Preclinical Research and Clinical Trials

Code:

EBE0239

Acronym:

IPCEC

Keywords
Classification	Keyword
OFICIAL	Molecular Biotechnology

Instance: 2020/2021 - 1S

Active?	Yes
Responsible unit:	Imuno-Physiology and Pharmacology
Course/CS Responsible:	Master in Bioengineering

Cycles of Study/Courses

Acronym	No. of Students	Study Plan	Curricular Years	Credits UCN	Credits ECTS	Contact hours	Total Time
MIB	27	Syllabus	4	-	6	42	162

Teaching language

Portuguese

Objectives

The course is designed to cover principles of applied clinical and preclinical research focusing in the development of new drugs and medical devices. On completion of the course, the students must have attained competencies in the following topics: (1) Scientific concepts and research design (from basic research to drug/medical device approval); (2) Ethical and participant safety considerations; (3) Preclinical development and regulation of new medicines (medical product); (4) Clinical trials design and operation (good clinical practices); (5) Study and site management; (6) Data management and informatics; (7) Leadership and professionalism; (8)  Communication and teamwork. Additional practical skills will be gained in laboratory animal science and disease models to test the efficacy and safety of new medicines (drugs or medical devices).

Learning outcomes and competences

The Preclinical Research and Clinical Trials program prepares graduates in Bioengeneering (Molecular Biotechnology branch) to be able to follow and take part as research team members in research design and preclinical / clinical research trials.  The program offers a multidisciplinary curriculum, covering the theory and practice of research methods, the ethics of human subject and animal research, the science of drug targets and medical products safety and regulation, and the management and regulatory issues of preclinical development and clinical trials to final approval of medications and medical devices. Students without prior pharmacology coursework will be offered the opportunity to follow an introdutory course emphasising the principles of drug targeting using a systems- and a mechanism-based approach. The students will also be exposed to the fundaments of medical product development and regulations geverning the conduct of clinical research, including study sponsors, investigators, and institutional review boards. The broad intend of this course is to highlight the importance of ethics in biomedical research and to explore how critical ethical thinking can be used to analyze personal-decision making, public regulation, and the law concerning advanced biomedical sciences/technologies and their clinical applications. The course will highlight the principles of clinical research operations from study site selection to study closure from the perspective of sponsors and clinical research sites including an introduction to database design, management, quality assurance and report.  Research design and methods used in clinical and preclinical research include measurement issues, bias and confounding, statistical considerations, critical evaluation of published clinical and preclinical research designs, and protocols for development improvement.

Working method

Presencial

Program

Basic research - drug targets and in vitro pharmacology (mechanism-based vs system-based approach); identification of lead compounds, pharmaceutical processing and synthesis scale-up; conception, design and control tests of a medical device; tests is disease models and laboratory animals (good laboratory practices).

Preclinical development - pharmacokinetic tests; metabolism and metabolic stability; pharmacogenomic, mutagenecity and toxicological safety (in vitro and in vivo); Sterilization, mechanical testing, biocompatibility and packaging of medical devices; validation development and animal testing of medical devices (biomedical research ethics and responsible conduct).

Clinical trials - Ethics and regulatory review; Management and quality assurance of phases I, II and III clinical trials; long-term and reproductive toxicity; Flexibility and efficacy of medical devices (good clinical practices).

Oficial approval (e.g. EMA, FDA) - Regulator review and re-evaluation

Mandatory literature

Karlberg and Speers; Reviewing Clinical Trials: A Guide for the Ethics Committee, 2010. ISBN: 978-988-19041-1-9
Bert B et al; The animal experimentation quandary: stuck between legislation and scientific freedom. EMBO reports 17, 2016. ISBN: 10.15252/embr.201642354
Yong et al; Establishing a knowledge trail from molecular experiments to clinical trials. New Biotechnology 28 , 2011. ISBN: 10.1016/j.nbt.2011.03.016
de Vries et al; A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies. Evidence-based Preclinical Med 1, 2015. ISBN: 10.1002/ebm2.7
Guimarães S et al; Terapêutica medicamentosa e suas bases farmacológicas , 2014. ISBN: 972-0-06029-8
Katzung Bertram G. ed.; Basic & clinical pharmacology , 2014. ISBN: 007-121931-5

Comments from the literature

Regulatory decrees, reflection articles and consensus standards of pre-clinical research and clinical trial (Portuguese and European).

Teaching methods and learning activities

LAB CLASSES (principles of pharmacokinetics and examples of drug targeting)

Introduction to laboratory procedures. - Lab animal welfare and handling. - Salicylic acid uptake in an acidic and basic gastric environment in rat. - Biotransformation of zoxozolamine by hepatic microsomes “in vitro”. - Renal elimination of aspirin metabolites in humans. - The effects of local anaesthetics in hypotonic haemolysis of rat erythrocytes. - Comparison of the anaesthetic effect of procaine and cocaine in the cornea of guinea pig. The influence of vasoconstrictors in the duration of local anaesthesia. - Action of anti-epileptics in nervous conduction. - Relaxing muscle agents (depolarizing and non-depolarizing). - Concentration-response curves: contractile effect of acetylcholine in the guinea-pig ileum. - "In vivo" pharmacology (e.g. effect of a "loop diuretic" and anticoagulant effect of heparine in the anaesthetized rabbit). - Electrical pacing: chronotropic and inotropic effects of drugs in the rat atrium.

 TUTORIALS (team work, presentations and discussions)

Clinical research management - Regulatory affairs (mechanisms of approval, trading and control of medications / medical devices in the european context) - Safety pharmacology - Clinical pharmacology - Special regulatory issues of medical devices. - Personalized therapeutics and pharmacogenomics. - Pharmaceutical safety and risk management.

Theoretical (and theoretical-practical) information is consolidated in laboratory classes, as these illustrate fundamental topics of drug actions such as drug absorption, biotransformation e elimination; molecular, electrophysiological and therapeutic basis of medications and its influence by medical devices. Within each chapter, emphasis is directed towards discussion of the molecular mechanisms of action of diverse drug groups and prototypes rather than offering repetitive detail about individual drugs. Selection of the subject matter and the order of its presentation are based on the accumulated experience of teaching for many years, which are also guided by the consensus meetings worldwide regarding any given drug / medical device group. Despite this, new drugs under clinical trials and/or old drugs used with off-label applications will also be discussed at theoretical-practical classes, in order to push the students to keep critical open minds regarding innovation in drug research and to urge them to maintain updated their bibliographic resources. 

 

Evaluation Type

Distributed evaluation with final exam

Assessment Components

Designation	Weight (%)
Exame	37,50
Prova oral	32,50
Trabalho escrito	7,50
Trabalho laboratorial	15,00
Trabalho prático ou de projeto	7,50
Total:	100,00

Amount of time allocated to each course unit

Designation	Time (hours)
Apresentação/discussão de um trabalho científico	12,00
Estudo autónomo	60,00
Frequência das aulas	28,00
Trabalho de campo	8,00
Trabalho escrito	8,00
Trabalho laboratorial	14,00
Total:	130,00

Eligibility for exams

>75% attendance to practical lessons and >3.0/6.0 points in the practical course.

Calculation formula of final grade

- Theoretical classes: Video projection.

- Practical lessons (compulsory): Lab work + Presentation and Discussion of Themes/Monographs related to Preclinical Development and Clinical Trials (autonomous work).

Type of evaluation: Distributed evaluation with final examination.

Practical Evaluation (mandatory, classification is valid for 2 years, 6 points):

- Monograph and Theme Discussion (team work, 2-3 students) – Oral presentation (~20 min) and discussion of a written piece of work (monograph)

- Experimental reports

Theoretical Evaluation (Test + Oral examination, 14 points)

- Multiple choice test + written short answers

Admission: >75% attendance to practical lessons and >3.0/6.0 points in the practical course.

-Oral examination: Waived if >7.5/14.0 points in the test. Compulsory if >6.0/14.0 points in the test

Final Score = 0.3* practical score + 0.7* theoretical Score

Practical classes score = 0,2*monograph/theme + 0,1*Practical classes

 

 

Special assessment (TE, DA, ...)

Oral exam.

Classification improvement

Oral exam.

Observations

Practical course notes are valid for 2 years.