Day 1 :
Keynote Forum
Eugenia Hong
The Royal Melbourne Hospital Clinical Trials Pharmacy, Melbourne Health, Australia
Keynote: The role of clinical trials pharmacist in study medication adherence
Time : 10.00-10.45
Biography:
Eugenia Hong is a senior pharmacist in charge of clinical trials pharmacy at the Royal Melbourne Hospital, Melbourne Health, Australia. She leads clinical trials pharmacy which provides a wide-range of clinical research services for over 300 studies conducted in Melbourne Health. Eugenia Hong is a committee member of Specialty Practice (COSP) in Investigational Drugs in The Society of Hospital Pharmacists of Australia and published the Standards of Practice for Pharmacy Investigational Drugs Services in Australia and Clinical Trials Starter Kit as a member of COSP.
Abstract:
The adherence of participants on study medication is critical to the accurate interpretation of study results. As patient education and counselling are important responsibilities for pharmacists in all practice settings, clinical trials pharmacists should also be actively involved in counselling the participants on study medications. The effects of clinical trials pharmacist counselling on medication adherence were previously studied and the results were presented at the Pharmacovigilance conference in 2012 (99% in participants with counselling from pharmacists vs 89% in participants without (p>0.05)). A replication study was conducted in 2015 and the adherence rate for participants who received counselling from pharmacists was 98% compared to 76% for participants who did not. This assures the positive effects of counselling by clinical trials pharmacist on participant adherence in clinical trials medication. It was also noted that the participant adherence declined as the dosing frequency was increased. The decrease was more significant (81% to 67%) when the participants had not been counselled by the pharmacist (p<0.05). For those participants who received counselling by the pharmacist, the decrease (98% to 97%) was not significant (p>0.1). The results signify the importance of participant counselling by pharmacist when the treatment regimen are more complicated. In the clinical trial setting where the measurement of medication adherence is essential for interpretation of the results, counselling by the pharmacist could contribute to more accurate outcomes. Often the role of pharmacist in clinical research is somewhat limited to drug management, but it should be recognized that the clinical trials pharmacist has an in-depth knowledge of pharmacotherapy and study protocol and is capable of providing comprehensive clinical services for study participants.
Keynote Forum
Nathan Cummins
Mayo Clinic, USA
Keynote: Investigation of Efavirenz discontinuation in multi-ethnic populations of HIV-positive individuals by genetic analysis
Time : 10.45-11.30
Biography:
Nathan Cummins completed his MD at the University of Kentucky, and Internal Medicine and general Infectious Diseases training at the University of Cincinnati. He completed further subspecialization fellowship training in Transplant Infectious Diseases at the Mayo Clinic Rochester. He is currently an Assistant Professor of Medicine in the Mayo Clinic College of Medicine, and Senior Associate Consultant in the Division of Infectious Diseases, Department of Medicine, Mayo Clinic. He has published more than 30 peer-reviewed scientific papers in reputed journals.
Abstract:
Efavirenz (EFV) based antiretroviral therapy is expanding worldwide. However discontinuation of EFV containing regimens is common, due most often to neuropsychiatric side effects. We genotyped CYP2A6, CYP2B6 and CYP3A4, which encode enzymes principally involved in EFV metabolism, from HIV positive patients enrolled in multinational studies, for whom outcome data of treatment adherence was available. Patients with loss or decrease of function single nucleotide polymorphisms (SNPs) in the above genes were assigned a risk score based upon the number of SNPs present. Cox regression models were used to study the association between high genetic risk and time from initiation to EFV discontinuation other than for virologic failure or protocol determined discontinuation. Patients with highest pharmacogenetic risk had an increased risk of discontinuation of EFV containing therapy compared to patients with lower genetic risk scores (adjusted HR 1.9, P=0.009). High genetic risk score was not associated with an increased risk of discontinuing atazanavir or nevirapine. High genetic risk was present more often in blacks compared to non-blacks (Adjusted OR 4.5), and treatment discontinuation was also increased in blacks overall (Adjusted HR 1.4). However, high genetic risk was more associated with treatment discontinuation than race alone for both blacks (Adjusted OR 1.9) and non-blacks (Adjusted OR 5.3). Premature discontinuation of ART delays the time to effective long term viral suppression, and is associated with significant morbidity. Pharmacogenetics may predict those at high risk of EFV discontinuation, and therefore should be considered in patients in whom initiation of EFV based ART is being considered.
Keynote Forum
Alexey Skripkin
BIOCAD, Russian Federation
Keynote: Postmarketing safety surveillance program results of the first Russian interferon beta-1b biosimilar
Time : 11.45-12.30
Biography:
Alexey Skripkin, MD. He graduated from Rostov State Medical University (Rostov-on-Don, Russia) in 2005, passed Residency in neurology (2005-2007) and postgraduate training program (2007-2010) at the Moscow State Medical Academy n.a. I.M. Sechenov (Moscow, Russia). He continues his neurological practice. Alexey has 6 years of experience in pharmacovigilance, has passed a number of comprehensive pharmacovigilance and pharmacoepidemiology trainings in 2010-2016. He was an neurolology medical affairs manager at BIOCAD in 2010-2012. He is the BIOCAD’s Qualified Person for Pharmacovigilance since 2010, and the Head of Drug Safety Department since 2013.
Abstract:
The first Russian interferon beta-1b biosimilar was registered by CJSC BIOCAD in September of 2009 in the territory of the Russian Federation, and by the end of 2015 the exposure was 14 789 patient-years. BIOCAD initiated an intensive monitoring program. By the April of 2016 there were 1903 ICSR processed. The bulk of notifications, 58.5% (n=1115) was received by the company specialists: 805 notifications (42.3%) were received from the patients, 300 notifications (15.7%) – from the patient support team members, 10 notifications (0.5%) – from the healthcare specialists. There were 788 notifications (41.1%) received from the national regulatory authority (Roszdravnadzor). Additionally, BIOCAD has initiated a non-interventional observational study. 650 patients were included, at this stage the study database is being prepared for the final analysis. Most often the patients had injection site reactions (n=1256), general reactions (n=1189), as well as the nervous system reactions (n=383). There were 8 cases of injection site necrosis, that, taking into account exposure and intense monitoring, is a low value. 41 notifications on the lack of efficacy do not contradict the information about the drug product as about 25% of patients had no response. There were 8 reports of pregnancy. Four of them resulted in a birth of a healthy child, three were spontaneously interrupted (one in the stage of 5 weeks because of thrombocytopenia, two – in the stage of 14 weeks), one pregnancy still continues. Unexpected reactions have low levels of causality, new risks have not been identified. The received information confirms the known risk/benefit ratio.
- Pharmacovigilance Scope & Significance | Pharmacovigilance Risk Management | Drug Safety
Location: Conference Room 4
Chair
Eugenia Hong
The Royal Melbourne Hospital Clinical Trials Pharmacy, Australia
Co-Chair
Mario Bertazzoli
Helsinn Healthcare SA, Switzerland
Session Introduction
Cristina Damatarca
Agility Clinical, USA
Title: Unique challenges and opportunities in conducting Pharmacovigilance for orphan drug
Time : 12.30-13.00
Biography:
Dr. Damatarca has over 17 years of experience in the biopharmaceutical industry, across all stages of development and product commercialization. In her current position as Vice President of Medical Affairs and Pharmacovigilance at Agility Clinical, Dr. Damatarca provides oversight for all medical affairs and drug safety activities for Agility Clinical, which focuses on rare diseases.Before joining Agility Clinical, Dr. Damatarca was Vice President and Head of Drug Safety and Pharmacovigilance at Clovis Oncology, where she provided oversight for all safety aspects of the clinical development program for Clovis oncology molecules. Before that, Dr. Damatarca served as Executive Director and Head of Safety at Avanir Pharmaceuticals, where her responsibilities included oversight of clinical trials and postmarketing safety, pharmacovigilance, medical review, signal detection, aggregate reporting, and risk management. Previous functions included senior roles in Pharmacovigilance as Therapeutic Area Head for the Oncology Signaling Franchise at Genentech-Roche and before that, as Global Safety Officer and Global Safety Forum Chair at Amgen for various products in Oncology, Oncology–Hematology, and Inflammation-Internal Medicine. While at Amgen, she also served as the Chair of the Global Safety Forum, an internal advisory board for safety issues. Prior to Amgen, Dr. Damatarca worked in drug safety at several pharmaceutical companies. At Amylin Pharmaceuticals, she worked on products within the company’s product portfolio in the diabetes and metabolic disorders pipeline, most notably on two new molecular entities in diabetes. At Ligand Pharmaceuticals, she worked on several drugs in Oncology and Pain, and served as safety officer for various international clinical trials. During her tenure in drug safety and pharmacovigilance at various pharmaceutical companies, Dr. Damatarca participated in several Drug Advisory Committees and served on the teams who developed REMS - RiskMAP – risk management programs for various products, some of these having played a key role in optimizing the benefit-risk profile of the products.
Abstract:
Diseases that manifest in patient populations representing at the maximum 6–8% of the world population are defined as rare diseases or orphan diseases. These are pathologies whose incidence at birth is less than 1 in 2000. Orphan diseases are often so rare that a physician may observe only 1 case a year or less, and proper treatment may only be a personalized encounter between doctor and patient. One way to fill this therapy vacuum is by developing orphan drugs. Orphan drugs are a significant part of personalized medicine. In order to optimize the benefit-risk of these medicines, innovative pharmacovigilance methods need to be put in place that take into consideration the unique challenges of drug development for orphan indications as well as the realities of the patient population. The presentation will provide a summary of the existing methodologies for performing targeted pharmacovigilance for orphan drugs, as well as new innovative methods developed to address some of these challenges.
Cristina Damatarca
Agility Clinical, USA
Title: Unique challenges and opportunities in conducting Pharmacovigilance for orphan drug
Biography:
Dr. Damatarca has over 17 years of experience in the biopharmaceutical industry, across all stages of development and product commercialization. In her current position as Vice President of Medical Affairs and Pharmacovigilance at Agility Clinical, Dr. Damatarca provides oversight for all medical affairs and drug safety activities for Agility Clinical, which focuses on rare diseases.Before joining Agility Clinical, Dr. Damatarca was Vice President and Head of Drug Safety and Pharmacovigilance at Clovis Oncology, where she provided oversight for all safety aspects of the clinical development program for Clovis oncology molecules. Before that, Dr. Damatarca served as Executive Director and Head of Safety at Avanir Pharmaceuticals, where her responsibilities included oversight of clinical trials and postmarketing safety, pharmacovigilance, medical review, signal detection, aggregate reporting, and risk management. Previous functions included senior roles in Pharmacovigilance as Therapeutic Area Head for the Oncology Signaling Franchise at Genentech-Roche and before that, as Global Safety Officer and Global Safety Forum Chair at Amgen for various products in Oncology, Oncology–Hematology, and Inflammation-Internal Medicine. While at Amgen, she also served as the Chair of the Global Safety Forum, an internal advisory board for safety issues. Prior to Amgen, Dr. Damatarca worked in drug safety at several pharmaceutical companies. At Amylin Pharmaceuticals, she worked on products within the company’s product portfolio in the diabetes and metabolic disorders pipeline, most notably on two new molecular entities in diabetes. At Ligand Pharmaceuticals, she worked on several drugs in Oncology and Pain, and served as safety officer for various international clinical trials. During her tenure in drug safety and pharmacovigilance at various pharmaceutical companies, Dr. Damatarca participated in several Drug Advisory Committees and served on the teams who developed REMS - RiskMAP – risk management programs for various products, some of these having played a key role in optimizing the benefit-risk profile of the products.
Abstract:
Diseases that manifest in patient populations representing at the maximum 6–8% of the world population are defined as rare diseases or orphan diseases. These are pathologies whose incidence at birth is less than 1 in 2000. Orphan diseases are often so rare that a physician may observe only 1 case a year or less, and proper treatment may only be a personalized encounter between doctor and patient. One way to fill this therapy vacuum is by developing orphan drugs. Orphan drugs are a significant part of personalized medicine. In order to optimize the benefit-risk of these medicines, innovative pharmacovigilance methods need to be put in place that take into consideration the unique challenges of drug development for orphan indications as well as the realities of the patient population. The presentation will provide a summary of the existing methodologies for performing targeted pharmacovigilance for orphan drugs, as well as new innovative methods developed to address some of these challenges.
Mario Bertazzoli
Helsinn Healthcare SA,Switzerland
Title: Netupitant-palonosetron: safety profile of a novel fixed-dose combination drug in the prevention of chemotherapy-induced nausea and vomiting
Time : 13.00-13.30
Biography:
Mario Bertazzoli is a physician and a registered specialist in Human Reproduction Pathology. He received both medical and specialization degrees from the University of Milan, Italy. He worked since 1995 for international pharmaceutical companies as pharmacovigilance and pharmaco-epidemiology physician. He is currently the Head of Corporate Drug Safety and Reference Physician to the EU Qualified Person for Pharmacovigilance for the Helsinn Group. He is founder and treasurer of the International Society of Pharmacovigilance, Swiss-Austrian Chapter.
Abstract:
Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy that may seriously impair patient quality of life, cause nutritional and metabolic disturbances, and interfere with the motivation of patients to follow recommended treatment regimens. Of all the known predictive factors, the intrinsic emetogenicity of a given chemotherapeutic agent is the predominant factor in predicting the development of CINV. The netupitant-palonosetron combination (Akynzeo®) is an oral fixed dose combination of 300 mg netupitant and 0.5 mg palonosetron hydrochloride with a safety profile comparable to that of its single components. Netupitant is a neurokinin-1 receptor antagonist (NK1 RA) while palonosetron is a serotonin type 3 (5-HT3) RA which has been used extensively for the prevention of CINV since 2003. To evaluate the most important identified and potential risks of the single active ingredients with those of the fixed combination. A conservative approach was adopted with the known and potential risks identified for palonosetron considered in the evaluation of the risks associated with netupitant. Thorough QT studies in healthy volunteers showed no sign of any effect on atrioventricular conduction or cardiac depolarization or any new clinically relevant morphological changes. Phospholipidosis and serotonin syndrome were considered potential risks; the former having only been observed in netupitant pre-clinical studies and the latter potentially related to palonosetron. No additional risks were generated by the combination of the two constituents. Routine risk minimization measures were considered adequate in the EU-RMP while REMS was not required by the FDA.
Silvia Cacho-Elizondo
IPADE Business School, USA
Title: Consumer acceptance of mobile-assisted smoking cessation programs
Time : 14.15-14.45
Biography:
Dr. Silvia Cacho-Elizondo is an Associate Professor of Marketing and Academic Director for In-Company Programs at IPADE Business School in México. She has been lecturer in several business schools in Europe and Latin America. She earned her PhD at HEC Paris, (thesis: The impact of online services on the consumer-brand relationship). Her research interests: Consumer Behaviour, Brand Relationships, Innovation Adoption Processes, Mobile Services and CSR. She has published in: Journal of Retailing and Consumer Services, Journal of Health Marketing Quarterly, International Journal of Technology and Human Interaction, ISTMO, International Business Research Journal, International Journal of Hospitality Management, American Journal of Management, among others.
Abstract:
As countries move towards digital health services (e-health), advances in information and communication technologies (ICTs) are maximized with governments working towards integrating these technologies into their delivery of health care programs (Hyppönen, 2007). Therefore, the emergence of interactive communication technologies has added new dimensions to the delivery of health and lifestyle interventions and cessation programs (Brouwer et al., 2009; Della, Eroglu, Bernhardt, Edgerton, & Nall, 2008; Paek, Bae, Hove, & Yu, 2011; Portnoy, Scott-Sheldon, Johnson, & Carey, 2008). Herein, our goal is to present an overview of key findings emerged from different studies assessing smokers’ perceptions, motivations, and intentions towards the adoption of mobile-assisted smoking cessation programs. The technology acceptance model (TAM) was one of the core theoretical frameworks applied. Among the variable tested were: perceived ease of use, perceived usefulness and subjective norms on intention to use this intervention, as well as the mediation effects of perceived monetary value, enjoyment and annoyance.The vicarious innovativeness of smokers (perceptions, motivations and intentions) towards the adoption of mobile-assisted smoking cessation intervention programs was also evaluated. The methodologies combine qualitative and quantitative approaches to analyze smokers’ experiences and perceptions regarding this type of mobile services. Topics covered include: a) tobacco consumption, b) cessation initiatives, c) smoking giving up planned actions and d) attitudes towards mobile counseling. The findings to be discussed contribute to theory and practice.
- Preclinical and Clinical Trials | Data Quality Management and Analysis
Location: Conference Room 4
Chair
Eugenia Hong
The Royal Melbourne Hospital Clinical Trials Pharmacy, Australia
Co-Chair
Mario Bertazzoli
Helsinn Healthcare SA, Switzerland
Session Introduction
Eleni Konstantinou
Harvard Medical School, USA
Title: Mechanism of high MW complexes formation by Verteporfin (VP) can form high molecular weight complexes, which can impair the growth of cancer cells
Time : 17.00-17.30
Biography:
Eleni Konstantinou has completed her MD at the age of 24 years from Athens Medical School, National and Kapodistrian University of Athens and she is pursuing her postdoctoral studies in Harvard Medical School, Department of Ophthalmology, MEEI.
Abstract:
Verteporfin was first used in Photodynamic therapy (PDT), where a non-thermal 689nm light activates VP in the presence of oxygen to produce highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage. In addition, it has been shown VP can interfere with the HIPPO pathway in the absence of light and inhibit the growth of hepatocellular carcinoma, retinoblastoma and uveal melanoma. More recently we observed that VP can lead to the formation of dimers and high molecular weight aggregates. In a series of experiments, uveal melanoma (MEL 270), human embryonic kidney (HEK) and breast cancer cells (MCF7) were treated with either low (1.25ug/ml) or a high (7.5 ug/ml) dose of VP for 0, 6 and 24 hours. Dark and light conditions before and after lysis of the cells were examined in order to identify the exact cell cycle phase that the high molecular weight complexes occurred. We have demonstrated that VP aggregate formation requires light-activation and oxidization of VP. These high molecular weight complexes are toxic for the cells, leading to growth restriction and cell death. This work demonstrates yet another potential therapeutic mechanism of action of verteporfin.
Lisa Engelhardt
University Hospital of Wuerzburg, Germany
Title: Impedance spectroscopy for the non-destructive evaluation of in vitro epidermal models
Time : 17.30-18.00
Biography:
Lisa Engelhardt, M.Sc., has studied Life Science Engineering and graduated from Friedrich-Alexander University Erlangen-Nuremberg, Germany, in 2015. She is now working on her PhD at the Department Tissue Engineering and Regenerative Medicine at the University Hospital of Wuerzburg, Germany/ Translational Center “Regenerative Therapies for Oncology and Musculoskeletal Diseases”, branch of the Fraunhofer Institute for Interfacial Engineering IGB and Biotechnology in Wuerzburg, Germany, focusing on the development of vascularized skin models, the design of bioreactors for tissue engineering, 3D bioprinting, and impedance spectroscopy.
Abstract:
Reconstructed human epidermis (RHE) is standardly used for the risk assessment of chemical compounds. However, analysis is dependent on invasive methods such as histological processing or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. As an alternative to these methods, impedance spectroscopy can be performed as a nondestructive technology to analyze the integrity of epidermal equivalents. Therefore, RHEs were generated and impedance spectra were recorded during culture time and under different culture conditions. From these spectra, we extrapolated electrical characteristics such as the capacitance and the ohmic resistance. Furthermore, the measurable electrical parameters were used to quantify the effects of mechanical and chemical disruption of the epidermal integrity. A fully matured RHE exhibits typical impedance spectra in a frequency ranging between 1 Hz and 100 kHz, which is comparable to the spectra of freshly isolated human epidermal biopsies. We could show that, during RHE maturation, these characteristics change significantly. Thus, capacitance and ohmic resistance can be employed as a criterion for the quality control of skin equivalents. Additionally, our application of impedance spectroscopy reveals sufficient sensitivity to detect a transient decreased ohmic resistance caused by 2-propanol, which is classified as a non-irritant by MTT assays. These results indicate that impedance spectroscopy can be employed as a non-destructive complementary method to assess mild irritative effects, which is currently not possible. Besides testing for irritative potential of substances, mechanical wounding and subsequent wound healing by reepithelialization can be monitored non-invasively demonstrating the feasibility of the method for the assessment of reepithelialization.