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are at NEJM.org The FDa has recently released given to drugs in development, it From the Center for Drug Evaluation and draft guidance on expedited pro- will be some time before the pro- Silver spring, MD dru ditions, including the break- tant therapies can be assessed. 1.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, 2013PERSPECTIVE 1880 n engl j med 369;20 nejm.org november 14, 2013 Expediting Drug Development in application of the accelerated￾approval pathway and clarified the use of an intermediate clini￾cal end point as a basis for ac￾celerated 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 pro￾grams for drugs for serious con￾ditions, including the break￾through-therapy designation.1 The draft guidance outlines the qual￾ifying 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 des￾ignation program is of great in￾terest to patients and patient ad￾vocates. Because designations are given to drugs in development, it will be some time before the pro￾gram’s effect on access to impor￾tant therapies can be assessed. This program may represent the initiation of a new paradigm for investigational drugs undergoing development in a setting of ex￾tensive mechanistic understand￾ing of disease pathogenesis. As the pace of scientific discovery continues to increase, drug-devel￾opment 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 pro￾grams 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 accu￾rate, since we were accus￾tomed 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 disheart￾ened. We were simply appalled. We met Tommy Davis in our hospital’s clinic for indigent per￾sons in March 2013 (the name and date have been changed to protect the patient’s privacy). He and his wife had been chroni￾cally uninsured despite working full-time jobs and were now fac￾ing disastrous consequences. The week before this appoint￾ment, Mr. Davis had come to our emergency department with ab￾dominal 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 sim￾ilar symptoms and visited a pri￾mary care physician, who had tak￾en a cursory history, told Mr. Davis he’d need insurance to be ade￾quately 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 obstruct￾ed 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 evalua￾tion. 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 gnaw￾ing suspicion that he had cancer. “If we’d found it sooner,” he con￾tended, “it would have made a dif￾ference. But now I’m just a dead man walking.” For many of our patients, pov￾erty 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 be￾cause 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 re￾sponse to this problem has, at times, seemed toothless. In our clinic, uninsured patients frequently find necessary care un￾obtainable. An obese 60-year-old woman with symptoms and signs of congestive heart failure was re￾cently evaluated in the clinic. She couldn’t afford the echocardio￾gram and evaluation for ischemic heart disease that most internists would have ordered, so furose￾mide treatment was initiated and adjusted to relieve her symptoms. This past spring, our colleagues saw a woman with a newly dis￾covered 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