PERSPECTIVE EXPEDITING DRUG DEVELOPMENT in application of the accelerated- drugs, and it describes features ing of disease pathogenesis. As approval pathway and clarified of the program that are intended the pace of scientific discovery the use of an intermediate clini- to streamline drug development continues to increase, drug-devel cal end point as a basis for ac- for highly promising agents. opment pathways will need to elerated approval. In Table 2, we he breakthrough-therapy des- evolve in parallel compare the qualifying criteria ignation program is of great in- Disclosure forms provided by the authors and features of each of the four terest to patients and patient ad- are available with the full text of this article expedited program vocates. Because designations are at NEJM.org The FDa has recently released given to drugs in development, it From the Center for Drug Evaluation and draft guidance on expedited pro- will be some time before the pro- Silver spring, MD dru ditions, including the break- tant therapies can be assessed. 1. Guidance for industry: expedited through-therapy designation 1 The This program may represent the grams to siever s con m ood arug s an draftguidanceoutlinesthequalinitiationofanewparadigmforAdministration(http://www.da.govDrugs ifying criteria and the process for investigational drugs undergoing requesting a breakthrough-therapy development in a setting of ex- DO: 10.1056/NEJR designation for investigational tensive mechanistic understand- Copyright 21311439 husetts Medical Society. Dead Man Walking Michael Stillman, M.D. and Monalisa Tailor. M. D. << C hocked"wouldn,'t be accu- ilar symptoms and visited a pri- afford bus fare to a dermatology Urate, since we were accus- mary care physician, who had tak- appointment. We sometimes pay tomed to our uninsured patients' en a cursory history, told Mr. Davis for our patients'medications be- receiving inadequate medical care. he'd need insurance to be ade- cause they are unable to cover even "Saddened"wasn't right, either, quately evaluated, and billed him a $4 copayment. But a fair number only pecking at the edge of our $200 for the appointment. Since of our patients- the medical response. And "disheartened"just Mr Davis was poor and ineligible "have-nots"-are denied basic smacked of victimhood. After for Kentucky Medicaid, however, services simply because they lack hearing this story, we were neither he'd simply used enemas until he insurance, and our country's re shocked nor saddened nor disheart. was unable to defecate. By the sponse to this problem has, at ened. We were simply appalled. time of his emergency department times, seemed toothless We met Tommy Davis in our evaluation, he had a fully obstruct- In our clinic, uninsured patients hospital's clinic for indigent per- ed colon and widespread disease frequently find necessary care un sons in March 2013(the name and chose to forgo treatment. and date have been changed to Mr. Davis hadhad an inkling woman with symptoms and signs protect the patient's privacy). He that something was awry, but he'd of congestive heart failure was re and his wife had been chroni- been unable to pay for an evalua- cently evaluated in the clinic. She cally uninsured despite working tion. As his wife sobbed next to couldn't afford the echocardio full-time jobs and were now fac- him in our examination room, he gram and evaluation for ischemic ing disastrous consequences recounted his months of weight heart disease that most internists The week before this appoint- loss, the unbearable pain of his would have ordered, so furose ment, Mr. Davis had come to our bowel movements, and his gnaw- mide treatment was initiated and emergency department with ab- ing suspicion that he had cancer. adjusted to relieve her symptoms dominal pain and obstipation. His "If we'd found it sooner, "he con- This past spring, our colleagues examination, laboratory tests, and tended, "it would have made a dif- saw a woman with a newly dis CT scan had cost him $10,000 ference. But now I'm just a dead covered lung nodule that was (his entire life savings), and at man walking highly suspicious for cancer. She evenings end he'd been sent home For many of our patients, pov- was referred to a thoracic surgeon, with a diagnosis of metastatic erty alone limits access to care. but he insisted that she first have colon We recently saw a man with aids a PET scan -a test for which The year before, he'd had sim- and a full-body rash who couldnt she couldn,'t possibly pay N ENGLJ MED 369: 20 NEJM.ORG NOVEMBER 14, 2013
PERSPECTIVE 1880 n engl j med 369;20 nejm.org november 14, 2013 Expediting Drug Development in application of the acceleratedapproval pathway and clarified the use of an intermediate clinical end point as a basis for accelerated approval. In Table 2, we compare the qualifying criteria and features of each of the four expedited programs. The FDA has recently released draft guidance on expedited programs for drugs for serious conditions, including the breakthrough-therapy designation.1 The draft guidance outlines the qualifying criteria and the process for requesting a breakthrough-therapy designation for investigational drugs, and it describes features of the program that are intended to streamline drug development for highly promising agents. The breakthrough-therapy designation program is of great interest to patients and patient advocates. Because designations are given to drugs in development, it will be some time before the program’s effect on access to important therapies can be assessed. This program may represent the initiation of a new paradigm for investigational drugs undergoing development in a setting of extensive mechanistic understanding of disease pathogenesis. As the pace of scientific discovery continues to increase, drug-development pathways will need to evolve in parallel. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. From the Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD. 1. Guidance for industry: expedited programs for serious conditions — drugs and biologics. Silver Spring, MD: Food and Drug Administration (http://www.fda.gov/Drugs/ GuidanceComplianceRegulatoryInformation/ Guidances/default.htm). DOI: 10.1056/NEJMp1311439 Copyright © 2013 Massachusetts Medical Society. Dead Man Walking Michael Stillman, M.D., and Monalisa Tailor, M.D. “Shocked” wouldn’t be accurate, since we were accustomed to our uninsured patients’ receiving inadequate medical care. “Saddened” wasn’t right, either, only pecking at the edge of our response. And “disheartened” just smacked of victimhood. After hearing this story, we were neither shocked nor saddened nor disheartened. We were simply appalled. We met Tommy Davis in our hospital’s clinic for indigent persons in March 2013 (the name and date have been changed to protect the patient’s privacy). He and his wife had been chronically uninsured despite working full-time jobs and were now facing disastrous consequences. The week before this appointment, Mr. Davis had come to our emergency department with abdominal pain and obstipation. His examination, laboratory tests, and CT scan had cost him $10,000 (his entire life savings), and at evening’s end he’d been sent home with a diagnosis of metastatic colon cancer. The year before, he’d had similar symptoms and visited a primary care physician, who had taken a cursory history, told Mr. Davis he’d need insurance to be adequately evaluated, and billed him $200 for the appointment. Since Mr. Davis was poor and ineligible for Kentucky Medicaid, however, he’d simply used enemas until he was unable to defecate. By the time of his emergency department evaluation, he had a fully obstructed colon and widespread disease and chose to forgo treatment. Mr. Davis had had an inkling that something was awry, but he’d been unable to pay for an evaluation. As his wife sobbed next to him in our examination room, he recounted his months of weight loss, the unbearable pain of his bowel movements, and his gnawing suspicion that he had cancer. “If we’d found it sooner,” he contended, “it would have made a difference. But now I’m just a dead man walking.” For many of our patients, poverty alone limits access to care. We recently saw a man with AIDS and a full-body rash who couldn’t afford bus fare to a dermatology appointment. We sometimes pay for our patients’ medications because they are unable to cover even a $4 copayment. But a fair number of our patients — the medical “have-nots” — are denied basic services simply because they lack insurance, and our country’s response to this problem has, at times, seemed toothless. In our clinic, uninsured patients frequently find necessary care unobtainable. An obese 60-year-old woman with symptoms and signs of congestive heart failure was recently evaluated in the clinic. She couldn’t afford the echocardiogram and evaluation for ischemic heart disease that most internists would have ordered, so furosemide treatment was initiated and adjusted to relieve her symptoms. This past spring, our colleagues saw a woman with a newly discovered lung nodule that was highly suspicious for cancer. She was referred to a thoracic surgeon, but he insisted that she first have a PET scan — a test for which she couldn’t possibly pay
PERSPECTIVE DEAD MAN WALKING However unconscionable we deliberate over whether to imple- Seventy percent of our clinic may find the story of Mr. Davis, ment health insurance exchanges patients have no health insurance, a U.S. citizen who will die because and expand Medicaid eligibility, and they are all frighteningly vul he was uninsured, the literature how can we as physicians ensure nerable; their care is erratic, they suggests that it's a common tale. that the needs of patients like Mr. are disqualified from receiving a 2009 study revealed a direct Davis are met certain preventive and screening correlation between lack of in First, we can honor our funda- measures, and their lack of re- surance and increased mortality mental professional duty to help. sources prevents them from par and suggested that nearly 45, 000 Some have argued that the onus ticipating in the medical system American adults die each year for providing access to health care And this is not a community-or because they have no medical rests on society at large rather state-specific problem. arecent coverage. 1 And although we cant than on individual physicians, study showed that underinsured confidently argue that Mr. Davis yet the Hippocratic Oath compels patients have higher mortality would have survived had he been us to treat the sick according to rates after myocardial infarction, 4 insured, research suggests that our ability and judgment and to and it is well documented that possibility; formerly uninsured keep them from harm and injus- our country's uninsured present adults given access to Oregon tice. Even as we continue to hope with later-stage cancers and more Medicaid were more likely than for and work toward a future in poorly controlled chronic diseases those who remained uninsured which all Americans have health than do patients with insurance.5 to have a usual place of care and insurance, we believe it's our indi- We find it terribly and tragically outpatient medical visits, and to to treat people in need onsibility inhumane that Mr Davis and tens a personal physician, to attend vidual professional resp of thousands of other citizens of receive recommended preventive Second, we can familiarize our- this wealthy country will die this care.2 Had Mr. Davis been in- selves with legislative details and year for lack of insurance. sured, he might well have been educate our patients ab e forms provided by the authors offered timely and appropriate posed health care reforms. with the full text of this article screening for colorectal cancer, our appointment with Mr. and his abdominal pain and ob- he worried aloud that under the stipation would surely have been AcA, "the government would tax sity of Louis ville school of Medicine, Louis. him for not having insurance. Elected officials bear a great He was unaware(as many of our deal of blame for the appalling vul- poor and uninsured patients may This article was published on October 23 nerability of the 22% of American be) that under that law's final rule 2013, at NEJM.org adults who currently lack insur- he and his family would meet the 1. wilper AP, Woolhandler S, Lasser KE, Mc (ACA)-the only legitimate legis- and hence have access to compre- Am]Public Health 2009 99:2289.95 lative attempt to provide near-uni- hensive and affordable care 2. Finkelstein A, Taubman S, Wright B, et al versal health coverage remains Finally, we can pressure our The Or health insurance experiment under attack from some members professional organizations to de- evidence from the first year.QJEcon 2012: of Congress, and our own two sen- mand health care for all. The 3. Huddle ts. Centor RM. retainer ators argue that enhancing mar- American College of Physicians, cine: an ethically legitimate form of ketplace competition and enacting the American Medical Association, that can improve primary care. Ann tort reform will provide security and the Society of General Internal ed2011:155:633- In discussing (and grieving ciple of universal health care cov- mortality after an D), Lau B Young JH enough for our nation,'s poo Medicine have endorsed the prin-In over)what has happened to Mr. erage yet have generally remained in Maryland. J Gen Intern Med 2012:27 1368 Davis and our many clinic patients silent during years of political 5. Institute of Medicine. America's unin- whose health suffers for lack of debate. Lack of insurance can be sur insurance, we have considered our lethal, and we believe our profes- National Academies Press, February 23 gations.Assomeconsionalcommunityshouldtreat2009(http://www.iom.edu/reports/2009/ gresspeople attempt to defund inaccessible coverage as a public Americas Uninsured Crisis.Consequences bamacare, and as some states' health catastrophe and stand be- for-Health-and-Health-Care. aspx) Do:10.1056/NEMp1312793 governors and attorneys general hind people who are at risk. Copyright @2013 Massachusetts Medical Society. N ENGL J MED 369: 20 NEJMO VEMBER 14, 2013 1881
n engl j med 369;20 nejm.org november 14, 2013 PERSPECTIVE 1881 However unconscionable we may find the story of Mr. Davis, a U.S. citizen who will die because he was uninsured, the literature suggests that it’s a common tale. A 2009 study revealed a direct correlation between lack of insurance and increased mortality and suggested that nearly 45,000 American adults die each year because they have no medical coverage.1 And although we can’t confidently argue that Mr. Davis would have survived had he been insured, research suggests that possibility; formerly uninsured adults given access to Oregon Medicaid were more likely than those who remained uninsured to have a usual place of care and a personal physician, to attend outpatient medical visits, and to receive recommended preventive care.2 Had Mr. Davis been insured, he might well have been offered timely and appropriate screening for colorectal cancer, and his abdominal pain and obstipation would surely have been urgently evaluated. Elected officials bear a great deal of blame for the appalling vulnerability of the 22% of American adults who currently lack insurance. The Affordable Care Act (ACA) — the only legitimate legislative attempt to provide near-universal health coverage — remains under attack from some members of Congress, and our own two senators argue that enhancing marketplace competition and enacting tort reform will provide security enough for our nation’s poor. In discussing (and grieving over) what has happened to Mr. Davis and our many clinic patients whose health suffers for lack of insurance, we have considered our own obligations. As some congresspeople attempt to defund Obamacare, and as some states’ governors and attorneys general deliberate over whether to implement health insurance exchanges and expand Medicaid eligibility, how can we as physicians ensure that the needs of patients like Mr. Davis are met? First, we can honor our fundamental professional duty to help. Some have argued that the onus for providing access to health care rests on society at large rather than on individual physicians,3 yet the Hippocratic Oath compels us to treat the sick according to our ability and judgment and to keep them from harm and injustice. Even as we continue to hope for and work toward a future in which all Americans have health insurance, we believe it’s our individual professional responsibility to treat people in need. Second, we can familiarize ourselves with legislative details and educate our patients about proposed health care reforms. During our appointment with Mr. Davis, he worried aloud that under the ACA, “the government would tax him for not having insurance.” He was unaware (as many of our poor and uninsured patients may be) that under that law’s final rule, he and his family would meet the eligibility criteria for Medicaid and hence have access to comprehensive and affordable care. Finally, we can pressure our professional organizations to demand health care for all. The American College of Physicians, the American Medical Association, and the Society of General Internal Medicine have endorsed the principle of universal health care coverage yet have generally remained silent during years of political debate. Lack of insurance can be lethal, and we believe our professional community should treat inaccessible coverage as a public health catastrophe and stand behind people who are at risk. Seventy percent of our clinic patients have no health insurance, and they are all frighteningly vulnerable; their care is erratic, they are disqualified from receiving certain preventive and screening measures, and their lack of resources prevents them from participating in the medical system. And this is not a community- or state-specific problem. A recent study showed that underinsured patients have higher mortality rates after myocardial infarction,4 and it is well documented that our country’s uninsured present with later-stage cancers and more poorly controlled chronic diseases than do patients with insurance.5 We find it terribly and tragically inhumane that Mr. Davis and tens of thousands of other citizens of this wealthy country will die this year for lack of insurance. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. From the Department of Medicine, University of Louisville School of Medicine, Louisville, KY. This article was published on October 23, 2013, at NEJM.org. 1. Wilper AP, Woolhandler S, Lasser KE, McCormick D, Bor DH, Himmelstein DU. Health insurance and mortality in US adults. Am J Public Health 2009;99:2289-95. 2. Finkelstein A, Taubman S, Wright B, et al. The Oregon health insurance experiment: evidence from the first year. Q J Econ 2012; 127:1057-106. 3. Huddle TS, Centor RM. Retainer medicine: an ethically legitimate form of practice that can improve primary care. Ann Intern Med 2011;155:633-5. 4. Ng DK, Brotman DJ, Lau B, Young JH. Insurance status, not race, is associated with mortality after an acute cardiovascular event in Maryland. J Gen Intern Med 2012;27:1368- 76. 5. Institute of Medicine. America’s uninsured crisis: consequences for health and health care. Consensus report. Washington, DC: National Academies Press, February 23, 2009 (http://www.iom.edu/Reports/2009/ Americas-Uninsured-Crisis-Consequences -for-Health-and-Health-Care.aspx). DOI: 10.1056/NEJMp1312793 Copyright © 2013 Massachusetts Medical Society. Dead Man Walking
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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission