1. David Tyas Global HEOR - Lundbeck
Example of Health Technology Assessment (HTA) of a therapy for the reduction of alcohol consumption
David Tyas
Global HEOR - Lundbeck

2. Contents Introduction into a HTA process Summary of our submission
Use SMC as an example but equally could be from many other countries
Summary of our submission
Main argument
Types of analysis
Clarification question stage
Summary of questions (what sort)
Final recommendation

3. Economic Evaluations in Europe
Norway: Pharmacoeconomic data required for reimbursement; official guidelines in operation.
Finland:
Pharmacoeconomic evidence mandatory for evaluating new
therapies for reimbursement and may also be requested for
existing therapies.
UK:
NICE, SMC, and AWMSG evaluates the cost effectiveness of medicines.
Sweden:
Cost-effectiveness data required for reimbursement.
Ireland: Guidelines for pharmacoeconomic studies prepared; cost-effectiveness data may be requested.
Denmark:
Cost-effectiveness data may be requested for
reimbursement decisions.
Netherlands:
Pharmacoeconomic evidence explicitly required for reimbursement of new products.
France:
Not a formal requirement but
increasingly used in
reimbursement decisions.
Guidelines prepared.
Poland:
C/E and BIA may be requested. HTA agency.
Belgium:
Formal requirement for economic evaluation.
Spain:
Health technology assessment at a regional level.
Germany:
Guidelines prepared. Institute for Quality and Efficiency in the Health Service established in 2004.
Italy:
Cost-effectiveness considered in pricing and reimbursement decisions.
Greece: Guidelines for pharmacoeconomic studies prepared; cost-effectiveness data may be requested.
Portugal:
Cost-effectiveness data incorporated
into reimbursement decisions.

4. SMC process Manufacturers submission Clarification questions
Draft advice
Final recommendation

5. Example of a HTA submission dossier - SMC requirements
Chapter 1 Registration Details
Chapter 2 Overview and Positioning
Chapter 3 Comparative Efficacy
Chapter 4 Comparative Safety
Chapter 5 Clinical Effectiveness
Chapter 6 Pharmaco-Economic Evaluation
Chapter 7 Resource Implications
Total ~ 100 pages

6. Nalmefene
Main arguments and data

7. Total Alcohol Consumption (g/day)
Indication
Nalmefene is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (DRL), without physical withdrawal symptoms and who do not require immediate detoxification.
WHO category
Total Alcohol Consumption (g/day)
Women
Men
Very high-risk consumption
> 60
> 100
High-risk consumption
40–60
60–100
Medium-risk consumption
20–40
Low-risk consumption
1–20
1–40

8. Relative risk for all-cause mortality by average daily intake of alcohol

10. Stages of alcohol abuse/ dependence
Place in therapy
Abstinence
Reduction
Treatment intensity
Brief intervention
Early
Middle
Late
Stages of alcohol abuse/ dependence

11. 3 RCTs in patients with alcohol dependence
Clinical efficacy
3 RCTs in patients with alcohol dependence
Study name
Study duration
Patients enrolled
High drinking risk
ESENSE 1
(Mann 2013; Wim van den Brink 2013)
24-week
604 ( )
350
ESENSE 2
(Gual 2013; Wim van den Brink 2013)
718 ( )
317
( )
SENSE
(Wim van den Brink 2014)
52-week
675 ( )
187
Lundbeck’s sponsored phase III programme for nalmefene comprises three clinical trials, all if them multi-centre, randomised, double-blind, placebo-controlled, parallel group studies of 20 mg nalmefene, as-needed use, in patients with alcohol dependence according to the DSM-IV criteria. The aim of the program was to demonstrate the efficacy, safety, and tolerability of nalmefene, as-needed use, for the reduction of alcohol consumption in patients with alcohol dependence.
Two of the studies were of 6-month duration (ESENSE 1 and ESENSE 2) with a randomisation 1:1 and the third one was a 12-month study (SENSE) with a randomisation 3:1 as it was primarily designed as a safety study, therefore the larger intended exposure to nalmefene.
Please note that the selected dose, 20 mg of nalmefene hydrochloride salt, corresponds with 18 mg NMF base, and that will be the strenght specified in the label following approval.
The three studies were conducted in Europe and enrolled about 2,000 individuals with alcohol dependence. Medical advice and support to enhance motivation and adherence were included in all treatment arms in the studies. No abstinence treatment goal was imposed and abstinence was not required when entering the study.
Mann et al Biol Psychiatry 73(8)
Gual et al Eur Neuropsychopharmacol 23(11)
Wim van den Brink et al J Psychopharmacol
Wim van den Brink et al Alcohol and Alcoholism. 1–9

12. Pharmaco Economic analysis
Objective:
To show nalmefene is cost-effective
Treatment alternatives:
Nalmefene + psychosocial support
Psychosocial support alone
Perspective:
Healthcare system
Time horizon:
1 year: period covered by RCTs
5 years
Population:
nalmefene indication as informed by phase III clinical programme

13. General concept of the model
Decrease
costs
Reduction of alcohol intake
Reduction of
alcohol-attributable
harms and mortality
Increase
QALYs
Severe morbidities and injuries considered:
Transport injuries
Injuries other than transport
Ischaemic heart disease
Ischaemic stroke
Liver cirrhosis
Pancreatitis
lower respiratory infections
Quality-Adjusted Life Year (QALY)
QALY=patient quality of life * patient survival

14. Clarification questions

15. Patient discontinuation
Calculation of number of days taking therapy
Application of utility in the model
Proportion who receive care at a specialist level
Real world discussion of relapse rate

16. Final recommendation

18. Questions….