Clinical Economics-Changing
Our Thinking about Clinical Study Design to Gain the Most Benefit for Public
Health Improvements
The healthcare community is inundated with scientific information
about new studies, often proclaiming specious benefits for improved health
outcomes and a dearth in studies which actually improve public health in a real
world setting. Private review boards and investigations done to promote
medications are not uncommon. This article reviews clinical economics, a new
field for evaluating the real-world application and effectiveness of health
care interventions, which is fundamental to delivering value for health systems
and patients. Dr. Franz Peszolt, head of the Institute for Clinical Economics
in Ulm, Germany, states, “Scientists tell us what they see and clinicians tell
us what they hope to see in their practices from clinical and pragmatic trials.”[1] In
research, the scientific study tests hypothesis to follow a new line of inquiry
for potential benefits and the gold standard for these are randomized control
trials or RCT’s. The next phase of inquiry is to determine if the findings
under ideal controlled scientific conditions can be replicated in a pragmatic
trial, which determines how the intervention works in a real-world clinical
environment. However, both of these
studies lack patient input in terms of the actual value of the intervention,
their likelihood to continue with the treatment after the study concludes, and
the absolute value to the patient. Dr. Norman Hadler has discussed this
phenomenon in his book(s) and he always encourages patients to ask their doctor
about absolute values when a treatment or intervention is encouraged. In real
terms, this means, asking questions such as, “In a patient population has this
treatment been shown to extend life expectancy and if so, by how much?”[2]
For example, for cancer patients, a scientific finding which extends life by a
few months may be valid, but not enough to motivate the actual patient to
undergo an expensive and painful treatment. Chemotherapy comes to mind, as it
may extend patient life, but nausea and susceptibility to infections are the side
effects. Thankfully, more patients are now receiving palliative care
information for end-of-life treatment, which incorporates comfort and patient
values into the care process. Palliative care is an example of a health
treatment which has a high utility value in clinical economics.
Scientific Findings
in Real World Deployment Must Produce Significant Results
Examining scientific findings and their application in real
world situations for individual patients can be confusing, so let’s examine
prostate cancer treatment and see how clinical economics applies to treatment
protocols. Prostate cancer can be slow growing and nonfatal, but treatment
protocols vary little for the disease, chemotherapy and surgical interventions
are the norm. This flies in the face of scientific evidence and the side effects
(impotence). Patient fear is a driver in
the decision to pursue this drastic treatment. Genomic Health has developed a
new blood test, which can show the efficacy of a treatment for patients, based
on their genomic profile. This has the potential to improve patient’s quality
of life, because the decision to use chemotherapy or a new drug regime can be
tailored to the patient profile. A blood
test developed by Epic Sciences Inc. can detect a mutation in the blood which
shows a poor response to two new cancer drugs, Xtandi and Zytiga. This has the
potential to be a game changer for health systems as it provides insight into treatment
which can avoid costly treatments which don’t improve outcomes for some prostate
cancer patients.[3] Applying
clinical economics can avoid over treatment and target optimization of results
per patient. In other words,
one-size-doesn’t-fit-all.
The Difference
Between Efficacy and Effectiveness
Efficacy is meant to determine if the hypothesis for a
medical intervention shows a statistically significant scientific difference,
as demonstrated through the randomized control trial. Effectiveness is the real
world trial of a product with actual patients, called a pragmatic trial and is
meant to show clinical effectiveness, in other words, does it work. In the
actual clinical setting, there are many more variables than in a randomized
control trial, so this can confound the expected results or mute the clinical
benefits for the patient population. Sometimes in the pragmatic trial, harmful
effects of the treatment are so significant the trial is stopped.[4]
Dr. Porzsolt and his collaborators have outlined problems
with reconciling findings from both randomized control trials and pragmatic
trials and some methods to assure consistency for the purposes of adoption of
treatment and deployment in a population. For example, one of the problems that
has occurred with the advent of independent review boards, which function as
for profit companies, is the tendency to stop a trial too early if some
positive result is found. This makes the results weaker, but may be lucrative
for the company which is funding the research, the future patent holder, by
gaining FDA and CMS approval earlier. Secondly, before deployment of a medical
intervention in a real world patient setting, the actual results must show
scientific and clinical effectiveness, which is also not always the case. In
pragmatic trials, patients are allocated to groups based on their preferences,
which is not the case in a randomized control trial, which would cause bias in
an RCT, but is a real element of variance in clinical practice. There are still
concerns in the clinical community about proving real world value of some
scientific studies, which have not adhered to all standards for bias control,
published results too early in the trial, or published results that were only
valid in the scientific trial (RCT) and not the pragmatic clinical test. For
example, cost-benefit analysis done in a randomized trial isn’t necessarily applicable
for a clinical trial, where there are many more patient and environmental
variables.
Concerns About Proof
of Clinical Value from Scientific Studies
In the United States, where a lot of the health system
expenditures are paid by private companies and individuals, there are inherent
conflicts between a cost reduction in one sector, which reduces revenue
impacting cash flows for another aspect of patient care in the same
system. Changing the reimbursement
method for health care services could alieve some of this dissonance. If a
patient is able to find a lower cost treatment which generates desired clinical
outcomes, this should be applauded as a health system advancement, not
discouraged because it reduces revenues. Currently, the Centers for Medicare
and Medicaid has chosen to pay a patient management fee for patients with
targeted complex care diagnosis, but most of the reimbursement is merely based
on the cost of the service. However, CMS has just announced an initiative to
pay physicians more for care coordination, planning, and primary care.[5] One
of the ways we can gauge the value of scientific studies and their potential
worth in a real-world setting is to conduct meta-analysis on studies which are
similar or heterogeneous to the targeted clinical setting.
In any quest for wisdom, the first step is to understand the
questions, and from that we can better discern how to gauge articles about
clinical studies and their actual value for a patient group. For more
information on this topic health care professionals and policymakers may wish
to read the following journal articles:
Porsolt, Frans, Galito Rocha, Natalia, Toledo-Arruda,
Alessandra, et, al, Efficacy and effectiveness trials have different goals, use
different tools, and generate different messages. Pragmatic and Observational
Research, Dove Press, November 4, 2015
Metge CJ. What comes after producing the evidence? The
importance of external validity to translating science to practice. Clin
Ther. 2011; 33(5):578–580
Jüni P, Altman DG, Egger M. Systematic reviews in health
care: assessing the quality of controlled clinical trials. BMJ. 2001; 323:42–46
Ioannidis JP. How to make more published research true. PLoS
Med. 2014; 11: e1001747. doi: 10.1371/journal.pmed.1001747
Weiss AP, Guidi J, Fava M. Closing the
efficacy-effectiveness gap: translating both the what and the how from
randomized controlled trials to clinical practice. J Clin Psychiatry.
2009; 70:446–449
And this is the healthpolicymaven signing off wishing you
truly informed consent, feel free to share this article virally. The
healthpolicymaven is a trademark of Roberta E. Winter and Praevalere Inc., a
Washington Corporation. She is the author of Unraveling U.S. Healthcare-A
Personal Guide, published by Rowman & Littlefield in 2013. https://www.amazon.com/Unraveling-U-S-Health-Care-Personal/dp/1442222972
[1]
Frans Porzsolt, Natália Galito Rocha, Alessandra
C Toledo-Arruda, et, al,
Efficacy and
effectiveness trials have different goals, use different tools, and generate
different messages, Observational Research, Dove Press, November 4, 2015
[2]
Nortin M. Hadler, MD, The Citizen Patient-Reforming Health Care for the Sake of
the Patient, Not the System, The University of North Carolina Press, Chapel
Hill, 2013
[3]
Ron Winslow, Test Helps Prostate Cancer Treatment, Wall Street Journal, July 7,
2016
