Clinical Development Strategies and Considerations for Zika Vaccine Licensure.

The Zika outbreak that began in 2015 has spread from Brazil to countries across the Western Hemisphere including the United States, presenting global public health challenges that call for the expedited development and availability of preventive vaccines to protect against Zika virus disease. While the general principles guiding the nonclinical and clinical development for Zika vaccines are the same as those of other preventive vaccines, unique considerations apply, in particular if development occurs during a public health emergency. Furthermore, incomplete information about the pathogenesis of Zika virus disease and the mechanism by which candidate preventive vaccines potentially may confer protection presents additional challenges to their clinical development. Nevertheless, definition of clinical development strategies to enable sound regulatory assessment, with a goal toward licensure is critical for these products. This article will provide an overview of the regulatory considerations for the clinical development and licensure of Zika vaccine candidates including a discussion of clinical study designs, approaches to demonstrate vaccine effectiveness, and regulatory pathways to licensure.

Safety in numbers: the development of Leapfrog's composite patient safety score for U.S. hospitals.

OBJECTIVE: To develop a composite patient safety score that provides patients, health-care providers, and health-care purchasers with a standardized method to evaluate patient safety in general acute care hospitals in the United States. METHODS: The Leapfrog Group sought guidance from a panel of national patient safety experts to develop the composite score. Candidate patient safety performance measures for inclusion in the score were identified from publicly reported national sources. Hospital performance on each measure was converted into a "z-score" and then aggregated using measure-specific weights. A reference mean score was set at 3, with scores interpreted in terms of standard deviations above or below the mean, with above reflecting better than average performance. RESULTS: Twenty-six measures were included in the score. The mean composite score for 2652 general acute care hospitals in the United States was 2.97 (range by hospital, 0.46-3.94). Safety scores were slightly lower for hospitals that were publicly owned, rural in location, or had a larger percentage of patients with Medicaid as their primary insurance. CONCLUSIONS: The Leapfrog patient safety composite provides a standardized method to evaluate patient safety in general acute care hospitals in the United States. While constrained by available data and publicly reported scores on patient safety measures, the composite score reflects the best available evidence regarding a hospital's efforts and outcomes in patient safety. Additional analyses are needed, but the score did not seem to have a strong bias against hospitals with specific characteristics. The composite score will continue to be refined over time as measures of patient safety evolve.

Perspective: a culture of respect, part 1: the nature and causes of disrespectful behavior by physicians.

A substantial barrier to progress in patient safety is a dysfunctional culture rooted in widespread disrespect. The authors identify a broad range of disrespectful conduct, suggesting six categories for classifying disrespectful behavior in the health care setting: disruptive behavior; humiliating, demeaning treatment of nurses, residents, and students; passive-aggressive behavior; passive disrespect; dismissive treatment of patients; and systemic disrespect.At one end of the spectrum, a single disruptive physician can poison the atmosphere of an entire unit. More common are everyday humiliations of nurses and physicians in training, as well as passive resistance to collaboration and change. Even more common are lesser degrees of disrespectful conduct toward patients that are taken for granted and not recognized by health workers as disrespectful.Disrespect is a threat to patient safety because it inhibits collegiality and cooperation essential to teamwork, cuts off communication, undermines morale, and inhibits compliance with and implementation of new practices. Nurses and students are particularly at risk, but disrespectful treatment is also devastating for patients. Disrespect underlies the tensions and dissatisfactions that diminish joy and fulfillment in work for all health care workers and contributes to turnover of highly qualified staff. Disrespectful behavior is rooted, in part, in characteristics of the individual, such as insecurity or aggressiveness, but it is also learned, tolerated, and reinforced in the hierarchical hospital culture. A major contributor to disrespectful behavior is the stressful health care environment, particularly the presence of "production pressure," such as the requirement to see a high volume of patients.

Perspective: a culture of respect, part 2: creating a culture of respect.

Creating a culture of respect is the essential first step in a health care organization's journey to becoming a safe, high-reliability organization that provides a supportive and nurturing environment and a workplace that enables staff to engage wholeheartedly in their work. A culture of respect requires that the institution develop effective methods for responding to episodes of disrespectful behavior while also initiating the cultural changes needed to prevent such episodes from occurring. Both responding to and preventing disrespect are major challenges for the organization's leader, who must create the preconditions for change, lead in establishing and enforcing policies, enable frontline worker engagement, and facilitate the creation of a safe learning environment.When disrespectful behavior occurs, it must be addressed consistently and transparently. Central to an effective response is a code of conduct that establishes unequivocally the expectation that everyone is entitled to be treated with courtesy, honesty, respect, and dignity. The code must be enforced fairly through a clear and explicit process and applied consistently regardless of rank or station.Creating a culture of respect requires action on many fronts: modeling respectful conduct; educating students, physicians, and nonphysicians on appropriate behavior; conducting performance evaluations to identify those in need of help; providing counseling and training when needed; and supporting frontline changes that increase the sense of fairness, transparency, collaboration, and individual responsibility.

Apology for errors: whose responsibility?

When things go wrong during a medical procedure, patients' expectations are fairly straightforward: They expect an explanation of what happened, an apology if an error was made, and assurance that something will be done to prevent it from happening to another patient. Patients have a right to full disclosure; it is also therapeutic in relieving their anxiety. But if they have been harmed by our mistake, they also need an apology to maintain trust. Apology conveys respect, mutual suffering, and responsibility. Meaningful apology requires that the patient's physician and the institution both take responsibility, show remorse, and make amends. As the patient's advocate, the physician must play the lead role. However, as custodian of the systems, the hospital has primary responsibility for the mishap, for preventing that error in the future, and for compensation. The responsibility for making all this happen rests with the CEO. The hospital must have policies and practices that ensure that every injured patient is treated the way we would want to be treated ourselves--openly, honestly, with compassion, and, when indicated, with an apology and compensation. To make that happen, hospitals need to greatly expand training of physicians and others, and develop support programs for patients and caregivers.

Commentary: how can we make diagnosis safer?.

Diagnostic errors are common and are a leading cause of patient dissatisfaction and malpractice suits. Because of its traditional heavy reliance on memory and lack of standardization, the diagnostic process is particularly error prone. A study by Zwaan and colleagues on diagnostic failures in treating dyspneic patients makes several important contributions: examining the process behind the diagnosis, seeking insights as to the reasons for the process failures by interviewing the treating physicians, and using the Delphi process with experts to map the optimal diagnostic process. There is considerable confusion about definitions in the field of diagnostic errors. The authors of this commentary use a Venn diagram to clarify distinctions and relationships between diagnosis processes errors, delayed diagnosis and misdiagnosis, and adverse outcomes. A key question is whether a much more rigorous process should be employed for diagnosis, specifically the routine use of algorithms or guidelines, and whether barriers to achieving it can be overcome. The authors propose an alternate simpler approach: six-part checklists for the top 20 or 30 clinical symptoms or problems. The elements of these checklists for minimizing diagnostic errors include essential data elements, don't-miss diagnoses, red-flag symptoms, potential drug causes, required referral(s), and follow-up instructions. These checklists could-and should-be developed by collaborative efforts of the main users, primary care physicians, and emergency physicians, working with specialist physicians on specific symptoms and diagnoses. Absent such professional commitment, progress in diagnostic accuracy is likely to be slow.

Patient participation: current knowledge and applicability to patient safety.

Patient participation is increasingly recognized as a key component in the redesign of health care processes and is advocated as a means to improve patient safety. The concept has been successfully applied to various areas of patient care, such as decision making and the management of chronic diseases. We review the origins of patient participation, discuss the published evidence on its efficacy, and summarize the factors influencing its implementation. Patient-related factors, such as acceptance of the new patient role, lack of medical knowledge, lack of confidence, comorbidity, and various sociodemographic parameters, all affect willingness to participate in the health care process. Among health care workers, the acceptance and promotion of patient participation are influenced by other issues, including the desire to maintain control, lack of time, personal beliefs, type of illness, and training in patient-caregiver relationships. Social status, specialty, ethnic origin, and the stakes involved also influence patient and health care worker acceptance. The London Declaration, endorsed by the World Health Organization World Alliance for Patient Safety, calls for a greater role for patients to improve the safety of health care worldwide. Patient participation in hand hygiene promotion among staff to prevent health care-associated infection is discussed as an illustrative example. A conceptual model including key factors that influence participation and invite patients to contribute to error prevention is proposed. Further research is essential to establish key determinants for the success of patient participation in reducing medical errors and in improving patient safety.

Rating recommendations for consumers about patient safety: sense, common sense, or nonsense?

BACKGROUND: Although many organizations offer advice about the consumer's role in improving patient safety, little is known about these recommendations. METHODS: The Internet and medical literature were searched to identify patient safety recommendations for consumers. Recommendations were classified by type and tabulated by frequency. Nine investigators rated each recommendation for the quality of supporting empirical evidence, magnitude of benefit, and likely patient adherence. For a consumer perspective, 22 relatives of the investigators who were also mothers rated each recommendation. RESULTS: Twenty-six organizations identified 160 distinct recommendations; 115 (72%) addressed medication safety, 37 (23%) advised patients about preparation for hospitalization or surgery, and 18 (11%) offered general advice. Organizations most frequently advised patients to make a list of their medications (92% of organizations), to ask questions about their health and treatment (81%), to enlist an advocate (77%), and to learn about possible medication side effects (77%). Investigators assigned high scores to 11 of the 25 most frequently cited recommendations and to 4 of the 25 least common recommendations. There was little association between the frequency with which recommendations were promulgated and investigators' ratings (r = 0.27, p < .001). Investigators' scores correlated with those of the mothers (r = 0.71, p < .001). DISCUSSION: Contrary to expectation, there was little overlap among the 160 recommendations offered by the 26 organizations. Health care organizations offer many patient safety recommendations of limited value. These organizations should offer a concise and coherent set of recommendations on the basis of evidence, magnitude of benefit, and likely adherence.

Errors in medicine.

Modern awareness of the problem of medical injury--complications of treatment--can be fairly dated to the publication in 1991 of the results of the Harvard Medical Practice Study, but it was not until the publication of the 2000 Institute of Medicine (IOM) report, To Err is Human that patient safety really came to medical and public attention. Medical injury is a serious problem, affecting, as multiple studies have now shown, approximately 10% of hospitalized patients, and causing hundreds of thousands of preventable deaths each year. The organizing principle is that the cause is not bad people, it is bad systems. This concept is transforming; it replaces the previous exclusive focus on individual error with a focus on defective systems. Although the major focus on patient safety has been on implementing safe practices, it has become increasingly apparent that achieving a high level of safety in our health care organizations requires much more: several streams have emerged. One of these is the recognition of the importance of engaging patients more fully in their care. Another is the need for transparency. In the current health care organizational environment in most hospitals, at least six major changes are required to begin the journey to a culture of safety: 1. We need to move from looking at errors as individual failures to realizing they are caused by system failures; 2. We must move from a punitive environment to a just culture; 3. We move from secrecy to transparency; 4. Care changes from being provider (doctors) centered to being patient-centered; 5. We move our models of care from reliance on independent, individual performance excellence to interdependent, collaborative, interprofessional teamwork; 6. Accountability is universal and reciprocal, not top-down.

Scope of problem and history of patient safety.

Creating a safe environment in our incredibly complex health care system requires a major culture change. While it may be frustratingly slow and halting, that change is occurring and beginning to show results. This article addresses the issue of patient safety, discussing its history, and organizations and practices that are helping to make it more of a reality in today's health care environment.

Reconciling medications at admission: safe practice recommendations and implementation strategies.

BACKGROUND: Fifty hospitals collaborated in a patient safety initiative developed and implemented by the Massachusetts Coalition for the Prevention of Medical Errors and the Massachusetts Hospital Association. METHODS: A consensus group identified safe practices and suggested implementation strategies. Four collaborative learning sessions were offered, and teams monitored their progress and shared successful strategies and lessons learned. Reports from participating teams and an evaluation survey were then used to identify successful techniques for reconciling medications. RESULTS: For the 50 participating hospitals, implementation strategies most strongly correlated with success included active physician and nursing engagement, having an effective improvement team, using small tests of change, having an actively engaged senior administrator, and sending a team to multiple collaborative sessions. DISCUSSION: Adoption of the reconciling safe practices proved challenging. The process of writing medication orders at patient transfer points is complex. The hospitals' experiences demonstrated that implementing the proposed safe practices requires a team effort with leadership support and vigilant measurement.