The adoption of new technology in radiation oncology should rely on evidence-based medicine
New technologies are constantly being introduced in radiation oncology primarily because they are new and not because they are clearly better than the technologies they are replacing. Often there is a “belief” that the new technology “ought” to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the concern debated in this month's Point/Counterpoint. Arguing for the Proposition is Christopher Njeh, Ph.D. Dr. Njeh obtained his Ph.D. degree in Medical Physics from Sheffield Hallam University, UK, and, after graduation, he worked at the Addenbrooke's Hospital in Cambridge and Queen Elizabeth's Hospital, Birmingham, UK. He then came to the United States as a Visiting Postdoctoral Fellow at the University of California, San Francisco, where he was subsequently appointed as an Assistant Professor of Radiology. He later completed a Medical Physics residency at Johns Hopkins University, Baltimore, and is currently Chief Medical Physicist at Texas Oncology in Tyler, TX, and holds an adjunct faculty position at the University of Texas at Tyler. Dr. Njeh is certified in Therapeutic Radiologic Physics by the ABR. His major research interests include image-guided radiation therapy and accelerated partial breast irradiation. He is author or coauthor of over 50 papers and 10 book chapters and is coeditor of two books. Arguing against the Proposition is Dr. Christian McDonald Langton. Dr. Langton obtained his M.Sc. degree in Medical Physics from the University of Aberdeen and his doctoral degrees from the University of Hull. After working in industry for two years, he returned to academia in the UK and ultimately attained the rank of Professor of Medical Physics at the University of Hull. In 2008, Dr. Langton was appointed Professor of Medical Physics at Queensland University of Technology in Brisbane, Australia, and Director of the Queensland Cancer Physics Collaborative. Dr. Langton's main research interest has been in quantitative bone imaging and characterization, and his work on the science, technology, and clinical utility of ultrasound assessment of cancellous bone and osteoporosis has resulted in over 1800 publication citations. He holds several related patents and there are seven commercial devices currently available adopting his broadband ultrasonic attenuation technique, with over 12 000 systems utilized worldwide. Medical technology encompasses all drugs, devices, and medical and surgical procedures used in medical care as well as the organizational supportive systems within which such care is provided.1 Radiation oncology has recently witnessed an explosion in innovation including but not limited to: proton therapy, CyberKnife, tomotherapy, IGRT, and IMRT. Efficacy, safety, and cost effectiveness, however, remains the focus in the provision of optimal care to patients. While some of these innovations offer unprecedented breakthroughs for some patients, they have the potential to also result in unintended harm if not used appropriately. It is, therefore, essential that adoption of these new technologies be evidence based. Evidence-based medicine can be perceived as “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.”2 Its practice presupposes the integration of individual clinical expertise with the best available external clinical evidence from systematic collection and synthesis of data, including patients’ values and expectations.3 The gold standard for the attainment of level 1 evidence is usually through randomized controlled trials (RCTs) and meta-analysis of such trials. There are many reported instances in the scientific literature where RCTs refuted evidence from theoretical, observational, physiologic studies or common sense. In the 1890s, Dr. William Halsted, for instance, developed radical mastectomy for breast cancer. His procedure was performed unchallenged for over 80 years. It was, however, not until an RCT was conducted in the late 1980s that it dawned upon the scientific community that radical mastectomy had no advantage over simpler forms of treatment for early-stage breast cancer.4 Another more recent example is vascular brachytherapy that was used to treat in-stent restenosis until an RCT showed that this therapy yielded comparatively inferior outcomes to polymer-based slow-release paclitaxel-eluting stents.5 Opponents of RCTs may be surprised to learn that not all new therapies amount to an improvement compared to the standard of therapy. For example, an analysis of outcome data from 58 RCTs, including a total of 12734 patients, conducted between 1968 and 2002 by the Radiation Therapy Oncology Group, found that, overall, experimental and standard arms were equally successful.6 They also found that treatment-related mortality and morbidity were, on average, higher in the innovative arm. In contemplating these facts, we are reminded of the economist who once said “…man's wants are numerous but his means are limited.” His view is applicable to national health care. Were one to place the cost of new technology into proper context it would be safe to assert that U.S. health care costs have risen faster than the gross domestic product (GDP), often by a substantial margin. While in 1960 approximately 5% of the GDP of the United States was spent on medical care,1 by 2004 it accounted for over 15% and is expected to be as much as 20% of GDP by 2015.7 According to a landmark study by The Kaiser Family Foundation,8 new technology has been identified as one of the causes of this exponential rise in health care cost. I submit, therefore, that new technology needs to fulfill the triple condition of efficacy, safety, and cost-effectiveness so that our limited resources can be put to the most judicious use. Evidence-based medicine is commonly defined as “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.”9 These are admirable words, but what do they really mean? Are they a realistic aspiration for adoption of new technologies in radiation oncology? A key factor is the validity of the evidence, so variable in reality that a number of category levels are widely utilized. For example, the U.S. Preventative Services Task Force10 lists three levels of “quality of evidence,” the highest level being “evidence obtained from at least one properly designed randomized controlled trial.” For the laudable randomized clinical trial, there has been a dramatic expansion in the number of publications associated with “radiation oncology” alone. Considering “Web of Science” publications per year using the topic search category of (“RCT” or “randomized clinical trial” or “randomized control trial”) and (“radiation oncology” or “radiotherapy”) yields: 1989 = 2, 1994 = 32, 1999 = 55, 2004 = 107, and 2009 = 228. How do we arrive at a consensus based upon such a wealth of information? Will a comparison be made against an untarnished “gold standard” or with current practice? The latter will inevitably necessitate large cohort numbers in each study arm, often impracticable from a recruitment perspective. Is there potential for a high attrition rate? Will it be difficult to assign and maintain inclusion and exclusion criteria? Will it be difficult to avoid bias? Very few cases are truly “equivalent.” Noting the understandable need to maintain a primary focus on patient welfare, as circumstances potentially change, will it be difficult to maintain a rigid protocol? Will the protocol be readily and reliably transferable multicenter and multinational? How long will it be before the technique could be routinely adopted? Technology developments appear at a fast time rate and may evolve during the course of an RCT such that they are used differently at the end of a trial than at the beginning and might even become outdated before the trial is over. How important are factors such as quality of life and secondary cancer risk? Other criticisms of adopting “evidence-based medicine” include stagnation, bland uniformity, and lowering of standards through deskilling practitioners. Instead of using clinical judgment, they will be encouraged to follow protocols that treat all patients as essentially interchangeable.9 There is also a threat to the adoption of new techniques in radiation oncology through a growing movement of “lack-of-evidence based medicine” that has been used to restrict access to a number of therapies,11 particularly by the UK's National Institute of Clinical Excellence. Perhaps the hottest “new technology in radiation oncology” debate relates to proton verses photon IMRT, with a question raised as to whether large randomized phase III comparative trials should be performed?; that would inherently encompass a significant number of scientific and ethical issues11,12 — I will end with that thought! The sheer volume of information available in the literature is more reason for a unified and systematic approach to synthesize them. Recruitment bias can be avoided by proper randomization.13 EBM makes decision making more thoughtful and more transparent, providing a stronger scientific backbone to medical practice. Not all studies are carried out with the same degree of rigor (quality, quantity, and consistency) hence a need to grade the quality of the research such as required by SORT,14 GRADE,15 or the Center for Evidence Based Medicine. The FDA is not thorough enough in its technology approval process. Recent studies have shown that the FDA premarket approval process is often based on weak studies.16 Ethical dilemmas in RCTs are eliminated by the acknowledgement of the equipoise principle which assumes that the two arms in a study have an equal chance of performing well.17 This principle has been validated by the fact that only 25%–50% of new technology is better than traditional technology.18 Another issue with pursuing RCTs has to do with the vested interests of three players if the RCT proves that the procedure is ineffective: the physician (new technology is accompanied by higher reimbursement), the hospital (need to pay for the equipment), and the manufacturer (need to make a profit).19 In conclusion, obtaining the relevant high quality evidence is a challenging, demanding, time-consuming, and costly pursuit. Nevertheless, it is a rigorous process, which we must demand of new technology so as to remain accountable to our patients. Having carefully considered my opponent's Opening Statement, I am confident that the arguments provided within my own Opening Statement remain valid and wholly intact. There are two primary components of my opposition to the proposition. First, it is impossible in reality to acquire irrefutable evidence as to whether a “new technology” will indeed improve individual patient care. Second, it is impossible to create a single unifying consensus based upon reported data. Allied to this, there has been a dramatic increase in the number of evidence-based medicine derived “clinical guidelines,” so much so that there has been a call for “guidelines for clinical guidelines” within a British Medical Journal Editorial.20 A fundamental question that we must address is whether so-called “evidence-based medicine” serves its purpose of helping clinicians make better decisions for the individual patient; related not only to the primary factors of diagnosis and treatment, but also encompassing prognosis, benefit, risk, and cost. Continuing this somewhat broader perspective, I wish to consider another component of the proposition's title, specifically, what do we really mean by “new technology in radiation oncology”? Are many so-called “new technologies” simply part of a fundamentally evolutionary advancement process? Noting the age-old tenet of “maximally treating the cancer by maximally sparing normal tissue,” are we in danger of being distracted away from aspects of radiation oncology that are of greater importance from an individual patient's perspective? For example, are we in need of true “new technologies” that better target regions of a particular tumor or organ that require, or maybe do not require, “treatment;” and to determine how these relate to both static and temporal anatomy? In summary, while appreciating the ideological paradigm that “the adoption of new technology in radiation oncology should rely on evidence-based medicine,” in reality, this cannot be achieved and we should concentrate on the primary role of helping clinicians make better decisions for the individual patient.
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