Education and training of clinical research professionals and the evolution of the Joint Task Force for Clinical Trial Competency.

Clinical research professionals play a critical role in the design, conduct, and oversight of clinical trials, and they must have the knowledge, skills, and abilities to ensure that trials are conducted ethically, safely, and in accordance with regulatory requirements. As clinical research has evolved from being a necessary activity for the development and regulatory approval of new medicines to an accredited academic discipline and, more recently, to a globally recognized profession, the methods of education and training of professionals have also evolved. Initially, on-the-job informal coaching and specialized training organizations led to formalized and accredited academic degree programs and, more recently, to international competency standards and competency maintenance through continuous professional development. The Joint Task Force (JTF) for Clinical Trial Competency is a multidisciplinary, international group of experts who came together to aggregate and refine competency standards for clinical research professionals, first published in 2014. The 8 domains and 49 specific core competencies of the JTF Framework have become a globally recognized standard upon which education and training programs, role descriptions, and upward mobility criteria for professionals are now based. The JTF meets regularly and, through its workgroups, continues to evolve in response to the changing needs of the profession. The JTF is committed to continuous improvement to ensure that clinical research professionals have the competence necessary to conduct safe, ethical, and high-quality clinical research.

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach.

BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.

The influence of the menstrual cup on female pelvic floor muscles variables: a prospective case series.

The aim was to assess and report the effects of menstrual cup on pelvic floor muscles (PFM) function and tone, as well as check the acceptability after a period of three menstrual cycles in healthy young women. The data collected in assessments and reassessments included the International Consultation on Incontinence Questionnaire - Vaginal Symptoms (ICIQ-VS) questionnaire, evaluation of PFM function through PERFECT Scheme, PFM muscle tone, and PFM manometry (Peritron 9300®). A diary regarding the overall colletor acceptability and satisfaction was collected. Ten healthy young women completed the study. There was an improvement in the mean values of maximal voluntary contraction (MVC) (p = 0.032), a decrease in the vaginal resting pressure (VRP) (p = 0.05), and an increase in the number of repetitions of sustained muscle contractions (p = 0.042). Seven women reported some discomfort while using the vaginal cup only in the first cycle while three revealed discomfort during the whole experiment. This study provides preliminary case-based evidence that the use of the vaginal cup for a period of three menstrual cycles changes the VRP, MVC, and PFM tone, as well as improves the repetitions of PFM assessed by digital palpation. Moreover, the women reported the use of vaginal cup as a positive experience.

Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

Linking the Declarations of Helsinki and of Taipei: Critical Challenges of Future-Oriented Research Ethics.

Expansion of data-driven research in the 21st century has posed challenges in the evolution of the international agreed framework of research ethics. The World Medical Association (WMA)'s Declaration of Helsinki (DoH) has provided ethical principles for medical research involving humans since 1964, with the last update in 2013. To complement the DoH, WMA issued the Declaration of Taipei (DoT) in 2016 to provide additional principles for health databases and biobanks. However, the ethical principles for secondary use of data or material obtained in research remain unclear. With such a perspective, the Working Group on Ethics (WGE) of the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP) suggests a closer scientific linkage in the DoH to the (Declaration of Taipei) DoT focusing specifically on areas that will facilitate data-driven research, and to further strengthen the protection of research participants.

Evolution of the Development of Core Competencies in Pharmaceutical Medicine and Their Potential Use in Education and Training.

The evolution of postgraduate vocational education and training in pharmaceutical medicine is described alongside the growth of this scientific-medical discipline and profession for the development of new medicines. Over the past 50 years, whilst the training of competent professionals for their work has been paramount, this has paralleled the need to engage with the rapid and complex changes in R&D technologies, patient and healthcare system needs, and the ethical and regulatory obligations applied to the development of medicines throughout their lifecycle. The move from unstructured training to formal programs with syllabus, curricula and assessments for certification, has been accompanied by educational changes to outcomes-based, learner-centered, competency-based programs. The evolution of education and training along with the development of the set of 57 core competencies for professional practitioners in pharmaceutical medicine are described within the competence framework of seven domains: discovery of medicines and early development; clinical development and clinical trials; medicines regulation; drug safety and surveillance; ethics and subject protection; healthcare marketplace; communication and management. The application of the core competencies in a harmonized, international platform of education and training in medicines development at the undergraduate, postgraduate and continuing professional development levels would invigorate the potential for having a competent workforce with the intent to provide faster access to better and appropriate medicines for patients worldwide.

Development and Use of Gene Therapy Orphan Drugs-Ethical Needs for a Broader Cooperation Between the Pharmaceutical Industry and Society.

Gene therapy orphan medicinal products constitute a unique group of new drugs which in case of hereditary diseases are usually administered only once at an early age, in the hope to provide sufficient gene product to last for the entire life of the patients. The combination of an exceptionally large single payment and the life-long clinical follow-up needed for understanding the long-term benefits and safety of gene therapy, represent new types of scientific, financial, social and ethical challenges for the pharmaceutical industry, regulators and society. With special consideration of the uniqueness and importance of gene therapy, the authors propose a three points plan for a close cooperation between the pharmaceutical industry and society to develop orphan gene therapy. (1) In fully transparent health technology negotiations a close and long-lasting, contractually fixed cooperation should be established between the manufacturers and local health-care stakeholders for sharing the medical and scientific benefits, the financial risks as well as the burdens of the post-authorization clinical and regulatory development. (2) The parties should agree on a fair, locally affordable drug price without the usually very high premium price calculated to compensate for the low number of patients. In case of high manufacturing costs, the companies should offer prolonged, 15-20 years long payment by installment with risk-sharing, especially considering that the late outcome of the treatment is unknown. Society should assist scientifically and financially organizing a specific patient registry, treatment in specialized hospitals and adequate long-term follow-up of patients, the coordinated management of financial transactions related to the risk sharing program. (3) The post-authorization treatment and prolonged observation of additional new cases coordinated by society should provide real world data needed for the modern complex regulatory evaluation of gene therapy products by the competent authorities. We assume that fair sharing of the benefits and risks as well as a well-organized cooperation of society with the industry in collecting real world evidence might result in better drug evaluation and improved accessibility due to lower prices. The outlined concept might support gene therapy more efficiently than the presently requested outstandingly high prices.

Corrigendum: Linking the Declarations of Helsinki and of Taipei: Critical Challenges of Future-Oriented Research Ethics.

[This corrects the article DOI: 10.3389/fphar.2020.579714.].

International Perception of Competence, Education, and Training Needs Among Biomedical Professionals Involved in Medicines Development.

The development of new medicines today, requires a multi-professional workforce, both in industry and the clinical research arena. Pharmaceutical physicians (PPs) and medicines development scientists (MDS) need a certain level of competence, achieved through on-the-job experience, with a postgraduate education foundation and continuous professional development programs. In order to assess the self-perception of competence, education and training needs, an on-line questionnaire based on the seven domains of competence, developed by IFAPP-PharmaTrain, was prepared and distributed among PPs and MDS members of IFAPP's affiliated professional associations in countries with facilities for postgraduate education. The data collection was run over a fixed period of three months in Japan, Italy, Brazil, and Spain during 2017. Results indicate low but variable levels of perceived competence for the various domains as well as seniority in the job. All respondents declared a significant need for continuing professional development in all domains. These results corroborate and support the continuous efforts, put in place by IFAPP and the PharmaTrain Federation, to foster the development of accredited education and training among professionals involved in medicines development.

Qualitative study of return to work following breast cancer treatment.

BACKGROUND: After 5 years' sick leave in Brazil, employees must retire due to disability. The duration from breast cancer surgery to the end of treatment should be ~9 months. However, diagnosis alone can take 6 months. Surveys administered soon after returning to work have highlighted problems regarding the slow speed of the treatment process and lack of protective legislation. AIMS: To assess the barriers and facilitators experienced and the coping strategies adopted by Brazilian women 30 days after return to work following breast cancer treatment. METHODS: A qualitative study of 12 women treated for breast cancer. The interviews were recorded, transcribed verbatim and independently analysed by two researchers using a standardized method of analysis. RESULTS: Women took an average of 583 days to return to work following breast cancer treatment. The return-to-work experience was considered good, with the physical barriers being fatigue and problems with the arms, and the work environmental barriers being related to discrimination from employers and overprotection from colleagues. Facilitators included social and emotional support given by colleagues/relatives/employers and jobs requiring more cognitive effort than physical exertion. Coping strategies were related to job role adjustments and reduction in tasks and working hours. CONCLUSIONS: Results were similar to those reported by previous studies, with the exception of the facilitators. Cognitive effort is commonly considered a barrier. However, the present study had an unusually long duration before return to work, possibly reducing the acute effects of chemotherapy on cognition.

The Shared Ethical Responsibility of Medically and Non-medically Qualified Experts in Human Drug Development Teams.

The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many non-medically qualified scientists in multi-disciplinary non-clinical and clinical drug development teams world-wide. In this introductory paper to the "IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists" it is argued that all members of such multidisciplinary teams must share the scientific and ethical responsibilities since they all influence directly or indirectly both the outcome of the various phases of the medicines development projects and the safety of the research subjects involved. The participating medical practitioner retains the overriding responsibility and the final decision to stop a trial if the well-being of the research subjects is seriously endangered. All the team members should follow the main ethical principles governing human research, the respect for autonomy, justice, beneficence and non-maleficence. Nevertheless, the weighing of these principles might be different under various conditions according to the specialty of the members.

Female sexual function and urinary incontinence in nulliparous athletes: An exploratory study.

OBJECTIVES: To estimate the prevalence of Female Sexual Dysfunction (FSD) and Urinary Incontinence (UI) symptom in nulliparous athletes and analyze the risk factors for these dysfunctions. DESIGN: A cross-sectional study. SETTING: The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF) and the Female Sexual Function Index (FSFI) were applied to assess the UI and the FSD. PARTICIPANTS: 50 athletes with ≥18 years old. RESULTS: We found a prevalence of 48% of UI and 44% of FSD among nulliparous athletes. The rate of athletes having concomitant FSD and UI was 24%. We found a significant difference between high and low impact sports in the ICIQ-UI-SF score (p = 0.028). Hours of training (p = 0.007; R2 = 0.21) was found to be a risk factor for UI. Incontinent athletes demonstrated a Relative Risk of 2.7 to develop sexual desire problem when compared to the continents (p = 0.04; 95% CIs: 1.50-4.89). CONCLUSIONS: This study found a high prevalence of both UI and FSD among nulliparous athletes. Furthermore, nulliparous athletes practicing high-impact modalities are the most susceptible to UI. The hours of training per day was considered a risk factor to develop UI, and incontinent athletes have more chances of showing difficulties in sexual desire.

Fostering Competence in Medicines Development: The IFAPP Perspective.

IFAPP (International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine) is a nonprofit organization with the mission to promote Pharmaceutical Medicine & Medicines Development (PM&MD) by enhancing the competencies and maintaining high research ethical standards of Pharmaceutical Physicians and other professionals involved in medicines development worldwide, leading to the availability and appropriate use of medicines for the benefit of patients and society. About 30 national professional associations related to PM&MD, involving 7000 professionals, are affiliated to IFAPP. Medicines development has traditionally been a challenging enterprise, with high risk, high investment, and potentially high returns in the lengthy and complex process of identifying a new chemical entity as a candidate for development and possibly succeeding in bringing it as a pharmaceutical product to the market. However, the emergence of genomics, translational research, biomarkers, and precision medicine pose challenges going forward involving allocation of resources, price, market access, and cost-effectiveness as opposed to the traditional concepts of "efficacy" and "safety." Education and Continuing Professional Development (CPD) are a major focus of IFAPP. The International Conference on Pharmaceutical Medicine (ICPM) is the largest event for our organization; ICPM is held every 2 or 3 years and is aimed to provide the state of the art in key areas for our discipline and profession. The paper is a reflection on the role of competency-based education and training for Pharmaceutical Physicians and medicines development scientists, as was discussed during the recent ICPM 2016 held in Sao Paulo, Brazil on April 18-19, with the support of the Brazilian Association of Pharmaceutical Medicine, and gathered around 200 representatives from the pharmaceutical, clinical research and regulatory arenas from all over the world,.

Manejo de factores de riesgo cardiovascular en Venezuela mediante educación de los médicos que trabajan en atención primaria de salud / Management of cardiovascular risk factors in Venezuela by educating physicians working in primary healthcare services

Estudios recientes en América Latina corroboraron la prevalencia de la hipertensión arterial, el colesterol elevado en plasma, los trastornos metabólicos y otros factores de riesgo cardiovascular (FRCV), todo esto sumado a la falta de control de la enfermedad, la escasa adhesión al tratamiento y el uso de pocas medidas preventivas, lo que derivó en la necesidad de educar tanto al médico como al paciente. Se han realizado estudios limitados para demostrar la eficacia del desarrollo profesional continuo y su capacidad de influir positivamente en los indicadores de salud del paciente. En Venezuela se llevó a cabo un estudio para tratar de medir la efectividad de un curso combinado basado en actividades online y presenciales sobre el manejo de los FRCV, dirigido a médicos que trabajan en atención primaria. Un grupo piloto de 37 médicos de atención primaria del área metropolitana de Caracas completó una intervención educativa de 12 semanas, la cual consistió en sesiones semanales en línea, utilizando la estrategia educativa basada en problemas sobre el manejo de los FRCV, así como talleres presenciales relacionados con los cambios de comportamiento del médico y del paciente, utilizando los principios de la educación terapéutica. Se trabajó con una cohorte de 303 pacientes con hipertensión arterial de grado I-II no controlada y/o colesterol plasmático elevado, y se llevó a cabo un seguimiento durante seis meses. Los resultados evidenciaron cambios significativos en los médicos respecto a los aspectos cognitivos y al estilo de su práctica profesional en el manejo de los FRCV. Los participantes se mostraron muy satisfechos con el contenido y el formato de la intervención educativa. De igual manera, encontramos un resultado positivo en la inducción de cambios en toda la cohorte de pacientes, sobre todo en el perfil lipídico, la presión arterial y la modificación del estilo de vida. Sería interesante su aplicación a mayor escala para medir su efectividad a largo plazo

Recent studies in Latin-America corroborated the prevalence of hypertension, elevated plasma cholesterol, metabolic disorders and other cardiovascular risk factors (CVRF) along with lack of disease awareness. Treatment and preventive measures indicated the urgent need for patient and physician education. Limited studies have been conducted to demonstrate the effectiveness of continual professional development (CPD) and its ability to positively improve health care outcomes. A study was done in Venezuela to measure the effectiveness of a blended web-based education in the management of CVRF by primary health care physicians (PCP), working in primary care services. A pilot group of 37 PCP, from the Caracas metropolitan area, completed a 12-week educational intervention consisting of weekly online problem based sessions on CVRF management and face-to-face workshops on physician and patient behavioural changes, using principles of therapeutic education. A cohort of 303 of their patients with uncontrolled grade I-II arterial hypertension and/or elevated plasma cholesterol were included and followed up for a 6-month period. Significant changes in the cognitive aspects and attitudes about the management of CVRF occurred among the PCP, who were highly satisfied with the content and format of the educational intervention. We also found a positive role in inducing changes in the entire patient cohort, particularly on the plasma lipid profile, blood pressure, and lifestyle changes. Results of this pilot study reflect the effective use of CPD on patient care and PCP interactions in creating synergy and understanding with participating institutions. There is a need of large scale implementation and more extensive comparison with other educational approaches

Experiencia estratégica internacional para el desarrollo profesional continuo y su impacto en la atención primaria de salud / An international strategic experience for continuing professional development and its impact on primary health care

A los dinámicos y profundos cambios científicos, tecnológicos, demográficos y epidemiológicos en el área de la salud, se unen demandas de la población para mejores y más eficientes servicios. Se da el hecho de que la educación médica de pregrado y posgrado no garantiza las competencias de forma indefinida, lo que hace necesarios mecanismos que aseguren una mejor calidad asistencial. El Consorcio Proyecto Global (PGC) sugiere una estrategia integral de educación médica continua y de desarrollo profesional continuo estructurada, simplificada, evaluada y acreditada para contribuir a enfrentar estos desafíos. Se ejecutó el proyecto en dos países como prueba piloto (Rusia y Venezuela). Se implementó en cinco fases: construcción de relaciones institucionales, determinación de necesidades educativas, implementación y medición del impacto, difusión del mensaje y expansión de experiencias, y ajuste e institucionalización del proyecto. Se involucró a un número significativo de médicos que trabajan en los servicios de atención primaria de salud. Se identificaron y probaron estándares globales de educación médica continua y desarrollo profesional continuo, y se diseñó un currículo nuclear, comenzando con el área cardiovascular, con el objeto de mejorar los niveles de conocimiento y la práctica de los médicos participantes, y evidenciarlo en cambios positivos en indicadores de los pacientes usuarios. Finalmente, se llegó a la etapa de institucionalización y reforzamiento continuo, en la cual el PGC funcionó como un proyecto piloto de intercambio internacional y como posible proveedor de educación médica continua y desarrollo profesional continuo, con alta calidad, costos razonables y acreditación académica

Project Globe Consortium (PGC) integrated one simplified strategy in continuing medical education and continuing professional development. It was designed as an answer to the fast and intense changes in science, technology, demography, epidemiology, the increasing demands of the population, and the changing role of physicians in the current health care systems, under the awareness that the undergraduate medical education does not guarantee the required competencies indefinitely thus implying the need of necessary mechanisms to ensure quality and professional healthcare. The project was implemented in two pilot countries (Russia and Venezuela). It was developed in five phases: building up on institutional relationships, identifying local champions; identifying educational needs; implementation and impact measurement; sharing the message and experiences; maturing adjustments and institutionalization of the project. A significant number of physicians working in primary health care settings were involved. Global standards of continuing medical education and continuing professional development were identified and tested. A core curriculum was designed, starting with cardiovascular risk factors, to improve knowledge levels and professional practice of the physicians involved, along with significant changes in patient indicators as biomarkers. Finally, the project reached the stage of institutionalization and continuous reinforcement in which the PGC represented an international networking and potential continuing medical education and continuing professional development, provider of, high quality, at reasonable costs and with academic accreditation

Education and training for medicines development, regulation, and clinical research in emerging countries.

The aim of this satellite workshop held at the 17th World Congress of Basic and Clinical Pharmacology (WCP2014) was to discuss the needs, optimal methods and practical approaches for extending education and teaching of medicines development, regulation, and clinical research to Low and Middle Income Countries (LMICs). It was generally agreed that, for efficiently treating the rapidly growing number of patients suffering from non-communicable diseases, modern drug therapy has to become available more widely and with a shorter time lag in these countries. To achieve this goal many additional experts working in medicines development, regulation, and clinical research have to be trained in parallel. The competence-oriented educational programs designed within the framework of the European Innovative Medicine Initiative-PharmaTrain (IMI-PhT) project were developed with the purpose to cover these interconnected fields. In addition, the programs can be easily adapted to the various local needs, primarily due to their modular architecture and well defined learning outcomes. Furthermore, the program is accompanied by stringent quality assurance standards which are essential for providing internationally accepted certificates. Effective cooperation between international and local experts and organizations, the involvement of the industry, health care centers and governments is essential for successful education. The initiative should also support the development of professional networks able to manage complex health care strategies. In addition it should help establish cooperation between neighboring countries for jointly managing clinical trials, as well as complex regulatory and ethical issues.

HDL-C, triglycerides and carotid IMT: a meta-analysis of 21,000 patients with automated edge detection IMT measurement.

OBJECTIVE: Common carotid artery (CCA) intima-media thickness (IMT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not triglyceride levels, are markers of future cardiovascular events. The relationship between these three factors is, however, unclear. METHODS: We included six large observational studies that used the same harmonized, B-mode ultrasound protocol, the same software for IMT measurement by automatic edge detection on CCA in a plaque-free region, following the Mannheim consensus, and certification of all sonographers. Using the best view of the CCA, the sonographer had to confirm that the quality index was ≥ 0.5 on a measurement performed on 10-mm length. We used individual data meta-analysis to estimate the cross-sectional associations of lipids with CCA-IMT. RESULTS: Overall, 21,587 patients with complete information on lipids and CCA-IMT were available. Age- and sex-adjusted CCA-IMT differed by -7.8 µm (95% CI -9.1 to -6.5 µm, P < 0.001) per 1 SD higher HDL-C level. After further adjustment for other atherosclerosis risk factors, the relationship was attenuated, but remained significant (regression coefficient, -3.7 µm; P < 0.001). This was found regardless of LDL-C levels (P for heterogeneity = 0.70). After adjustment for age and sex, triglycerides were positively associated with CCA-IMT, overall and in each LDL-C subgroup, but not after further adjustments for other risk factors. CONCLUSIONS: Relationships between HDL-C and triglyceride levels and CCA-IMT were consistent with that previously observed with clinical events by the Emergency Risk Collaboration group, including at low LDL-C levels. This reinforces the need to verify whether raising HDL-C levels decreases both CCA-IMT and future clinical events.

Corrigendum: Core competencies for pharmaceutical physicians and drug development scientists.

[This corrects the article on p. 105 in vol. 4, PMID: 23986704.].