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PERSPECTIVE THE 21ST CENTURY CURES ACT An audio interview el with Dr. Avon; is available of NEJM.org than minimal risk" — a major departure from current human subject protections. It is not clear who gets to determine whether a given trial of a new drug poses "minimal risk." Embedded in the language of the 21st Century Cures Act are some good ideas that could streamline the devel- opment and evalua- tion of new drugs and devices; its call for increased NIH funding may prove to be its most useful component. But political forces have also introduced other provisions that could lead to the approval of drugs and devices that are less safe or effective than existing criteria would permit. Over the past 80 years, this country's regulatory approach has embraced steadily improving cri- teria for accurately assessing ther- apeutic efficacy and risk. Patients and physicians would not benefit from legislation that instead of catapulting us into the future, could actually bring back some of the problems we thought we had left behind in the 20th century. Disclosure forms provided by the authors are available with the full text of this ankle at NEJM.org. From the Program on Regulation. Thera- peutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeco- nomics, Department of Medicine. Brigham and Women's Hospital and Harvard Medi- cal School. Boston. This article was published on June 3. 2015, at NEJM.org. 1. 21st Century Cures Act. May 19. 2015 (http://docs.house.govimeetings/IF/IF00/ 20150519/103516/BILLS-1146ih.pdf). 2. Kesselheim AS, Tan YT. Avom J. The roles of academia, rare diseases. and repurposing in the development of the most transforma- tive drugs. Health Aff (Millwood) 2015:34: 256-93. 3. Downing NS. Aminawung JA, Shah ND. Krumholz HM. Ross JS. Clinical trial evi- dence supporting FDA approval of novel therapeutic agents. 2005.2012. JAMA 2014; 311:363.77. 4. Avom J. Approval of a tuberculosis drug based on a paradoxical surrogate measure. JAMA 2013:309:1349-50. 5. Dhruva SS. Bero LA. Redberg RF. Strength of study evidence examined by the FDA in premarket approval of cardiovascular devic- es. JAMA 2009;302:2679-1M DOI: 10.1056/NqMp1S06964 Coprir O ZOIS Mama a, Medal Soda Medical Facts versus Value Judgments —Toward Preference-Sensitive Guidelines Peter A. Libel, M.D. T he radiation oncologists apol- ogetically informed us that they would not be able to offer my wife Paula a sixth week of treatment — a "boost" therapy aimed at the place where her breast cancer had resided before she received her lumpectomy. This tumor bed was no longer localizable, because Paula had received immediate reconstruction that had obscured its location. I was aghast. Although Paula would receive 5 weeks of whole-breast irradiation, she would not receive the benefits of that final week of treatment, the boost therapy that, according to National Compre- hensive Cancer Network (NCCN) guidelines, is "recommended" for women like Paula, whose breast cancer is diagnosed before they are 50 years of age and who have axillary involvement.' After the radiation oncology appointment, I obtained the main clinical trial that had established the value of boost therapy' and looked for the survival curves that corresponded to the size and location of Paula's tumor. I could see how much boost therapy would have reduced her chance of local recurrence. But I could also see the downside of this treatment, which increased the risk of breast fibrosis. It made me wonder: how did the NCCN come to so definitively recom- mend boost therapy for women like my wife? A couple of years later, I stood in front of an audience of radia- tion oncologists, presenting a lec- ture on shared decision making. I asked them to imagine that they faced a choice between two types of radiation therapy for early-stage breast cancer. The first treatment would leave them with a 15% chance of local recurrence and a 10% chance of moderate or severe breast fibrosis. The second treat- ment would leave them with only an 8% chance of local recurrence but a 30% chance of moderate or severe fibrosis. The radiation oncologists raised their hands in almost equal numbers for the two treatments. Some believed the higher risk of fibrosis was unac- ceptable, given the treatability of most local recurrences, whereas others believed the trauma of re- currence outweighed the discom- fort of fibrosis. This division of opinion was not completely surprising. Often medical facts — such as data on rates of cancer recurrence versus rates of fibrosis — don't point toward an objectively superior N ENGL) M W 372:26 NEJ1A.ORG JUNE 25, 2015 The New England Journal of Medicine Downloaded from nejm.org on June 30, 2015. For personal use only. No other uses without pemtission. Copyright O 2015 Massachusetts Medical Society. All rights reserved. 2475 EFTA_R1_02147855 EFTA02715650 PERSPECTIVE MEDICAL FACTS VS. VALUE JUDGMENTS treatment but instead reveal trade- offs, whereby the best choice for an individual patient depends on her preferences, on how she weighs the relative pros and cons of her alternatives. Yet in one respect, the divided opinion was unexpected, because I had presented these specialists with an estimate of the outcomes my wife faced when she received radiation treatment for breast cancer. The first set of outcomes captured her prognosis if she were to receive 5 weeks of whole- breast radiation. The second cap- tured the impact of receiving boost therapy. Half the audience had rejected the "recommended" therapy. The NCCN, in crafting its treatment guidelines, had stepped beyond assessing medical facts to making a questionable value judgment, that the positive effect boost therapy has on local recur- rence outweighs its negative ef- fect on breast fibrosis. This distinction between facts and value judgments has long been emphasized by experts on decision making, and not just in the medical domain. In the mid- 1970s, amid substantial public debate about the proper role of scientific advisors in the govern- ment, Kenneth Hammond and Leonard Adelman wrote an arti- cle explaining that the integration of facts and values cannot be ac- complished using science alone but also requires value judgments.' They described a 1974 contro- versy that was mishandled in part because the community turned a problem over to scientists with- out recognizing that there was no purely scientific answer to the question at hand. The Denver Police Department had begun us- ing hollow-point bullets, because of their superior stopping power. The American Civil Liberties Union challenged this decision, contend- ing that the greater lethality of the bullets would result in greater harm to innocent bystanders. Ballistic experts were asked to provide their scientific opinion about which bullet was "best." If the new bullets had been both safer and more effective than the old ones, scientists could have answered this question by point- ing out those facts. But the new bullets presented a trade-off be- tween lethality for criminals and safety for the public. Science on its own cannot determine which is the right choice in such circum- stances. That choice depended on the relative importance the com- munity placed on the two goals. Ballistics experts were in no better position than laypeople to make this judgment. Like ballistics experts, physi- cians hold mastery over scientific facts that are relevant to impor- tant decisions and often assume the role of advisors to laypeople facing difficult choices. In this advisory capacity, physicians must recognize that their medical rec- ommendations sometimes involve value judgments and that reason- able people may disagree on the best course of therapy. The American Urological As- sociation recognized this distinc- tion in its guidelines for treat- ment of early-stage prostate cancer and wrote that patient preferences "should be considered in decision- making."' By contrast. NCCN guidelines do not include active surveillance as an available treat- ment Sr men with tumors with a Gleason score of 7 (the thresh- old for a high-grade tumor) who have a life expectancy of more than 10 years' This guideline ef- fectively treats patients' prefer- ences as irrelevant to treatment choices for men with such tumors. In the process, it ignores the possibility that a 62-year-old man who can't afford to miss work might want to pursue active sur- veillance so he doesn't lose his job, or that a newly married 65-year-old man might not want to have erectile dysfunction as a result of surgical or radiation therapy. Given that such choices seem quite reasonable, I believe the NCCN overstepped its profes- sional expertise when it implicit- ly recommended that physicians take this option off the table. The same holds true for the NCCN guidelines regarding boost therapy for women with certain types of breast cancer. Physicians crafting the guidelines went be- yond the medical facts and made the value judgment that women should accept the increased risk of breast fibrosis in order to re- duce their chance of a local re- currence. In some cases, I expect that the value judgments physicians and professional societies make are shared by their patients. But sometimes physicians' values dif- fer in important ways from those of many patients. When such value judgments are incorporated into professional treatment guide- lines, without any explicit ac- knowledgment that a reasonable patient might choose an alterna- tive course of treatment, they take potential choices away from patients. Good decision making re- quires familiarity with decision- relevant facts and recognition of the values relevant to weighing the pros and cons of the alterna- tives. If physicians or medical so- cieties — in presenting treatment alternatives to patients or devel- 2476 N ENGL J MED 322:26 NEJ14.O/1G JUNE 25, 2015 The New England Journal of Medicine Downloaded from nejm.org on June 30, 2015. For personal use only. No other uses without permission. Copyright O 2015 Massachusetts Medical Society. All rights reserved. EFTA_R1_02147856 EFTA02715651 PERSPECTIVE MEDICAL FACTS VS. VALUE JUDGMENTS oping guidelines laying out the standard of care — fail to recog- nize when they have gone be- yond the medical facts to make value judgments, they will harm patients by taking viable choices away from them. Disclosure forms provided by the author are available with the full text of this arti- cle at NEJM.org. From the School of Medicine, the Fuqua School of Business, and the Sanford School of Public Policy, Duke University, Dur- ham, NC. 1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer. 2015 (http://www.nccn.org/ profess iona Is/physician_gls/f_ guidelines .aspitsite). 2. Bartelink H, HorioUC.Poortmans PM, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol 2007: 25:3259-65. BECOMING A PHYSICIAN 3. Hammond KR, Adelman L. Science, val- ues, and human judgment. Science 1976394: 389.96. 4. Thompson I. Thrasher J13, Aus G. et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol 2007:177:2106-31. 5. National Comprehensive Cancer Network. NCCN guidelines for patients: prostate cancer. 2015 (http://www.nanorgipatients/ guidelines/prostate). DOI: 10.1056/NEJMp1504245 Conner 0 201$ LAnscclurtats Math? SCOOT, Breaking the Silence of the Switch — Increasing Transparency about Trainee Participation in Surgery Chryssa McAlister, M.D. W e stand and swap operating- room chairs, soundless in our socked feet. The room is si- lent as I run through the steps at the microscope: corneal in- cisions, viscoelastics, capsulo- rhexis — the tearing with for- ceps of a small circular hole in the anterior capsule to gain ac- cess to the lens. I breathe shal- lowly, trying to avoid making a sound with each inhale and ex- hale; the casual chit-chat com- mon in operating rooms is con- spicuously absent. I am relieved to hear the ding and musical crescendos of the phacoemul- sification machine as it uses fluid and ultrasound to remove the cataract fragments. Silence returns as I insert the new lens and complete the final steps of the procedure. Then Dr. X nudges me aside to remove the speculum that holds open the eyelids and she pulls off the sterile drape cow ering the patient's face, which also prevents him from seeing. "All done," says Dr. X. "Every- thing went well." She smiles, placing a shield over the patient's left eye, and he is wheeled out. Dr. X turns to me. "Well done," she says. She gives me a few tips on how to "chop" the lens more efficiently and grabs the next chart. Not all attending eye surgeons expect trainees to operate in si- lence, but many ophthalmology residents experience some varia- tion on this scenario. Some sur- geons speak openly as residents operate, and others even berate trainees for their technique, with little regard for patients' percep- tions. l never minded such tongue lashings; rather, I always dreaded the silent switch. The miming, soundless communication over the top of a fully alert patient is clearly deceptive and seems direct- ly at odds with the trust required in a good physician—patient rela- tionship. The problem of undisclosed trainee participation in care is not unique to ophthalmology — it is relevant to physicians train- ing to perform procedures of all kinds. A qualitative study of Canadian surgeons in multiple specialties revealed a lack of dis- closure to patients of the details of intraoperative participation by residents,' and surgery residents express moral angst over patients' lack of awareness of their role. It's relatively easy to keep the concept of resident participation abstract if a patient will be asleep or sedated during a procedure or if it must be performed by a team rather than an individual sur- geon. The resident's role is more evident, however, in single-oper- ator procedures such as cataract surgery, as an alert patient lies on the table waiting for someone to cut open his or her eye. The minimal sedation used forces the surgeon to either fully disclose the trainee's involvement or overt- ly deceive the patient to some de- N ENGL) 372:26 NEJ1A.ORG JUNE 25, 2015 The New England Journal of Medicine Downloaded from ncjm.org on June 30, 2015. For personal use only. No other uses without pemtission. Copyright 0 2015 Massachusetts Medical Society. All rights reserved. 2477 EFTA_R1_02147857 EFTA02715652