Day 2 :
Objective Clinical, USA
Time : 09:00-09:25
Colleen is the CEO of Objective Clinical which is a clinical research strategy and management firm located in the Nashville Tennessee area that supports clinical research leaders in strategic and financial planning, regulatory compliance and optimization of research operations. She brings 25 years of experience in development, management and operational direction of clinical research organizations. She has held senior positions with international clinical research organizations (CROs) including specialty CROs. She served as a committee member for International Business Communications on their Speakers Board for healthcare administration topics, as a Biotechnology Advisory Member for Bates Technical College in Tacoma Washington, and a Board of Director member for Seattle’s Children’s Home. She has been a presenter at ACRP. Colleen is a graduate of the University of Tennessee, College of Business.
The primary focus of clinical research is advancing science and to improve health outcomes. However, for a site or network to have ongoing success and support across the enterprise, the research program also must support overall business goals. There is a methodology to choosing the right clinical trials and the right technologies that fosters efficiency, productivity and enhanced compliance. Optimal study mix selection examples based on the research program’s attributes and goals will be presented and we will discuss how current and emerging offerings can help. Case studies include:
eConsent: This technology offers higher efficiency, consistency and quality with improved participant empowerment and understanding. Success depends on well managed implementation and staff adoption and transition from legacy processes.
Mining EMR with Objective Criteria: The monitoring and analysis of records can help identify qualified patients with less co-morbidity. Understanding the potential to enhance study success through better matching of sites and sponsors by using carefully selected enrollment criteria, while recognizing the challenges of medical data input quality within the EMR.
Wearable’s & ePRO Data: These emerging technologies offer dramatic potential to capture timely research data remotely and continuously, reducing the facility and labor costs and the overall study time required for on-site trials.
Remote Monitoring: Embracing the time saving benefits for data collection by remote monitoring, while ensuring the clarity of the roles of the clinical study team, is key to making this technology and practice work well.
Independent Consultant, USA
Keynote: Liver Let Die – Challenges and Opportunities in Developing Interventions for Fatty Liver Disease (NAFLD/NASH)
Time : 09:25-09:50
Clayton Dehn is a research physiologist with expertise in metabolic disorders. He is the co-inventor of a process and substance for disturbing the inheritance pattern of ion-channelopathic disorders, and the sole author of the first publication cautioning against the risk of SGLT-inhibition inducing ketoacidosis in insulinopenic populations. He serves on the editorial board of four peer-reviewed journals, and has served by gubernatorial appointment on the Arizona Biomedical Research Commission.
Non-Alcoholic Fatty Liver Disease (NAFLD) is a chronic metabolic disorder marked by excessive fat accumulation in the liver that may affect as much as 30% of the population. It is not related to alcohol consumption or viral infection. NAFLD may progress to Non-Alcoholic Steatohepatitis (NASH) and hepatocellular carcinoma (HCC). NASH was first named and described in a 1980 review of 20 Mayo Clinic patients. NASH is expected to overtake all other indications as the leading cause of liver transplantation in the next ten to twenty years. Although this is a serious emerging health concern that has been described as the next global epidemic, there are currently no medications specifically approved for treating NAFLD/NASH. Until recently drug development in this space was stifled by the lack of a clear pathway to approval, necessitating outcomes trials. In 2015 the Food and Drug Administration (FDA) and the American Association for the Study of Liver Diseases (AASLD) published a manuscript of their joint workshop suggesting the acceptance of pragmatic surrogate biomarker endpoints such as the reversal of steatohepatitis with no evidence of progression to advanced fibrosis. Three years ago a Deutsche Bank report projected a peak NASH market opportunity of 35 - 40 billion dollars by 2025. Consequently, NAFLD/NASH interventions are becoming increasingly prevalent in drug development pipelines.
Ethicare Clinical Trial Services, India
Time : 09:50-10:15
Milan C Satia is a PhD in Pharmacology with more than 22 years of experience working across the local pharma majors and CRO industry, playing key leadership roles. He has led operations at R&D for a pharma major and CROs, setting up of a Pharmacokinetic cell within technology center, managed client relationship, and has led teams of expert and played important role in contributing to strategies, developing new business opportunities and to provide scientific knowledge base. He is having a wide knowledge base and experience of varied facets of pharmaceutical research including pharmacology, toxicology, bioavailability and bioequivalence studies, clinical trials, medical writing and exposure to various international audits. He is also a conversant with regulatory framework globally and a crucial Member for setting up of CROs in India. Currently, he is a CEO of Ethicare Clinical Trial Services since 2009 and located at Ahmedabad, India. He is providing services from Phase I to Phase IV clinical trials along with data management services.
Clinical trials using human subjects are an integral part of the approval of new drugs and biologics. About 40% of clinical trials out of total trials registered in USA took place in emerging nations of Asia, Latin America and Africa. At the same time, clinical trials have become increasing costly ventures apart from its complex conduction, adding to the overall cost of developing a drug and, ultimately, the price that patients pay for drugs. The requirement of large sample sizes and the potential for fast recruitment leading to a speedy completion of clinical studies are probably the most important factors that have fueled globalization of studies. While an enlarged clinical trial universe certainly benefits patient recruitment and diversity, it also multiplies the operational and strategic obstacles that clinical trial professionals must circumvent. In addition to inexperience in conducting trials and differing quality standards, there are wide spread differences from country to country in customs knowledge, experience and laws. Other challenges include the need to manage logistics complicated by countries with limited infrastructure as well temperature sensitive biologics, especially outside major cities. There are regional idiosyncrasies -- differences of language, both spoken and unspoken, working patterns, culture and religion -- that add another layer of complexity. Above all, a high level of co-ordination between participating centers across the globe is a different level of challenge one has to handle. Big pharmas and small biotechs alike are looking for innovative ways to improve trial outcomes and, in turn, lower trial costs-this means increasing the efficiency in which they recruit patients, monitoring more closely how drugs are supplied and being more flexible about trial design. Pharmaceutical companies and some academic cooperative groups have been conducting challenging, large pivotal registration studies with multinational participation. Most importantly, the process of expanding the network of clinical research sites also fosters the integration and the development of closer relationships among investigators at a global level. Reduced operational costs and the ability to expedite the regulatory approval of drugs in various countries or regions are also important drivers. Some of the tools that are optimizing clinical trials today and help in overcoming current challenges will be discussed.
Harvard Medical School and VA Boston Healthcare System, USA
Keynote: Streamlining Clinical Trial Conduct in a National Healthcare System – Towards Pragmatic Cardiovascular Clinical Trials
Time : 10:15-10:40
Dr. Jacob Joseph is an Associate Professor of Medicine at Harvard Medical School and faculty in the Cardiovascular Divisions of Veterans Affairs Boston Healthcare System and Brigham and Women’s Hospital. He has published over 80 articles and edited a book. Dr. Joseph is a clinical trial leader of national VA consortia for major international clinical trials; and a member of the Executive Committee of the NIH-funded Influenza Vaccine to Effectively Stop Cardio-thoracic Events and Decompensated Heart Failure (INVESTED) trial, and the Steering Committee of the international Pemafibrate to Reduce cardiovascular OutcoMes by reducing triglycerides IN patiENts with diabeTes (PROMINENT) trial.
Pragmatic clinical trials (PCTs) aim to reduce the burden on patients, investigators and the clinical research ecosystem, without losing effectiveness compared to traditional or explanatory clinical trials. Various elements of a clinical trial can be “pragmatized” depending on the therapeutic hypothesis being tested. The Veterans Affairs Healthcare System (VAHS) offers unique resources for conduct of cardiovascular clinical trials including a large patient population with cardiovascular disease, a nationwide database with advanced search capabilities to identify eligible participants at participating sites, a pool of highly experienced investigators and study coordinators, established support services including research pharmacists and research administration, and a strong institutional commitment to conduct of research. We are leading an effort to streamline the conduct of traditional clinical trials in the VAHS by a focus on centralization, pragmatization, and innovation. We are pioneering a centralized approach to identifying sites, contracting and payments, and regulatory approvals to streamline trial onboarding for sites and trial sponsors. We have utilized the national VA database to identify lists of potential subjects at each VA site to enhance recruitment. In addition, a fully pragmatic trial funded by the VA with centralized patient recruitment and follow-up is also underway. Overall, a national healthcare system with a comprehensive and connected patient care database has the potential to revolutionize clinical trials and make them more pragmatic and less costly without losing effectiveness to answer key therapeutic questions. In addition, the Million Veteran Program also offers the opportunity to conduct trials of personalized medicine based on genotype-phenotype correlations.
- Sessions / Tracks:
Drug Discovery and Development | Clinical Research & Clinical Trials | Clinical Study Designs | Clinical Trials on different Diseases | Globalization of Clinical Trials | Innovations in Clinical Trials | Outsourcing in Clinical Trials | Clinical Trials Site and Supply Management | Medical and Clinical Case Reports | Post-marketing Surveillance
Objective Clinical, USA
Merck Research Laboratories, USA
Galveston Clinical Research Foundation, USA
Time : 11:00-11:20
F Buck Willis after suffering an unsurvivable plane crash conquered the challenges of a brain injury and a 3-year series of operations to rebuild his legs by earning four degrees and squatting 505lbs! He earned his medical degree (MBBS) in the British Commonwealth with a PhD in kinesiology before publishing 25 manuscripts in eight years and being chosen as a Fellow of the American College of Sports Medicine.
Abundant research has been conducted on connective tissue rehabilitation, focusing on contracture reduction. The purpose of this study was to examine the different testing methods and experimental designs used to conclusively prove protocols and modalities for contracture reduction. Sequential papers following the level of evidence (increases) have shown benefits in case studies, cohort trials (for population confirmation) followed by randomized, controlled trials with cross-over arms and or blinding. The highest level of evidence is the Meta Analysis or Systematic Review which is meaningful in proving efficacy of a therapeutic protocol with one dependent variable. An example of this was the series of studies on dynamic splinting for contracture reduction of joints including jaw, shoulder, elbow, wrist, knee, ankle, and toe. The connective tissue of these joints have different lengths and alignment but the molecular structures are similar so protocols for contracture reduction (low load, prolonged duration stretch) were hypothesized to yield the same results. This was proven in a systematic review by Furia et.al. (2013) which showed that a direct linear correlation existed between the hours of therapeutic stretching and reduced contracture as measured with active range of motion. Other variables were examined separately including animal studies for reducing surgically induced contracture, but the aggregate change in controlled trials was proven in the meta-analysis with change in AROM as the dependent variable. Different studies are beneficial in testing unique variables, and a progressive sequence of studies building the level of evidence to a meta-analysis is best to prove therapeutic protocols.
University of Southern California, USA
Title: Trial promoter: A web-based tool for boosting the promotion of clinical research through social media
Time : 11:20-11:40
Katja Reuter is Assistant Professor of clinical preventive medicine at the Institute for Health Promotion and Disease Prevention Research at the Department of Preventive Medicine, Keck School of Medicine of the University of Southern California (USC), and Director of Digital Innovation and Communication at the Southern California Clinical and Translational Science Institute at USC. She is a Scientist, Educator, and a Communications Professional trained and employed in Germany, New Zealand and the United States of America (USA) with over 15 years’ experience. She received her PhD in developmental neuroscience from the Free University in Berlin, Germany.
Participant recruitment into clinical trials represents a major barrier to clinical and translational research and is often associated with implementation delays and high costs. This hinders the translation of scientific discoveries into interventions that improve the health of individuals and the public across populations. Numerous barriers to clinical trial participant recruitment have been identified, including the lack of awareness among patients that trials are available. Several groups have demonstrated that social media such as Facebook and Twitter can be used to reach and enroll participants efficiently into clinical studies. To scale up the number of clinical trials that could potentially benefit from dissemination via SM, we developed and successfully tested trial promoter, a tool that automates the generation, distribution and assessment of clinical trial recruitment messages via social media. In order to test the tool and the correctness of the generated messages, clinical trials (n=46) were randomized into social media messages and distributed via the microblogging social media platform Twitter and the social network Facebook. The percent correct was calculated to determine the probability with which trial promoter generates accurate messages. During a 10-week testing phase, Trial Promoter automatically generated and published 525 social media messages on Twitter and Facebook. On average, trial promoter correctly used the message templates and substituted the message parameters (text, URLs, and disease hashtags) 97.7% of the time (1563/1600). Trial promoter may serve as a promising tool to render clinical trial promotion more efficient while requiring limited resources.
Sanofi Pharmaceuticals, USA
Time : 11:40-12:00
Raj Bandaru heads a data analytics and knowledge management function in Translational Informatics at Sanofi Pasteur. He is championing the adoption of cloud and big data analytics at Sanofi, bringing advances in clinical research together with big data and digital technologies. Over the past two decades, he has led data management and analysis across research and clinical development at various pharmacy and biotech companies and most recently led a data and analytics consulting practice. He has an MBA from Babson College, with a focus on clinical informatics and operations research and also holds graduate degrees in statistics and genetics.
Like much of the pharmaceutical industries, we at Sanofi are also experiencing a shift in clinical development strategies to adopt more digital technologies and analytics placing greater emphasis on data and model driven approaches. We have set up a strong integrated capability across quantitative systems models, disease progression models and empirical models driving a rigorous clinical trial simulation process to inform design and key decisions in our clinical research. To this end, access to historical clinical trial data has been central. However, using clinical study data for broader clinical research use has several limitations and challenges. We are implementing several processes and intelligent informatics solutions to enable easier access to clinical study results and conducting integrated analytics using state of the art methods and tools. Here we describe some of the informatics solutions we are developing and how these could eventually be applied to support trial submission activities. One example is in the use of a machine learning methods to index data and make it searchable without compromising data security or patient privacy. We are also applying intelligent approaches to data de-identification and harmonization across multiple studies to support meta-analysis. A pilot effort using a learning based approach to data harmonization has shown significant promise and we are exploring other applications including management of metadata and terminologies using machine learning approaches. Some challenges however still exist primarily in the governance of data access and patient privacy issues. We are working on developing clear rules and guidelines that will eventually also help with automating data governance activities. Another challenging area will be in handling genomic and digital health data and we foresee an opportunity for automated machine learning algorithms to help in not only managing the data, but to also discover patterns and associations to clinical outcomes.
1National Institutes of Health, USA
Title: More is not better: The result from a US government sponsored multi-center randomized international clinical trial to prevent tuberculosis in HIV/AIDS population
Time : 12:00-12:20
Jing Bao is a Medical Officer at the Division of AIDS, National Institute of Allergy and Infectious Diseases, Columbus Technologies and Services, Inc., with extensive experience in international clinical trial oversight and global regulations. She manages and oversees the US government (National Institutes of Health) funded/sponsored international multi-center clinical trials on treatment development for HIV/AIDS and co-infections. She received her MD from China and was a Medical Director for two hospitals before she received a PhD from Israel. She has published influential research findings in world leading journals. She is the Member of Asian American Executives Networ and will be graduated from its Senior Executive Service Candidate Development Program in April 2017.
Background: Tuberculosis (TB) and HIV/AIDS have been closely linked since the beginning of AIDS epidemic. TB is the most common co-infection and cause of death among the AIDS population. And yet, there isn’t rapid, accurate, and reliable diagnosis methodology for TB testing, especially in resource-limited countries. Treating HIV/AIDS patients with the available 4 TB drugs has been utilized in some African countries to manage AIDS patients that were potentially afflicted with TB not diagnosed. In order to evaluate this treatment/prevention strategy for such patient population, the Division of AIDS at the National Institute of Allergy and Infectious Diseases, one of the 27 institutes and Centers of the National Institutes of Health, funded / sponsored a multicenter international clinical trial project.
Methods: An open label, randomized clinical trial was conceived in 2008 and the first patient was enrolled in October 2011. The study has completed the last patient follow-up in June 2014. The protocol included two arms. Arm A has received standard anti-HIV treatment therapy plus four anti-TB drugs, isonizid (INH), Rifampin (RIF), pyrozinamide (PZA), and Ethambutol (EMB). Arm B has received standard anti-HIV treatment plus isoniazid, a WHO recommended strategy to prevent TB. All participants had CD4 counts less than 50 per μL.
Results & Conclusion: The trial enrolled 850 patients and conducted in 18 clinical trial sites in Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda. We hypothesized that the empirical treatment would reduce the mortality in this patient population. However, the results from the trial showed that the mortality rate was same for both study arms. Furthermore, the TB incident rates in Arm A were significantly higher in the treatment arm compared to control arm (33 versus 19). The results illustrated that adding RIF, PZA, and EMB were not helpful, and possibly harmful. Drug-drug interactions maybe one of the reasons and the real-time drug concentration tests are among the other measurements to explain these study results.
Geraldine has completed her PhD in Statistics from The Ohio State University. She is currently section manager of the Statistical Sciences department at Abbott Nutrition R&D. In this role, she provides statistical leadership in the design, monitoring, analysis, and interpretation of clinical trial data, contributes to regulatory submissions and registration efforts globally, assists legal, QA and Food Safety groups, and manages the strategic direction of the Statistical Sciences group.
Randomized controlled trials provide a high level of evidence regarding the cause and effect relationship between intervention and a predefined primary outcome. Adequate well-controlled trials do not come with a low price tag. When the primary outcome show small non-significant positive trends, what can be done to salvage the trial? While these neutral trials fall short of providing convincing evidence of efficacy, sponsors are well served in mining the data for potential answers to the following (1) are there any subgroups that may potentially benefit from the intervention?, and (2) are there any posthoc analyses that may help elucidate the treatment effect? Posthoc analyses may help improve study design and in some cases establish care pathway. Subgroup analyses are a useful hypotheses generating activity for future trials. Preferably, they have been prespecified in the study protocol, based on the study primary outcome, found by tests for interactions [Wang, Lagakos, Ware, et al] and based on baseline risk categorization [Pocock and Lubsen]. We present examples based on the sponsor experience and from the literature.
Sensoplex, Inc., USA
Title: A high prescision gait analysis system for in community monitoring of patients with neurological and musculoskeletal disorders
Time : 12:40-13:00
Hamid Najafi is currently the CEO of Sensoplex, Inc. a company specialized in development of wearables, software, and algorithms for clinical trials, which he co-founded in 2012. Prior to Sensoplex, he was General Manager of Invensense International at Invensense, a leading Silicon Valley manufacturer of MEMS motion sensors. He co-founded Broadlink Research Inc. in 2005 which developed the first disney mobile phone which was marketed by Vodafone in Europe. He was the founder of wireless link, a developer of advanced wireless products. He has 14 patents. He received his PhD in electrical engineering from Stanford University in 1983.
Neurological disorders, such as Parkinson’s, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) and musculoskeletal disorders, such as muscular dystrophy, significantly affect the patients’ gait. Monitoring, analyzing, and quantifying patients’ gait with high precision is achieved in motion analysis laboratories using optical systems as well as pressure sensitive mats. This method has inherent limitations and disadvantages such as having the patient to go to these labs, the expense of conducting the tests, the limitation of time when data is collected, and more. By contrast, an in community wearable system does not suffer from the disadvantages listed above, as long as it is accurate enough to produce medical/clinical quality data. The system presented here consists of a small wearable device worn around the ankle of the patient and high precision motion analysis algorithms and software that accurately measures gait parameters such as stride length, stride speed, double support time, cadence, distance traveled, 25-ft straight walk speed, six-minute walk speed and distance and more. It also detects context such as walking up/down stairs, running vs. walking, walking on a non-straight line, etc. The above information is used as a biomarker of how the patient is doing, the severity of the disease, its progression over time, and the effectiveness of treatments. Case studies for sroke, MS, and muscular dystrophy patients are presented from patient data collected over extended periods of time.
Carolinas HealthCare System, USA
Time : 13:40-14:00
Lindsay Lowe currently serves as a Research Coordinator for the Department of Family Medicine. She has been with Carolinas HealthCare System for nine years and spent the last three years working in research on medication and software studies. Lindsay has a BS degree in Exercise Science from the University of North Carolina at Charlotte.
Clinical trials actively engage participants in their healthcare, exposing them to innovative treatments that may improve their condition and help others. Effective programs select studies that positively impact their patients’ health. Carolinas HealthCare System (CHS) is one of the nation’s largest healthcare systems. The CHS Department of Family Medicine Clinical Trials Division is home to the Mecklenburg Area Partnership for Primary Care Research, a practice-based research network. The research group is physically collocated within a family medicine residency training program, offering convenient access to providers and patients within a network of 6 ambulatory primary care practices with 30 faculty physicians, 69 resident physicians, and 5 advanced care practitioners, caring for 22,000 patients. A unified electronic medical record provides seamless communication amongst the large multidisciplinary research team and referring providers. Partnerships with the healthcare system’s advanced analytics and research finance departments support screening and fiscal efforts respectively. Over the past 8 years, the department has generated over 10 million dollars in revenue, brought on 14 clinical trials and enrolled nearly 600 participants. The team has maintained high rates of retention as a result of exceptional participant and teammate satisfaction. Most clinical studies have been phase 4 trials, funded by federal agencies and pharmaceutical companies, studying diabetes, hypertension, dementia, chest pain, retinopathy, and gastroesophageal reflux disease. Having varied funding source has allowed for low turn-over of team members, which maintains continuity for the study participants, and has enabled growth within the department.
HCA Healthcare, USA
Time : 14:00-14:20
David is a well-known leader and change agent in the clinical research industry. He was born and raised in New Orleans, Louisiana. He has a Masters degree in both Social Work and Business Administration and holds the additional status of Certified IRB Professional (CIP) and Regulatory Affairs Certification (RAC). He is the Responsible Executive for Clinical Research for Hospital Corporation of America (HCA). He is and has been in many industry leader roles both in the United States and globally, including Chair of the Board of Trustees for the Association of Clinical Research Professionals (ACRP). He is also the President of the Nashville Angel Capital Group. He is married with 2 children and lives south of Nashville, Tennessee where he involves himself in work, family life as well as other charitable and entrepreneurial opportunities. David was recently honored with the “Outstanding Speaker” award, presented at the 2015 MAGI West conference.
This session will explore innovative approaches to workforce development, including collaborative initiatives to develop and standardize core competencies for clinical research professionals. While many initiatives are bringing forth process and technology solutions to clinical development, less focus has been given to workforce development despite the persistence of FDA inspection findings, shortages in the workforce, and considerable variance in overall trial conduct. This session will outline the changing roles and responsibilities of CRAs and CRCs, and ACRP-led, collaborative initiatives to define competence standards for professionals conducting monitoring and study conduct activities.
Nucleon Therapeutics, India
Title: PVG amd drug safety- Pharmacovigilance in India and emerging markets: An industrial perspective
Time : 14:20-14:40
Ujwala V Salvi has over 15 years of experience across the global and local Pharmaceutical/CRO, tier I Medical Devices and BPO industry. A MBA from Indian Institute of Management, Kolkata, Doctorate in Applied biology, trained Six Sigma Black Belt and various Project management tools, with core Experience in a wide range of Therapeutic Areas, and worked at all stages of clinical development from Phase II to production of clinical documentation necessary for product license applications. She has worked in large global operations, managed strategic relationships, and played a key role in winning new business, setting up off-shored partnerships and in identifying new BU service lines and growing existing ones. Her areas of expertise include Clinical Trial operations, Risk Based Monitoring, Medical Writing and data publication, Clinical Data Management, and feasibilities of new drug development and Analytics. She is an industry expert, has been involved in key global industry forums such as the DIA, SCDM, CII and CPHI.
Development and implementation of evidence-based, public-health focused, collaborative, globally electronic and regulatory compliant approach is need of hour to gain comprehensive Pharmacovigilance (PV) system. The authors discuss development of a model for uniform PV data input-output across industry. Authors contemplate data collection; data analysis; data processing; medical review and data distribution systems as basic PV process. Data collection systems should include detailed process of collecting various adverse events (AEs) from literature searches, healthcare professionals (HCP), non-HCP, spontaneous, clinical trials, patient registries, post marketing surveillance etc. Data should be processed in CIOMS form I by using ARGUS, ARISg, MedDRA, WHO drug dictionary and company drug repository or local regulatory AE form, etc. It should be medically reviewed followed by distribution to respective regulatory authorities where thorough signal identification, prioritisation and investigation will be performed. Signal detection can be done by using Medline/PubMed, Springer, OVID database, reactions weekly, local publications etc. Non-english cases/literature reports should be translated to english via authorised vendor or in-house translation system. Safety data from license partners and third party manufacturers should be collected and processed by maintaining safety data exchange agreements (SDEA). PV model can be fully in-house end to end or part in-house and part outsourced or fully outsourced. In conclusion, an effective implementation of PV activities like robust PV systems, signal detection and SDEAs could definitely yield robust patient safety data from India and emerging markets.
Valmont Pharma, USA
Time : 14:40-15:00
Sergio Guerrero holds a longstanding experience organizing, managing and conducting clinical trials in the Latin American region for the US and international pharmaceutical and biotechnology industry on new drug and medical devices development in accordance with US FDA, the ICH/GCP guidelines, EMA, and local regulations. For numerous years, he worked as Director of a Clinical Research Center in Mexico where he managed a multispecialty medical group and investigators in the conduct of clinical trials phase I-IV. He also has been a Regional Director of Latin American for a CRO based in Raleigh, North Carolina where he managed clinical teams and medical researchers in the conduct of multinational clinical trials; Previously, he was the Director of an SMO in Mexico City managing of multi institutional research alliances in the conduct of clinical trials for the pharmaceutical industry. With more than 18 years of experience in the clinical and medical research activities he has held numerous positions to include Director of Clinical Operations, Manager, Investigator, Project Manager, Quality Assurance Auditor, and trainer for the International pharmaceutical/ CRO/SMO industry. He received his Medical Degree from the School of Medicine of the Universidad in Juarez, Mexico. Initiated his medical research career in Bethesda, MD (USA) participating in the transplant research technology that later lead him to coordinate and manage the operation according to the Food and Drug Administration of the United States.
The globalization of R&D into emerging regions has continue to grow more in the last decade in Latin America, driven by many factors including improved regulatory environment, commercial markets, favorable economics with lower relative costs, access to highly skilled professional and a large pool of patients in the region. But, now with a better established atmosphere and a strong healthcare infrastructure, Latin America offers a number of advantages as a location for clinical trials, and at the same time, the region presents other challenges particularly related to the industry that must be anticipated and managed appropriately, because we still confronting significant logistical battles and delays in implementing clinical trials in the region due to improper planning of the developments by the industry, that potentially could interfere with any new regional improvements and potentially interrupt results. If the clinical research industry is willing to take the moment and better understand their processes adapting new approaches to support an efficient global drug development program in the region, the results can be notable on time and manner. This session is intended to analyze key issues, opportunities (Good), challenges (Bad) and the unknown of doing clinical trials implementation in Latin America, and to review and understand a better planning when selecting the Latin American region to participate in a Global Clinical Trial.
Thomas Jefferson University, USA
Title: Conceptual progress in the management of sickle cell pain from individualized trial and error approach to a specific pharmacologic precision medicine
Time : 15:00-15:20
Samir K Ballas received his MD with distinction from the American University of Beirut-Lebanon in 1967. He completed his training in Hematology at Thomas Jefferson University in Philadelphia, Pennsylvania. He is board certified in internal medicine, hematology, blood banking, pain medicine and pain management. He is currently Emeritus Professor of Medicine and Pediatrics at Thomas Jefferson University and honorary Staff Member of Hemorio, the Hematology Institute in Rio de Janeiro, Brazil. He has authored or co-authored over 800 articles, book chapters and abstracts. He also published two editions of a book on sickle cell pain in 1998 and 2014 respectively.
Sickle cell disease (SCD) is an inherited disorder that affects 100, 000 African Americans and about 100 million individuals globally. Upon deoxygenation, the sickle hemoglobin polymerizes and initiates a series of events leading to vascular occlusion, tissue hypoxia, pain and progressive organ damage. Recurrent acute painful episodes are the hallmark of SCD that require treatment in the emergency department and/or hospital with relatively large doses of opioids. Up to the 1960s, SCD was primarily a disease of children. In the 1970s, survival increased and transfer to adult care increased progressively. Soon adult programs were overwhelmed with a large number of patients with frequent utilization of medical facilities, heavy consumption of opioids and suboptimal insurance coverage. As a result, patients with SCD were accused of drug-seeking behavior and addiction. Consequently, pain was under treated and, at best, was on the basis of trial and error for each patient. As the controversy about the treatment of sickle cell pain was brewing, the advent of precision medicine came to the rescue. Pharmacodynamically, opioids function as ligands that bind to and activate specific helical receptors in the central nervous system. If an opioid does not activate receptors, its analgesic effect would be absent. Pharmacokinetically, each drug is metabolized into specific active or inactive metabolites depending on the presence of genetically determined enzymes. The net effect of an opioid depends on the specific receptors and enzymes in each patient. This explains why different patients responded differently to an opioid. Pain management should be precision medicine-dependent.
Howard University, USA
Time : 15:20-15:40
Dr. Lennox A. Graham is an innovative educator and practitioner with extensive experience in the design, delivery, evaluation, and enhancement of effective instructional programs and management assessment models. He is a highly articulate and effective communicator with excellent team building and interpersonal skills. Dr. Graham's training, inclusive of his Master of Science Degree in Education and his Doctoral Degree in Management and Organizational Leadership, have equipped him for leadership. Dr. Graham has several notable awards which affirm the significance of his experience; and he understands and acts with integrity in all of his pursuits.
Historically, Blacks have been disproportionately, underrepresented in clinical trials. In addition to limiting the generalizability of results of these clinical trials to the Blacks population, the determinants of their participation in clinical research remain poorly understood. Outcomes of suboptimal participation include poor understanding of the predictors and treatment of the disease, increasing health disparities, poor health equity, and suboptimal wellness of the nation. To address this gap in the literature, we analyzed our recruitment data to identify the most effective strategies for enrolling older Blacks in clinical trials. Of the total 3,266 screened, we included 2,830 Blacks volunteers for further analysis. Overall, more women than men (73.8% vs. 26.2%) participated in our recruitment activities. However, a significantly higher proportion of men than women were engaged through family (3.86% vs. 1.30%, p = 0.0004) and referral sources (5.89% vs. 2.59%, p = 0.0005). Compared to other recruitment sources, we encountered a higher proportion of volunteers at health fairs (42.95%), and through advertisements (14.97%). In our sample, years of education and age did not appear to influence the likelihood of an encounter, screening and potential participation. These findings indicate that we mostly recruited Black men and women from health fairs, and through advertisements tailored to their health needs and interests. Conversely, we mostly recruited Blacks men through family referrals and persons known to them, indicating a need for trust in their decision to engage study personnel and or participate in clinical trials.
International Centre for Diarrhoeal Disease Research, Bangladesh
Time : 16:00-16:20
Wasif Khan, a medical graduate from Bangladesh; performed Graduate Training Program in Clinical Investigation (GTPCI) from Johns Hopkins Bloomberg School of Public Health; obtained fellowship in Clinical Pharmacology from Division of Pharmacology, Johns Hopkins School of Medicine. Has over 26 years of experience in Clinical Trials. At present actively involved in promoting clinical trials on non-communicable diseases to collaborate with other national institutes and specialized physicians within Bangladesh and the global CROs / multi-national pharmaceuticals looking for new sites with patient naïve population.
Lower costs to conduct clinical trials and availability of treatment-naïve patients have attracted many pharmaceutical companies to conduct clinical trials in developing countries in Africa, China, India, and parts of Eurasia. However, despite having a large patient base and diverse disease profiles, until recently Bangladesh could not appropriately participate in global clinical trials due to the lack of clinical research infrastructure. In a recently conducted study in lupus nephritis (LN) study conducted over 80 sites from 23 countries – Bangladesh was included as second tier when recruitment was alarmingly slow with the first tier. LN is a rare disease requiring the use of a global approach to recruitment. The total time required in Bangladesh to obtain central as well as the site IRB approvals was 4 months. Although the initial country target was to enroll a maximum of 25 patients from Bangladesh, quality in clinical care and ensuring the ICH-GCP guidelines were closely and constantly maintained allowed for an increase in countrywide enrollment. This resulted in ultimate highest patient enrollment from Bangladesh (n=46) out of total n=265 patients enrolled globally. In this study 80% of clinical studies fail to meet enrollment deadlines, and 50% of sites enroll 1 or no patients. Bangladesh a country of over 160 million with many treatment naïve patients; increased number of lifestyle diseases are emerging with the change of the economy of the country from low to middle income country. Young physician Investigator has the medical training in English and trained in the same standard as UK Investigators. The combination of population availability, high quality Investigators and the common use of English points to Bangladesh as a potential new hub for international clinical trials and global CROs to explore in this newly emerged clinical research country. That results in faster recruitment, saving unnecessary investigations and reducing overall study cost. Most importantly new drugs those are in the pipeline are evaluated much faster through Clinical trials for regulatory approval and thus the neediest patients are privileged with newer medicines that could benefit both morbidity and mortality.
Tarleton State University, USA
Time : 16:20-16:40
Myoung-Gwi Ryou has completed his PhD in 2008 from University of North Texas Health Science Center and Postdoctoral studies from University of Texas Southwestern Medical School. He is the Director and an Assistant Professor, Dept of Medical Labolatory Science and Adjunct Faculty in the UNTHSC. He has published more than 23 papers and chapters in reputed journals and has been serving as an Editorial Board Member of several peer review journals.
Ischemia and reperfusion (I/R) injuries are critical life-threatening diseases and may end up with serious adult disability, but FDA-approved treatment is limited. Classical chemicals such as methylene blue (MB) and pyruvate have been revisited to evaluate protective roles in I/R injuries including ischemic stroke and myocardial infarction. Oxidative stress and inefficient energy metabolism are the pivotal contributors to I/R diseases. Results from bench studies support that both pyruvate and MB increases ATP production and have potent antioxidant effect. However, detailed mechanisms of beneficial effects are different between pyruvate and MB. MB rather prevents electron leakage through electron transport chain in the mitochondria and by which energy metabolism enhanced. On the other hand, pyruvate enhanced endogenous redox state, such as the ratio of GSH to GSSG, and improves ATP production by providing metabolic resources required for the glucose metabolism. Furthermore, the effects of MB and pyruvate on the gene regulation have been investigated. Both MB and pyruvate enhances cellular ability to resist against ischemic stress by activating hypoxia inducible factor-1. In conclusion, pyruvate and MB, old chemicals, have two-phase effects on I/R injury. Short-term effect, MB and pyruvate can protect the victims of various I/R diseases by reducing oxidative stress and enhancing energy metabolisms. The long-term effects of MB and pyruvate allow the conversion of gene profiles to help protect and restore from I / R damage.
Islamic Azad university, Iran
Title: The effect of Progressive Resistance Exercises (PRE) with knee flex device made by researcher to increase muscular power and ROM after knee arthroplasty operation
Time : 16:40-17:00
Bijan Goodarzi has completed his PhD at the age of 47 years from Mysore University. He is the assistance profossor of Department of sport phathology in islamic Azad university of Borujerd. He has published more than 27 papers in reputed journals and has been serving as an editorial board member of repute.
One of the most important problems of knee arthroplasty operations is the speed of rehabilitation in patients. The object of this study wase to analyze the progressive resistance exercises (PRE) with knee flex device and its effect in increasing muscular power and specially decreasing the angle of ROM in people who had Arthroplasty operation.
This study was to Quasi – experimental and has done on 30 voluntary male patients between 55–60 who had knee arthroplasty. These patients were randomly divided in 2 groups of control and experimental each with 15 samples and then completed standard questionnaire (oxford score knee) and described their physical situation, and their life after knee arthroplasty. In the first evaluation to register the knee ROM and determine the power of Quadriceps femoris muscle, the digital set square and dynamometer device were used. To measure their pain we used the Visual Analogue Scale (VAS). The experimental group in 8 weeks and 3 sessions per week were done exercise with different degrees of knee flex device and at the end data were collect in both groups and analyzed by descriptive and dependent – independent (t) test .
The results showed that working with knee flex device and doing progressive resistance exercises is meaningful in decreasing the angle of knee and increasing power and decreasing the muscle pain in experimental group p<0.05
Doing resistant exercises with knee flex device decreases the knee flexion angle, increases the power of Quadriceps femoris muscle and also decreases the pain of knee in people who had knee arthroplasty
- Workshop on
Current State of Statistical Methods in Handling Missing Data in Clinical Trials
Merck Research Laboratories, USA
Richard Entsuah is a Fellow of the American Statistical Association. He completed his PhD from University of Michigan. He was an Assistant Professor of Biometry at University of Illinois in Chicago. He joined Wyeth Research from 1988 to 2007 and left as an Assistant Vice President of Global Biostatistics and Programming. He joined Merck Research Labs as Executive Director of Late Development Statistics and is the Research Group 4 Head for Neuroscience and Respiratory of and Immunology.
The issue of missing data in clinical trials seems to be an ongoing challenge resulting in different statistical methods that have been proposed to deal this ongoing problem. We shall discuss mitigation strategies to prevent missing data which can help minimize dropout rates. This workshop will provide an overview of various methods that have been adopted by applied statisticians in drug submissions in recent years. The focus will be on longitudinal continuous data using both parametric and non-parametric methods. The choice of primary estimands is gaining lots of attention in the filed recently and we shall discuss these points. The concept of missing at Random (MAR) and missing not at random (MNAR) which has gained much attention in the last two decades will be discussed. This will include techniques like mixed model repeated measure (MMRM), selection models, pattern mixture models, jump to reference, dipping point, multiple imputations and ETRANK®-a nonparametric method.