Clinical trials are used to elucidate the most appropriate preventive, diagnostic, or treatment options for individuals with a given medical condition. Perhaps the most essential feature of a clinical trial is that it aims to use results based on a limited sample of research participants to see if the intervention is safe and effective or if it is comparable to a comparison treatment. Sample size is a crucial component of any clinical trial. A trial with a small number of research participants is more prone to variability and carries a considerable risk of failing to demonstrate the effectiveness of a given intervention when one really is present. This may occur in phase I (safety and pharmacologic profiles), II (pilot efficacy evaluation), and III (extensive assessment of safety and efficacy) trials. Although phase I and II studies may have smaller sample sizes, they usually have adequate statistical power, which is the committee's definition of a "large" trial. Sometimes a trial with eight participants may have adequate statistical power, statistical power being the probability of rejecting the null hypothesis when the hypothesis is false. Small Clinical Trials assesses the current methodologies and the appropriate situations for the conduct of clinical trials with small sample sizes. This report assesses the published literature on various strategies such as (1) meta-analysis to combine disparate information from several studies including Bayesian techniques as in the confidence profile method and (2) other alternatives such as assessing therapeutic results in a single treated population (e.g., astronauts) by sequentially measuring whether the intervention is falling above or below a preestablished probability outcome range and meeting predesigned specifications as opposed to incremental improvement.

Data sharing can accelerate new discoveries by avoiding duplicative trials, stimulating new ideas for research, and enabling the maximal scientific knowledge and benefits to be gained from the efforts of clinical trial participants and investigators. At the same time, sharing clinical trial data presents risks, burdens, and challenges. These include the need to protect the privacy and honor the consent of clinical trial participants; safeguard the legitimate economic interests of sponsors; and guard against invalid secondary analyses, which could undermine trust in clinical trials or otherwise harm public health. Sharing Clinical Trial Data presents activities and strategies for the responsible sharing of clinical trial data. With the goal of increasing scientific knowledge to lead to better therapies for patients, this book identifies guiding principles and makes recommendations to maximize the benefits and minimize risks. This report offers guidance on the types of clinical trial data available at different points in the process, the points in the process at which each type of data should be shared, methods for sharing data, what groups should have access to data, and future knowledge and infrastructure needs. Responsible sharing of clinical trial data will allow other investigators to replicate published findings and carry out additional analyses, strengthen the evidence base for regulatory and clinical decisions, and increase the scientific knowledge gained from investments by the funders of clinical trials. The recommendations of Sharing Clinical Trial Data will be useful both now and well into the future as improved sharing of data leads to a stronger evidence base for treatment. This book will be of interest to stakeholders across the spectrum of research-from funders, to researchers, to journals, to physicians, and ultimately, to patients.

The most recent Ebola epidemic that began in late 2013 alerted the entire world to the gaps in infectious disease emergency preparedness and response. The regional outbreak that progressed to a significant public health emergency of international concern (PHEIC) in a matter of months killed 11,310 and infected more than 28,616. While this outbreak bears some unique distinctions to past outbreaks, many characteristics remain the same and contributed to tragic loss of human life and unnecessary expenditure of capital: insufficient knowledge of the disease, its reservoirs, and its transmission; delayed prevention efforts and treatment; poor control of the disease in hospital settings; and inadequate community and international responses. Recognizing the opportunity to learn from the countless lessons of this epidemic, the National Academies of Sciences, Engineering, and Medicine convened a workshop in March 2015 to discuss the challenges to successful outbreak responses at the scientific, clinical, and global health levels. Workshop participants explored the epidemic from multiple perspectives, identified important questions about Ebola that remained unanswered, and sought to apply this understanding to the broad challenges posed by Ebola and other emerging pathogens, to prevent the international community from being taken by surprise once again in the face of these threats. This publication summarizes the presentations and discussions from the workshop.

The 2014â€"2015 Ebola epidemic in western Africa was the longest and most deadly Ebola epidemic in history, resulting in 28,616 cases and 11,310 deaths in Guinea, Liberia, and Sierra Leone. The Ebola virus has been known since 1976, when two separate outbreaks were identified in the Democratic Republic of Congo (then Zaire) and South Sudan (then Sudan). However, because all Ebola outbreaks prior to that in West Africa in 2014â€"2015 were relatively isolated and of short duration, little was known about how to best manage patients to improve survival, and there were no approved therapeutics or vaccines. When the World Heath Organization declared the 2014-2015 epidemic a public health emergency of international concern in August 2014, several teams began conducting formal clinical trials in the Ebola affected countries during the outbreak. Integrating Clinical Research into Epidemic Response: The Ebola Experience assesses the value of the clinical trials held during the 2014â€"2015 epidemic and makes recommendations about how the conduct of trials could be improved in the context of a future international emerging or re-emerging infectious disease events.

Since the 2014 Ebola outbreak many public- and private-sector leaders have seen a need for improved management of global public health emergencies. The effects of the Ebola epidemic go well beyond the three hardest-hit countries and beyond the health sector. Education, child protection, commerce, transportation, and human rights have all suffered. The consequences and lethality of Ebola have increased interest in coordinated global response to infectious threats, many of which could disrupt global health and commerce far more than the recent outbreak. In order to explore the potential for improving international management and response to outbreaks the National Academy of Medicine agreed to manage an international, independent, evidence-based, authoritative, multistakeholder expert commission. As part of this effort, the Institute of Medicine convened four workshops in summer of 2015 to inform the commission report. The presentations and discussions from the Workshop on Research and Development of Medical Products are summarized in this report.

This guidance is an update of WHO global influenza preparedness plan: the role of WHO and recommendations for national measures before and during pandemics, published March 2005 (WHO/CDS/CSR/GIP/2005.5).

The 2014â€"2015 Ebola epidemic in western Africa was the longest and most deadly Ebola epidemic in history, resulting in 28,616 cases and 11,310 deaths in Guinea, Liberia, and Sierra Leone. The Ebola virus has been known since 1976, when two separate outbreaks were identified in the Democratic Republic of Congo (then Zaire) and South Sudan (then Sudan). However, because all Ebola outbreaks prior to that in West Africa in 2014â€"2015 were relatively isolated and of short duration, little was known about how to best manage patients to improve survival, and there were no approved therapeutics or vaccines. When the World Heath Organization declared the 2014-2015 epidemic a public health emergency of international concern in August 2014, several teams began conducting formal clinical trials in the Ebola affected countries during the outbreak. Integrating Clinical Research into Epidemic Response: The Ebola Experience assesses the value of the clinical trials held during the 2014â€"2015 epidemic and makes recommendations about how the conduct of trials could be improved in the context of a future international emerging or re-emerging infectious disease events.