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SECTION III: REGULAR AND SPECIAL FEATURES

An Altruistic Approach to Clinical Trials: The National Clinical Trials Consortium (NCTC)

Weinstein, James, N

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Clinical Orthopaedics and Related Research: September 2006 - Volume 450 - Issue - p 246-248
doi: 10.1097/01.blo.0000224046.63754.78

We find ourselves working in a healthcare system in which $1.9 trillion dollars are spent to have the U.S. rank 37th in world health.1 Clearly, our health expenditures don't necessarily coincide with better outcomes. There is evidence to suggest our healthcare system is fundamentally broken. The Dartmouth Atlas studies have provided ample evidence that our healthcare is irrationally distributed, and that patients in high utilization areas had more inpatient treatment, more diagnostic tests, and increased use of specialists.2 Frequently, technologies or diagnostic tests are brought to market (increasingly, directly marketed to patients) despite a paucity of good studies providing solid evidence of proven efficacy and or effectiveness. We continue to bring new technologies into practice with studies that are often underpowered and without clearly defined endpoints. Unfortunately these studies can provide a false sense of security to our practicing physicians and to the patients to whom these treatments are directly marketed. Inadequate follow up and failure to report negative findings can undermine the very scientific process that has advanced medicine.

Naturally, given their investment, industry-supported trials are driven by the need for swift FDA approval in order to get a device or drug to market. However, we know that industry-supported projects yielded a nearly 73% positive result, whereas unfunded research had a much more even distribution of results, with positive at 46.2%, neutral at 45.6% and negative at 8.2%. Therefore, we should also pay close attention to the affiliations of those in academia that perform research. At university campuses around the country we are seeing a greater influence of large corporations in the naming of science centers, departments, professorships, and, ironically, schools of ethics. So carefully reading the disclosure statements of articles reporting the results of a trial is imperative to interpreting and understanding the results. Thus, caution is justified in adopting new technology that has not been evaluated with the rigor that affords us more than a modicum of confidence that we are doing what is best for our patients.

Dr. Elias Zerhouni has outlined a new initiative at the NIH called the Clinical and Translational Science Awards (CTSA), targeting some of the most basic systemic barriers in medicine as practiced today.4 Recognizing that we currently depend on two problematic systems to perform scientific research-the first being companies with much to gain financially from a positive result that their trials of effectiveness should be critically assessed and the second being that many overworked clinicians and basic scientists are being asked to cram the three careers of teacher, practitioner, and researcher into one lifetime. The CTSA hopes to partner with institutions who are already “grappling with the complex challenges posed by the clinical and translational science of the 21st century.” This program is an acknowledgment that the changes necessary to reform all aspects of health care are profound, difficult, and complex.

Such change doesn't involve easy or quick fixes, or shiny new technology. Only the earnest collaboration of everyone who cares deeply about the state of our health care environment will bring this about. To this end, I'm recommending formation of a National Clinical Trials Consortium (NCTC) (Fig 1). This should be formed and run by physicians and surgeons and their PhD colleagues. It should have an oversight board from independent professional societies, and appropriate specialty societies as well as public members. This consortium would be supported by industry, payers, FDA, NIH, and others, including the public, with vested interest in the clinical research enterprise. There should also be a data safety and monitoring board with public members. The primary function of the consortium would be to promote and direct high- quality clinical trials less susceptible to conflict of interest, affording them more face validity and almost certainly less bias.

Fig. 1
Fig. 1:
Proposed national clinical trials consortium

Such a structure would be both tangibly and conceptually constructive. Funding of an independent consortium cannot and will not eradicate all conflicts, but would provide checks and balances to minimize true as well as apparent conflicts. Answering the most pressing and relevant clinical questions would be the priority. The NCTC would fund innovative practicing physicians and PhDs with collective expertise in those aspects of clinical trials most prone to weakness: study design consistent with ones' stated hypothesis and specific aims; protocol development; data collection and data monitoring; complex longitudinal statistical analysis; intention-to-treat analysis and appropriate adjustments in an as-treated analysis; and appropriate oversight by an independent data and safety monitoring board. Another advantage of such a well-organized consortium would be more rapid enrollment and completion of projects with required open dissemination of results to all relevant public and private groups. This structure would serve to increase credibility and validity and possibly lessen medical liability.

We must avoid using a technique or device on our patients only to find out weeks, months, or years later that it failed to achieve what we had understood from available literature. The NCT consortium could also be used for postmarket surveillance in collaboration with our industry partners, FDA, Medicare, Medicaid, and independent private payers. The hope remains that a National Clinical Trials Consortium with broad geographic representation would allow us to bring the focus of our profession back to serving our diverse patient needs while minimizing the costs incurred by the current extensive network of various individual(s) trial group(s) conflicted in mission and purpose.

Barriers

There are many potential barriers to establishing the utopian clinical trials consortium. First, we must have the will to do this. We must avoid further fragmentation. We must trust one another and we must commit the time and resources necessary to accomplish this most important endeavor. Second, we must proactively change the current process by which technology is adapted by surgeons and colleagues to the benefit of our patients without any unintended detriment. In so doing we will be empowered to regain our focus, diminishing the noise of reimbursement and medical liability demands that currently drown out everything else. Breaking down barriers is not easy. Knowing the right thing is hard enough; doing the right thing is even harder. Most of us find reasons to avoid it: “I'm too busy” is a common complaint. “This will cut into my practice.” “This interferes with my physician/patient relationship.” “My results are already good and I don't need more data.”

Reality

External forces are now coming to bear on these issues. Ford automotive company and General Motors stock has been relegated to “junk bond” status, in part related to the high cost associated with their medical benefits. Recently, the American automobile industry has changed its strategy for long-term benefits-employees now share in their long- term health expenditures. Failure to do so would be prohibitive for the U.S. auto industry and its capacity to remain competitive in world markets. United Airlines, a leader in air transportation, is another example where the toll of ever increasing healthcare cost is pushing their company and this industry toward bankruptcy with a corporate pension plan at risk. Today, fuel cost is partly responsible but escalating healthcare costs have been omnipresent and loom larger each year. Clearly, our major industries can no longer afford to pay for health care that doesn't work, and we can't afford to provide care without scientific evidence to support our work. Medicare and other large private payers can no longer afford to pay for medications, diagnostic tests, surgeries, or other treatments that are not proven to be effective.

Winston Churchill said “Americans do the right thing after they have tried everything else.” I hope in our case that will not be true. There are many examples today in which well-designed clinical trials have benefited our profession and more importantly our patients. One recent example is in patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone.5

Being transparent in our mission, vision and our research is the best medicine we can give to society. A

National Clinical Trials Consortium offers industry, our profession and our patients the results we all want, an altruistic, selfless means to determine the most effective treatment alternatives. Our patients are having to take more and more responsibility for their own health care. As true partners, we along with our patients, industry, government and the private sector can have a major impact in moving our nation's health forward.

Acknowledgment

Thank you to Tamara Morgan for her editing and graphical assistance.

References

1. The World Health Report 2000: Health Systems-Improving performance. Geneva, Switzerland: World Health Organization, 2000.
2. Dartmouth Atlas of Health Care. Chicago, IL: American Hospital Association Press, 2000.
3. Shah RV, Albert TJ, Bruegel-Sanchez V, Vaccaro AR, Hilibrand AS, Grauer JN. Industry support and correlation to study outcome for papers published in Spine. Spine. 2005;30:1099-1104. Discussion 1105
    4. Zerhouni EA. Translational and clinical science-time for a new vision. N Engl J Med. 2005;353:1621-1623.
    5. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, Jackson CG, Lange M, Burge DJ. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999;340:253-259.
    © 2006 Lippincott Williams & Wilkins, Inc.