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A New Vision for Clinical Research
Editorials
A New Vision for Clinical Research A recent workshop on “Transforming Clinical Research in the United States: Challenges and Opportunities” sponsored by the Institute of Medicine proposed establishment of a new model for clinical trials.1,2 The impetus for this proposal was based on the perceived failure of the health care system in the United States to generate medical evidence in a manner that could efficiently and meaningfully be translated into practice. The processes of performing clinical trials, according to this Workshop report, had become too expensive and lengthy, had involved an increasingly burdensome number of regulatory hurdles, were hampered by a weak and limited infrastructure, and, therefore, were viewed as unattractive to health care providers and potential subjects for study.2 To address these issues, the Workshop participants sought to “examine regulatory, administrative and structural barriers to the effective conduct of clinical research, develop a vision for a stable, continuously funded clinical research infrastructure, and consider strategies. . .to facilitate more robust public engagement in the clinical research enterprise.”2 The participants envisioned a new system that would encompass 4 workforce groups: 1) community practitioners, who would participate in trials as part of their clinical practices; 2) implementers, clinical research coordinators and managers at the research sites who would implement clinical trials; 3) investigators, who would design and lead the clinical trials; and 4) methodologists, who would study methods and policies pertaining to the clinical trials, and provide data interpretation and outcome results.1 When commenting on the deficiencies in our clinical research system, Janet Woodcock, Director of the Food and Drug Administration Center for Drug Evaluation and Research, discussed “needs to bridge the divide between research and the clinical practice of medicine” by actively involving community practitioners in the clinical trials process.2 When addressing possible causative factors for these deficiencies, Robert Califf, Director of the Duke Translational Medical Institute, noted “the time and demands of clinical practice, the increasing complex0022-5347/12/1881-0008/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
8
www.jurology.com
AND
RESEARCH, INC.
ity of regulations, the lack of local supportive infrastructure, inadequate research training, less enjoyment from participation and data collection challenges, difficulties in locating funding, the burden of completing large amounts of associated paperwork, inefficiencies in patient recruitment, and inadequate reimbursements” which had led to a situation in clinical research “that has progressively worsened in recent years.”2 According to the Workshop report, much if not all of this related to the “absence of a nationalized health care system in which services” could be “provided to all citizens through government-funded providers” and because of which “physicians have disincentives to refer patients to clinical trials.”2 I had developed a particular interest in these issues as a member of my institution’s investigation review board when reviewing clinical study protocols and as Associate Editor of this journal and Editor of Urologic Oncology when reviewing clinical study reports. I found that many of these protocols and reports were limited by small numbers of subjects, retrospective design, reliance upon incompletely vetted databases and statistical analyses often with only marginal clinically useful information, each reflecting in part the burdens and deficiencies noted at the Workshop. However, I was especially spurred by my recollection of a similar situation nearly 20 years ago when the Clinton White House was proposing to redesign our health care system and the parallels the Workshop’s recommendations seemed to have with several ideas I had proposed on how the then-anticipated changes might be used to improve clinical research. Concerns with escalating costs, deteriorating access and delivery, variable and unpredictable insurance coverage, growing manpower shortages and worrisome issues on quality of care were not unlike those we continue to face today. Among the health policy proposals at that time were the establishment of a single payer system and transition to a universal health insurance system. The seeming inevitability of these changes prompted me to suggest using the new health care model to implement randomized prospective trials to address fundamental questions in medicine and Vol. 188, 8-9, July 2012 Printed in U.S.A. DOI:10.1016/j.juro.2012.04.029
NEW VISION FOR CLINICAL RESEARCH
potentially obtain data for more cost-effective, evidence-based treatment paradigms. An important issue for urologists at the time concerned the comparative effectiveness of surgery versus radiation therapy for treating organ confined prostate cancer. I reasoned that this issue might provide a good model for seeking to integrate clinical studies within the new health care framework. Thus, might it be possible that all patients diagnosed with clinically organ confined prostate cancer be randomized to undergo the then standard treatments of radical surgery, brachytherapy or external radiation? Conceivably, the increasing number of men being diagnosed with prostate cancer through prostate specific antigen screening (then ⬃150,000 new cases a year) would provide an opportunity to generate sufficient substantive data in various substratified categories, allow statistical power in assessment of results, and offer clinically relevant and meaningful analyses and interpretations. Patients would be treated either by their own physician or by physicians at central institutions as per their and their physician’s choice, and then be followed according to protocol either by their treating physician or by their primary physician. Compensation for each participant physician/investigator would be based upon physicians submitting all required data to a central processing site at which an assigned group of urologists, medical oncologists, radiation oncologists, trialists and statisticians would monitor and collate results, analyze these data and offer evidence-based conclusions in identifying risk factors, assessing treatment efficacy and deriving valid cost/benefit interpretations in developing a basis for health care policy. Implicit in the success of this proposal would be the active involvement of all participants (physicians and patients) through a centralized single payer system and universal health insurance. Ultimate overall cost savings would be based upon identifying the most effective method of treating a condition (in this instance organ confined prostate cancer) while limiting or discarding less or ineffective approaches. A significant objection I encountered to this proposal concerned the question of patient choice in selecting treatment rather than being randomly assigned. Indeed, the public health experts and those experienced in government policy who I consulted suggested that “choice” was considered an inherent right by the American population and would make a
9
true randomization design politically difficult at best and likely impossible to achieve. However, statisticians who I consulted suggested that even if patient choice were maintained, the large numbers of patients available to be assigned to each treatment group would overcome the absence of blinded randomization and achieve the statistical power and validity to allow meaningful interpretations. All of this became moot with the subsequent collapse of the Clinton efforts. Now 20 years later, accelerating costs, pressures to institute universal health insurance, concerns with ever declining reimbursements, escalating calls for a single payer system and ongoing issues with the for-profit insurance, fee-for-service health care model continue to spur suggestions for change and make them increasingly urgent. In this context, possibilities to integrate the clinical trials process as part of a changing health care system as this might lead to substantive cost savings and valuable evidence-based information may seem increasingly attractive and perhaps ultimately necessary. The Institute of Medicine Workshop has called for the exploration of opportunities to accomplish an integrative, streamlined, constructive and effective overhaul of the clinical trials system. Development of a clinical trials infrastructure involving medical practitioners in the broader medical community (in private practice, through hospitals and at academic centers) would create disease specific networks designed to evaluate interventions for a given condition.2 Standardized protocols and prospective data collection through use of improved health information technology would reduce overall costs and increase efficiency and productivity. Accumulation of large volumes of clinical data increasingly accessible in electronic format would accelerate the translation of clinical research into clinical practice.1 The concomitant facilitation of public education on a “best approach” health care policy would consolidate the ultimate benefits of optimized care and cost savings to achieve a greatly enhanced integrated health system. The Institute of Medicine has proposed 2020 as the target year for transforming our clinical trials system.1 The likely benefits and advantages suggest the earlier the better. Michael J. Droller Associate Editor
REFERENCES 1. Eastman P: IOM component envisions new model for clinical trials by 2020. Oncology Times, January 10, 2012; pp 21–22.
2. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation: Transforming Clinical Research in the United States: Challenges
and Opportunities: Workshop Summary. Washington DC: National Academies Press (US) 2010; preface, pp 22, 23 and 27.
A New Vision for Clinical Research A recent workshop on “Transforming Clinical Research in the United States: Challenges and Opportunities” sponsored by the Institute of Medicine proposed establishment of a new model for clinical trials.1,2 The impetus for this proposal was based on the perceived failure of the health care system in the United States to generate medical evidence in a manner that could efficiently and meaningfully be translated into practice. The processes of performing clinical trials, according to this Workshop report, had become too expensive and lengthy, had involved an increasingly burdensome number of regulatory hurdles, were hampered by a weak and limited infrastructure, and, therefore, were viewed as unattractive to health care providers and potential subjects for study.2 To address these issues, the Workshop participants sought to “examine regulatory, administrative and structural barriers to the effective conduct of clinical research, develop a vision for a stable, continuously funded clinical research infrastructure, and consider strategies. . .to facilitate more robust public engagement in the clinical research enterprise.”2 The participants envisioned a new system that would encompass 4 workforce groups: 1) community practitioners, who would participate in trials as part of their clinical practices; 2) implementers, clinical research coordinators and managers at the research sites who would implement clinical trials; 3) investigators, who would design and lead the clinical trials; and 4) methodologists, who would study methods and policies pertaining to the clinical trials, and provide data interpretation and outcome results.1 When commenting on the deficiencies in our clinical research system, Janet Woodcock, Director of the Food and Drug Administration Center for Drug Evaluation and Research, discussed “needs to bridge the divide between research and the clinical practice of medicine” by actively involving community practitioners in the clinical trials process.2 When addressing possible causative factors for these deficiencies, Robert Califf, Director of the Duke Translational Medical Institute, noted “the time and demands of clinical practice, the increasing complex0022-5347/12/1881-0008/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
8
www.jurology.com
AND
RESEARCH, INC.
ity of regulations, the lack of local supportive infrastructure, inadequate research training, less enjoyment from participation and data collection challenges, difficulties in locating funding, the burden of completing large amounts of associated paperwork, inefficiencies in patient recruitment, and inadequate reimbursements” which had led to a situation in clinical research “that has progressively worsened in recent years.”2 According to the Workshop report, much if not all of this related to the “absence of a nationalized health care system in which services” could be “provided to all citizens through government-funded providers” and because of which “physicians have disincentives to refer patients to clinical trials.”2 I had developed a particular interest in these issues as a member of my institution’s investigation review board when reviewing clinical study protocols and as Associate Editor of this journal and Editor of Urologic Oncology when reviewing clinical study reports. I found that many of these protocols and reports were limited by small numbers of subjects, retrospective design, reliance upon incompletely vetted databases and statistical analyses often with only marginal clinically useful information, each reflecting in part the burdens and deficiencies noted at the Workshop. However, I was especially spurred by my recollection of a similar situation nearly 20 years ago when the Clinton White House was proposing to redesign our health care system and the parallels the Workshop’s recommendations seemed to have with several ideas I had proposed on how the then-anticipated changes might be used to improve clinical research. Concerns with escalating costs, deteriorating access and delivery, variable and unpredictable insurance coverage, growing manpower shortages and worrisome issues on quality of care were not unlike those we continue to face today. Among the health policy proposals at that time were the establishment of a single payer system and transition to a universal health insurance system. The seeming inevitability of these changes prompted me to suggest using the new health care model to implement randomized prospective trials to address fundamental questions in medicine and Vol. 188, 8-9, July 2012 Printed in U.S.A. DOI:10.1016/j.juro.2012.04.029
NEW VISION FOR CLINICAL RESEARCH
potentially obtain data for more cost-effective, evidence-based treatment paradigms. An important issue for urologists at the time concerned the comparative effectiveness of surgery versus radiation therapy for treating organ confined prostate cancer. I reasoned that this issue might provide a good model for seeking to integrate clinical studies within the new health care framework. Thus, might it be possible that all patients diagnosed with clinically organ confined prostate cancer be randomized to undergo the then standard treatments of radical surgery, brachytherapy or external radiation? Conceivably, the increasing number of men being diagnosed with prostate cancer through prostate specific antigen screening (then ⬃150,000 new cases a year) would provide an opportunity to generate sufficient substantive data in various substratified categories, allow statistical power in assessment of results, and offer clinically relevant and meaningful analyses and interpretations. Patients would be treated either by their own physician or by physicians at central institutions as per their and their physician’s choice, and then be followed according to protocol either by their treating physician or by their primary physician. Compensation for each participant physician/investigator would be based upon physicians submitting all required data to a central processing site at which an assigned group of urologists, medical oncologists, radiation oncologists, trialists and statisticians would monitor and collate results, analyze these data and offer evidence-based conclusions in identifying risk factors, assessing treatment efficacy and deriving valid cost/benefit interpretations in developing a basis for health care policy. Implicit in the success of this proposal would be the active involvement of all participants (physicians and patients) through a centralized single payer system and universal health insurance. Ultimate overall cost savings would be based upon identifying the most effective method of treating a condition (in this instance organ confined prostate cancer) while limiting or discarding less or ineffective approaches. A significant objection I encountered to this proposal concerned the question of patient choice in selecting treatment rather than being randomly assigned. Indeed, the public health experts and those experienced in government policy who I consulted suggested that “choice” was considered an inherent right by the American population and would make a
9
true randomization design politically difficult at best and likely impossible to achieve. However, statisticians who I consulted suggested that even if patient choice were maintained, the large numbers of patients available to be assigned to each treatment group would overcome the absence of blinded randomization and achieve the statistical power and validity to allow meaningful interpretations. All of this became moot with the subsequent collapse of the Clinton efforts. Now 20 years later, accelerating costs, pressures to institute universal health insurance, concerns with ever declining reimbursements, escalating calls for a single payer system and ongoing issues with the for-profit insurance, fee-for-service health care model continue to spur suggestions for change and make them increasingly urgent. In this context, possibilities to integrate the clinical trials process as part of a changing health care system as this might lead to substantive cost savings and valuable evidence-based information may seem increasingly attractive and perhaps ultimately necessary. The Institute of Medicine Workshop has called for the exploration of opportunities to accomplish an integrative, streamlined, constructive and effective overhaul of the clinical trials system. Development of a clinical trials infrastructure involving medical practitioners in the broader medical community (in private practice, through hospitals and at academic centers) would create disease specific networks designed to evaluate interventions for a given condition.2 Standardized protocols and prospective data collection through use of improved health information technology would reduce overall costs and increase efficiency and productivity. Accumulation of large volumes of clinical data increasingly accessible in electronic format would accelerate the translation of clinical research into clinical practice.1 The concomitant facilitation of public education on a “best approach” health care policy would consolidate the ultimate benefits of optimized care and cost savings to achieve a greatly enhanced integrated health system. The Institute of Medicine has proposed 2020 as the target year for transforming our clinical trials system.1 The likely benefits and advantages suggest the earlier the better. Michael J. Droller Associate Editor
REFERENCES 1. Eastman P: IOM component envisions new model for clinical trials by 2020. Oncology Times, January 10, 2012; pp 21–22.
2. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation: Transforming Clinical Research in the United States: Challenges
and Opportunities: Workshop Summary. Washington DC: National Academies Press (US) 2010; preface, pp 22, 23 and 27.