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CHALLENGES IN COST-EFFECTIVENESS AND SAFETY OF ANTICANCER
DRUGS
Felix Nguyen ([email protected])
eventually propagate into massive tumors whose cells can
very easily metastasize [5]. The difficulty of stopping cancer
growth lies in the range of mutations that exist. With
hundreds of different cancer cell lines, some starkly different
than others, it is difficult to pinpoint the exact genetic
malfunctions that occur and create treatments for those
specific problems. The problem has undermined doctors’
goal of “personalized medicine” [1] in which doctors hope to
be able to administer cancer therapies that target the specific
genetic mutation in each and every patient. While the
tailoring of drugs to an individual patient would be
advantageous with its cost benefits and effectiveness,
medical practitioners still do not have the tools to make this
reality. Furthermore, keeping track of the genomic
sequences of massive populations, especially in poorer areas
of the world, would be extremely difficult and unorganized.
This presents the need for broader treatments to fight cancer
in a larger variety of people.
POTENTIAL PROMISES AND PITFALLS
OF YERVOY
A new generation of technology has ushered in greater
opportunities to solve the most important issues facing
society today. The National Academy of Engineering is at
the forefront of this movement, naming 14 “Grand
Challenges for Engineering” that will further society [1].
“Engineering better medicines” is of particular interest to me
because scientific breakthroughs have allowed us to tackle
medical problems that have plagued us for centuries. Skin
cancer is one such problem, and despite years of harrowing
research and arduous experimentation, a cure has yet to be
found. Almost 9000 people a year die from melanoma, the
most dangerous form of skin cancer, and by 2013, 1 in 50
people will obtain it [2]. However, engineers are hard at
work advancing future treatments to battle metastatic
melanoma. Just this year, the Food and Drug Administration
approved an immunotherapeutic drug called Ipilimumab,
commercially known as Yervoy [3]. Early tests have shown
that it has greater promise in reducing tumor sizes and
prolonging life in cancer patients than other drugs currently
being employed. Like other drugs, its side effects range from
minor nuisances to deadly health issues [4]. This, along with
the high cost of the drug, downplays the usefulness of
Ipilimumab and other experimental drugs over current
chemotherapy and individualized medicines [3]. Despite
valid concerns and disadvantages, Ipilimumab is a vital part
of the next generation of cancer drugs that should be
promoted.
While it is important to look at the potential benefits of
Yervoy, it is easy to overlook the ethical implications of
creating it. Money is necessary for pharmaceutical
companies to function and fund expensive research projects,
and so higher prices are needed to counter costs. Engineers,
though, must look beyond financial needs and put the safety
of the public first. The engineers’ role in helping society
must be emphasized early on to students to allow them to
fully grasp the gravity of the decisions they will make and
the work involved in fulfilling them.
MECHANISM OF YERVOY AND THE
IMMUNE SYSTEM
Thus, Yervoy is an alternative to the more focused
treatments currently being researched. Yervoy, created by
Bristol-Myers Squibb, is a bioengineered, monoclonal
antibody most often used for the treatment of fast-growing,
metastatic cancer that has already spread to multiple parts of
the body once surgery has failed. It augments the activity of
T-cells, making the body more able to kill and contain
persistent cancer cells using its own mechanisms [6]. This
gives the drug several advantages that make it highly
promising. Since the immune system’s ability to reach all
parts of the body is extensive, the T-cells can help control
fast-spreading metastases whose primary strength is to travel
to the distant corners of the body. Most importantly,
however, these T-cells target antigens that are found on a
large number of different cancer cell lines [6]. This allows
the drug to be effective in a greater diversity of malignancies
with varying genetic makeups. Although Yervoy has only
been extensively tested in advanced melanoma, its functions
are speculated to work in additional cancers. As researchers
continue to pursue new targeted therapies for specific
cancer-causing mutations, people can have the option of
choosing Yervoy.
TREATING CANCER IN A VARIED
POPULATION
Cancer is often caused by mutations of genes that favor cell
growth and viability. Genes that promote proliferation are
rapidly created, and genes that inhibit growth and maintain
proper cell cycle control are either blocked or degraded. This
creates a dangerous series of continual cell divisions that
OUTCOMES OF EARLY CLINICAL DATA
Its FDA approval came with promising results that further
support its effectiveness as a next generation chemotherapy
University of Pittsburgh
Swanson School of Engineering
November 1st, 2011
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Felix Nguyen
drug. According to a recent clinical trial by the National
Cancer Institute, the three-year survival rate of patients
treated with this drug improved, and the mean survival time
increased from 9.2 months to 11.2 months [7]. In a small
study of 82 patients, 23% of those who received the drug
lived beyond two years, an increase over the 14% of those
who did not have the treatment [8]. In addition, melanoma
tumors progressively shrunk for over 19 months in people
using Yervoy as opposed to only 8 months in those using
conventional chemotherapy [9]. While it is true that such
results are largely preliminary and a far cry from a cure, it is
a substantial improvement over current chemotherapy
offerings.
restraints on what organ systems and cells to attack. There is
great uncertainty in how a patient may react to the drug, and
so autoimmune reactions such as diarrhea, hepatitis,
dermatitis, enterocolitis, and neuropathy may all occur [3].
These problems occurred in nearly 10% of patients in the
clinical trial, which, while seemingly small, can be
significant over a larger population. Treatment must stop in
patients who experience severe reactions, thus totally
negating Yervoy’s effectiveness in them. Although the
Federal Drug Administration puts guidelines on the allowed
toxicity of approved drugs, it is ultimately the bioengineers
and researchers who must draw the line as to how likely the
drug will cause side effects before putting it out in the
market. Despite some shaky negative results, Yervoy can
certainly improve and further testing will reduce adverse
responses [4]. Additionally, Bristol-Myers has approved a
risk evaluation and mitigation strategy (REMS) with Yervoy
that informs doctors of proper treatment approaches that will
minimize the danger [14].
ETHICAL ISSUES IN THE PRODUCTION
OF EXPERIMENTAL DRUGS
The above disadvantages in Yervoy highlight the problem
that faces engineers every day, particularly in a struggling
economy. The Biomedical Engineering Society formed their
own Code of Ethics that explains the biomedical engineer’s
obligation to public service and professional practice. It
states that engineers should, “consider the broader
consequences of their work in regard to cost, availability and
delivery of health care,” which involves products at
reasonable costs, most importantly when the economy is
struggling and consumer sentiment is at its lowest [10].
Yervoy, while improving patient outlook and survival by
several months to years, costs consumers $120,000 for a
single regimen [3]. There is great controversy over whether
its benefits outweigh the price tag, and whether the
bioengineers have made enough innovative changes that
justify its release to the public. Opposition has come from
the National Institute for Health and Clinical Excellence in
the UK which has prevented the sale of Yervoy in England
because of the heavy premiums [11]. Many of the other most
effective drugs such as AstraZeneca’s Faslodex and
Navartis’ Tasigna costs similarly, though [12]. With few
other alternatives to treating metastatic melanoma, Yervoy
still remains one of the most potent treatments regardless of
price and should continue to be used, especially when there
is finally a great chance of giving patients new hope through
volatile financial weather.
Safety is another vital aspect of medicines that is
highly variable and difficult to predict from patient to
patient. The National Society of Professional Engineers
created a Code of Ethics that outline the necessary conduct
and attitude engineers must have to ensure the highest
quality innovations to benefit all aspects of society. In their
Rules of Practice, they state that “Engineers shall hold
paramount the safety, health, and welfare of the public [13].”
This is certainly important when analyzing the potential side
effects of a medical breakthrough. Because the immune
systems in patients treated with Yervoy become highly
active from the increase in T-cells, there are no longer any
THE IMPORTANCE OF ENGINEERING
ETHICS EARLY IN COLLEGE
EDUCATION
The immense significance in the choices that bioengineers
must make is one of the key aspects of the professions that
early college students must fully appreciate. Bioengineering,
like almost every other discipline of engineering, focuses on
improving the lives of people. Mistakes and poor decisionmaking, though, can be completely detrimental to this
process. Patients put their health, income, and lifeline into
the hands of doctors and bioengineers who need to deliver
the best service they can offer. If immunotherapeutic agents
like Yervoy, Avastin, Herceptin, Arzerra were not made
specific enough for cancer cells, high toxicity to normal cells
would dampen chances of a smooth recovery and potentially
kill patients [15]. The earlier this is understood by students,
the greater their insight will be in the responsibility of the
engineer in serving the public. When working to improving
artificial organ function, drug delivery, or biosensor
technology, students will be able to predict the social,
economic, and political risks of their solutions [16].
THE FUTURE OF CANCER
THERAPEUTICS AND THEIR EFFECT ON
SOCIETY
Beyond the problems that new anticancer drugs bring, the
promise of an effective treatment still exists: Yervoy offers
impressive efficacy. Immunotherapeutic agents are not the
only types of treatments surfacing. Researchers have created
drugs such as Dacarbazine that cause cancer cell DNA to
replicate incorrectly, preventing it from being successfully
passed on to new cells [7]. Scientists and bioengineers agree
University of Pittsburgh
Swanson School of Engineering
November 1st, 2011
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Felix Nguyen
[16] Herkert, Joseph. "Engineering ethics education in the USA: content,
pedagogy and curriculum." European Journal of Engineering
Education 25.4 (2000): 303-313. European Journal of Engineering
Education. Web. 29 Oct. 2011.
that in order to eradicate cancer these drugs need to be
combined to synergize their effects. With no existing “cure”
yet, this is the best and most effective method that can be
used. However, we must always be wary of the
repercussions that will result. Enormous costs and additive
side effects are just a few of the dilemmas engineers will
face. All is not bleak, and with early exposure to the future
of their moral duties, the next generation of bioengineers
will be able make greater decisions that will better impact
the world.
ADDITIONAL SOURCES
Amadei, Bernard. "Engineering for the Developing World - Engineering
Challenges."Grand Challenges for Engineering. N.p., n.d. Web. 1 Oct.
2011. <http://www.engineeringchallenges.org/cms/7126/7356.aspx>.
Fitch, Kate, and Bruce Pyenson. "Cancer Patients Receiving Chemotherapy:
Opportunities for Better Management." Milliman Client Report 30 Mar.
2010: 1-27. Print.
Edwards, Jim. "Some Inconvenient Facts About Yervoy, Bristol-Myers’
New “Holy Grail” Cancer Drug." BNET - The CBS Interactive Business
Network. N.p., n.d. Web. 28 Oct. 2011. <http://www.bnet.com/blog/drugbusiness/some-inconvenient-facts-about-yervoy-bristol-myers-new8220holy-grail-8221-cancer-drug/7769>.
(2011) “Introduction to the Grand Challenges for Engineering.” National
Academy of Engineering Grand Challenges for Engineering. [Online: Web
site]. Available: http://www.engineeringchallenges.org/cms/8996/9221.aspx
"Ipilimumab ." Comprehensive Cancer Information - National Cancer
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<http://www.cancer.gov/cancertop ics/druginfo/ipilimumab>.
Miller, David . "Bristol-Myers Squibb Ipilimumab: Why FDA May Not
Approve
Drug,
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Pasdur's
Options
|
Markets
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Minyanville.com." Minyanville -- Stock Market, Investment, Finance,
Money, Hoofy & Boo. N.p., 23 Mar. 2011. Web. 3 Oct. 2011.
<http://www.minyanville.com/businessmarkets/articles/ipilimumab-drugapproval-pazdur-richard-pazdur/3/23/2011/id/33497>.
"Ofatumumab Injection." National Center for Biotechnology Information.
N.p., n.d. Web. 31 Oct. 2011.<http://www.ncbi.nlm.nih.gov/pubmedhe
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Revkin, Andrew. "How Many 'Grand' Engineering Challenges Are Really
Policy Challenges? - NYTimes.com." Natural Resources and the
Environment - Dot Earth Blog - NYTimes.com. N.p., n.d. Web. 3 Oct.
2011.
<http://dotearth.blogs.nytimes.com/2008/02/20/how-many-grandengineering-challenges-are-really-policy-challenges/>.
Stephen H. Unger, “Responsibility in Engineering: Victor Paschkis vs
Wernher von Braun. IT Professional, Volume 12 Issue 3, 2010, p. 6-7, DOI
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<http://www.engineeringchallenges.org/cms/8996/9129.aspx>.
[2] "What are the key statistics about melanoma? ." American Cancer
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<http://www.cancer.org/Cancer/SkinCancerMelanoma/DetailedGuide/melanoma-skin-cancer-key-statistics>.
[3] Pollack, Andrew. "Yervoy, a Melanoma Drug, Wins F.D.A. Approval NYTimes.com." The New York Times - Breaking News, World News &
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<http://www.nytimes.com/2011/03/26/business/26drug.html?_r=1>.
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[6] Sondak, Vernon. "Ipilimumab."Nature Reviews Drug Discovery10
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ACKNOWLEDGEMENTS
I would like to thank Andrew Abboud, my roommate, Chris
Trevoy, my suitemate, Bobby Dumont, Justin Fleischmann,
and Dr. Schaub for their undivided time and guidance with
this assignment.
University of Pittsburgh
Swanson School of Engineering
November 1st, 2011
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