Postmarket sequential database surveillance of medical products

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 193-212).This dissertation focuses on the capabilities of a novel public health data system - the Sentinel System - to supplement existing postmarket surveillance systems of the U.S. Food and Drug Administration (FDA). The Sentinel System is designed to identify and assess safety risks associated with drugs, therapeutic biologics, vaccines, and medical devices that emerge post-licensure. Per the initiating legislation, the FDA must complete a priori evaluations of the Sentinel System's technical capabilities to support regulatory decision-making. This research develops qualitative and quantitative tools to aid the FDA in such evaluations, particularly with regard to the Sentinel System's novel sequential database surveillance capabilities. Sequential database surveillance is a "near real-time" sequential statistical method to evaluate pre-specified exposure-outcome pairs. A "signal" is detected when the data suggest an excess risk that is statistically significant. The qualitative tool - the Sentinel System Pre- Screening Checklist - is designed to determine whether the Sentinel System is well suited, on its face, to evaluate a pre-specified exposure-outcome pair. The quantitative tool - the Sequential Database Surveillance Simulator - allows the user to explore virtually whether sequential database surveillance of a particular exposure-outcome pair is likely to generate evidence to identify and assess safety risks in a timely manner to support regulatory decision-making. Particular attention is paid to accounting for uncertainties including medical product adoption and utilization, misclassification error, and the unknown true excess risk in the environment. Using vaccine examples and the simulator to illustrate, this dissertation first demonstrates the tradeoffs associated with sample size calculations in sequential statistical analysis, particularly the tradeoff between statistical power and median sample size. Second, it demonstrates differences in performance between various surveillance configurations when using distributed database systems. Third, it demonstrates the effects of misclassification error on sequential database surveillance, and specifically how such errors may be accounted for in the design of surveillance. Fourth, it considers the complexities of modeling new medical product adoption, and specifically, the existence of a "dual market" phenomenon for these new medical products. This finding raises non-trivial generalizability concerns regarding evidence generated via sequential database surveillance when performed immediately post-licensure.by Judith C. Maro.Ph.D

Centers for Disease Control and Prevention transition briefing book

The Centers for Disease Control and Prevention (CDC) is pleased to present the 2016-2017 Presidential Transition Owner's Manual. CDC is the nation's health protection agency. CDC works 24/7 to conduct critical science and provides health information that protects our nation against dangerous health threats, and responds when these arise. CDC promotes quality of life and prevents the leading causes of disease, injury, disability, and death. CDC is committed to maximizing the impact of every dollar entrusted to the agency and continuing critical work to increase public health capacity at local, state, national, and global levels.CDC's pledge to the American people is to:1. Be a diligent steward of the funds entrusted to the agency2. Provide an environment for intellectual and personal growth and integrity3. Base all public health decisions on the highest quality scientific data that is derived openly and objectively4. Place the benefits to society above the benefits to this institution5. Treat all persons with dignity, honesty, and respec

Annual Report of the University, 2001-2002, Volumes 1-4

VITAL ACADEMIC CLIMATE* by Brian Foster, Provost/Vice President of Academic Affairs A great university engages students and faculty fully in important ideas and issues ... not just to learn about them, but to take them apart and put them back together, to debate, deconstruct, resist, reconstruct and build upon them. Engagement of this sort takes concentration and commitment, and it produces the kind of discipline and passion that leads to student and faculty success and satisfaction in their studies, research, performance, artistic activity and service. It is also the kind of activity that creates a solid, nurturing spirit of community. This is what we mean when we talk about a vital academic climate. We are striving for an environment that will enrich the social, cultural and intellectual lives of all who come in contact with the University. Many things interconnect to make this happen: curriculum, co-curricular activities, conferences, symposia, cultural events, community service, research and social activity. Our goal is to create the highest possible level of academic commitment and excitement at UNM. This is what characterizes a truly great university. *Strategic Direction 2 New Mexico native Andres C. Salazar, a Ph.D. in electrical engineering from Michigan State University, has been named the PNM Chair in Microsystems, Commercialization and Technology. Carrying the title of professor, the PNM Chair is a joint appointment between the School of Engineering and the Anderson Schools of Management. Spring 2002 graduate John Probasco was selected a 2002 Rhodes Scholar, the second UNM student to be so honored in the past four years. The biochemistry major from Alamogordo previously had been awarded the Goldwater Scholarship and the Truman Scholarship. Andres c. Salazar Biology student Sophie Peterson of Albuquerque was one of 30 students nationwide to receive a 2002-2003 Award of Excellence from Phi Kappa Phi, the oldest and largest national honor society. Regents\\u27 Professor of Communication and Journalism Everett M. Rogers was selected the University\\u27s 4 71h Annual Research Lecturer, the highest honor UNM bestows upon members of its faculty. John Probasco honored by Student Activities Director Debbie Morris. New Mexico resident, author and poet Simon}. Ortiz received an Honorary Doctorate of Letters at Spring Commencement ceremonies. Child advocate Angela Angie Vachio, founder and executive director of Peanut Butter and Jelly Family Services, Inc., was awarded an Honorary Doctorate of Humane Letters. American Studies Assistant Professor Amanda}. Cobb won the 22 d annual American Book Award for listening to Our Grandmothers\\u27 Stories: The Bloomfield Academy for Chickasaw Females, 1852-1949

On the Fundamentals of Law and Public Policy

We subsist under the law where we claim our rights and are obliged to do something enforced. What is a law? The question would be perplexing in history, and one of crucial themes with many lawyers or legal philosophers. As we know, two most important perspectives had earned a universal and historical forge in academics, to say, the natural law and legal positivism. The concept of natural law deals in its primacy for the humanity and natural order which often can be traded as something inviolable or inalienable. The concept has strands in several aspects; (i) its anchor with the civil democratic revolution around 17 and 18 centuries (ii) its supremacy with the new constitutional states (iii) less quality as a realist law from ambiguities and lack of clear definition. The concept of public policy may be related with the social justice, ethics and administration. It generally pursues a justice and desired state of public or community where the tension and conflict always exist between the ruling class and citizens. Historically, the public policy could be mightier to address the society than law where the benevolent Kings or Sovereigns liked to address both their needs and social justice. They may abrogate, more in endowment and divinity, the laws or social customs. The tension between the public power and private interests could be one reason as well as offers a good dualism in understanding the rule of law concept and advent of modern democracy. In this dimension, the King would no longer be divine nor entitled to exercise a plenary power of state rule. Instead, the popular sovereignty in the US democracy or parliamentary type in the UK were to be established to resolve a feudal conflict within the class and society. Lighted to be in vein of influence could arise the two contexts which are a contractarian view and plutocracy desire of the founding fathers. They underlay the mood and philosophical ethos of US revolution. Hence, three concepts as a pillar in private law were sanctified in the very foundation of US constitutional state, sanctity of property right, freedom of contract and due limits for the civil liability. The governmental power should be limited to protect the life and limb of citizens which addressed the Hobbes’ evil, “war against all the rest.” The due process concept was expressed as a fundamental principle of constitution where the human rights are inviolable and inalienable. The separation of powers principle could serve the freedom and wealth of new civil class in the continent, and bicameralism was devised for the check and balance within the federal congress. They see the role of judicial branch is important to preserve their civil interest. Then we can derive some assumptions between the law and public policy. First, a law plays to protect the private interest while the public policy pursues the social justice and mediates the competing interests, “private v. private” and “public v. private.” The civil courts may address a first nature of conflict and the law of takings or regulatory laws may deal with the second aspect. Second, the public or administrative law can shape a legal plane of bureaucracies or public administration, and may guarantee the rule of law ideals. It plays as an enabling authority and, on the other, monitors an arbitrariness and unfairness in the bureaucratic government. In this context, the unresponsive and unfathomable bureaucracy in the Kafka’s could be remedied. Third, for the welfare state in the late 19th and 20th century, a law can well be seen as one of authoritative expression of public policy to redress the evils of capitalist states. Some public laws, such as the Sherman Act classically and Lanham Act recently, may act to regulate the monopoly or oligopoly while other laws were enacted to restore justice between the labor and employers. Through the chapters, the fundamentals of law and public policy will be considered to address their proper status

Background Examples of Literature Searches on Topics of Interest

A zip file of various literature searches & some resources related to our work related to exposure after the Chernobyl accident and as we began looking at helping in Semey Kazakhstan----a collection of literature reviews on various topics we were interested in... eg. establishing a registry of those exposed for longterm follow-up, what we knew about certain areas like genetics and some resources like A Guide to Environmental Resources on the Internet by Carol Briggs-Erickson and Toni Murphy which could be found on the Internet and was written to be used by researchers, environmentalists, teachers and any person who is interested in knowing and doing something about the health of our planet. See more at https://archives.library.tmc.edu/dm-ms211-012-0060

Opioid Analgesic Prescribing and Overdose Mortality in North Carolina

Mortality from drug overdose has risen since the 1990s. Composite International Classification of Disease (ICD-10) overdose definitions in state vital statistics surveillance may include deaths that do not involve controlled substances while missing deaths that do. We evaluated seven ICD-10-based definitions using North Carolina mortality data from 2008 through 2011. Overdose deaths varied by definition, ranging from 734 to 1,202 per year. Up to 16.1% of deaths using the national definition showed no evidence of controlled substance involvement, however, additional deaths involving controlled substances were not identified. We propose a definition that includes deaths from substance use disorders, but removes deaths from pharmaceutical adverse events, resulting in 1,149 deaths per year from overdoses involving controlled substances. Strong associations have been observed between amount of opioids dispensed and overdose mortality. Yet, clinical trials consistently show safety of opioid analgesics at high doses. To explore this paradox we conducted a prospective cohort study among North Carolina residents in 2010 to quantify dose-dependent overdose risk in routine clinical practice. Dispensing data were matched to overdose deaths identified in medical examiner records. Incidence rates were estimated using regression models. Exposure of 1,133,957 person-years to opioid analgesics was observed, corresponding to 22.8% of residents. Incidence rates appeared to increase gradually at lower doses, but stayed elevated beyond 200 mg average daily milligrams of morphine equivalents. The dose-dependent effect was exacerbated by co-prescribed central nervous system (CNS) depressants; rates were ten times higher among opioid analgesic patients receiving benzodiazepines. Since 80% of patients were co-prescribed benzodiazepines, high dose opioid analgesic use during routine clinical practice was more risky than observed in trials that exclude patients receiving other CNS depressants. Exploring formulation impacts, incidence rates were ten times greater among those receiving combinations of extended-release (ER) and immediate-release (IR) opioid analgesics compared to those receiving only IR. At higher doses, for every 1,300 patients treated for a year with ER instead of IR, there would be one additional overdose death. As a society we urgently need to understand what level of prescribing would strike the correct balance between access to care concerns and inadequately trained physicians.Doctor of Philosoph

The Nurse Manager: An Ethnography of Hospital-Based First-Line Nurse Managers Practicing in an Expanded Role

The behaviors, beliefs and values that characterize everyday practice of first-line nurse managers role were analyzed. Ethnographic field research techniques were used including nine months of observation and in-depth interviews with practicing nurse managers. After reviewing historical events that shaped the role of the nurse manager, the role was then placed within the economic, social and health care context of the 1970\u27s and 80\u27s. Research and anecdotal descriptions of the manager role of the past twenty years were also explored. Research was conducted in two voluntary acute care, multi-service hospitals. One manager was observed intensively for two months to develop a semi structured open-ended interview guide. The guide was then used to conduct extensive ethnographic interviews with 16 inpatient managers. In addition, six nurse administrators were interviewed, institutional documents examined and a variety of techniques used to triangulate observations and theories that emerged and to examine issues of validity and reliability. Managers described their role as four processes: (1) social control, establishing, monitoring and maintaining standards; (2) resourcing, the provision of emotional support, goods and services; (3) translating/ interpreting/negotiating among unit-based or related constituencies; and, (4) facilitating change. Administrators concurred with the managers\u27 descriptions emphasizing social control. Managers described themselves as desiring control/power to make beneficial changes; being stimulated by a changing work environment and deriving satisfaction from staff development. They identified essential skills for role enactment as communication/interpersonal expertise, clinical knowledge, flexibility, a strong ego and political savvy. The study then examined how managers analyze the complexity of change, alter their management strategies accordingly and create a working culture that is maximally adaptable to an unstable health care environment. They identified ways to enhance success and avoid or respond to failure, using knowledge acquired primarily through experience. Finally, the study examined the common culture of nursing management within the context of its historical roots, particularly the necessity for a bicultural identity that incorporates beliefs and values of both manager/employee and professional clinician/nurse. Structured mentoring was explored as a bridging strategy to enhance enculturation and skill acquisition

Ways of Being in Trauma-Based Society: Discovering the Politics and Moral Culture of the Trauma Industry Through Hermeneutic Interpretation of Evidence-Supported PTSD Treatment Manuals

One hundred percent of evidence-supported psychotherapy treatments for trauma related disorders involve the therapist learning from and retaining fidelity to a treatment manual. Through a hermeneutic qualitative textual interpretation of three widely utilized evidence-supported trauma treatment manuals, I identified themes that suggested a particular constitution of the contemporary way of being—a traumatized self—and how this traumatized self comes to light through psychotherapeutic practice as described by the manuals. The manuals included: 1) a trauma focused cognitive-behavioral therapy for children; 2) an eye-movement desensitization and reprocessing therapy for adults; and, 3) an early intervention and debriefing therapy series for post-traumatic stress disorder and other trauma related problems of military service members. Through the interpretation, I conceptualized trauma as a way of human being in contemporary culture, and in particular, as an unacknowledged way of expressing enactments of dissociated, unformulated, or unarticulated political arrangements and events. I identified and interpreted the following shared themes and exemplars across the three manuals: mind-brain as protector and the political use of cognitivist ideology; the healed trauma survivor as functional worker; trauma as universal and culture-free; and, indoctrination into a social void of scientistic managed care. I discussed how trauma treatment manuals instantiate how to be human in contemporary society through compliance with managed care and the embodiment of scientistic and cognitivist ideology. I then discussed how the way of being that contemporary society creates and idealizes is one in which people easily assume the identity of trauma survivor: an enterprising, functional and fiercely individual member of a warrior cult. In the warrior cult society, to think or talk about social causes and public solutions to daily political suffering is thought of as either non-germane or dangerous; individuals are seen as free from all dependencies and social ties, able to overcome personal and public adversity by arming or forifying their brain and replacing thoughts in their computer-like mind. In conclusion, I raised questions about how evidence-based trauma therapies may contribute to perpetuating a particular constitution of self that has disavowed society’s violent ethics and practice