EFTA02715650.pdf

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