Saturday, August 6, 2016
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.” 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?” 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. 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.
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. 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
 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
 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
 Ron Winslow, Test Helps Prostate Cancer Treatment, Wall Street Journal, July 7, 2016