Reasons for Premature Conclusion of Late Phase Clinical Trials: An Analysis of ClinicalTrials.gov Registered Phase III Trials.

BACKGROUND: Confirmatory phase III trials aim to provide decisive evidence about a medical product's safety and efficacy. Although these trials are planned and conducted based on accumulated knowledge, they are not without risk or uncertainty. A trial prematurely concluding contributes to great loss in both financial and human research resources. METHODS: We categorized and evaluated trials concluded prematurely after recruitment had begun, as registered in Clinical Trials.gov between January 2013 and August 2017. RESULTS: We found 9828 registered interventional phase III trials; of those, 320 were concluded prematurely. Many clinical trials were concluded prematurely for reasons related to reducing participant risk, such as interim stopping for safety, efficacy, or futility. Yet, 70% trials were halted for other reasons, such as insufficient recruitment (the most often cited reason) or unspecified business decisions. Of all prematurely concluded trials, 102 trials evaluated 72 different novel therapeutics; in 66.7% of these trials, the clinical development program was stopped entirely. Most of the prematurely concluded trials (78%) had not provided results to ClinicalTrials.gov at the time of this analysis. CONCLUSIONS: Evaluation of the factors that influence premature conclusion could inform solutions for improving research participation and help ensure trial completion. Registering and reporting results acknowledges the voluntary contribution and consent expectations of research participants.

A comprehensive review of the FDA-approved labels of diabetes drugs: Indications, safety, and emerging cardiovascular safety data.

AIMS: FDA-approved drug labels are an important source of information for clinicians who prescribe medications for treatment of diabetes. We reviewed drug labels to (1) understand the landscape of classes of medications approved for type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), (2) explore the indications and safety information and (3) examine their cardiovascular safety. METHODS: We searched four public references and reviewed all FDA-approved labels for "indication and usage," "adverse effects," "warnings and precautions," and "cardiovascular outcomes" from October 1982 to July 2016. We also reviewed FDA drug-safety communications from January 2015 to May 2017. RESULTS: The labels reveal 12 classes of medications approved for T2DM with only 2 classes approved for T1DM. There is emerging evidence about cardiovascular safety and risk reduction from diabetes medications which is now being incorporated in drug labels. CONCLUSIONS: All currently available diabetes medications are approved for adults with T2DM with a remarkably limited number for adults with T1DM and children with T1DM or T2DM. The incorporation of emerging data on cardiovascular outcomes in FDA drug labels is expected to influence the way physicians treat patients with diabetes.

Advancing a Vision for Regulatory Science Training.

Regulatory science, a complex field which draws on science, law, and policy, is a growing discipline in medical-related applications. Competencies help define both a discipline and the criteria to measure high-quality learning experiences. This paper identifies competencies for regulatory science, how they were developed, and broader recommendations to enhance education and training in this burgeoning field, including a multifaceted training approach.

Data sharing for public health research: A qualitative study of industry and academia.

Data sharing is a key biomedical research theme for the 21st century. Biomedical data sharing is the exchange of data among (non)affiliated parties under mutually agreeable terms to promote scientific advancement and the development of safe and effective medical products. Wide sharing of research data is important for scientific discovery, medical product development, and public health. Data sharing enables improvements in development of medical products, more attention to rare diseases, and cost-efficiencies in biomedical research. We interviewed 11 participants about their attitudes and beliefs about data sharing. Using a qualitative, thematic analysis approach, our analysis revealed a number of themes including: experiences, approaches, perceived challenges, and opportunities for sharing data.

Climate change, human health, and biomedical research: analysis of the National Institutes of Health research portfolio.

BACKGROUND: According to a wide variety of analyses and projections, the potential effects of global climate change on human health are large and diverse. The U.S. National Institutes of Health (NIH), through its basic, clinical, and population research portfolio of grants, has been increasing efforts to understand how the complex interrelationships among humans, ecosystems, climate, climate variability, and climate change affect domestic and global health. OBJECTIVES: In this commentary we present a systematic review and categorization of the fiscal year (FY) 2008 NIH climate and health research portfolio. METHODS: A list of candidate climate and health projects funded from FY 2008 budget appropriations were identified and characterized based on their relevance to climate change and health and based on climate pathway, health impact, study type, and objective. RESULTS: This analysis identified seven FY 2008 projects focused on climate change, 85 climate-related projects, and 706 projects that focused on disease areas associated with climate change but did not study those associations. Of the nearly 53,000 awards that NIH made in 2008, approximately 0.17% focused on or were related to climate. CONCLUSIONS: Given the nature and scale of the potential effects of climate change on human health and the degree of uncertainty that we have about these effects, we think that it is helpful for the NIH to engage in open discussions with science and policy communities about government-wide needs and opportunities in climate and health, and about how NIH's strengths in human health research can contribute to understanding the health implications of global climate change. This internal review has been used to inform more recent initiatives by the NIH in climate and health.