-use EML
Country Bleo CarboP CisPCyclo (IV) Cyclo (tab) DTIC Dox. Epir. Etop (IV) 5FU Ifos.
MTX (IV)
MTX (tab) VBL VCR
ArgentinaAustraliaCanadaChileCyprusIsraelJapanKorea, SouthOmanQatarSaudi ArabiaSingaporeUnited Arab EmiratesUSAAlgeriaBrazilChinaColombiaIranKazakhstanLebanonMalaysiaMexicoPeruSouth AfricaThailand TunisiaTurkeyBangladeshEgyptGhanaIndiaKenyaMoroccoPakistanPalestineSudanVietnamZambiaAfghanistanBurkina FasoTanzaniaUgandaZimbabwe
COST AND AVAILABILITY
Metastatic breast cancer (formulary inclusion and cost to patients): Anti-Her2 therapy
Trastuzumab
Trastuzumab TDM-1
TDM-1
Lung cancer :formulary inclusion and cost to patients: Targeted therapy
Erlotinib Crizotinib
Erlotinib Crizotinib
The pharmaceutical company requests marketing authorization Evaluation by EMA (high degree of transparency!)
Approval by the European Commission
Time 0: the new drug is effective and safe – valid for whole EU
Europe explodes into 28 (27...) different countries…
The present scenario
5 yrs 10 yrs2 yrs
The development of an ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS)
ESMO• Recognizes the need for clear and unbiased statements regarding the
magnitude of clinical benefit from new therapeutic approaches supported by credible research
• Wants to highlight treatments which bring substantial improvements
to the duration of survival and/or the QoL of cancer patients
use the scale for accelerated: registration reimbursement evaluation incorporating ESMO-MCBS,
value and cost effectiveness considerationsCherny, N et al, Ann Oncol epub 30 May 2015
How will the ESMO-MCBS be used?
• When a new anticancer drug is EMA approved, its benefit will be «scaled» by a dedicated ESMO committee
• Drugs which obtain the highest scores (A&B or 5&4):
1. will be highlighted in the ESMO guidelines2. represent the highest priority for rapid
endorsement by national bodies across Europe
54321
A
B
C
Curative Non-curative
Cherny, N et al, Ann Oncol epub 30 May 2015
Factors taken into account for ESMO-MCBS
Magnitude of Clinically Benefit
Overall survival,
Progression free survival
Toxicity
Costs
Prognosis of the
condition
Quality of Life
HR,Long term survival,
RR
Cherny, N et al, Ann Oncol epub 30 May 2015
Field testing Breast CancerMedication Trial Setting Primary
outcomePFS
controlPFS gain
PFS HR OS control
OS gain
OS HR QoL ESM0MCBS
Chemo +/-trastuzumab
HERA (Neo)AdjuvantHER-2 positive tumors
DFS 2 y DFS 77.4%
8.4% 0.54 (0.43-0.67)
A
T-DM1 vs capecitabine + lapatinib
EMILIA 2nd line metastatic after trastuzumab failure
PFS & OS 6.4 m 3.2 m
0.65 (0.55-0.77)
25 m 6.8m
0.68 (0.55-0.85)
Laterdeterioration
5
Trastuzumab + chemo +/-pertuzumab
CLEOPATRA1st line metastatic PFS 12.4 m 6 m 0.62(0.52-0.84)
40.8 m 15.7 m
0.68(0.56-0.84)
~ 4
Lapatinib +/-trastuzumab
EGF104900
3rd line metastatic PFS 2 m 1 m 0.73(0.57-0.93)
9.5 m 4.5 m
0.74 (0.57-0.97)
4
Capecitabine+/- lapatinib
Geyer, 2006
2nd line metastatic after trastuzumab failure
PFS 4.4 m 4 m 0.49 (0.34-0.71)
NS 3
Eribulin vs other chemo
EMBRACE 3rd line metastaticafter anthracycline& taxane
OS 10.6 m 2.5 m
0.81 (0.66-0.99)
2
Paclitaxel +/-bevacizumab
Miller, 2007
1st line metastatic PFS 5.9 m 5.8 m
0.6 (0.51-0.70)
NS ~ 2
Exemestane+/- everolimus
BOLERO-2 Metastatic after failure aromatase inhibitor+PFS >6 m
PFS 4.1 m 6.5 m
0.43 (0.36-0.54)
NS ~ 2
Example of using MCBS data: Breast cancer, Romania
Medication SettingPrimary outcome
ESMO-MCBS
Availability and cost
Preapproval (Barrier to
access) Chemotherapy +/-trastuzumab
(Neo)adjuvant HER-2 positive tumours
DFS A Yes YesT-DM1 vs lapatinib + capecitabine
2nd line metastatic after trastuzumab failure
PFS and OS 5 NoTrastuzumab + chemotherapy +/-pertuzumab
1st line metastatic PFS 4 No
Lapatinib +/-trastuzumab
3rd line metastatic PFS 4 NoCapecitabine +/-lapatinib
2nd line metastatic after trastuzumab failure
PFS 3 NoEribulin vs other chemotherapy
3rd line metastatic after anthracycline and taxane
OS 2 NoPaclitaxel +/-bevacizumab
1st line metastatic PFS 2 Yes Yes
Exemestane +/-everolimus
Metastatic after failure of aromatase inhibitor (with PFS > 6 mth)
PFS 2 No
COST AND AVAILABILITY
Level Economic Development Country Lapat. (MBC) Pertuz. (MBC) TDM-1 (MBC) Erlot (Lung) Gefit (Lung) Afatnin (Lung) Crizot (Lung) Cetux (CRC) Panitum (CRC) Sunit (RCC) Pazop (RCC) Axitin (RCC) Soraf (RCC) Everol (RCC) Temsir(RCC) Ipilim (Melan)Vemuraf. (Melan.) Abirat. (Prost) Enzalut. (Prost)
ESMO-MCBS 4 4 3 4 4 4 4 4 4 4 4 4 3 3 4 A/3 4 4 4
High Income
Argentina
Australia
Canada
Chile
Cyprus
Israel
Japan
Korea, South
Oman
Qatar
Saudi Arabia
Singapore
United Arab Emirates
USA
Upper mIddle Income
Algeria
Brazil
China
Colombia
Iran
Kazakhstan
Lebanon
Malaysia
Mexico
Peru
South Africa
Thailand
Tunisia
Turkey
Lower middle income
Bangladesh
Egypt
Ghana
India
Kenya
Morocco
Pakistan
Palestine
Sudan
Vietnam
Zambia
Low income
Afghanistan
Burkina Faso
Tanzania
Uganda
Zimbabwe
AlwaysUsuallyHalf the timeOccasionallyNeverNot availableMissing data
New Medications with ESMO-Magnitude of Clinical Benefit Scale score >3
Value based payment
• Payment for cancer medicines is a budget decision for the health care system
• Decisions must be made on objective and verifiable criteria where expenditures are compared to relevant alternative uses within and outside cancer care
• Value based payment requires development of sophisticated systems where payment is based on outcome in clinical practice
APHINITY: Intent-to-Treat Primary Endpoint Analysis Invasive Disease-free Survival
4yr iDFS absolute benefit = 1.7%
Number needed to treat: 112
Presented by Gunter von Minckwitz at 2017 ASCO Annual Meeting
112 * 48182=5.396.384 EURO!!
Recent statement by the American Statistical Association about p-values
• P-values do not measure the probability that a hypothesis is true.
• Scientific conclusions and policy decisions should not be based only on p <0.05.
• A p-value does not measure the size of an effect or the importance of a result.
• By itself, a p-value does not provide evidence regarding a model or hypothesis.
July-6-18
Clinical Benefit, Price and Approval Characteristics of FDA-approved New Drugs for Treating Advanced Solid Cancer, 2000-2015 A. Vivot, Ann OncolDOI:https://doi.org/10.1093/annonc/mdx053Published: 08 February 2017
There is a very poor link between spending and outcomes…
this does not mean that countries such as Romania do not need more funding
Quality of Care !!!
What are the solutions to improve cancer medicine access?
Health professionals
PharmaNational bodies
Care about benefit: MagnitudeOf Clinical Benefit Scale
Justum PretiumReimburse the reasonable medicines(public policy)
PatientAccess to
Cancer Medication
Conclusions Disparities exist in access to cancer medicines Drug shortages affect several “essential”, old and inexpensive
drugs THIS SHOULD BE UNACCEPTABLE !
Inequalities exist in availability and patient costs, especially for newer, more expensive drugs, across Europe
Stratified guidelines (BHGI, NCCN) and benefit scales (ASCO framework, ESMO MCBS) can inform the process of prioritization access to medicines, when resources are limited
Open discussions among stakeholders regarding cost, value and reimbursement priorities are a must ( and have started) to identify sustainable solutions
Way forward
The current situation, where new therapies providing marginal benefit in highly selected patients are approved at high price, is neither desirable nor sustainable
Consideration of “clinical benefit” and “value” that includes quality and consistency of evidence for effectiveness, toxicity, and cost is welcome
Pressure should be put on registration agencies (FDA, EMA) to use a criterion of value for approval, rather than statistical significance of an outcome measure
WE, as oncologists, should stop saying it is not our problem, and act using these evidence
July-6-18