The FDAThe FDA

The author of FDA: Inside and Out, Dr Suzanne Parisian, comes by her firsthand knowledge of the inside workings of the US Food and Drug Administration (FDA) through her years spent on the staff there. Dr Parisian served in a variety of positions that gave her familiarity with the overall objectives and day-to-day functioning of different sections within this large institution.

Parisian provides some interesting data about the FDA, which can be considered one of the nation's oldest consumer protection agencies. The FDA is charged by Congress with the protection of US consumers through enforcement of the requirement of the Federal Food, Drug and Cosmetic Act and several related public health laws.

To perform the Congressional mandate, FDA has some 1,100 investigators and inspectors that monitor and inspect the country's 95,000 FDA-regulated businesses. . . . FDA investigators and inspectors visit more than 15,000 facilities a year. As part of their inspections, they collect about 80,000 domestic and imported product samples for examination by FDA scientists for label checks. About 3,000 products per year are found to be unfit for consumers and are withdrawn from the marketplace. . . . In addition, about 30,000 import shipments a year are declined at the port of entry because the goods appear to be unacceptable for use in the United States.

The scientific expertise needed to back up FDA's legal cases and actions comes from the agency's 2,100 scientists, including 90 chemists and 300 microbiologists, who work in 40 laboratories in the Washington, DC area and around the country.

A large operation, indeed!

The purpose of this book, as stated by the author, is to provide a single resource that could describe the overall functioning and requirements of the FDA. As such, it should be of particular use to those planning to submit a product for review by the agency. The book contains separate and detailed chapters on the FDA overall, the Center for Food Safety and Applied Nutrition (CFSAN), CFSAN's regulation of cosmetics and colors, the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, the Center for Veterinary Medicine, the National Center of Toxicological Research, and the Center for Devices and Radiological Health and provides chapters specifically devoted to mechanical devices. The author also provides detailed information and advice on clinical trial organization including Institutional Review Boards; informed consent; responsibilities of the investigators, sponsors, and monitors; and study design, pitfalls, and application submission.

Included as a supplement are useful notes from a lecture Dr Parisian delivered to new FDA staff while at the agency. The text is also filled with details about the founding and history of the FDA and specific case reports of product evaluation, which make interesting reading for a more general medical audience. The reader who spends any significant amount of time perusing this book will learn something new about the FDA or some new approach to this complex organization that is so critical to safeguarding the foods and drugs we use daily.

This is an extremely readable, entertaining, and user-friendly manual of clinical trials prepared by two members of the Duke Clinical Research Institute, which is arguably the preeminent clinical research faculty in the country (no offense to my colleagues here at Harvard who may seize the title soon!). The authors state that they prepared this manual because there was no readily available resource to demystify the world of clinical research.

The title alludes to one of the many events that influenced the development of regulations affecting clinical research. In 1901 a horse named Jim was used to prepare an antitoxin for diphtheria. After the death of 13 children who received the antitoxin, authorities discovered that the horse had developed tetanus and therefore contaminated the antitoxin. As a result of this tragedy, Congress passed the Biologic Control Act of 1902, giving the government regulatory power over antitoxin and vaccine development.

As someone who has recently found the need to become more conversant in this area, I can readily confirm the difficulty of finding readable and comprehensive surveys of the clinical research field. Therefore, I am pleased to report that Liu and Davis have been successful in their effort and have prepared a volume that can be perused from cover to cover in 3 to 4 hours, even by a relatively uninitiated reader such as myself.

The first half of the manual is organized into chapters that provide the historical framework, rules and regulations, definitions, and necessary oversight of clinical trials. These chapters follow a logical pattern of progressively and entertainingly introducing the reader to the nuances of clinical trials. The text is generously supplemented by explanatory illustrations and boxes containing summaries of the important points.

The remaining chapters focus on how clinical trials are conducted at the investigative sites, with an emphasis on the practical applications of the information presented in the first half of the manual. These later chapters not only give tips on organizing and conducting clinical trials at the site, but also provide examples of forms and documents that might be used in a clinical trial.

The manual concludes with six useful appendices that include, along with a variety of procedures and forms, the World Medical Association Declaration of Helsinki, the Belmont Report (Ethical Principles and Guidelines for the Protection of Human Subjects of Research), and the complete consolidated guidelines from the Federal Register on Good Laboratory Practice. Thus, there is something in this manual for everyone (nurse, doctor, technician, medical student, and curious lay person). Each chapter is referenced with pertinent articles, many of which are accessible through Web sites and therefore immediately accessible to the reader interested in obtaining more detail.

While this manual may lack some depth on certain aspects of medical research, I have yet to find a more comprehensive and readable book on clinical trials. The authors have done a wonderful job and have provided a commendable service to the medical community. They state that they use this manual for their staff to quickly and accurately find information related to the proper conduct of clinical trials. I now understand how the Duke Clinical Research Institute maintains top billing in the field. Its secrets are revealed in this manual, which I highly recommend.

Say Little, Do Much addresses the contributions to nursing in the 19th century by vowed women of various religious orders. ("Vowed women" is a generic term for nuns, sisters, and deaconesses, who, as described by the author, are "women who separated themselves from the rest of the world to live in a community according to a set of religious precepts.") Contemporary historians and writers, although aware of some of the religious influences on the professional development of nursing, usually have said little about these women's contributions, instead starting the story with the heroic work and reforms of Florence Nightingale. Sioban Nelson's book now brings from the shadow of this legend a new truth and tribute to a group of dedicated women.

Several stories are told: the foundational work that religious orders provided in the development of modern professional nursing; the development of the orders' own hospitals, which were highly efficient and effective; and the power struggles experienced with the male social hierarchy, to a lesser extent with men of medicine and to a greater extent with men of the clergy.

Through five case studies about religious nursing, spanning a century, three continents, and four confessions (Roman Catholic, Anglican, Lutheran, and Methodist), stories unfold about the political and business savvy vowed women exhibited as they overstepped gender boundaries to address the health care needs of poor immigrants, frontier settlers, soldiers, and victims of epidemics.

What can be learned from this book that may give guidance to today's nurses? A first point is how invisibility has plagued nurses and women generally in gaining recognition and compensation for their great work. Nelson discusses the fact that women in religious orders worked collectively and were not recognized individually, so that this perhaps has not made them popular subjects for historians to study and write about. But, the fact that they worked and lived collectively may be one of the prime reasons for their success, unlike contemporary nurses who strive for individuality and miss the power of collective action.

Another critical point is that these women recognized opportunity and seized it. In 1885 the Sisters of Providence in Seattle, Wash, competed with a physician who had set up a hospital based on the billet or ticket system, in which he contracted with companies to provide services to workers based on prepurchased admission tickets. Although it was a distasteful practice to the sisters, they also began selling tickets that entitled bearers access to free care in the hospital with their choice of doctor, and in 2 years the sisters profited while the physician and his hospital went bankrupt.

The women's reputation of steadfast service contributed to their development of collaborative relationships with community leaders and physicians. As the Sisters of Charity in Baltimore, Md, opened hospitals on the East coast, they developed arrangements with private medical practices and medical school faculty to provide teaching facilities for medical residents but retained control over the residency programs—opening and closing them to suit their needs and economics. By opening their hospitals to private, nonsectarian practitioners, they also fostered relationships between the physicians and the student nurses that had potential for leading to postgraduation employment.

As the author documents, between 1829 and 1900 Catholic sisters founded a total of 299 hospitals in the United States, and by 1917 their hospitals accounted for half the US health care system. In all regards, these nurses were experts in their craft—clinically, politically, financially—and understood the value of these elements in furthering their work. Because of their religious ethos, they devoted their lives to the care of the sick. The author's research supports their contribution to the profession through the "emergence of a role for women as part of a professional work force."

A major distinction between vowed women of the 1800s and nurses today is the need for the latter to juggle multiple roles in professional and personal life. The combination of skill and evangelism was pivotal in the success in nursing of vowed women; its absence may also be why modern nursing has not risen to the level exemplified by these pioneers. Vowed women were singularly dedicated and, being mainly single, did not need to bridge the traditional women's roles of homemaker and mother with a professional life. Women today still enter nursing with a strong sense of altruism and desire to provide service, but within a societal structure that casts the woman as the pivotal person in managing home and family, even while pursuing a professional life. (I recall working with a physician on a major grant-writing project long into the night for several days running. When we negotiated the hour at which to begin the evening's work after a full day in the clinical setting, he told me to call his wife at about 7 PM to see if he was up from his nap after the dinner that his wife had made. As I headed home to prepare dinner and stabilize my family, I quickly surmised that what I needed was a wife, too!)

Contemporary role-juggling may seem like a stretch from the story of 19th century women, but the shortage of recruits to nursing today relates to this personal/professional interface. As dedicated to their work as most nurses are, long hours, little control over schedule, and mandated overtime, with minimal supports for either professional work or personal life, make it a challenge to maintain the high standard of service exhibited by the women of an earlier time.

The light Nelson sheds on these vowed women contributes to continuous truth-seeking about nursing's heritage and provides guidance for today's practitioners as they confront the challenges of practice, education, and research.

After centuries of inflicting illness and death, malaria was nearly gone from the United States by the 1950s and was officially certified as eradicated in 1970. How did this occur, and what were the key factors that influenced its disappearance? These are the questions that Margaret Humphreys attempts to address in Malaria: Poverty, Race and Public Health in the United States. As a physician and medical historian who grew up in the southern United States, Dr Humphreys is well qualified to write on this subject.

The book chronicles in seven chapters the rise and fall of malaria transmission in the United States, from the perspectives of physicians, people, and the parasite. Humphreys readily admits that information about physicians' (and public health workers') and parasites' perspectives was easily traceable, but information on people, especially those most afflicted by the disease, was much more difficult to obtain. Chronicles of the lives of the Southern poor are scarce. Still, the author does an eloquent job of weaving together a fascinating story.

Humphreys begins by introducing the reader to the biology of the parasite. Unfortunately, this is the weakest chapter. Misstatements such as "P. malariae acts much like P. vivax" and "Ovale does not occur outside of West Africa" lead the reader to question the authoritativeness of this material. Later in the chapter, the author attempts to tackle the question of whether "race is purely a social construct or a significant biological reality" and concedes that the oft used argument of sickle-cell hemoglobin trait conferring malaria immunity supports the case that race is a biological phenomenon. While the literature is replete with evidence that sickle-cell trait is protective against severe malaria, the author implies that this is the main protective immunity, downplaying the importance of acquired immunity.

In subsequent chapters, Humphreys settles into more familiar territory, medical history, and through the results of exhaustive research, recounts an incredible tale of malaria's rise and fall. As she describes in the second chapter, malaria in the United States reached its peak with 19th century frontier expansion only to succumb to economic prosperity; however, it settled into the American South where it remained for the next century. The bulk of the book's analysis on malaria, race, and poverty occurs in the third chapter. While this chapter is factual, I found the lack of a more thorough analysis of the interactions of social class, poverty, and malaria frustrating. Humphreys discusses the economic disparity between farmers and sharecroppers and how that affects exposure risk due to location and quality of housing. However, other than a scant mention of Jim Crow laws, she does not explore the social forces of racism, its resulting inequalities, and how those may have influenced the distribution of malaria morbidity and mortality. Rather, the chapter's discussion on "Blacks and Malaria" retreats to the topic of acquired immunity and neglects a social analysis of the prevailing racial beliefs of the era.

The book recounts US malaria control efforts of the 20th century in chapters 4 through 6, beginning after the elimination of yellow fever and William Gorgas' successful conquest of the "Panama Canal fevers" while serving with the Panama Canal Commission. Humphreys details the role of such notable organizations as the Rockefeller Foundation, Tennessee Valley Authority, and US Public Health Service in efforts to control malaria. In the final chapter, she discusses the factors that led to the elimination of malaria transmission in the United States, including the work of the predecessor of the Centers for Disease Control and Prevention (CDC), the Malaria Control in War Areas program.

Humphreys argues that malaria remained in the South well into the 20th century because of numerous factors, including poor housing, areas for competent vectors to breed, host reservoirs on which the mosquito could feed, and lack of adequate access to medical care for migrating farm laborers. In the final pages she notes that the CDC malaria surveillance is currently used to "quench any outbreak before it extends beyond a few cases." The last malaria outbreak that the CDC investigated occurred in the rural South in 1999. Interestingly, the risk factors found for this case of locally transmitted malaria were the same: substandard housing, competent vector breeding sites, and the presence of probable parasitic reservoirs in migrating farm laborers who had poor access to health care.

Though not the threat of 100 years ago, malaria transmission in the United States continues to occur sporadically, often facilitated by the same socioeconomic factors as at the turn of the last century. For readers looking for information on the pathophysiology of malaria, a textbook in tropical medicine is the better source. However, the insights offered in this book are of great interest to those who continue working in malaria control or are intrigued by medical history.

There are currently in the United States more than 1 million adults with congenital heart disease. In addition, a rapidly growing number of young people have had palliative or corrective cardiac surgery for congenital heart disease. All these individuals present unique management challenges to internists and adult cardiologists who, for the most part, have had little or no formal training in the diagnosis and treatment of patients with congenital heart disease. The cardiovascular section of the American Board of Internal Medicine therefore has requested that training programs provide formal instruction in the diagnosis and management of congenital heart disease to all trainees in adult cardiology.

With these facts in mind, I readily accepted the invitation to review this textbook and update my knowledge on congenital heart disease in the adult. I recalled as a cardiology trainee glancing at the congenital heart disease section in Nadas' massive tome on pediatric cardiology and the more recent textbook on congenital heart disease in adults by Perloff. Having mentally prepared myself for long hours of careful study, I was surprised to find that Congenital Heart Disease in the Adult is a mere 304 pages. Despite the book's small size, Welton M. Gersony and Marlon S. Rosenbaum have carefully summarized their 20 to 40 years of clinical experience to provide the reader with the most essential and practical information about patients with congenital heart disease.

The book has three parts: acyanotic heart disease, cyanotic heart disease, and pregnancy and genetics. In the first two parts, each chapter focuses on a specific important congenital heart lesion, from straightforward problems, such as atrial and ventricular septal defects, to complex problems, such as transposition of the great arteries and single ventricle. The anatomy, clinical presentation, various surgical repairs, and long-term problems of each lesion are concisely reviewed. The authors stress the use of physical diagnosis, echocardiography, and, when necessary, invasive ventriculography to determine not only abnormal cardiac anatomy and physiology but also complications that can occur after surgical palliation or correction. Anatomical drawings by Richard Gersony illustrate the pathological defects in the major congenital heart problems and simple and complex surgical procedures, such as the atrial baffle in the Mustard operation for D-transposition; the Fontan operation for the treatment of single ventricle; and the repairs of L-transposition, truncus arteriosus, and Ebstein anomaly. The chapter on Eisenmenger syndrome presents practical guidelines for the medical management of patients with large ventricular septal defects and severe pulmonary vascular obstructive disease who are not candidates for surgical repair. The section on pregnancy in patients with congenital heart disease provides very useful information on risk assessment and guidelines on cardiovascular drug therapy. The chapter on the genetics of congenital heart disease focuses on Mendelian inheritance and chromosomal syndromes and is most suited for the practitioner who does genetic counseling.

The presentation of the material is straightforward and the text easy to read. In addition, each chapter contains a summary of important information and an algorithm with frequency of visits, appropriate testing, and specific criteria for intervention. The chapter bibliographies contain predominantly recent references for more in-depth information. Congenital Heart Disease in the Adult will be of special value to the consulting cardiologist, the adult and pediatric cardiology trainee, and the internist or medical resident who encounters patients with congenital heart disease.