This document provides an overview of the methodology used in clinical trials. It defines key terms like randomized controlled trials, control groups, randomization, and blinding. It describes the various phases of clinical trials including phases 1-3 and post-marketing studies. Phase 1 trials test safety in healthy volunteers while phases 2 and 3 test efficacy in larger patient populations. The goals of each phase are explained as well as important demographic information. The document also outlines the drug development process from preclinical research through regulatory approval and commercialization.
Cross over design, Placebo and blinding techniques Dinesh Gangoda
A crossover design is a modified randomized block design in which each block receives more than one treatment at different dosing periods.
A block can be a patient or a group of patients.
Patients in each block receive different sequences of treatments.
A crossover design is called a complete crossover design if each sequence contains all treatments under investigation.
A placebo is a dummy medicine containing no active substance.
This substance has no therapeutic effect, used as a control in testing new drugs.
Latin- ‘ I shall please’
Criticisms of orthodox medical ethics, importance ofsupriyawable1
ethics is a very large and complex field of study with many branches .medical ethics is the branch of ethics that deals moral issues in medical practice. principles of medical ethics - autonomy ,beneficence ,confidentiality,do not harm,equity .importance of communication .
Medical Research: conflicts between autonomy and beneficence/non maleficence, euthanasia, informed consent, confidentiality, criticisms of orthodox medical ethics
Research Methodology_UNIT_I_General Research Methodology M. Pharm (IIIrd Sem.)Prachi Pandey
General Research Methodology: Research, objective, requirements, practical
difficulties, review of literature, study design, types of studies, strategies to eliminate
errors/bias, controls, randomization, crossover design, placebo, blinding techniques.
Cross over design, Placebo and blinding techniques Dinesh Gangoda
A crossover design is a modified randomized block design in which each block receives more than one treatment at different dosing periods.
A block can be a patient or a group of patients.
Patients in each block receive different sequences of treatments.
A crossover design is called a complete crossover design if each sequence contains all treatments under investigation.
A placebo is a dummy medicine containing no active substance.
This substance has no therapeutic effect, used as a control in testing new drugs.
Latin- ‘ I shall please’
Criticisms of orthodox medical ethics, importance ofsupriyawable1
ethics is a very large and complex field of study with many branches .medical ethics is the branch of ethics that deals moral issues in medical practice. principles of medical ethics - autonomy ,beneficence ,confidentiality,do not harm,equity .importance of communication .
Medical Research: conflicts between autonomy and beneficence/non maleficence, euthanasia, informed consent, confidentiality, criticisms of orthodox medical ethics
Research Methodology_UNIT_I_General Research Methodology M. Pharm (IIIrd Sem.)Prachi Pandey
General Research Methodology: Research, objective, requirements, practical
difficulties, review of literature, study design, types of studies, strategies to eliminate
errors/bias, controls, randomization, crossover design, placebo, blinding techniques.
(I) MEDICAL RESEARCH_ UNIT_III_RESEARCH METHODOLOGY & BIOSTATISTICS.pptxRAHUL PAL
Research Methodology and Biostatistics syllabus:
Medical Research: History, values in medical ethics, autonomy, beneficence, non-maleficence, double effect, conflicts between autonomy.
Medical research has a long and varied history. It has evolved from rudimentary practices to sophisticated, evidence-based methodologies. Some key milestones include the development of the scientific method, the use of randomized controlled trials, the discovery of antibiotics, and the mapping of the human genome. Ethical concerns have also played a significant role in shaping the history of medical research, especially in response to various ethical violations, such as the Tuskegee Syphilis Study and the Nuremberg Trials.
Resolving conflicts between these principles often requires careful consideration, ethical analysis, and, in some cases, consultation with ethics committees or boards. The specific course of action may vary based on the individual circumstances and ethical frameworks employed by healthcare professionals and researchers. Ethical guidelines and regulations also play a significant role in addressing and preventing these conflicts in medical research.
MEDICAL RESEARCH: UNIT_III_ EUTHANASIA, COI, CONFIDENTIALITY RESEARCH METHODO...RAHUL PAL
Medical research in clinical settings is the study of human health and disease in people. It is the primary way that researchers determine if a new form of treatment or prevention, such as a new drug, diet, or medical device, is safe and effective in people.
A clinical trial is designed to learn if a new treatment is more effective or has less harmful side effects than existing treatments.
Clinical trail is basically have 4 phases: Phase I, Phase II, Phase III, Phase IV
General Research Methodology: Research, objective, requirements,
practical difficulties, review of literature, study design, types of studies,
strategies to eliminate errors/bias, controls, randomization, crossover design,
placebo, blinding techniques.
(I) MEDICAL RESEARCH_ UNIT_III_RESEARCH METHODOLOGY & BIOSTATISTICS.pptxRAHUL PAL
Research Methodology and Biostatistics syllabus:
Medical Research: History, values in medical ethics, autonomy, beneficence, non-maleficence, double effect, conflicts between autonomy.
Medical research has a long and varied history. It has evolved from rudimentary practices to sophisticated, evidence-based methodologies. Some key milestones include the development of the scientific method, the use of randomized controlled trials, the discovery of antibiotics, and the mapping of the human genome. Ethical concerns have also played a significant role in shaping the history of medical research, especially in response to various ethical violations, such as the Tuskegee Syphilis Study and the Nuremberg Trials.
Resolving conflicts between these principles often requires careful consideration, ethical analysis, and, in some cases, consultation with ethics committees or boards. The specific course of action may vary based on the individual circumstances and ethical frameworks employed by healthcare professionals and researchers. Ethical guidelines and regulations also play a significant role in addressing and preventing these conflicts in medical research.
MEDICAL RESEARCH: UNIT_III_ EUTHANASIA, COI, CONFIDENTIALITY RESEARCH METHODO...RAHUL PAL
Medical research in clinical settings is the study of human health and disease in people. It is the primary way that researchers determine if a new form of treatment or prevention, such as a new drug, diet, or medical device, is safe and effective in people.
A clinical trial is designed to learn if a new treatment is more effective or has less harmful side effects than existing treatments.
Clinical trail is basically have 4 phases: Phase I, Phase II, Phase III, Phase IV
General Research Methodology: Research, objective, requirements,
practical difficulties, review of literature, study design, types of studies,
strategies to eliminate errors/bias, controls, randomization, crossover design,
placebo, blinding techniques.
From History to Application Procedure OF CLINICAL TRIALS IN INDIA. PHASES 0,1,2,3,4 & 5.IMPORTANCE, advantages, guidelines global and India. Types, Design & blinding technique.
Adithyaelearning provides SAS CDM Online Training to the candidates having knowledge in the SAS. Throughout this course the participants will become qualified on the Clinical programming models as well as their usage in field of clinical research. The center areas for the course incorporate data integration, data manipulation, data listings production, figures and tables as per Statistical Examination Plan, as well as generation of reports and graphs. Besides this participants can be trained based on fundamental principles as well as concepts in the statistical methodology as well as clinical trials.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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.
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
1. Methodology (II)
Tamer Hifnawy MD. Dr.PH
Associate Professor
P u b l i c H e a l t h & C o m m u n i t y M e d i c i n e
F a c u l t y O f M e d i c i n e – B S U - E g y p t
C o l l e g e O f D e n t i s t r y T a i b a h U n i v e r s i t y - K S A
V i c e D e a n F o r Q u a l i t y , D e v e l o p m e n t & I n t e r n a t i o n a l A f f a i r s
C e r t i f i e d T r a i n e r F o r I n t e r n a t i o n a l R e s e a r c h E t h i c s
2. What is a Clinical Trial?
A prospective study comparing the effect
and value of intervention (s) against a
control in human being.
Friedman, 1998
6. What Is The RCT ?
It is one of the simplest, most powerful,
revolutionary tools of research in which ;
Participants
are allocated at Random
into 2 or > groups (one of them is Control)
to receive one or more Interventions, then
Followed up in time, and
Outcomes are compared
7. Clinical Trials
A research study to test new treatments in
people for specific illnesses or conditions
(Malaria, HIV, Cancer, etc).
Clinical Trials are the fastest and safest way to
find out which treatments work
8. Definition of Clinical Trials
Pre-Planed usually Controlled
studies of the Safety, Efficacy, or
Optimum Dosage schedule of one or
more Diagnostic, Therapeutic, or
Prophylactic drugs in humans
selected according to pre-determined
criteria of Eligibility and observed for
pre-defined evidence of Favorable
and Unfavorable effects.
9. Goals of Clinical Trials
Finding Drugs or
Treatments that
WORK
Those that
do
NOT WORK
10. Uses of Clinical Trials
Treatment: test experimental treatments,
combinations of drugs, new approaches.
Prevention: look for better way to prevent
disease or its recurrence.
Diagnostic: develop better tests.
Screening: to detect diseases or health
conditions.
Quality of Life (or Supportive Care): improve
comfort and QOL in chronic disease states.
11. Common Clinical Trial Terms
CONTROLLED STUDY: A study in which a test
article is compared with a treatment / placebo
A test drug is given to one group of people. This
group is often called the “treatment group.”
Another drug, or no drug, is given to a second
group of people with the same illness. This is
often called the “control group.”
Then the results of the two groups are compared.
12. PLACEBO
A pill, liquid, or powder that contains
no drug and has no treatment value.
A placebo looks just like the real drug.
14. Examples of control arm
Standard care.
Placebo.
Careful follow-up.
Early or late application of
same intervention.
Higher or lower dose level.
16. Randomization
Means that subjects recruited from
the study population are allocated
to either intervention or control
arm by chance.
Random procedure = haphazard
procedure
17. Why Randomization
Ensures comparability of the two arms
regarding known and unknown factors.
Avoid selection bias.
Provides basis for standard statistical
analysis.
Differences in baseline characteristics of
the study arms indicate break in
randomization.
18. Why Randomization is difficult
Any randomization technique must insure:
1. Every new subject has an equal
chance to be allocated to either
arms (alternation?!)
2. Nearly equal number of subjects
in each arm (coin toss?!).
21. Blocked Randomization
Blocks containing specific number of
participants are generated ( 5 blocks each
containing 4 participants for a study with
total of 20 participants).
Within each block, participants are
randomly allocated to either arms.
TCTC CCTT TTCC
TCCT CTCT
24. Design of the trial
Methodology section should include
the following:
1-Patient inclusion criteria.
2-Time of patients inclusion in the study.
3-Presence of a comparison group.
4-Matching criteria of the two groups.
5-Method used for randomization.
26. Why Blindness(continued):
To reduce selection bias.
to avoid bias in outcome measures.
Blinding is not possible in all studies
so, one needs to consider how
important it is, and to what extent it
can be achieved.
27. Trials are often described as:
Single-blind: subject
Double-blind: subject & investigators
(clinician, interviewers, laboratory personnel).
Triple blind: subject, investigators &
Statistitian.
Blindness (continued)
29. Complex designs
1- Multiple treatment groups
More than 2 different treatments (or doses) may
be compared with a control group.
Sample population
Control Drug A Drug B Drug C
30. Complex designs
2- Cross-over trial
Each subject receives both the active and
control treatments during two periods
separated by a wash-out period.
31. Outcome No outcome Outcome No outcome
Cross-Over Enrolled Population
Wash-out period
Drug APlacebo
Outcome No outcome Outcome No outcome
Drug APlacebo
32. Complex designs for clinical trials
3- Factorial design
used to evaluate the separate and combined
effects of two different factors:
1. Group 1: Placebo.
2. Group 2:. Iron
3. Group 3: Folate.
4. Group 4: Iron + Folate
Sample population
Control Surgery Radiotherapy Surgery+Radio
34. Losses to follow-up
•One of the most important sources of
bias, since those lost may be different
from those seen.
•Compare drop-outs to non-drop-outs.
•Perform sensitivity analysis.
35. Interpretation of trial
1- Reporting the data.
2- Statistical methods.
3- Statistical analysis.
4- Power.
P < 0.05 ??
36. Good RCT should report
Clear definition of patients.
Comparison group.
Randomization and blindness.
Outcome criteria and variables.
Compliance and completeness.
Complications of treatment.
Statistical manipulation.
37. Risks and Benefits of Clinical Trials
Risks:
Unpleasant or serious side effects
You may receive a placebo
No guarantee that the experimental drug will be an effective
treatment for you.
Benefits:
May experience health benefits from a new treatment
Free lab tests and expert treatment
Contributing to the development of a new medication
38.
39. Statistics
Only 1 in 10,000 of the compounds synthesized
for potential drug use ever reach market
Of all drugs tested in human beings, only 1 in 10
becomes a new medicine
Only 33% of all drugs that are marketed make
profits that exceed the costs of development
The average cost of bringing a drug to market is
$800 million
The average number of studies conducted on a
new drug prior to market approval are 64
Did you know that...
42. Goals and Objectives
Basic understanding of drug development process as a
whole, i.e.
How a drug goes from test tube to market
Connections between preclinical testing, chemistry and
clinical research as they relate to drug development
Understanding of what goes into an Investigational New
Drug Application (IND) and New Drug Application
(NDA), including FDA involvement
Know how GLP, GMP, and GCP regulations and
guidelines fit into the drug development picture
44. The Pipeline Concept of Drug Development
Drug Discovery Period
(Pre-Clinical)
Drug Development Period Commercialization
Idea
for
New
Drug
Synthesis
&
Purification
Specific
Biological
Activity
Found
Animal
Testing
Candidate
Compound
Chosen and
More Testing
Compound
Evaluated
to Project
Status
IND
Plan
Set
IND
Filed
With
FDA
Clinical
Studies
Planned
and
Started
NDA
Prepared
and
Submitted
to FDA
NDA
Approval
Drug
Launched
Post-
Marketing
Studies
Begun
New
Clinical
Uses
Pursued
Activities
to Support
Market
New Dosage Forms
and Formulas
Developed
Clinical Trials
Phases I, 2, & 3
Clinical Trials --
Phase 4
3.5 Years 8.5 Years 8 Years Left on Patent
(patent applied for)
45. The Pipeline Concept of Drug
Development
While in the pipeline, the drug could be
halted for several reasons.
Pre-Clinical Marketed
Lack of Safety
Lack of Funds Lack of Efficacy
Unethical Conduct
46. Pre-Clinical Research
Why?
Per FDA requirement, a sponsor must
first submit data showing that the drug is
reasonably safe for use in initial, small-
scale clinical studies
Therefore:
Preclinical research must be initiated
prior to submission of Investigational
New Drug application (IND)
48. Animal Testing
Provide sufficient information to support
selection of initial human dose and safe
duration of exposure
Evaluate drug’s toxic and pharmacologic
effects
Toxicology: predicts potential hazards in man
Pharmacology: investigates action of drug
Pharmacokinetics
Pharmacodynamics
49. Animal Testing (cont.)
Pharmacodynamics The effect the drug has on the
body. Looks at bodily responses
to pharmacological, biochemical,
physiological, and therapeutic
effects: ED50, LD50
Pharmacokinetics The effect the body has on the
drug: ADME.
50. Drug Development
Drug Development Period
Compound
Evaluated
to Project Status
IND
Plan
Set
IND
Filed
With
FDA
Clinical
Studies
Planned and
Started
NDA Prepared
and
Submitted to
FDA
NDA
Approval
Drug
Launched
Clinical Trials
Phases I, 2, & 3
51. Clinical Studies
Phases 1, 2, 3
Ultimate premarket testing ground for
unapproved drugs
Investigation drug administered to humans and
evaluated for its safety and effectiveness
Results from trials decide approval or
disapproval of drug
Involves three phases of clinical studies
(21 CFR 312.21)
52. Phase 1 Objectives
Main purpose: assessing safety of drug
Human Pharmacology (PK and PD –e.g. ADME)
Typically non-therapeutic objectives
Determine tolerability of dose range expected to be
needed for later trials (Maximum tolerated Dose -MTD)
Determine nature of adverse reactions that can be
expected
Assess clearance of drug and to anticipate possible
accumulation of parent drug or metabolites and potential
drug-drug interactions
53. Phase 1 Demographics
Usually healthy volunteers or certain types of patients (e.g.
new chemotherapeutic agent for cancer patients with end
stage disease)
Often conducted in a medical setting
20-100 patients
Trials can last up to several months
Open label –everyone knows what they are getting.
70% of drugs successfully complete Phase 1 and continue
on to Phase 2
54. Phase 2 Objectives
Therapeutic Exploratory
Main purpose: assessing efficacy for particular indication
(Efficacy-A product's ability to produce beneficial effects on
the course or duration of a disease)
Initial evaluation:
Safety (side-effect profile-AE / SAE)
Well-controlled, closely monitored studies
Active or placebo controlled -- double blind
Includes dose-response and/or dosing schedule studies
Determine dose and regimen for Phase 3
55. Phase 2 Demographics
200-300 (up to 1000) patients with targeted indication
Diseased patients; selected by relatively narrow criteria
Trials last from several months to 2 years
Experienced physicians in the specialty
Early Phase 2 trials may be called Phase 2a or pilot studies
33% of drugs successfully complete Phase 2 and continue
on to Phase 3
56. Phase 3 Objectives
Therapeutic Confirmatory
Main purpose: safety, effectiveness - confirm therapeutic
benefit for use in intended indication and recipient
population
Effectiveness-The desired measure of a drug's influence on a disease
condition as proved by substantial evidence from adequate and well-
controlled investigations such as clinical trials.
Evaluate overall benefit-risk relationship
Provide adequate basis for marketing approval
Extrapolate results to put in labeling
25-30% of drugs complete Phase 3 trials
57. Phase 3 Demographics
Several hundred to several thousand
patients
Patients with the disease; more diverse
population
Inclusion/Exclusion criteria less
restrictive
Trials last from 1-4 years
Less experienced investigators -
Approaches general use (the “real world
population)
Overall: on average, 20%
of drugs ultimately gain FDA
approval to market
60. Phase 4- Post Marketing Trial
Post Marketing trials are studies (other than routine
surveillance) performed after drug approval and related to
the approved indication(s).
These trials go beyond the prior demonstration of the
drug’s safety, efficacy and dose definition.
These trials may not be considered necessary at the time
of new drug approval but may be required by the
Licensing Authority for optimizing the drug’s use.
They may be of any type but should have valid scientific
objectives.
61. Phase 4
Increases patient experience
Safety in practice environment
Information to support marketing claims / change
labeling
Pharmacoeconomics, quality of life, Pediatric
patent extension trials
62. Post Marketing Surveillance
Continued evaluation of adverse events after
marketing
FDA reporting required
May result in labeling changes or restrictions or
in extreme cases withdrawal from market