PERSPECTIVE HE RANDOMIZED REGISTRY TRIAL prominent role Will registry data Scandinavia, in places where be possible to design and conduct (or data coming from other digi- health care and clinical data are megatrials with what we have al sources, such as electronic fragmented and of lower quality? bigger data and smaller budgets health records) be of high enough Some American investigators are Yet we must also recognize and quality? Will too many data fields already using the approach (e. g, acknowledge the daunting chal- be missing? How will we balance the Study of Access Site for En- lenges that diverse groups of re- we transition single registries nary Intervention for Women; overcome to get there ders must efficacy versus effectiveness? Can hancement of Percutaneous Coro- searchers and stakehe from efficacy to effectiveness, NCTo1406236) But even if we can The view ssed in this article are making it possible to assess ex- perform many more randomized those of the authors and do not necessarily ternal validity much more expedi- registry trials in the United States, tional Heart, Lung, and Blood Institute. Dr tiously than we do now? What are we must recognize that the ap- Lauer is the National Institutes of Health lations to study? How will we ap- lems we have with trials. For tee ot the tate pcortered ne of ome iwe roach concerns about privacy certain kinds of trials, such as expressed here represent those of PCORI or and informed consent (particu- metabolic efficacy studies that its Methodology Committee larly in the context of trials that focus on complex physiologic and closure forms provided by the authors are available with the full text of this article compare acceptable standards of metabolic pathways hypothesized at NEJM.org care and use cluster-randomiza- to respond to changes in diet or ble?Will researchers be able to agents, current organizational Cardiovascular Sciences, the Natons o tion methods)? Is blinding possi- to experimental pharmacologic From the Office of the Director, Division of Heart, Lung, and Blood Institute, Bethesda obtain long-term follow-up or structures would probably work MD(MSL); and the Mathematics and Sta- measure composite outcomes? much better with only minor tistics Department, Boston University, and How will we standardize and ad- modifications judicate certain outcomes? Can The randomized registry trial that even within a registry there a technology that transforms ex- 2013, at NE/M.org. hed on September I we assure representativeness, given represents a disruptive technology, This article was published on September may be systematic differences be- isting standards, procedures, and tween patients who are and are cost structures. Will it be given 1. Antman EM, Harrington RA Transform not eligible for randomization or serious consideration as a way to mission critical for health and economic between those who do or do not resolve the recognized limitations well-being. JAMA 2012:308: 1743.4 2. Pocock S), Elbourne DR Randomized tri- consent of current clinical-trial design? als or observational tribulations? N Engl J These are only some of the Theodore Roosevelt once said, Med 2000:342: 1907-9 problems we will have to address. "Do what you can, with what you 3. Frobert o, Lagergvist B, Gudnason The TASTe trial was performed have, where you are. " Today we myocardial infarction in Scandinavia(TASTE Scand afford care and information technology randomized effectiveness trials ized, controlled clinical registry trial based environments are markedly dif. that cost tens or hundreds of mil- ty Registry(SCAAR)platform: study design ferent from those elsewhere in lions of dollars. But today we alse the world. Can randomized regis- have registries and other power- Dol: 10.1056/NEJMp1310102 try trials be undertaken outside ful digital platforms. Today it may Copyright o 2013 Massachusetts Medical. Smoothing the Way to High Quality, Safety, and Economy Eugene Litvak, Ph. D, and Harvey V. Fineberg, M. D, Ph D n recent years, health care in- aid Services is implementing fections associated with ventila- have awakened to multiple incentives and penalties tors or central venous catheters the need to provide safe, high- intended to help realize this have had demonstrated success quality care at lower cost. The goal. For example, innovations We believe that greater attention Centers for Medicare and Medic- designed to reduce the rate of in- to a frequently overlooked param- N ENGLJ MED 369: 17 NEJM.ORG OCTOBER 24, 2013n engl j med 369;17 nejm.org october 24, 2013 PERSPECTIVE 1581 The Randomized Registry Trial prominent role. Will registry data (or data coming from other digi￾tal sources, such as electronic health records) be of high enough quality? Will too many data fields be missing? How will we balance efficacy versus effectiveness? Can we transition single registries from efficacy to effectiveness, making it possible to assess ex￾ternal validity much more expedi￾tiously than we do now? What are the best populations or subpopu￾lations to study? How will we ap￾proach concerns about privacy and informed consent (particu￾larly in the context of trials that compare acceptable standards of care and use cluster-randomiza￾tion methods)? Is blinding possi￾ble? Will researchers be able to obtain long-term follow-up or measure composite outcomes? How will we standardize and ad￾judicate certain outcomes? Can we assure representativeness, given that even within a registry there may be systematic differences be￾tween patients who are and are not eligible for randomization or between those who do or do not consent? These are only some of the problems we will have to address. The TASTE trial was performed in Scandinavia, where the health care and information technology environments are markedly dif￾ferent from those elsewhere in the world. Can randomized regis￾try trials be undertaken outside Scandinavia, in places where health care and clinical data are fragmented and of lower quality? Some American investigators are already using the approach (e.g., the Study of Access Site for En￾hancement of Percutaneous Coro￾nary Intervention for Women; NCT01406236). But even if we can perform many more randomized registry trials in the United States, we must recognize that the ap￾proach cannot solve all the prob￾lems we have with trials. For certain kinds of trials, such as metabolic efficacy studies that focus on complex physiologic and metabolic pathways hypothesized to respond to changes in diet or to experimental pharmacologic agents, current organizational structures would probably work much better with only minor modifications. The randomized registry trial represents a disruptive technology, a technology that transforms ex￾isting standards, procedures, and cost structures. Will it be given serious consideration as a way to resolve the recognized limitations of current clinical-trial design? Theodore Roosevelt once said, “Do what you can, with what you have, where you are.” Today we can no longer afford to undertake randomized effectiveness trials that cost tens or hundreds of mil￾lions of dollars. But today we also have registries and other power￾ful digital platforms. Today it may be possible to design and conduct megatrials with what we have: bigger data and smaller budgets. Yet we must also recognize and acknowledge the daunting chal￾lenges that diverse groups of re￾searchers and stakeholders must overcome to get there. The views expressed in this article are those of the authors and do not necessarily represent the official positions of the Na￾tional Heart, Lung, and Blood Institute. Dr. Lauer is the National Institutes of Health representative on the Methodology Commit￾tee of the Patient-Centered Outcomes Re￾search Institute (PCORI); none of the views expressed here represent those of PCORI or its Methodology Committee. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. From the Office of the Director, Division of Cardiovascular Sciences, the National Heart, Lung, and Blood Institute, Bethesda, MD (M.S.L.); and the Mathematics and Sta￾tistics Department, Boston University, and the Harvard Clinical Research Institute — both in Boston (R.B.D.). This article was published on September 1, 2013, at NEJM.org. 1. Antman EM, Harrington RA. Transform￾ing clinical trials in cardiovascular disease: mission critical for health and economic well-being. JAMA 2012;308:1743-4. 2. Pocock SJ, Elbourne DR. Randomized tri￾als or observational tribulations? N Engl J Med 2000;342:1907-9. 3. Fröbert O, Lagerqvist B, Gudnason T, et al. Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial): a multicenter, prospective, random￾ized, controlled clinical registry trial based on the Swedish Angiography and Angioplas￾ty Registry (SCAAR) platform: study design and rationale. Am Heart J 2010;160:1042-8. DOI: 10.1056/NEJMp1310102 Copyright © 2013 Massachusetts Medical Society. Smoothing the Way to High Quality, Safety, and Economy Eugene Litvak, Ph.D., and Harvey V. Fineberg, M.D., Ph.D. I n recent years, health care in￾stitutions have awakened to the need to provide safe, high￾quality care at lower cost. The Centers for Medicare and Medic￾aid Services is implementing multiple incentives and penalties intended to help realize this goal. For example, innovations designed to reduce the rate of in￾fections associated with ventila￾tors or central venous catheters have had demonstrated success. We believe that greater attention to a frequently overlooked param-