1. Study identification
EU PAS Register NumberEUPAS18568
Official titleBudget impact analysis of discontinuing Tyrosin Kinase Inhibitors in patients with chronic myeloid leukemia achieving a complete molecular response by using probabilistic Markov approach
Study title acronymECOSTIM
Study typeObservational study
Brief description of the studyChronic myeloid leukemia (CML) is an hematopoietic stem cell disorder in which a t(9;22) (q34;q11) reciprocal chromosomal translocation gives rise to Philadelphia chromosome (Ph) and generates the BCR-ABL1 fusion gene encoding a constitutively activated tyrosine kinase protein. Over the past decade, a broad array of drugs designed to selectively inhibit protein tyrosine kinases [i.e., tyrosine kinase inhibitors, (TKI)] have emerged as novel therapies. These treatments induce durable responses and prolong survival allowing CML patients to have a near-normal life expectancy. Two important issues must be then considered in the future: 1-the quality of life and ethical aspects of the lifetime treatment during lifetime, 2- the economic impact of treating patients during lifetime.
One of the best ways to consider these two points is to ask the question about stopping TKI in good responder patients. Previous studies showed promising results concerning patients who remained in complete molecular remission (CMR, i.e. undetectable residual disease on quantitative RT-PCR), for at least two years after imatinib was withdrawn. All molecular relapsing patients were sensitive when imatinib was re-challenged. Around 40% of these patients remain in a prolonged treatment-free remission (TFR) after treatment cessation. Considering the cost of imatinib and the number of months without treatment based on these studies, the savings in France would be 9 million €. However, since only 40 % of patients are in treatment free remission, a study, assessing the real budget impact for the healthcare system of stopping TKI in the eligible population seems necessary as no published study has ever addressed this question in France. The French National Health Insurance database (SNIIR-AM) is well suited to conduct this study since it provides exhaustive information about total costs induced by CML patients in France in both strategies (continuing or stopping TKI treatment).
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research grouppharmacoepidemiology
Organisation/affiliationUniversity of Bordeaux
Details of (Primary) lead investigator
Title Professor
Last name MOORE
First name Nicholas
Is this study being carried out with the collaboration of a research network?
Yes
Dr Antoine Bénard (Methodologist) - Bordeaux University Hospital – CHU de Bordeaux Clinical Trial Unit (Unité de soutien Méthodologique à la recherche Clinique et épidémiologique, USMR)
Nathalie Hayes (Health economist) - Bordeaux University Hospital – CHU de Bordeaux Clinical Research Department (Direction de la recherche Clinique et de l’innovation, DRCI)
Pr François-Xavier Mahon (Hematologist) - Bergonie Institut, Bordeaux
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
France
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed29/12/2016
Start date of data collection31/12/201722/03/2018
Start date of data analysis31/03/201815/06/2018
Date of interim report, if expected
Date of final study report28/02/201908/04/2019
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government bodyDirection Générale de l’Offre de Soins (DGOS)100
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name BOSCO-LEVY
First name Pauline
Address line 1146 rue Léo Saignat
Address line 2
Address line 3
CityBordeaux
Postcode33000
CountryFrance
Phone number (incl. country code)33557579209
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name BOSCO-LEVY
First name Pauline
Address line 1146 rue Léo Saignat
Address line 2
Address line 3
CityBordeaux
Postcode33000
CountryFrance
Phone number (incl. country code)33557579209
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)L01XE
7. Medical conditions to be studied
Medical condition(s)Yes
chronic myeloid leukemia
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects800
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources not registered with ENCePP
SNIIRAM (French nationwide claims and hospital database), France
Sources of data
Administrative database, e.g. claims database
11. Scope of the study
What is the scope of the study?
Medico-economic study
Primary scope : Medico-economic study
12. Main objective(s)
What is the main objective of the study?
The main objective of the study is to assess the budget impact, of discontinuing TKI treatment in patients with CML, treated since at least 3 years and achieving deep molecular response compared with current practice (treatment during entire life), between 2008 and 2015 from the healthcare system point of view, by using a probabilistic Markov model.
Are there primary outcomes?No
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
The follow-up will last at least 1 year after inclusion (date of TKI discontinuation) or until death whatever occurs first.
15. Data analysis plan
Please provide a brief summary of the analysis method
The following analyses will be performed for the cohort:
• A flow chart depicting the number of patients and sequences of treatment
available in the database satisfying the cohort criteria and follow-up
duration;
• Description of baseline characteristics, comorbidities and CML diagnosis;
• Description of the duration and causes of TKI discontinuation and the
resumed TKI in case of treatment resumption in the year following the
discontinuation;
• Description of the healthcare resources use and costs