Pharmacoeconomic analysis Clinical trials • Pharmacoeconomic evaluation is more concerned about what• Clinical trials evaluate happens in “real life”.the efficacy and safetyof therapies • Pharmacoeconomic study• Clinical trial focuses on is more interested inmedical indicators (eg. effectivenessBlood pressure level) • Pharmacoeconomic study• Intensive monitoring is measure differnt outcomesnecessary (resource consumption, productivity, OoL etc)
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
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
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?ICER = (total cost A- total cost B) / rQALY (A –B)à rQALY (A –B)* ICER = tot cost A - tot cost Bà rQALY (A –B)* ICER + tot cost B = tot cost Atot 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
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 F. Cankat Tulunay, 2008
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► 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)
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
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► 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
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► Newdrugs 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 QALYØ 25% offer >0.1 – 0.5 QALYØ 13% offer >0.5 – 1.0 QALYØ 12% offer >1 QALYMedian 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► Someinnovative 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► Realinnovation 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”