Pharmacoeconomic aspects of cancer drugs and pharmacoeconomic approach.

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

2. DOCTORS
PHARMACISTS
DRUG
COMPANIES
MOH
ACADEMICIANS PATIENTS
SOCIAL
SECURIT
AGENCY
F.C. Tulunay, 2009

3. Actual Reasons For Healthcare
Expenses
• Ten reasons why it costs so much. Two of the ten add value: #1 and
#2 improve the quality and length of our lives. Numbers 3 through
10 add no value. THAT is where you can save money without losing
something we want.
1. Treatments available now that did not exist before
2. More people living longer
3. Action without evidence
4. Cost of regulations and compliance
5. Inefficiency
6. Perverse incentives
7. Defensive medicine
8. Adverse outcomes and errors
9. Profits taken out of healthcare system
10. Embezzlement and fraud (outright theft).

4. USA
• USA spends $2 trillion on
healthcare.
• $680billion (34%) "goes to" the
doctors
• $600b (30%) to hospitals
• $340b (17%) to outpatient services
• $300b (15%) to for medications.

5. Costs of Cancer
NIH estimated the 2008 overall annual costs of cancer were as
follows:
• Total cost: $228.1 billion
• Direct medical costs (total of all health expenditures): $ 93.2
billion
• Indirect morbidity costs (cost of lost productivity due to
illness): $ 18.8 billion
• Indirect mortality costs (cost of lost productivity due to
premature death): $116.1 billion
• About 24% of Americans aged 18 to 64, 13% of children had no health insurance
for at least part of the past year.
• This year, about 562,340 Americans are expected to die of cancer -- that's
more than 1,500 people a day. Cancer is the second most common cause of death
in the United States, exceeded only by heart disease. Cancer accounts for nearly
1 out of every 4 deaths in the United States
American Cancer Society. Cancer Facts & Figures 2009. Atlanta, GA. 2009.

6. 6

8. LIFE AFTER CANCER – costs of cancer care
National Cancer Institute ● Cancer Trends Progress Report – 2005 Update ● http://progressreport.cancer.gov

9. Efficacy, safety, and cost of new anticancer drugs
Silvio Garattini, director and Vittorio Bertele', head, regulatory policy laboratory
Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy
Correspondence to: S Garattini sgarattini@marionegri.it
BMJ. 2002 August 3; 325(7358): 269–271
• New anticancer drugs reaching the European market
in 1995-2000 offered few or no substantial
advantages over existing preparations, yet cost
several times—in one case 350 times—as much
• The greatest changes have been 4500 fewer deaths
from childhood tumours and 4000 fewer from
lymphomas (Hodgkin's disease) each year over the past
four decades.
• Among solid tumours, advances have been made in
treating breast cancer, in which tamoxifen increases 10
year survival by 6% for node negative and 11% for node
positive tumours,3 and chemotherapy increases survival
by 7% and 11%, respectively.4
• For most other common solid tumours such as those of
lung, oesophagus, stomach, or pancreas, only limited
survival gains have been achieved.2,5,6

10. • U.K. rejected NEXAVAR for liver
cancer
• Nexavar was estimated to cost
65,900 pounds ($102,000) for every
“quality adjusted year of life,”
Not:
• NEXAVAR: 200 mg 112 tab: 8.270 TL
ödenmez (SGK)

11. Miracle Cancer Drug Extends Life With
$48,720 Cost
March 05, 2010
 It was called SU11248 (SUTENT), and
Pfizer Inc. had just acquired the company
developing it. Tumors were shrinking in two
thirds of the digestive tract cancer
patients in the clinical trial Demetri had
been running since February 2002. One
dying man’s malignancy had stopped growing
so suddenly after five doses that it was a
“miracle,” the oncologist said.

12. BMJ. 2002 August 3; 325(7358): 269–271

13. • Sunitinib is recommended, as a
treatment option for people with
unresectable and/or metastatic
malignant gastrointestinal stromal
tumours if:
• imatinib treatment has failed because
of resistance or intolerance, and
• the drug cost of sunitinib (excluding
any related costs) for the first
treatment cycle will be met by the
manufacturer.
• The use of sunitinib should be
supervised by cancer specialists with
experience in treating people with
unresectable and/or metastatic
malignant gastrointestinal stromal
tumours after failure of imatinib
treatment because of resistance or
intolerance.

14. SUTENT
• Costs
• Sunitinib is marketed by Pfizer as Sutent, and is subject to patents and
market exclusivity as a new chemical entity until February 15, 2021
• Sutent is one of the most expensive drugs widely marketed. Doctors
and editorials have criticized the high cost, for a drug that doesn't
cure cancer but only prolongs life.
• In the U.S., insurance companies have refused to pay for all or part of
the costs of Sutent.
• In the UK NICE refused (late 2008) to recommend suntinib for late
stage renal cancer (kidney cancer) due to the high cost per QALY,
estimated by NICE at £72,000/QALY and by Pfizer at £29,000/
QALY.[21] It was also refused by NICE in 2008 for the treatment of
kidney cancer.[22] This refusal/guidance was updated Feb 2009 after
negotiations on price for the first course of treatment
• TÜRKİYEDE BİR SİKLÜS İLAÇ GİDERİ: 17.346 TL

15. 'We'll sell our house for this
drug (sutent)'
• The treatments are used for advanced kidney cancers
• A row has broken out over the funding of four drugs
for advanced kidney cancer after the drugs advisory
body NICE said they should not be available on the
NHS.
• Andrew Crabb, from Abingdon in Oxfordshire, got the
news on the first anniversary of his diagnosis with the
disease - but says he will do everything he can to carry
on receiving his drug.
BBC news, 7 August 2008

16. • FOLOTYN is a folate analogue metabolic inhibitor indicated for the treatment of patients with
relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is based on overall response
rate. Clinical benefit such as improvement in progression free survival or overall survival has not been
demonstrated. (FDA Prospektüs)
• The drug was approved by the Food and Drug Administration in late September as a treatment for
peripheral T-cell lymphoma, 30.000 dolar/month
• In the clinical trial, the median duration of use was 70 days, which would cost roughly $70,000 to $80,000.
But some patients used the drug for many months.
• Folotyn has not yet shown an effect on longevity. In the clinical trial that led to approval of the drug, 27
percent of the 109 patients experienced a reduction in tumor size. The reductions lasted a median of 9.4
months.
• But considering all the patients in the trial, only 12 percent had a reduction in tumor size that lasted for
more than 14 weeks. The trial did not compare Folotyn to another drug or a placebo.
• Genzyme’s Clolar for pediatric leukemia costs about $34,000 a week, though the company says that only
two weeks of treatment are typically needed.
• GlaxoSmithKline is charging up to $98,000 for a six-month treatment course of Arzerra, a drug approved in
late October for chronic lymphocytic leukemia
• The colon cancer drug Erbitux, for instance, costs $10,000 a month and the drug Avastin about $8,800
when used to treat lung cancer.

17. GSK: Allen ROSES
• A SENIOR EXECUTIVE WITH
BRITAIN'S BIGGEST DRUGS
COMPANY HAS ADMITTED
THAT MOST PRESCRIPTION
MEDICINES DO NOT WORK
ON MOST PEOPLE WHO
TAKE THEM.

18. Dr. ROSES
• DRUGS FOR ALZHEIMER'S DISEASE
WORK IN FEWER THAN ONE IN THREE
PATIENTS,
• WHEREAS THOSE FOR CANCER ARE
ONLY EFFECTIVE IN A QUARTER OF
PATIENTS.
• DRUGS FOR MIGRAINES, FOR
OSTEOPOROSIS, AND ARTHRITIS WORK
IN ABOUT HALF THE PATIENTS, ,

19. Charles Nemeroff caught with his hands
in the Glaxo till…
• “…From 2000 through 2006, Dr.
Nemeroff received just over
$960,000 from Glaxo….”

20. GSK
 COURT EXPOSED GSK/RESEARCHERS FRAUD
The court documents released as a result of one of the lawsuits in
October 2008 indicated that GSK "and/or researchers may have
suppress
 MISLEADING PUBLIC
For 10 years, GlaxoSmithKline's marketing of the drug stated that
it was "not habit forming". In 2002, the U.S. Food and Drug
Administration published a new product warning about the drug, and
the International Federation of Pharmaceutical Manufacturers
Associations (IFPMA) declared GSK guilty of misleading the public
about paroxetine on US television. ed or obscured suicide risk data
during clinical trials"

21. Drugs Giants GlaxoSmithKline In
Iraq Probe
• Pharmaceutical companies
GlaxoSmithKline and AstraZeneca have
been linked to an investigation into bribes
allegedly paid to Saddam Hussein's
former regime.
• The oil-for-food programme was supposed to
allow the Iraqi government to sell limited
amounts of oil to buy foreign food and
medicines.

22. Is there an EVİDENECE-BASED
pharmacotherapy?
PHARMACOTHERAPY

23. EVIDENCE BASED
PHARMACOTHERAPY
OR
FRAUD BASED
PAHARMACOTHERPY?

25. REGULATORY AGENCIES
PHYSICIANS
INDUSTRY
PHARMACYST
PATIENTS

26. 7U RATIONAL DRUG USE
7R
l Uygun endikasyon l Right indication
l Uygun ilaç l Right drug
l Uygun yol, doz ve süre l Right route, dosage, duration
l Uygun hasta l Right patient
l Uygun hasta bilgilendirilmesi l Right patient information
l Uygun değerlendirme l Rigtht evaluation
l Uygun fiyat l Right price
Hastaların klinik ihtiyaçlarına “Patients receive medications
göre, ihtiyaç duyduğu dozda, appropriate to their clinical
sürede ve kendisi ve toplum needs, in doses that meet
için en ucuz maliyette ilaç their own individual
bulabilmesidir. requirements, for an adequate
period of time, and at the
(WHO 1985)
lowest cost to them and their
community.” (WHO, 1985).

27. WHO advocates 12 key interventions to
promote more rational use:
1 Establishment of a multidisciplinary national body to coordinate
policies on medicine use.....NO
2. Use of clinical guidelines.....NO
3. Development and use of national essential medicines list...NO
4. Establishment of drug and therapeutics committees in districts and
hospitals...NO
5. Inclusion of problem-based pharmacotherapy training in undergraduate
curricula...NO
6. Continuing in-service medical education as a licensure requirement:
7. Supervision, audit and feedback...NO
8. Use of independent information on medicines...NO
9. Public education about medicines...NO
10. Avoidance of perverse financial incentives...NO
11. Use of appropriate and enforced regulation...NO
12. Sufficient government expenditure to ensure availability of medicines
and staff...NO

28. Factors affecting irrational
drug use
Rule and Regulations
Industry Regulatory agencies
Physician
Patient • Unethical
• Inadequate graduate • Political pressure
practice by • Inadequate
and post all means
• Wrong bgraduateeducation registration system
information • Fraud • Inadequate
• No drug information • Corruption reimbustment
• False informatin source
• No-oto system
• Press, TV • Over loaded patient control • No tratement
duty guidelines
• False beliefs
• Prescription • No rational drug
• Unable explane pressure: Pharmacist policy
problems • No
• Industry
• No relaible pharmacoeconomy
information • Patients • Inadequate • No..No..No..!!!!
source • Promotions education
• Self medication • Corruption
• Unethical drug
business!! • Unethical
• Komşusunun practice
ilacını kullanma • Corruption
• No prescription
• Economical! control Tulunay 2008

29. Outcomes of irrational drug use
Degeneration
of treatment Increased Psycho-social
quality Waste of risk of outcomes
resources
adverse
effect risk
• morbidity
• mortality • Unneeded
• Adverse reactions expectations from
• Decrease drugs
availability • Bacterial resistans
• Feeling of unhealing
• Increased price • Suicite
ECONOMICAL LOSTS
COST OF HUMAN BEING?
SHAME OF 21st CENTURY Tulunay 2008

30. Medical journals and pharmaceutical companies: uneasy bedfellows
Richard Smith, editor
BMJ 2003;326:1202-1205 (31 May)
• Free newspapers for doctors depend completely on
income from pharmaceutical advertising, but many
journals also depend heavily on such advertising
• The advertising is often misleading
• Editorial coverage is much more valuable to drug
companies than advertising, and scientific studies
can be manipulated in many ways to give results
favourable to companies
• Many medical journals have a substantial income
from supplements and reprints paid for by drug
companies
• In one sense, all journals are
bought by the pharmaceutical
HADİ RICHARD...BİZ BİRBİRİMİZE MUHTAÇIZ industry. The industry dominates
health care, and most doctors have
been wined and dined by it.

31. Future European health care: Cost containment, health care
reform and scientific progress in drug research
G.Emilien, Int.J.Health Plan.Manag. 12:81-101, 1997
• A= Terapoetic efficacy Top 25 products Top 50 products
internationally proven
• B= Second choise, open Not
for abuse A B C A B C necessary
• C= Non-effective drugs **
(1993)
Italy 11 7 7 25 15 10 21.2
• In Germany 4.128 billion
dolar worth suspicious drug
(1992) France 16 4 5 26 14 10 20.5
Germany 19 5 1 35 9 6 11.9
UK 24 1 0 46 4 0 NA
** % of total drug use

32. Another
!
GARDASİL.... 806 TL
CERVARIX.... 734 TL

33. 8 October 2009, BMJ 2009;339:b3884
Cost effectiveness analysis of including boys in a human
papillomavirus vaccination programme in the United States
Jane J Kim, assistant professor, Sue J Goldie, professor
1 Harvard School of Public Health, Department of Health Policy and Management, Center for Health Decision
Science, 718 Huntington Avenue, Boston, MA 02115, USA
• Given currently available information,
including boys in an HPV vaccination
programme generally exceeds
conventional thresholds (QALY over
100.000$) of good value for money,
even under favourable conditions of
vaccine protection and health
benefits

34. Hysteria over genital warts?
New York Times,2008
•
In a New York Times article published last year, Dr. Harper spoke about the fear-based
marketing of Gardasil by Merck: "'Merck lobbied every opinion leader, women's group, medical
society, politicians, and went directly to the people -- it created a sense of panic that says you
have to have this vaccine now..."
This behavior by drug companies -- using fear tactics to promote a particular disease in order to
sell the "treatment" -- is called disease mongering. Most of the pharmaceutical profits generated
today are based on precisely this tactic: Spread the fear, then sell the treatment.
Why is disease mongering so important to the profits of the drug companies? They figured out
many years ago that selling drugs only to those people who are sick was a very limited income
opportunity. To rake in the real profits, they needed to devise a way to sell drugs to healthy
people (i.e. people who don't need them). That's what cervical cancer vaccines really are: A
scheme to sell vaccines to people who aren't suffering from any disease at all.
That one of the industry's own researchers is willing to speak out against this is not just highly
unusual; it's also highly courageous. It makes you wonder: Who, exactly, is this Dr. Harper?
Dr. Diane Harper
• Dr. Harper is a graduate of the Massachusetts Institute of Technology. She studied additional courses at Stanford and received her medical degree
from the University of Kansas. She was a key researcher in both Gardasil and Cervarix vaccines, and she's one of the most experienced researchers
in the world on HPV-related diseases. She's done work for both Merck and GlaxoSmithKline.

35. Top researcher who worked on cervical
cancer vaccine warns about its dangers
8.10.2009 www.NaturalNews.com
• One of the key researchers involved in the clinical trials for both Gardasil and Cevarix cervical
cancer vaccines has gone public with warnings about their safety and effectiveness. Dr. Diane
Harper openly admitted the vaccine doesn't even prevent cervical cancer, stating, "[The vaccine]
will not decrease cervical cancer rates at all."
Dr. Harper also warned that the cervical cancer vaccine was being "over-marketed" and that
parents should be warned about the possible risk of severe side effects from the vaccine. She
even concluded that the vaccine itself is more dangerous than the cervical cancer it claims
to prevent!
Dr. Harper's warnings about cervical cancer vaccines are especially relevant considering her
expertise in the cost/benefit analysis of vaccines. Her conclusion is that cervical cancer
vaccines aren't worth the risks, nor are they worth all the effort being put into hyping them to
the public. "This may not be the best use of our resources at this time," she said in a Washington
Post article.
So why do cervical cancer vaccines continue to be pushed by doctors and health authorities
across the US, UK and other first-world nations? Because Big Pharma is the great corporate
puppeteer that's pulling the strings of legislators. With enough money and lobbyists, you can
always overcome scientific thinking with fear-based marketing and under-the-table deal-making.
Science-based medicine has no place in a world where disease is big business.

36. Press Release For immediate release
9th October 2009
ALLIANCE FOR NATURAL HEALTH CALLS FOR AN URGENT
SCIENTIFIC INQUIRY INTO THE HPV VACCINE USED IN THE UK
The Alliance for Natural Health (ANH) today calls for an
independent Inquiry into the safety of HPV vaccine, and appeals to
all Members of Parliament to press for this.
• Reports of serious and even lethal adverse reactions to the
Human Papilloma Virus (HPV) vaccine, Cervarix, manufactured by
GlaxoSmithKline, raises grave concern over the safety of the
vaccine. While its closely related vaccine, Gardasil,
manufactured by Merck, is recognised by the US Centers for
Disease Control (CDC) to trigger severe reactions, namely
hospitalisation, permanent disability, life-threatening illness or
death, equivalent data in the UK appears not to be publicly
available.

37. NEXAVAR?? (1month cost is 8.270 TL=5.500 USD)
Which one is wright!!??
Bayer
• Bayer, Onyx Pill Doesn’t Slow Breast • Wednesday - September 23, 2009 Phase II
Cancer in Study Study in Advanced Breast Cancer:
Sept. 30 (Bloomberg) -- Bayer AG and
Onyx Pharmaceuticals Inc.’s Nexavar cancer
• Nexavar® in Combination with
drug failed to slow the progression of breast Chemotherapy Demonstrates 74
cancer in the second of four studies that Percent Improvement in
combine the medicine with different types of
chemotherapy. Progression-Free Survival
• September 30, 2009 • First presentation of results at joint ECCO-
ESMO congress in Berlin, Germany
Mid-stage breast cancer trial of • Abstract # 3LBA
Bayer, Onyx's Nexavar misses Berlin, September 23, 2009 – Bayer
primary endpoint HealthCare AG and Onyx Pharmaceuticals,
Inc. today announced the full results from
Last Updated:September 30, 2009 00:30 their first collaborative group-sponsored
Preliminary results showed that a Phase II trial randomized, double-blind, placebo controlled
of Bayer and Onyx’s Nexavar (sorafenib) in Phase II trial showing that Nexavar®
combination with paclitaxel in patients with (sorafenib tablets) in combination with the
advanced breast cancer did not meet its oral chemotherapeutic agent, capecitabine,
primary endpoint of progression-free survival, significantly extended progression-free
the companies announced on Wednesday. Dimitris survival in patients with advanced breast
Voliotis, vice president of global clinical cancer by 74 percent. The data were
development oncology at Bayer, said the “data presented at the joint 15th European CanCer
require further analysis and interpretation before Organisation (ECCO) and 34th European
we determine the appropriate path forward." Society for Medical Oncology (ESMO)
• Multidisciplinary Congress in Berlin, Germany.

38. FDA probe of Pfizer's anti-smoking
drug continues
April 6 2009
• The FDA is investigating reports of injury, visual
impairment and other problems connected with
the medication, which is designed to ease
smokers' withdrawal symptoms. The agency
began probing the problems last fall.
• The Federal Aviation Administration last year
banned the use of Chantix by pilots after a spike
in patients reporting blackouts, some of which
led to traffic accidents

40. Innovation worries the decision maker
R&D Activity in Main Therapeutic Areas
R&D Activity in Main Therapeutic Areas
20%
Growth of sales 2004-2009*
18% Innovative approaches Oncology (L1, L2)
set to drive strong CNS (N3A, N5A, N6A)
16% growth in oncology Osteoporosis (M5B, G3H, H4A, H4V)
HIV antivirals (J5D)
14% Oral antidiabetics (A10B)
12%
Cardiovascular (C8, C9, C10A)
Epoetins (B3C)
1% A large number of innovative PPIs (A2B2)
candidate makes the oncology Anti-platelet inhibs (B1C)
8% pipeline the largest in the
industry
6%
4%
Size of bubble:
2% Forecast sales 2009
0%
-50 0 50 100 150 200 250 300 350 400 450 500
# phase II & onwards pipeline products
Source: IMS Management Consulting analysis

41. e.g. New drug vs. current care
(health care payer perspective)
Current
New
Current Net Savings
New New
Current
Cost of drug +TreatmentOther
Average
Costs
= Total Cost
physicians
hospital
surgery
other drugs 41
tests

42. e.g. New drug vs. current care (2)
New
Current
Current
New
New
Current
Cost of drug
+TreatmentOther =
Average
Costs
Total Cost
physicians
hospital
surgery
other drugs 42
tests

43. e.g. New drug vs. current care (3)
New
ts
Cos
Net
Current
New
Current
New
Current
Cost of drug +TreatmentOther =
Average
Costs
Total Cost
physicians
hospital
surgery
other drugs 43
tests

44. How do we value innovation?
• Steve Pearson, President of the Institute for Clinical and
Economic Review at Harvard, identified two options for judging
innovation.
• The first is by setting criteria for success before the innovation
has been introduced, such as measuring whether an intervention
works. Mr Pearson said this would be “difficult to do in a way
which makes sense”, as it is hard to define criteria for an
innovation’s success before the innovation itself has been
created.
• Another method of judging innovation would be to assess its
performance once introduced. This again poses difficulties, as it
depends on an agreed definition of “value”. Suggested
definitions include the speed of penetration of the innovation
into a healthcare system, or the destination of venture capital -
which he said could be cosmetic surgery in the case of the US.
• 9 December 2009 44

45. 45

46. 46

47. Evidence to support chronic myeloid
leukaemia drugs "very poor"
• NICE is unable to recommend the use of dasatinib and nilotinib for the treatment of chronic
myeloid leukaemia in patients who cannot tolerate the first-line treatment imatinib, after
finding that the evidence to support their use is “very poor”.
• Neither of the drugs fits the NICE end-of-life criteria, introduced to allow Appraisal
Committees to consider expensive medicines licensed for terminal illnesses, as the available
evidence on life extension is too weak.
• But even if the end-of-life criteria had been met, the exceptionally high costs of dasatinib
and nilotinib, taken together with poor quality evidence on the drugs’ effectiveness, would
not allow NICE to consider the drugs a cost-effective use of NHS resources.
• This latest draft guidance comes after the independent Appraisal Committee met, last
month, to discuss issues around the cost-effectiveness modelling raised during the first
public consultation.
• Professor Peter Littlejohns, clinical and public health director at NICE, said: “The
Committee heard from clinical specialists that in their opinion dasatinib and nilotinib are
clinically effective. However, the evidence available to support this was very poor, with no
studies comparing either drug to other treatments.
• “The cost of the drugs is also extremely high and before committing limited NHS resources
to fund them, we need to be sure they are effective. It would be heartening to hear that the
pharmaceutical company manufacturers are prepared to share some of the very high cost of
the drugs with the NHS.”
• The independent committee will next met on 9 March 2010 to consider any further evidence
before issuing the next draft guidance.
• 9 February 2010
47

48. 48