The slide provides a basic understanding about Clinical Research process and the various Phases of Drug Discovery and Development. It also explains about the various trial designs and techniques in research such as blinding and randomization. It may be useful for giving a basic class for Fourth Year B.Pharm Students.
NEW DRUG DEVELOPMENT
WHAT DOES DRUG MEAN?
TRADITIONAL SYSTEM OF MEDICINES
NEW DRUG DEVELOPMENT PROCESS
PHASES OF CLINICAL RESEARCH
OVERVIEW OF EACH PHASE
PHASE-0
PHASE-1
PHASE-2
PHASE-3
PHASE-4
CONSIDERATION BEFORE STARTING CLINICAL RESEARCH
AIMS AND OBJECTIVES OF EACH PHASES
.
.
.
FOR MORE RELATED QUERIES CONTACT US ON- 9028839789
FOR ENROLLMENT IN NEXT BATCH CONTACT ON ABOVE MENTIONED NUMBER
https://www.youtube.com/watch?time_continue=4&v=F4jiJD0O8T8
NEW DRUG DEVELOPMENT
WHAT DOES DRUG MEAN?
TRADITIONAL SYSTEM OF MEDICINES
NEW DRUG DEVELOPMENT PROCESS
PHASES OF CLINICAL RESEARCH
OVERVIEW OF EACH PHASE
PHASE-0
PHASE-1
PHASE-2
PHASE-3
PHASE-4
CONSIDERATION BEFORE STARTING CLINICAL RESEARCH
AIMS AND OBJECTIVES OF EACH PHASES
.
.
.
FOR MORE RELATED QUERIES CONTACT US ON- 9028839789
FOR ENROLLMENT IN NEXT BATCH CONTACT ON ABOVE MENTIONED NUMBER
https://www.youtube.com/watch?time_continue=4&v=F4jiJD0O8T8
A sponsor in literal terms is defined as an individual or a company or an institution that takes the responsibility for the initiation, management and/or financing of a clinical study.
In case an investigator independently initiates and takes full responsibility for a trial, he/she automatically assumes the role of a sponsor.
A Clinical Research Associate (CRA) is a professional who plays a crucial role in the management and monitoring of clinical trials. CRAs are typically employed by pharmaceutical companies, contract research organizations (CROs), or academic research institutions. Their primary responsibility is to ensure that clinical trials are conducted in compliance with the study protocol, applicable regulations, and Good Clinical Practice (GCP) guidelines
Table of contents
-Definition of CRF
-What is CRF
-Types & Methods of filling of CRF
-CRF Input team
-CRF Approval team
-Review team
-Facts about CRF
-Purpose of CRF
-CRF Development process & Guidelines
-Elements of CRF
-CRF Design
-CRF completion checklist
-CRF Design tools
-CRF use
-GCP connection
When a new drug/device/surgical procedure/treatment or other potential medical innovation is developed it must be thoroughly tested to ensure that it is safe and does what it is supposed to be.
This presentation will provide a basic overview of clinical research process.
“CSR is a detailed regulatory document which gives the information about the methods and results (related to efficacy and safety) of a clinical trial. CSRs are created as a part of the process of submitting applications to the Regulatory Authorities for new medical treatments and for its approval. CSRs can be full, abbreviated, synopsis, supplementary, observational etc as per the results and requirements”.
In any work or process documents that are needed before initiation, Between or generally the end of the process just like in a clinical trial those “Documents which permit evaluation of the conduct of a trial and the quality of the data produced. It is given in the 8th section of the ICH-GCP.
A Clinical Research Coordinator (CRC) is a healthcare professional who plays a crucial role in the execution and management of clinical research studies. The CRC acts as a liaison between the study sponsor, principal investigator (PI), study participants, and other members of the research team. Their primary responsibility is to ensure the smooth conduct of clinical trials and adherence to protocol requirements. Here are some key responsibilities of a Clinical Research Coordinator
A Trial Master File (TMF) is set up at the beginning of the trial. It is a collection of all essential documents pertaining to the trial, which in turn will allow for effective monitoring and supervision (audit). In order to demonstrate compliance with the applicable regulations, Good Clinical Practice (GCP) guidelines and the protocol – a well organised TMF is essential.
According to the GCP guidelines, it is the responsibility of the sponsor to ensure that the TMF includes all relevant essential documents, and is stored in a secure location, with restricted access. Generally, the TMF is maintained at the sponsor’s office, co-ordinating site or by the Contract Research Organisation (CRO), if contracted. In addition to the TMF, copies of all relevant documents must be kept at each participating site, in an Investigator Site File (ISF). The ISF will also include all site-specific essential documents. For example, site preparedness log or site visit logs, etc.
A member of the research or trial team should be delegated with the task of updating, maintaining and reviewing the TMF and ISF, periodically throughout the course of the clinical trial as per the defined SOPs. Ideally, the documents included in the TMF are:
Trial documents (protocol, investigator’s brochure, participant information documents, SOPs, instructions, manuals, guidelines, etc.)
Documents related to the Investigational Product (certificates of analysis, shipment records, storage records, etc.)
Training documentation for the trial team
Details of the laboratories, if applicable.
Contracts, agreements, budgets, etc.
Monitoring visit reports (for each site visit onsite or central)
Documents related to the safety reporting
Ethics Committees documents (composition of the EC, approvals, notifications, reports, etc.)
Site-specific documents (list of site staff and their curriculum vitae, investigator’s undertaking, site preparedness documents, training of site staff, etc.)
Audit related documents, if available (if an audit was conducted).
Significant communications
Others
The GCP guidelines provide comprehensive guidance regarding the documents to be included in a Trial Master File categorised according to the lifecycle of the trial. This information can also be accessed here.
It shall be the responsibility of the sponsor to make arrangements for the safe and secure custody of all study-related documents and material for a period of three years after the completion of the study or submission of the data to the regulatory authority(ies) whichever is later.
Example of an innovative clinical trial design for a group of medical devices (in this case absorbable hemostats) to support a particular clinically relevant claim
A sponsor in literal terms is defined as an individual or a company or an institution that takes the responsibility for the initiation, management and/or financing of a clinical study.
In case an investigator independently initiates and takes full responsibility for a trial, he/she automatically assumes the role of a sponsor.
A Clinical Research Associate (CRA) is a professional who plays a crucial role in the management and monitoring of clinical trials. CRAs are typically employed by pharmaceutical companies, contract research organizations (CROs), or academic research institutions. Their primary responsibility is to ensure that clinical trials are conducted in compliance with the study protocol, applicable regulations, and Good Clinical Practice (GCP) guidelines
Table of contents
-Definition of CRF
-What is CRF
-Types & Methods of filling of CRF
-CRF Input team
-CRF Approval team
-Review team
-Facts about CRF
-Purpose of CRF
-CRF Development process & Guidelines
-Elements of CRF
-CRF Design
-CRF completion checklist
-CRF Design tools
-CRF use
-GCP connection
When a new drug/device/surgical procedure/treatment or other potential medical innovation is developed it must be thoroughly tested to ensure that it is safe and does what it is supposed to be.
This presentation will provide a basic overview of clinical research process.
“CSR is a detailed regulatory document which gives the information about the methods and results (related to efficacy and safety) of a clinical trial. CSRs are created as a part of the process of submitting applications to the Regulatory Authorities for new medical treatments and for its approval. CSRs can be full, abbreviated, synopsis, supplementary, observational etc as per the results and requirements”.
In any work or process documents that are needed before initiation, Between or generally the end of the process just like in a clinical trial those “Documents which permit evaluation of the conduct of a trial and the quality of the data produced. It is given in the 8th section of the ICH-GCP.
A Clinical Research Coordinator (CRC) is a healthcare professional who plays a crucial role in the execution and management of clinical research studies. The CRC acts as a liaison between the study sponsor, principal investigator (PI), study participants, and other members of the research team. Their primary responsibility is to ensure the smooth conduct of clinical trials and adherence to protocol requirements. Here are some key responsibilities of a Clinical Research Coordinator
A Trial Master File (TMF) is set up at the beginning of the trial. It is a collection of all essential documents pertaining to the trial, which in turn will allow for effective monitoring and supervision (audit). In order to demonstrate compliance with the applicable regulations, Good Clinical Practice (GCP) guidelines and the protocol – a well organised TMF is essential.
According to the GCP guidelines, it is the responsibility of the sponsor to ensure that the TMF includes all relevant essential documents, and is stored in a secure location, with restricted access. Generally, the TMF is maintained at the sponsor’s office, co-ordinating site or by the Contract Research Organisation (CRO), if contracted. In addition to the TMF, copies of all relevant documents must be kept at each participating site, in an Investigator Site File (ISF). The ISF will also include all site-specific essential documents. For example, site preparedness log or site visit logs, etc.
A member of the research or trial team should be delegated with the task of updating, maintaining and reviewing the TMF and ISF, periodically throughout the course of the clinical trial as per the defined SOPs. Ideally, the documents included in the TMF are:
Trial documents (protocol, investigator’s brochure, participant information documents, SOPs, instructions, manuals, guidelines, etc.)
Documents related to the Investigational Product (certificates of analysis, shipment records, storage records, etc.)
Training documentation for the trial team
Details of the laboratories, if applicable.
Contracts, agreements, budgets, etc.
Monitoring visit reports (for each site visit onsite or central)
Documents related to the safety reporting
Ethics Committees documents (composition of the EC, approvals, notifications, reports, etc.)
Site-specific documents (list of site staff and their curriculum vitae, investigator’s undertaking, site preparedness documents, training of site staff, etc.)
Audit related documents, if available (if an audit was conducted).
Significant communications
Others
The GCP guidelines provide comprehensive guidance regarding the documents to be included in a Trial Master File categorised according to the lifecycle of the trial. This information can also be accessed here.
It shall be the responsibility of the sponsor to make arrangements for the safe and secure custody of all study-related documents and material for a period of three years after the completion of the study or submission of the data to the regulatory authority(ies) whichever is later.
Example of an innovative clinical trial design for a group of medical devices (in this case absorbable hemostats) to support a particular clinically relevant claim
FDA 2013 Clinical Investigator Training Course: Issues in Clinical Trials Des...MedicReS
FDA 2013 Clinical Investigator Training Course: Issues in Clinical Trials Designs for Devices
Owen Faris, Ph.D.,Deputy Director, Division of Cardiovascular Devices, Office of Device Evaluation, CDRH, FDA
Well-trained clinical research professionals are in high demand. The tremendous increase in medical technology and information in the last decade has resulted in an explosion of potential new drugs, devices and biologics that must be tested before being released for use by the public. The profession is constantly challenged to improve and streamline the clinical research programs in order to shorten the development timelines and control the cost for new product development
Clinical Research Associate (CRA) - A Growing Career Path in Biotechnology / ...SOCRA CCRP Certification
SOCRA study guide - ES’ SOCRA CCRP Exam Study Guide – A resource to help those who is preparing for the SOCRA Certified Clinical Research Professional (CCRP) certification.
Target identification, target validation, lead identification and lead
Optimization.
• Economics of drug discovery.
• Target Discovery and validation-Role of Genomics, Proteomics and
Bioinformatics.
• Role of Nucleic acid microarrays, Protein microarrays, Antisense
technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins.
• Role of transgenic animals in target validation.
Modern drug discovery process|| M pharm Pharmacology.pptxRohit chaurpagar
Modern drug discovery is a complex, multidisciplinary process that involves several stages and utilizes advanced technologies. The goal is to develop new therapeutic agents that can safely and effectively treat diseases. Here’s an overview of the key stages in the modern drug discovery process
Introduction
History
How are new drug discovered?
Bioinformatics in drug discovery
Tools for drug discovery
Successful drug
Software for drug discovery
Conclusion
References
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Evaluation of antidepressant activity of clitoris ternatea in animals
Clinical Research, A Basic Understanding...........
1. Clinical Research – A
Basic Understanding
Jobin Kunjumon Vilapurathu
Asst. Professor,
Grace College of Pharmacy, Palakkad
2. Definition for drug according to US Food, Drugs
and Cosmetics act
• A substance used in the diagnosis, treatment, or
prevention of a disease or as a component of a
medication recognized or defined by US Food, Drug
and Cosmetic Act.
• A drug can be chemical, biologic, synthetic or non
synthetic
3. • Drug discovery is the process by which drugs are
identified and / discovered.
• Drug development is a process which takes a drug
from initial discovery to the pharmacy shelves.
• The entire drug discovery and development process
takes an average of 12 – 15 years to complete and
costs around ~$950 million
• About 75% (~$700 million) of this cost is attributable
to failure during development
• 90% of all drug development candidates fail to make
it to the market.
4.
5. • New Drug development is divided to 4 phases
1. Drug Discovery
2. Pre clinical development
3. Clinical Trial
4. Post approval
6. Drug Discovery
• In past most of the drugs were discovered by
• Identifying the active ingredients from traditional
medicines
• Serendipitous discovery
• Later the trend was to alter the structure of existing
molecules and make them more active
• i.e. SAR
• Most modern approach
• Understand how a disease is controlled at molecular
and physiologic levels and target that entities
7. .
• Why to extract active ingredients from plants?
• Plants even though they are effective may contain
more than 400 chemicals.
• eg : Quinine ( Antimalarial) from Cinchona bark.
• Serendipitous discovery
• Penicillin by Alexander Fleming
• Altering the structure of compounds
• Nalorphine from Morphine
• Target specific molecules
• Levodopa for Parkinson's disease
8. Drug discovery process can be summarized as
Drug
Target
Identificati
on
Target
Validatio
n
Lead
Compo
und
Identific
ation
Lead
Optimizat
ion
9. Drug Target Identification
• "target" is the naturally existing cellular or molecular
structure involved in the pathology of interest that the
drug-in-development is meant to act on.
• It has been estimated that 10 genes contribute to
multifactorial disease
• These disease genes are linked to another 5-10 genes
in physiologic circuits
• If these number is multiplies with number of known
diseases there are ~5000 – 10000 potential drug
targets
10. .
• Current therapy is based upon less than 500 molecular targets
• 45% of which are G-protein coupled receptors
• 28% are enzymes
• 11% are hormones and factors
• 5% ion channels
• 2% nuclear receptors
• New techniques for target identification are
1. Genomics
2. Bioinformatics
3. Proteomics
• Genomics
• Evolved from 2 independent advances
a) Automation - resulting in a significant increase in the number
of experiments that could be constructed in a given time. (eg.
DNA sequencing)
11. a) Informatics- the ability to transform raw data into
meaningful information by applying computerized
techniques for managing, analyzing, and interpreting
data.
• the identification of new biological targets has benefited
from the genomics approach
• Sequencing of microbial genomes will enable the
identification of novel drug targets, especially when
comparing to the human genome
• Bioinformatics
• identification of novel drug targets is now feasible by
systematically searching for paralogs (related proteins
within an organism) of known drug targets (eg. may be
able to modify an existing drug to bind to the paralog).
12. • Using gene expression microarrays and gene chip
technologies, a single device can be used to evaluate and
compare the expression of up to 20000 genes of healthy
and diseased individuals at once.
• Proteomics
• It is a large scale study of proteins, particularly their
structure & functions
• The word "proteome" is a blend of "protein" and "genome“
• It is becoming increasingly evident that the complexity of
biological systems lies at the level of the proteins, and that
genomics alone will not suffice to understand these systems.
• Therefore, the analysis of proteins (including protein-
protein,protein-nucleic acid, and protein-ligand
interactions) will be utmost importance to target discovery
13. Target Validation
• Involves demonstrating that a particular target is relevant to
the disease being studied through complicated experiments
in both living cells and in animal models of disease.
• Since strong interactions between a protein and its ligand
are characterized by a high degree of complementarity,
knowledge of the protein three dimensional structure will
enable the prediction of “druggability” of the protein.
• Lead Compound identification
• Compounds are mainly identified using random (screening)
or rational (design) approaches.
1. High-throughput Screening
• Used to test large numbers of compounds for their ability
to affect the activity of target proteins.
14. • Uses robotics, data processing and control software,
liquid handling devices, and sensitive detectors and it
allows a researcher to quickly conduct millions of
biochemical, genetic or pharmacological tests.
• Structure Based Drug Design
• Three dimensional structures of compounds from
virtual or physically existing libraries are docked into
binding sites of target proteins with known or
predicted structure.
• Once hits have been identified via the screening
approach, these are validated by re-testing them and
checking the purity and structure of the compounds.
15. Lead Optimization
• Leads are characterized with respect to
pharmacodynamic properties such as efficacy and
potency in vitro and in vivo, physiochemical
properties, pharmacokinetic properties, and
toxicological aspects in order to obtain compounds
with suitable properties to become a drug.
16. Preclinical Studies
• Involve in vitro studies and trials on animal
populations.
• Wide ranging dosages of the compounds are
introduced to the cell line or animal in order to obtain
preliminary efficacy and pharmacokinetic information.
• designed primarily to assess the safety and viability of
new molecular entities.
• Prior to clinical studies, the sponsor needs evidence
that the compound is biologically active, and both
sponsor and the FDA need data showing that the drug
is reasonably safe for initial administration to humans.
17. Clinical Trials/Study
• Any investigation in human subjects intended to
discover or verify the clinical, pharmacological
and/or other pharmacodynamic effects of an
investigational product(s), and/or to identify any
adverse reactions to an investigational product(s),
and/or to study absorption, distribution, metabolism,
and excretion of an investigational product(s) with
the object of ascertaining its safety and/or efficacy.
The terms clinical trial and clinical study are
synonymous.
18. Phases of Clinical Trials
• Phase 0
• A recent designation for exploratory, first-in-human trials.
• also known as human micro dosing studies and are
designed to speed up the development of promising drugs.
• Phase 0 trials include the administration of single sub
therapeutic doses of the study drug to a small number of
subjects (10 to 15) to gather preliminary data on the agent's
pharmacokinetics and pharmacodynamics
• Phase I
• a small group of healthy volunteers (20-80) are selected to
assess the safety, tolerability, pharmacokinetics, and
pharmacodynamics of a therapy.
19. • normally include dose ranging studies so that doses
for clinical use can be set/adjusted.
• There are three kinds of phase I trials
• Single Ascending Dose (SAD) studies- a small group of
patients are given a single dose of the drug and then are
monitored over a period of time. If they do not exhibit any
adverse side effects, the dose is escalated and a new group
of patients is given the higher dose.
• Multiple Ascending Dose (MAD) studies- a group of
patients receives multiple low doses of the drug, while
blood (and other fluids) are collected at various time points
and analyzed to understand how the drug is processed
within the body.
• Food effect- designed to investigate any differences in
absorption caused by eating before the dose is given.
22. • Phase II
• performed on larger groups (20-300) and are designed to
assess how well the drug works, as well as to continue Phase
I safety assessments in a larger group of volunteers and
patients.
• Phase II studies are sometimes divided into Phase IIA and
Phase IIB
• Phase IIA is specifically designed to assess dosing
requirements.
• Phase IIB is specifically designed to study efficacy.
23.
24. • Phase III
• randomized controlled multicenter trials on large patient
groups (300–3,000 or more)
• Phase III trials are the most expensive, time-consuming
and difficult trials to design and run, especially in therapies
for chronic medical conditions.
25.
26. • Once a drug has proved satisfactory after Phase III
trials, the trial results are usually combined into a large
document containing a comprehensive description of
the methods and results of human and animal studies,
manufacturing procedures, formulation details, and
shelf life.
• Phase IV
• also known as Post Marketing Surveillance Trial.
• Phase IV trials involve the safety surveillance
(pharmacovigilance) and ongoing technical support
of a drug after it receives permission to be sold.
27.
28. Marketing of a Drug
• After Phase III all drug remains in the market for 4 years
as New Drug.
29. Trial Design
Parallel group Study
Cross over study
• Trial Designs Titration Designs
Cluster Randomization designs
30. Need For A Good Design
• Trial set up is achievable
• Subject recruitment at time
• Trial completed at time
• Result generated at time
• Dossier preparation in time
31. Parallel Group Study
• Patient/arm is administered to one and only one treatment
procedure, in a random fashion.
Test Arm
Control Arm
Basically of two types
I. Group comparison (parallel group)-
compares 2 or more treatments, most common in confirmatory trials
e.g. treatment grp v/s control grp
II. Matched pairs parallel design-
- complete block design with a block size of 2
- Patient is matched with another of similar prognostic
characteristics
32. Cross over study
• Each arm receives more than one treatment at different dosing
periods.
- Patients in each arm receives all treatments under
investigation.
- It allows a within-patient comparison between treatments.
Wash Out Period
Test arm
Control arm
33. Titration study
The dose are tittered for the subject
Why titration study?
-To expose the patients only to the amount of dose they need
- To provide a conservative and cautious approach in investigating the
dose-response relationship, and finally the therapeutic window.
In Phase-I
- Rising single-dose design
- Rising single-dose cross over design e.t.c
Standard titration design (phase-II)
- To characterize the dose response relationship which defines the
Therapeutic range of the Test drug
Therapeutic window = MTD – MED
34. • Forced Titration (Dose Escalation) study
- Used when drug is unlikely to be effective at lower dose
- Safety is in concern.
• Optional titration study
- A modified titration design with a concurrent placebo-
controlled group where subjects are titrated until they
show a well-characterised favorable/unfavourable
response.
35. Randomization
• The process of assigning trial subjects to treatment or
control groups using an element of chance to determine
the assignments in order to reduce bias.
• The main advantages are
1. Randomization removes the potential of bias in the allocation
of participants.
2. Tends to produce comparable groups, prognostic factors and
other characteristics at the time of randomization will be on an
average evenly distributed between the intervention and
control arms
3. Validity of statistical tests of significance is guaranteed.
37. Blinding
A procedure in which one or more trial related parties in the
trial are kept unaware of, which treatment the subjects receive
in a clinical trial.
• Single Blinding- subjects being unaware
• Double Blinding- both the subject and the investigator
are unaware
• Triple Blinding- A study in which the statistical analysis
is carried out without knowing which treatment
patients received, in addition to the patients and
investigator also being unaware.
38. Ethics Committee
• Rights, Safety and Well-being
A body constituted of medical and non-medical members
whose responsibility is to ensure the protection of rights
safety and well-being of human subjects, to provide public
assurance of that protection, by reviewing or approving
trial protocol, suitability of investigators, facilities and
methods and materials used in obtaining informed consent
of trial subjects
ICH-GCP E6 1.27
39. Ethics Committee Submission
What?
Submission of relevant study documents for review and
approval.
Study documents
Trial Protocol with date and version no:
• Title with signature of PI as attestation for conducting the study.
• Clear research objectives and rationale.
• Inclusion and exclusion criteria.
• Precise description of methodology, including sample size with
its justification, type of study design, intended intervention,
dosage of drugs, route of administration, duration of treatment
and details of invasive procedures, if any.
• Plan to withdraw or withhold standard therapies in the course of
research.
• Statistical plan.
40. • Safety of proposed intervention.
• An account of management of risk and injury in case
of research involving more than minimal risk.
• An account of storage and maintenance of all data.
• Plans for publication of results.
• A statement on probable ethical issues and steps
taken to tackle the same.
Inform Consent Form in English and/or vernacular
languages (including back translations) and Patient
information sheet.
IB with date and version number.
Subject recruitment procedures.
Insurance policy/compensation for participation and for
SAE.
CRFs
41. Investigator’s Undertaking.
Agreement to comply with national and international GCPs.
Current CV of PI.
Details of funding agency/sponsor and fund allocation.
Statement of relevant regulatory clearances.
For international studies, details about foreign collaborators and
documents for review by DCGI.
For exchange of biological material in international collaborative
study an MoU/ Material Transfer Agreement between the
collaborating partners.
A statement of Conflict-of-interest (COI), if any.
42. • Why?
• Regulatory requirement
• Needed for initiation of site.
• When?
• After site selection and before site initiation.
• Who?
• Responsibility of Investigator.
43. Informed Consent
• A process by which a subject voluntarily confirms
his or her willingness to participate in a particular
trial, after having been informed of all aspects of
the trial that are relevant to the subject's decision to
participate. Informed consent is documented by
means of a written, signed and dated informed
consent form.
44. Placebo
• is a simulated or otherwise medically ineffectual
treatment for a disease or other medical condition
intended to deceive the recipient.
• placebo effect
45. Terminologies
• Case Report Form (CRF)
• A printed, optical, or electronic document designed to
record all of the protocol required information to be
reported to the sponsor on each trial subject.
• Sponsor
• An individual, company, institution, or organization
which takes responsibility for the initiation,
management, and/or financing of a clinical trial.
• Contract Research Organization (CRO)
• A person or an organization (commercial, academic,
or other) contracted by the sponsor to perform one or
more of a sponsor's trial-related duties and functions.
46. • Investigator
• A person responsible for the conduct of the clinical
trial at a trial site. If a trial is conducted by a team of
individuals at a trial site, the investigator is the
responsible leader of the team and may be called
the principal investigator. See also Subinvestigator.
• Impartial Witness
• A person, who is independent of the trial, who
cannot be unfairly influenced by people involved
with the trial, who attends the informed consent
process if the subject or the subject’s legally
acceptable representative cannot read, and who
reads the informed consent form and any other
written information supplied to the subject.
47. • Protocol
• A document that describes the objective(s), design,
methodology, statistical considerations, and organization
of a trial. The protocol usually also gives the background
and rationale for the trial, but these could be provided in
other protocol referenced documents.
• Monitoring
• The act of overseeing the progress of a clinical trial, and
of ensuring that it is conducted, recorded, and reported in
accordance with the protocol, Standard Operating
Procedures (SOPs), Good Clinical Practice (GCP), and
the applicable regulatory requirement(s).
• Multicentre Trial
• A clinical trial conducted according to a single protocol
but at more than one site, and therefore, carried out by
more than one investigator.
48. • Serious Adverse Event (SAE) or Serious Adverse Drug
Reaction (Serious ADR)
• Any untoward medical occurrence that at any dose:
• - results in death,
• - is life-threatening,
• - requires inpatient hospitalization or prolongation of
existing hospitalization,
• - results in persistent or significant
disability/incapacity,
• - is a congenital anomaly/birth defect
• Adverse Drug Reaction (ADR)
• all noxious and unintended responses to a medicinal
product related to any dose should be considered
adverse drug reactions.