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 $50,000 per QALY gained, and discusses value-based pricing models.
4. Pharmacoeconomic analysis
Clinical trials • Pharmacoeconomic
evaluation is more
concerned about what
• Clinical trials evaluate happens in “real life”.
the efficacy and safety
of therapies • Pharmacoeconomic study
• Clinical trial focuses on
is more interested in
medical indicators (eg. effectiveness
Blood pressure level) • Pharmacoeconomic study
• Intensive monitoring is measure differnt outcomes
necessary (resource consumption,
productivity, OoL etc)
5. Can it work? = Efficacy (clinical trials)
Does it work in reality? =
Effectiveness (observational studies)
Is it worth doing it, compared to
other things we could do with the
same money?
= Cost-effectiveness
= Efficiency
=Value for money
6. PROBLEM: where is the threshold?
• HISTORICAL 50,000$ 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)
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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
9. Value based pricing?
ICER = (total cost A- total cost B) / rQALY (A –B)
à rQALY (A –B)* ICER = tot cost A - tot cost B
à rQALY (A –B)* ICER + tot cost B = tot cost A
tot cost A = Drug cost A + Adm c A + AEc A ....
Drug cost A = (rQALY (A –B)* ICER + tot cost B) -
Adm c A - AEc A ....
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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
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”