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In early 2012, the Breakthrough Therapy Act was introduced into the US House of Representatives and the Senate. The bills received bipartisan support and were included as an amendment to the Food and Drug Administration Safety and Innovation Act in the Prescription Drug User Fee Act V. On July 9, 2012, the breakthrough therapy designation was signed into law. As of June 13, 2014, a total of 48 products have been designated as breakthrough therapies by the Center for Drug Evaluation and Research, and 4 of those have received FDA new molecular entity approval.

The United States Food and Drug Administration (FDA) has long recognized the key role it plays in ensuring patients have timely access to safe and effective drugs. Over the past 25 years, FDA has developed multiple programs, including Fast Track, Accelerated Approval, and Priority Review, to expedite the development and review of new drugs for the patients who need them. With the passage of the Food and Drug Administration Safety and Innovation Act (FDASIA) in 2012, FDA has an additional tool to foster efficient drug development, Breakthrough Therapy designation. Building on past successes, like Fast Track, Breakthrough focuses on early collaboration and communication between drug developers and FDA. These programs reflect the growing recognition that robust scientific drug development must also be efficient and as timely as possible. FDA continues to look for opportunities to streamline drug development, especially in areas with unmet need, while focusing on those products that show real promise to posit...

Objective To raise pharmacist awareness about the needs and concerns of our patients with visual impairment and to review useful strategies to foster medication adherence. Summary As patient-centered pharmacists, we need to understand the challenges faced by our patients with low vision and tailor pharmaceutical care to best fit their needs. Evidence-based best practices in labeling and written communication have been developed by the American Foundation for the Blind in partnership with the American Society of Consultant Pharmacists. These recommendations include the use of specific font styles, minimum font size, and other standards known to enhance usability for those with limited vision. Recent advances in assistive technologies such as audio output and object recognition software can be used to ease the medication-taking process and effectively communicate important drug and safety information in a manner that can be understood by those with low vision. In July 2012, the Prescription Accessible Drug Labeling Promotion Act of 2012 (HR 4087) was signed into law. This new legislation is an addition to the Food and Drug Administration Safety and Innovation Act, which required the development and ultimate implementation by pharmacies of national best practices intended to improve the accessibility of prescription drug labeling for the visually impaired. Conclusion As a patient-centered profession, we need to advocate for our patients with special needs by partnering with government and patient groups to support and enact legislation intended to enhance people's ability to adhere to drug therapy.

Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population. Therefore, the development of drug dosing in pediatric oncology patients represents a special challenge. Potential approaches to pediatric dosing in oncology patients include extrapolation of efficacy from adult studies in those few cases where the disease is similar, inclusion of adolescent patients in adult trials when possible, and bridging the adult dose to the pediatric dose. An analysis of the recommended phase 2 dose for 40 molecularly targeted agents in pediatric patients provides some insight into current practices. Increased knowledge of tumor biology and efforts to identify and validate molecular targets and genetic abnormalities that drive childhood cancers can lead to increased opportunities for precision medicine in the treatment of pediatric cancers.

President Obama on July 9 signed into law the Food and Drug Administration Safety and Innovation Act, bipartisan legislation that many groups believe will preserve patients’ access to critical drugs. A prominent feature of the law’s provisions pertaining to drug shortages is the requirement for

The US Food and Drug Administration Safety and Innovation Act (FDASIA) was signed on 9 July 2012. This law created a new "breakthrough therapy" (BT) designation program for investigational drugs and biologics intended to treat a serious disease and having "preliminary clinical evidence [that] indicates that the drug may demonstrate substantial clinical improvement over existing therapies on one or more clinically significant endpoints."(1) Many questions have been posed about the impact of this new program on drug development.

In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential “breakthrough” drugs or treatments that show dramatic responses in early-phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a “Breakthrough Therapy”, the U.S. Food and Drug Administration (FDA) and sponsor would collaborate to determine the best path forward to abbreviate the traditional three-phase approach to drug development. The breakthrough legislation requires that an FDA guidance be drafted that details specific requirements of the bill to aid FDA in implementing requirements of the Act. In this article, we have proposed criteria to define a product as a Breakthrough Therapy, and discussed critical components of the development process that would require flexibility in order to enable expedited development of a Breakthrough Therapy. Clin Cancer Res; 19(16); 4297–304. ©2013 AACR.

In 2001, a sentinel publication from the Institute of Medicine, “Exploring the Biological Contributions to Human Health: Does Sex Matter?” concluded that ‘until the question of sex is routinely asked and the results—positive or negative—are routinely reported, many opportunities to obtain a better understanding of the pathogenesis of disease and to advance human health will surely be missed’ [1]. Given the acknowledged lack of enrolment of women in clinical trials, particularly cardiovascular trials, the National Institutes of Health (NIH) implemented guidelines in 1993, for the inclusion of women in all phases of clinical trials, and the requirement to design phase III clinical trials that specifically assess sex-based differences [2]. Nevertheless, an assessment of female enrolment in all NIH-funded clinical studies between 1993 and 1998 found one-fifth of the non-sex specific studies still failed to enroll female subjects. Furthermore, among the studies that did include women, 60 %–70 % did not analyze or report results based on sex [3]. Of note, European and other international trials, which lack legislation regarding inclusion of women in clinical studies, enroll a larger proportion of female subjects than do US-specific trials, although they still do not achieve levels representative of the diseased population [4]. The lack of information by sex and gender has very real implications for care. For example, between 2000 and 2007, the Food and Drug Administration (FDA) approved 78 highrisk cardiovascular devices, based on a patient population comprised mainly of men (67 %); 28 % of the studies did not even provide the sex-distribution of their populations; sexspecific analyses were reported in only 41 % (51/123) of studies [5]. The general lack of sex-specific analysis for new device approval is best illustrated by the implantable cardioverter-defibrillator experience where approval was granted despite very low enrolment of women in the key trials. The implications of this lack of data are now apparent; a metaanalysis has demonstrated a lack of efficacy of implantable cardioverter-defibrillators in primary prevention trials in women with heart failure [6]. A review of the key meta-analyses describing the efficacy of the key evidence-based medications for secondary prevention post-acute myocardial infarction reveals a general lack of data on women (women comprised between 18.8 % and 30 % of the populations analyzed) [7–9], and in the case of beta blockers, no evaluation of sex-specific outcomes were provided whatsoever [10]. These examples highlight the uneven approach to accommodating sex and gender issues in cardiovascular care and prevention, and they underscore the importance of conducting research that incorporates the study of sex differences in study design and reporting. Yet, important progress has been made recently. Legislation in the United States now requires sex-specific reporting. Recently enacted legislation, the Food and Drug Administration Safety and Innovation Act in 2012, requires the FDA to report annually and publicly on the extent to which applications for FDA approval of new drugs and medical devices are reported by sex, age, race, and ethnicity [11]. In Canada, the Canadian Institutes of Health Research (CIHR) established a Gender and Health Institute in 2000, which introduced guidelines requiring all applicants for CIHR funding to indicate whether they will consider sex/gender differences in their proposed research. And, there are indications that the Heart and Stroke Foundation of Canada will shortly follow suit. Nevertheless, these are only guidelines, and compliance with K. H. Humphries (*) Department of Medicine, University of British Columbia and Centre for Health Evaluation & Outcome Sciences, Vancouver, BC, Canada e-mail: Khumphries@providencehealth.bc.ca

Irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to "preantibiotic era." The threat is serious with the "Enterococcus, Staphylococcous, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter" organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum β-lactamases, carbapenamases and metallo-β-lactamases. Facing us is a situation where soon multidrug resistance would have spread across the globe with no antibiotics to withstand it. The infectious disease society of America and Food and Drug Administration have taken initiatives like the 10 × '20 where they plan to develop 10 new antibiotics by the year 2020. Existing classes of antibiotics against resistant bacteria include the carbapenems, oxazolidinones, glycopeptides, monobactams, streptogramins and daptomycin. Newer drugs in existing classes of antibiotics such as cephalosporins, aminoglycosides, tetracyclines, glycopeptides and β-lactamase inhibitors continue to get synthesized. The situation demands newer targets against bacterial machinery. Some of them include the peptidoglycantransferase, outer membrane protein of Pseudomonas, tRNA synthase, fatty acid synthase and mycobacterial ATP synthase. To curb the irrational and excessive usage of presently available antibiotics should be a priority if they are still to be kept in usage for the future.

For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV. In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise. This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper’s final section highlights case studies of successful examples that have incorporated biomarker endpoints into FDA approvals for rare disease therapies. The focus of this paper is on the situation in the Unites States, but the recommendations are reasonably applicable to any jurisdiction. Electronic supplementary material The online version of this article (doi:10.1186/s13023-014-0195-4) contains supplementary material, which is available to authorized users.