Applied Clinical Research, Clinical Trials and Regulatory Affairs - Volume 2, Issue 2, 2015

Successful fertilization in mouse and other studied species, including man, is a highly programmed process by which two radically different looking haploid cells, sperm and egg, unite to form a zygote, a diploid cell with somatic chromosome numbers. The process is the net result of a complex sequence of biological events that prepare ejaculated spermatozoa to recognize and irreversibly bind the egg's extra-cellular matrix, the zona pellucida (ZP). The species-specific tight binding of the opposite gametes results in the opening of Ca2+ channels on sperm plasma membrane (PM) and influx of Ca2+. The transient rise in intra-sperm Ca2+ triggers a signal transduction cascade that results in the fusion of the sperm PM and the underlying outer acrosomal membrane at multiple sites (i.e., induction of the acrosomal reaction). The hydrolytic action of the acrosomal enzymes (i.e., proteinases, glycohydrolases, sulphatases, esterases, etc.) released at the site of sperm-egg binding, along with the hyperactivated beat pattern of the bound spermatozoon are important factors that regulate the penetration of the acrosome-reacted spermatozoon through the ZP and fertilize the egg. This review focuses on the most important aspects of biological processes that prepare spermatozoa to fertilize an ovulated egg. Our intention is to discuss recent data from this and other laboratories that provide useful insights into the biology underlying sperm-egg interactions leading to fertilization.

Post approval changes are an integral part of pharmaceutical product life cycle management. These changes need to be carefully monitored and must follow proper regulatory path of given jurisdiction. The present work identifies the post approval changes, policies, guidelines and procedure for submission of post approval changes in Europe. The European medical agency (EMA) in their several guidelines has clearly defined the regulatory framework for post approval changes which are known as variation filing in Europe. The article further describes the types of changes, categorization and procedure for the submission of variation changes. In Europe, variations are classified as Type-IA for minor changes, Type-IB for moderate changes and Type-II for major changes. These minor changes can be implemented without an approval from the agency but should be reported and the major changes needs an approval letter from the agency. The case study on the product Humalog (insulin lispro) has been described to obtain better understanding of post approval changes in Europe.

Background: Juvenile Idiopathic Arthritis is the most common chronic, autoimmune, inflammatory joint disease affecting children under 16 years of age. Children with juvenile idiopathic arthritis may present with severe lower limb joint disability and dysfunction. The evidence base for treating lower limb problems in juvenile idiopathic arthritis is growing, however is currently uncoordinated and difficult for clinicians to access. This paper reports a protocol to systematically review the evidence for physical and mechanical interventions for lower limb problems in juvenile idiopathic arthritis. Methods/Design: The following electronic databases will be searched for eligible studies: MEDLINE, EMBASE, Cochrane Central Registar of Controlled Trials, PUBMED and CINAHL. Randomised control trials and quasi randomised control trials of physical and mechanical interventions for lower limb problems in children with juvenile idiopathic arthritis will be included. Two authors will independently screen studies for eligibility for inclusion and assess the risk of bias. One author will extract and analyse statistical data, which will be checked by a second author. Discussion: This systematic review aims to establish a best-practice pathway of non-invasive and non-drug interventions for lower limb complications of juvenile idiopathic arthritis and to highlight the areas of greatest need for future research.

Periodontitis, the most common chronic inflammatory disease known world-wide, is characterized by pathologically-excessive degradation of collagen and other connective tissue constituents and accelerated resorption of the alveolar bone in the periodontal supporting structures of the teeth including the gingiva, periodontal ligament and the alveolar bone. Nationwide, the prevalence of periodontal disease, in some form, is known to affect up to 50% of the adult population and is a substantial inflammatory burden which can be detrimental to over-all systemic health. In this regard, this common dental disease, chronic periodontitis, has, over the past few decades, been increasingly linked to a variety of medical diseases such as cardiovascular disease (CVD) and stroke, increased severity of diabetes, low birth weight babies (controversial), bacterial pneumonia, rheumatoid arthritis, osteoporosis, Crohn’s disease, HIV Diseases, and head and neck cancer. Decades ago it was thought that all adults were essentially equally susceptible to periodontal disease. More recently, various risk factors such as genetic factors have been identified which significantly impact the susceptibility to periodontitis. Therefore, identifying individuals at risk for development of severe periodontitis provides a way for early interventions.

Though there have been on-going discussions about transparency in clinical research for the last three decades, the first piece of regulation toward this end only came into being in 2005. Today many regulations and registry systems are in use globally and in Middle East countries naturally. Attempts to attain transparency in clinical research are currently paving the way for universal disclosure of all clinical trials.

Obesity is a global health risk. Demography of the world population has witnessed a dramatic change concerning body weight. The Increase in the prevalence of obesity is prevailing in the world nations in general and in industrialized nations in particular. There is a growing body of evidence showing reproductive age as a landmark for important contributor to this epidemic of obesity. Obesity prevention and management is a key health issue for the woman of reproductive age.

This editorial review article discusses the current status of disease registries, mainly focusing in oncology and rare disease condition. It has been shown that analysis of the real world data collected from disease registries and observational studies improve healthcare by gathering data on disease epidemiology, advance in information regarding safety and efficacy of new drugs and filling the gaps of randomized clinical trials. With the improvement in digital system and standardization of the nomenclature of electronic data capture system, the usage of disease registries as a source for research will increase significantly. Collaboration of all stakeholders, scientific, regulatory, caregivers, payers and patient advocate is required to overcome barriers.

A very simple and rapid bio-analytical method with high-throughput, appropriate sensitivity, selectivity, accuracy and precision has been developed and validated for the quantification of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) in human plasma using hydrochlorothiazide (HCTZ) as internal standard (IS) by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) with electronspray ionization (ESI). A simple technique of liquidliquid extraction was developed for plasma samples preparation of the analytes and the chromatographic separation was done under isocratic conditions by Phenomenex Kinetex C18 column (50 mm x 3 mm, 5 μm) with a run time of 1.8 min. The composition of mobile phase was acetonitrile and 10 mM ammonium formate in water (90:10, v/v). The precursor ion was deprotonated to product ion transitions for ASA, SA and HCTZ (IS) were measured on an operating in the multiple reaction monitoring (MRM) with negative ion mode by triple quadrupole mass spectrometer. The assay exhibited a calibration range of 10-15000 ng/mL for both ASA and SA. The bio-analytical validated method was successfully applied for bioavailability or bioequivalence studies to analyze human plasma samples.

Background: Visual aids are commonly used to supplement genetic counseling (GC) sessions focused on hereditary breast and ovarian cancer (HBOC), given the complexities of discussing inherited diseases with patients. Many genetic providers compile a binder of visual aids (BVA) for use during the GC session. In order to facilitate delivery of GC services across various settings, we sought to determine whether a self-contained genetic counseling aid (GCA) in the form of a self-contained booklet for use during the GC session (but additionally sent home with patients) was comparable to the BVA in terms of: 1) patient knowledge gains; and 2) provider preferences. Methods: Female patients evaluated for HBOC (N=254) participated in the study along with 5 genetic service providers. Patient knowledge was measured before and after GC using an eleven item scale. Pre-GC and post-GC knowledge scores were compared among the GCA (N=160) and BVA (N=94) groups and overall change in knowledge was evaluated. Descriptive statistics were performed to assess preferences for GCA or BVA among providers. Results: The median pre-GC knowledge score for patients in both the GCA and BVA groups was 5. The median post-GC score increased to 9 among both groups. Based on provider surveys, all rated the GCA as superior or equivalent to BVA on all characteristics except adaptability. Conclusion: Our findings suggest that the GCA was equivalent to the BVA in supplementing the GC session for HBOC, given similar increases in HBOC knowledge scores in both groups. Despite equivalent gains in patient knowledge, genetic providers rated the GCA higher on ease of use, compatibility, visual appeal, ability to facilitate patient sharing of information, and provision of personalized risk information and patient resources.

Medical registries are designed to determine epidemiological associations between disease and exposure, including those initiated by clinicians. Data driven analyses typically exclude bias, however it is important as ever to consider. Bioinformatics is allowing more data to be collected than ever before, to ultimately improve health care across the spectrum.