The document discusses pharmacoeconomic analysis and clinical trials. Pharmacoeconomic analysis is more concerned with what happens in real-life settings, examines effectiveness, and measures outcomes like resource consumption and quality of life. Clinical trials focus on efficacy and safety in a controlled setting. The document provides examples of pharmacoeconomic thresholds used to determine cost-effectiveness of treatments, such as $50,000 per QALY gained, and discusses value-based pricing models.

1. Prof. Dr.
F. Cankat Tulunay
Honorary President of EACPT

3. TURKISH TYPE
PHARMACOECONOMY

4. Pharmacoeconomic analysis
Clinical trials • Pharmacoeconomic
evaluation is more
concerned about what
• Clinical trials evaluate happens in “real life”.
the efficacy and safety
of therapies • Pharmacoeconomic study
• Clinical trial focuses on
is more interested in
medical indicators (eg. effectiveness
Blood pressure level) • Pharmacoeconomic study
• Intensive monitoring is measure differnt outcomes
necessary (resource consumption,
productivity, OoL etc)

5.  Can it work? = Efficacy (clinical trials)
 Does it work in reality? =
Effectiveness (observational studies)
 Is it worth doing it, compared to
other things we could do with the
same money?
 = Cost-effectiveness
 = Efficiency
 =Value for money

6. PROBLEM: where is the threshold?
• HISTORICAL 50,000$ per QALY:
= Annual cost of caring for a dialysis patient
• PUBLISHED THRESHOLDS
– Vary between 10,000 and 100,000 $ per QALY
• WHO: GDP per capita (e.g. Belgium = €29000)
• TURKEY: 24.000 $ (2 GDP) (F.C.TULUNAY)
6

7. The criteria for adopting a
technology or drug
• Reimbursing at a given price is generally
based on 6 criteria
a) Added therapeutical value
b) Safety and tolerance
c) Cost-effectiveness
d) Budget impact
e) Medical and therapeutical need
f) Industrial policy

8. Value based pricing
8

9. Value based pricing?
ICER = (total cost A- total cost B) / rQALY (A –B)
à rQALY (A –B)* ICER = tot cost A - tot cost B
à rQALY (A –B)* ICER + tot cost B = tot cost A
tot cost A = Drug cost A + Adm c A + AEc A ....
Drug cost A = (rQALY (A –B)* ICER + tot cost B) -
Adm c A - AEc A ....
9

10. Drugs:
" Same mechanisms of action
" Mainly me too molecules
(AceIs, ARBs, Calcium CBs, Statins, PPIs, Biphosphonates,
Cholinesterase inhibitors, SSRIs, etc)
" Same indication
" Similar safety outcomes
" Different price F. Cankat Tulunay, 2008

11. Advantages:
" Significant amount of saving
" Significant support to generic drugs.
" Industry
will know the
reimbursement band in advance..
" They will not try to push regulatory bodies
" Especially small companies will not try to
find “me too” molecules F. Cankat Tulunay, 2008

12. • ACE INHIBITORS: (26) – Moeksipril HCl
– Benazepril HCl – Perindopril
– Delapril – Perindopril erbumin
– Delapril HCl – Perindopril arginin
– Enalapril – Ramipril
– Enalapril maleat – Silazapril
– Fosinopril sodium – Spirapril
– Imidapril – Spirapril HCl
– Imidapril HCl – Temokapril
– Kaptopril – Temokapril Hcl
– KinaprilHCl – Trandolapril
– Lisinopril – Zofenopril Ca.
– Lisinopril dihidrat – Zofenopril

13. BRAND
INN+DDD
PACK.SIZE
PACK. PRICE
DDD TL
kaptoril
kaptopril25
50
5,9
0,11
kapril
kaptopril25
5,63
0,12
Reimbursement
48
sinopril
lisinopril10
30
6,4
0,21
Band for
vasolapril
enalapril10
20
4,62
0,23
enalap
enalapril10
20
4,9
0,24
enapril
enalapril10
20
4,91
0,24
konveril
enalapril10
20
5,67
0,28
Blokace
ramipril5
30
12,62
0,42
sandace
ramipril5
28
11,74
0,42
delix
ramipril5
28
13,87
0,49
kinateva
kinapril20
20
9,04
0,52
rilace
lisinopril10
28
15,38
0,55
Acuital
kinalapril20
20
11,35
0,56
renitec
enalapril10
20
12,86
0,64
zestril
lisinopril10
28
17,86
0,64
forsace
fosinopril20
20
14,67
0,73
inhibace
silazapril2,5
28
21,05
0,75
• Mean= 0.55 + 0.06 TL
gopten
trandolapril2
28
23,52
0,84
univasc
moeksipril15
20
17,49
0,87
• Mean+ SD= 0.55+0.29=
cibacen
benazepril10
28
25,06
0,9
0.84 TL
monopril
fosinopril20
20
18,33
0,91
coversil
perindopril5
28,93
0,96
• Median= 0.55 TL
30
zoprotec
zofenopril30
28
30,47
1,1
MEAN
0.55 TL
• Geometric mean= 0.46 TL
F.C. Tulunay, 2009

14. BRAND
INN+DDD
PACK.SIZE
PACK. PRICE
DDD TL
IMS
2008
YTL
Total: 96.516.867
kaptoril
kaptopril25
50
5,9
0,11
364,573
64.3 mil dolar
kapril
kaptopril25
48
5,63
0,12
772,131
sinopril
lisinopril10
30
6,4
0,21
1,724,681
vasolapril
enalapril10
20
4,62
0,23
120.512
enalap
enalapril10
20
4,9
0,24
49,155
enapril
enalapril10
20
4,91
0,24
2,114,173
27.810.000
konveril
enalapril10
20
5,67
0,28
268,246
18.5 mil dolar
Blokace
ramipril5
30
12,62
0,42
1,121,249
sandace
ramipril5
28
11,74
0,42
?
delix
ramipril5
28
13,87
0,49
17,746,026
kinateva
kinapril20
20
9,04
0,52
?
rilace
lisinopril10
28
15,38
0,55
1,147,843
Acuital
kinalapril20
20
11,35
0,56
2,381,412
renitec
enalapril10
20
12,86
0,64
199,995
zestril
lisinopril10
28
17,86
0,64
0
forsace
fosinopril20
20
14,67
0,73
?2008
inhibace
silazapril2,5
28
21,05
0,75
7,584,019
gopten
trandolapril2
28
23,52
0,84
5,995,584
univasc
moeksipril15
20
17,49
0,87
8,727
45 MİL.
cibacen
benazepril10
28
25,06
0,9
104,720
DOLAR
monopril
fosinopril20
20
18,33
0,91
3,461,346
coversil
perindopril5
30
28,93
0,96
36,664,923
zoprotec
zofenopril30
28
30,47
1,1
12,687,519
MEAN
0.55 TL
68,706,833
F.C. Tulunay, 2009

15. İlaç Etken Doz Fiyat tablet no DDD/TL BİPHOSPHANATE
Vegabon Alendronat 70 mg/hafta 78,36 12 0,93
Vegabon Alendronat 70 mg/hafta 27,99 4 1,00
Bonacton Ibandronic asid 70 mg 31.94 4 1,14
Bonemax Alendronat 70 mg/hafta 31,94 4 1,14
Andante Alendronat 70mg/hft 31,94 4 1,14
Osalen Alendronat 70mg/hft 31,94 4 1,14
Osteomax Alendronat 70mg/hft 31,94 4 1,14
Andante Alendronat 10mg/gün 32,86 28 1,17 REIMBURSMENT
Andante Alendronat 70mg/hft 99,72 12 1,18 BAND
Vegabon Alendronat 10 mg/gün 33,07 28 1,18
Osalen Alendronat 70 mg/hafta 99,74 12 1,19
Fosamax Alendronat 10 mg/gün 39,92 28 1,43
Fosamax Alendronat 70mg/hft 39,92 4 1,43
Arilex Risendronate 35 mg 126.68 12 1,51
Arilex Risendronate 35 mg 45,22 4 1,62
Bonviva İbandronik asit 150 mg 154,66 3 1,72
Goyart Risendronate 35 mg/hafta 50,43 4 1,80
Actonel Risendronate 150mg/ay 173.25 6 1,93
Actonel Risedronate 5 mg/gün 55,50 28 1,98
Actonel Risendronate 35mg/hafta 56.73 4 2,02
AVERAGE 1,39
F.C. Tulunay, 2009

16. Critical Drug Evaluation
of New Cancer Drugs
The Scottish Experience
Prof Ken Paterson
Chair – Scottish Medicines Consortium
Berlin – 18 February 2010

17. New Anti-Cancer Medicines
► Considerable pent-up demand
§ Patients
§ Clinicians
► Much media interest
§ “miracle drugs”, “life-saving treatment”
► Often political interest
§ …especially if threat not to make drug available
► Legitimate interest from pharma
§ Keen to sell drug and boost share price/profile

18. Does some ‘Hype’ Matter?
► May raise false hopes
► Often fails to represent the downside of
treatment
► May distort priority setting in health-care
§ Use of ineffective therapy
§ Failure to adopt new, effective therapy
► Subverts
true evidence-based practice
► How good are new anti-cancer drugs?
§ …and how hard is it to know this?

19. Scottish Medicines Consortium
► Rapidhealth technology assessment of all
new drugs – established 2002
§ Unique position in world new-drug HTA
► Manufacturer makes the case for use –
§ Clinical effectiveness
§ Cost-effectiveness
► Cost-utilityanalysis (cost per QALY) the
preferred approach
► Analysis of QALYs only (not cost)

20. Why QALYs?
► Can(should) capture all the benefits and
adverse effects of the medicine in question
§ Survival gain (or loss)
§ Improvement in quality of life from treatment
§ Reduction in quality of life from adverse events
§ Impact on quality of life of treatment protocol
§ Appropriate modelling very sensitive to change
► Allowscomparison across (and within)
disease areas

21. Oncology Assessments
► Fewer RCTs per drug (median 1 v 2)
► Longer follow-up (52 wks v 12 wks)
► Acceptance rate - 67%
§ About half with some restriction, usually to
specialist use
► Higher cost per QALY (£15K v £8.5K)

22. Special Cancer Issues - 1
► Oftenscanty phase 3 clinical data
► Complex regimens with poly-pharmacy make
comparators hard to define
§ RCTs often use comparators different from
current Scottish practice
§ May require indirect comparison
► Survival benefits often unclear
§ Overall v ‘progression-free’ survival
§ Extrapolation not clear-cut
§ Cross-over after “benefit proven” a problem

23. Special Cancer Issues - 2
► Quality of life assessment difficult
§ Impact of adverse events a problem
§ ? revaluation of QoL near life’s end
§ ? special benefit with low expectancy
► Increased niching by indication
§ …more (ultra-)orphan drugs
► …with expectations of “special case”
► Rule of Rescue - a rule??

24. Quality of Life
► Are the impacts of adverse events limited to
when they occur?
► With 3 months to live, if you say your QoL is
90%, is that true?
§ Are time-trade off/standard gamble useful?
► Is
3 months extra life worth more if you’ve
had the diagnosis for 3 months rather than 5
years?
§ ? discriminates against certain cancers?

25. Clinical Trial v Real World
► Are the patients similar?
§ ? older in real world
§ ? less good performance status
§ ? more co-morbidities
► Does the drug perform equally well?
§ ? effectiveness < efficacy
§ ? toxicity greater in real world
► Does this really all matter?
§ … only if benefit - risk - cost finely balanced!

26. SMC and Anti-Cancer Medicines
► 61 cancer medicines reviewed
§ 36 for advanced/metastatic cancer
§ 25 for earlier/adjuvant treatment
► Median QALY gain (over current treatment)
§ 0.38 for advanced cancer
§ 0.30 for earlier/adjuvant treatment
► Mean QALY gain (over current treatment)
§ 0.52 for both groups

27. What does this Mean?
► Median health gain
§ 6 months with quality of life 70% of normal
► Mean health gain
§ 8-9 months with QoL 70%
► Only 6 drugs (10%) offered ≥1 QALY
► 22 drugs (36%) offered ≤0.2 QALY
§ = ≤3 months at 70% of normal QoL
§ Note NICE ‘end-of-life’ decision-making

28. Is There No Good News- 1?
► Some of the greatest health-gains are with
really innovative drugs –
§ Trastuzumab – 2.4 QALYs
§ Nilotinib – 2.1 QALYs
§ Bortezomib – 1.1 QALYs
► Even if these are expensive, they offer good
‘value-for-money’

29. Is There No Good News – 2?
► Anti-cancer drugs are much like other drugs
§ Musculoskeletal (11) – 0.66 QALY
§ Infections (33) – 0.11 QALY
§ Endocrine (24) – 0.07 QALY
§ Cardiovascular (33) – 0.05 QALY
§ CNS and pain (55) – 0.04 QALY
► Newdrugs in general are not as valuable as
many would like to think!

30. How Good are New Drugs?
► 22% offer no health gain (=me too!)
Ø 28% offer >0 – 0.1 QALY
Ø 25% offer >0.1 – 0.5 QALY
Ø 13% offer >0.5 – 1.0 QALY
Ø 12% offer >1 QALY
Median health gain (n = 281) = 0.1 QALY!!

31. Caveats and Criticisms
► Health gain is as presented by pharma
§ May over-estimate true gain by a factor of 2!!
§ SMC did not always accept the QALY given
► QALY may not adequately capture benefits
§ Responder v non-responder
§ Problems with QoL assessment
► Clinical trial ≠ clinical practice
§ ?possible to maximise benefit & minimise S/E
► … targeted therapy the ‘Holy Grail’!

32. Conclusions - 1
► Assessing the real benefits of new cancer
medicines is not easy
► New medicines generally are rarely as
valuable as they might like to appear
► Health-gain from many new cancer
medicines is modest
§ …and often over-stated in media etc
► Someinnovative new drugs are breaking
the mould

33. Conclusions - 2
► The introduction of new medicines needs to
be managed to maximise risk:benefit
► Real world data on new cancer medicines
are urgently needed
§ … to see whether targeting really works!
§ … to get real advances to patients quickly
§ … to minimise burden on (or harm to) patients
► … and costs to health-care systems
► Realinnovation has nothing to fear from
such assessment!

34. WHAT DO WE NEED!
• A system without corruption
• A transperant system
• To prevent waste / wastefulness
• To be rational
• To realize that we all are sailing the same
boat
• To trust each other
• Harmonization on all subjects (patient
handout forms, education, etc.)

35. WHAT DO WE NEED!
• Pharmacoeconomic analysis of a treatment
• Not to have reimburse “drug is not a drug”
• Appropriate pricing according to the purchasing
power
• Medications to be available to everyone (EQUITY)
• Standardized diagnosis-treatment guidelines
• Standardized education at all universities
• Clinical, pharmacological and epidemiological research
• Independent "Govermental Drug Institution” and
“independent reimbursment institution”