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

TURKISH TYPE

PHARMACOECONOMY

• Clinical trials evaluate the efficacy and safety of therapies • Clinical trial focuses on medical indicators (eg. Blood pressure level) • Intensive monitoring is necessary

• Pharmacoeconomic evaluation is more concerned about what happens in “real life”. • Pharmacoeconomic study is more interested in effectiveness • Pharmacoeconomic study measure differnt outcomes (resource consumption, productivity, OoL etc)

Clinical trials

Pharmacoeconomic analysis

 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

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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)

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

Value based pricing

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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 .... 9

F. Cankat Tulunay, 2008

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

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

•  ACE INHIBITORS: (26) –  Benazepril HCl –  Delapril –  Delapril HCl –  Enalapril –  Enalapril maleat –  Fosinopril sodium –  Imidapril –  Imidapril HCl –  Kaptopril –  KinaprilHCl –  Lisinopril –  Lisinopril dihidrat

–  Moeksipril HCl –  Perindopril –  Perindopril erbumin –  Perindopril arginin –  Ramipril –  Silazapril –  Spirapril –  Spirapril HCl –  Temokapril –  Temokapril Hcl –  Trandolapril –  Zofenopril Ca. –  Zofenopril

BRAND   INN+DDD   PACK.SIZE   PACK. PRICE   DDD TL  kaptoril   kaptopril25   50   5,9   0,11  kapril   kaptopril25   48   5,63   0,12  

sinopril   lisinopril10   30   6,4   0,21  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  gopten   trandolapril2   28   23,52   0,84  univasc   moeksipril15   20   17,49   0,87  cibacen   benazepril10   28   25,06   0,9  monopril   fosinopril20   20   18,33   0,91  coversil   perindopril5   30   28,93   0,96  zoprotec   zofenopril30   28   30,47   1,1  

      MEAN   0.55 TL  

• Mean= 0.55 + 0.06 TL

• Mean+ SD= 0.55+0.29= 0.84 TL • Median= 0.55 TL

• Geometric mean= 0.46 TL

Reimbursement Band for

F.C. Tulunay, 2009

BRAND   INN+DDD   PACK.SIZE   PACK. PRICE   DDD TL   IMS  2008  YTL  kaptoril   kaptopril25   50   5,9   0,11   364,573  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  

konveril   enalapril10   20   5,67   0,28   268,246  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  cibacen   benazepril10   28   25,06   0,9   104,720  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  

45 MİL. DOLAR

27.810.000 18.5 mil dolar

Total: 96.516.867 64.3 mil dolar

F.C. Tulunay, 2009

İlaç Etken Doz Fiyat tablet no DDD/TL 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 Andante Alendronat 70mg/hft 99,72 12 1,18 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

BİPHOSPHANATE

REIMBURSMENT BAND

F.C. Tulunay, 2009

Critical Drug Evaluation of New Cancer Drugs

The Scottish Experience

Prof Ken Paterson Chair – Scottish Medicines Consortium

Berlin – 18 February 2010

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

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?

Scottish Medicines Consortium

► Rapid health 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-utility analysis (cost per QALY) the preferred approach

► Analysis of QALYs only (not cost)

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

► Allows comparison across (and within) disease areas

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)

Special Cancer Issues - 1

► Often scanty 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

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??

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?

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!

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

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

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’

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

► New drugs in general are not as valuable as many would like to think!

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!!

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’!

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

► Some innovative new drugs are breaking the mould

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

► Real innovation has nothing to fear from such assessment!

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.)

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”