Clinical trials involve testing investigational drugs or treatments on human subjects to determine safety and efficacy. They progress through several phases, beginning with small pre-clinical trials on animals. Phase 1 trials involve 20-50 healthy volunteers to assess pharmacokinetics and safety. Phase 2 trials enroll 50-300 patient volunteers to further evaluate safety and dosage. Phase 3 trials are large randomized controlled trials of 250-1000+ subjects comparing the investigational treatment to standard treatment or placebo. If Phase 3 is successful, the results are submitted to regulatory agencies for approval to market the new drug. Post-marketing Phase 4 trials monitor long-term safety and efficacy.
An overview of ICH-GCP guidelines of clinical trials.
Good clinical practice (GCP): a standard for the design , conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial subjects are protected.
ICH-GCP is an International Conference on Harmonization Good Clinical Practice.
The guideline was developed with consideration of the current good clinical practices of the European union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the world health organization
INSTITUTIONAL REVIEW BOARD (IRB/IEC).pptxRAHUL PAL
The International Council on Harmonisation (ICH) defines an institutional review board (IRB) as a group formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup. IRBs can also be called independent ethics committees (IECs).
An IRB/IEC reviews the appropriateness of the clinical trial protocol as well as the risks and benefits to study participants. It ensures that clinical trial participants are exposed to minimal risk in relation to any benefits that might result from the research.
IRB/IEC members should be collectively qualified to review the scientific, medical and ethical aspects of the trial.
Per the FDA, an IRB/IEC should have:
At least five members.
Members with varying backgrounds.
At least one member who represents a non-scientific area (a lay member).
At least one member who is not affiliated with the institution or the trial site (an independent member).
Competent members who are able to review and evaluate the science, medical aspects and ethics of the proposed trial.
This presentation is a brief overview of ICH-GCP guidelines. Although ICH-GCP is a very vast topic, still this presentation will cover almost all the points. The reader will be able to discuss about the roles and responsibilities of various personnel in clinical trials.
An overview of ICH-GCP guidelines of clinical trials.
Good clinical practice (GCP): a standard for the design , conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial subjects are protected.
ICH-GCP is an International Conference on Harmonization Good Clinical Practice.
The guideline was developed with consideration of the current good clinical practices of the European union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the world health organization
INSTITUTIONAL REVIEW BOARD (IRB/IEC).pptxRAHUL PAL
The International Council on Harmonisation (ICH) defines an institutional review board (IRB) as a group formally designated to protect the rights, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup. IRBs can also be called independent ethics committees (IECs).
An IRB/IEC reviews the appropriateness of the clinical trial protocol as well as the risks and benefits to study participants. It ensures that clinical trial participants are exposed to minimal risk in relation to any benefits that might result from the research.
IRB/IEC members should be collectively qualified to review the scientific, medical and ethical aspects of the trial.
Per the FDA, an IRB/IEC should have:
At least five members.
Members with varying backgrounds.
At least one member who represents a non-scientific area (a lay member).
At least one member who is not affiliated with the institution or the trial site (an independent member).
Competent members who are able to review and evaluate the science, medical aspects and ethics of the proposed trial.
This presentation is a brief overview of ICH-GCP guidelines. Although ICH-GCP is a very vast topic, still this presentation will cover almost all the points. The reader will be able to discuss about the roles and responsibilities of various personnel in clinical trials.
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
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.
The safety monitoring in a clinical trail accompanies by common practices in safety monitoring, communicating safety information among stakeholders in a clinical trail.
Clinical Trials: Types and Design
Experimental Study- RCT and Non RCT, Observation Study: Cohort, Case Control, Cross sectional
Clinical Trial Study Team Roles and responsibilities of Clinical Trial Personnel: Investigator, Study Coordinator, Sponsor, Contract Research Organization and its management.
Clinical study on human subjects according to all guidelines to form a ideal protocol and requirement to conduct clinical trial with very efficient way mainly considering to India and ICH associated countries
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.
The safety monitoring in a clinical trail accompanies by common practices in safety monitoring, communicating safety information among stakeholders in a clinical trail.
Clinical Trials: Types and Design
Experimental Study- RCT and Non RCT, Observation Study: Cohort, Case Control, Cross sectional
Clinical Trial Study Team Roles and responsibilities of Clinical Trial Personnel: Investigator, Study Coordinator, Sponsor, Contract Research Organization and its management.
Genetic Discrimination by Thalia EscobedoThaliae96
This powerpoint was part of the oral/visual component of the Advocacy Proposal, which was an important component, as it allowed me to talk about the social of genetic discrimination to my peers and propose my solution: The California Genetic Nondiscrimination Act of 2011.
EPharma day munich - RBM with EU Clinical Trials RegulationArtem Andrianov
The new EU Clinical Trials Regulation (CTR) becomes applicable not earlier than on 28th of May 2016. It introduces a number of changes in the clinical trial’s application, operations, documentation, and assessment. Although CTR is not taking the direct reference on RbM, it refers to principles of Good Clinical Practice (GCP) and Quality by Design (QbD). These principles are the underlying in RbM as well. Therefore, the author offers to apply RbM as a practical mechanism and process in order to embrace the new EU regulation.
Presented by N..SRIIKANTH, ASST..DIIRECTOR (AY) & G.S.LAVEKAR,
DIIRECTOR, CENTRAL COUNCIL FOR RESEARCH IN AYURVEDA AND SIDDHA
Department of AYUSH, Ministry of Health & Family Welfare, Govt. of India
I like this presentation to read by others
Georgina Gal, Regulatory Affairs Manager, AbbVie, Hungary
Presentation at EIPG – BIPA Symposium “Clinical Trials Research” at the Faculty of Pharmacy, Medical University of Sofia, Sofia 2014.
Clinical trials are divided into several phases to ensure the safety and effectiveness of new medical interventions, such as drugs, treatments, or medical devices, before they are approved for widespread use. Here are the typical phases of clinical trials:
Phase 0: Exploratory Study
Phase 0 trials are relatively new and not always a part of the clinical trial process. They involve a small number of participants and aim to gather initial data on how the drug or treatment behaves in the human body. These trials help researchers decide whether to move forward with larger Phase 1 trials.
Phase 1: Safety and Dosage Study
Phase 1 trials involve a small number of healthy volunteers or patients and focus on assessing the safety of the intervention and determining the appropriate dosage range. Researchers closely monitor participants for any adverse effects, evaluate how the intervention is metabolized, and gather initial data on its efficacy.
Phase 2: Expanded Safety and Efficacy Study
Phase 2 trials involve a larger number of patients who have the condition the intervention is intended to treat. These trials continue to assess safety, evaluate dosage regimens, and gather more data on the intervention's efficacy. Researchers may also explore different patient populations, dosages, or combinations with other treatments.
Phase 3: Confirmatory Study
Phase 3 trials are large-scale studies involving a significant number of patients to confirm the intervention's safety, effectiveness, and monitor any side effects. These trials often include a randomized and controlled design, comparing the new intervention against existing standard treatments or placebos. Phase 3 trials provide critical data for regulatory agencies to evaluate whether the intervention should be approved for widespread use.
Phase 4: Post-Marketing Surveillance Study
Phase 4 trials take place after the intervention has received regulatory approval and is available to the general public. They aim to monitor the intervention's long-term safety, effectiveness, and identify any rare or long-term side effects. Phase 4 trials may involve a larger and more diverse population than earlier phases.
Assignment on Experimental Study- RCT and Non RCT, Observation Study: Cohort, Case Control, Cross sectional, Roles and responsibilities of Clinical Trial Personnel: Investigator, Study Coordinator, Sponsor, Contract Research Organization and its management Guidelines to the preparation of documents, Preparation of protocol, Investigator Brochure, Case Report Forms, Clinical Study Report Clinical Trial Monitoring-Safety Monitoring in CT
Typically, researchers discover new drugs through: New insights into a disease process that allow researchers to design a product to stop or reverse the effects of the disease. Many tests of molecular compounds to find possible beneficial effects against any of a large number of diseases.
Drug discovery is a
process which aims
at identifying a
compound
therapeutically useful
in curing and treating
disease
Target identification is process of
identifying the direct molecular
target(protein, nucleic acid, or
small molecule).
Identifying the biological of the
disease and the potential targets
for involvement ,is the first step in
the discovery of a medicine
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.
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
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.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stock
Telegram: bmksupplier
signal: +85264872720
threema: TUD4A6YC
You can contact me on Telegram or Threema
Communicate promptly and reply
Free of customs clearance, Double Clearance 100% pass delivery to USA, Canada, Spain, Germany, Netherland, Poland, Italy, Sweden, UK, Czech Republic, Australia, Mexico, Russia, Ukraine, Kazakhstan.Door to door service
Hot Selling Organic intermediates
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
2. DEFINITION
• It is a prospective ethically designed investigation in human
subjects to discover/verify/compare the results of two or more
therapeutic measures /drugs.
• WHO definition: Prospectively assigned human participants to
one or more health related interventions to evaluate the effects on
health outcome.
3. DEFINITIONS
RANDOMIZATION:
Each study subject is randomly assigned to receive
either the study treatment or a control.
PLACEBO:
Pharmacologically inert substance given to please the
subjects
4. BLIND:
If the study is single blind, the subjects involved in the
study do not know which study treatment they receive.
If the study is double- blind, the researchers also do not
know which treatment is being given to any given subject.
This 'blinding' helps in preventing biases.
5. TYPES OF CLINICAL TRIALS
Treatment trials
Prevention trials
Diagnostic trials
Screening trials
Quality of life trials
8. PRE-CLINICAL TRIALS
The testing on animals to expose the pharmacological profile
of a prospective drug is called pre-clinical trials.
The major kinds of information expected from preclinical
toxicity studies are
(1) acute toxicity—effects of large single doses; (LD50)
(2) Sub acute and chronic toxicity—effects of multiple doses,
which are especially important if the drug is intended for
prolonged use in humans
9. PRE-CLINICAL TRIALS
(3) effects on reproductive functions, including teratogenicity and
postnatal development;
(4) carcinogenicity;
(5) mutagenicity.
(6) Pharmaco dynamics
(7) Pharmaco kinetics
(8) Assessment of safety index
12. Importance of pre clinical trials
• Triparanol is a drug that lowers the concentration of cholesterol in
plasma.
• It was marketed in the USA in 1959. In 1962, the Food and Drug
Administration (FDA) received a tip-off and undertook an
unannounced inspection. This revealed that toxicology data
demonstrating cataract formation in rats and dogs had been
falsified.
• Triparanol was withdrawn, but some of the patients who had been
taking it for a year or longer also developed cataracts
13.
14. ETHICS
The U.S. National Institutes of Health notes seven ethical
requirements that must be met before a clinical trial can begin.
These include
• social value,
• scientific validity,
• fair and objective selection of subjects,
• informed consent,
15. ETHICS
• favourable ratio of risks to benefits,
• approval and oversight by an independent/ institutional
review board (IRB),
• respect for human subjects.
17. INFORMED CONSENT FORM
• Voluntary
• Explained in simple nontechnical, native language
• Comprehensive information regarding the trials like
• Benefit of new therapy over existing ones
• Alternative treatments available
• All possible adverse reactions
• Freedom to withdraw from the trial
18. Clinical trials must have
a) Good laboratory practice
b) Good clinical practice
c) Good manufacturing practice
d) Good documentation practice
e) Good regulatory practice
19. IND(Investigational New Drug)
The IND includes
(1) information on the composition and source of the drug
(2) manufacturing information,
(3) all data from animal studies,
(4) clinical plans and protocols,
(5) the names and credentials of physicians who will conduct the
clinical trials.
20. DRUG REGULATORY AGENCY
A clinical trial can begin only when drug regulatory authority
approves for the conduct
Ex: Food and drug administration(FDA)
Central Standard Drug Control Organization (CDSCO)
Drug Controller General of India(DCGI)
21.
22. PHASE 0 / EXPLORATORY IND STUDIES
• MICRODOSING:
Extremely low, nonpharmacologically active doses of a
drug are used to define the agent’s pharmacokinetic profile in
humans.
• DEFINITION:
Microdosing means use of ‘less than 1/100 of the dose
calculated to yield a pharmacological effect of the test
substance to a maximum dose of <100 micrograms and a
maximum micro dose of <30 nanomoles for protein products.
23. • FEATURES:
limited number of subjects(10-15)
limited dosing duration(<=7 days)
evaluates pharmacodynamic and pharmacokinetic properties
24.
25. FEATURES MICRODOSING CONVENTIONAL
Time from preclinical to stage
1
6-8 months 12-18 months
Cost of early phase of drug
development
US$ 0.3 -.0.5 million US$ 1.5-5.0 million
Amount of drug required <100 micrograms About 100 grams
Special requirements C14 labelled compound AMS None required
Regulatory requirements Very few and limited Established firmly
26. Advantages:
• saves investment and resource utilization.
• less time.
• efficiency and success of successive trials can be improved.
• No adverse effects since the dose used has no pharmacological
action
• As per the regulatory requirement, animal studies, at least in one
species, are required to establish micro dose in humans, but at a
much reduced level.
27. Disadvantages:
• Drugs with non linear kinetics cannot be assessed Ex:warfarin
• False negative results can mislead (compound being rejected)
• No therapeutic or diagnostic conclusions can be made
• false positive results (compound acceptable based on micro
dose data but rejected subsequently when used in
pharmacological doses).
• Compound metabolism and solubility of compound.
28. Phase 1. Human pharmacology
20-50 subjects, open label, for 1 year
Healthy volunteers or volunteer patients, according to the class
of drug and its safety.
Objectives:
Pharmacokinetics (absorption, distribution, metabolism,
excretion).
Pharmacodynamics (biological effects)
tolerability, safety, efficacy.
29. Phase 2. Therapeutic exploration
50-300 subjects, open label, 2-3years
Patients.
Trials with inclusion and exclusion criteria
Primary and surrogate end points
Objectives:
Pharmacokinetics and pharmacodynamic dose-ranging
Therapeutic efficacy
30. • Phase 2a/ Early Phase
• 200 patients
• Single blind
• Potential therapeutic benefits
and side effects
• Phase 2b/ Late Phase
• 400 patients
• Double blind
• Potential therapeutic benefits
and side effects
31. Phase 3. Therapeutic confirmation
Randomised, double blind, multi-centric controlled trials; 250-
1000+
Cross over design
Patients
Objectives:
Efficacy on a substantial scale; safety;
comparision with existing drugs.
Drug interactions
Guidelines for use of drug
32. NEW DRUG APPLICATION
• If phase 3 results meet expectations, application is made for
permission to market the new agent.
• Marketing approval requires submission of a New Drug
Application (NDA) to the DRA.
• The application contains, often in hundreds of volumes, full
reports of all preclinical and clinical data pertaining to the drug
under review, package inserts.
• median standard approval time was 12.9 months.
33. Phase 4. Therapeutic use
2000-10000+, post-licensing studies
Periodic Safety Update Report(PSUR)
Objectives:
Surveillance for safety and efficacy
uncommon and long term adverse effects
marketing studies
pharmacoeconomic studies.
additional indications
34.
35. Phase 5. Therapeutic effectiveness
• The focus of Phase V studies, or "effectiveness" research, is on
determining whether "the therapeutic effect is realized in day-
to-day clinical practice".
• Generally, Phase V research is considered "field research" or
"community-based research" and is designed to test
generalization of the intervention to a larger sample and under
typical and somewhat variable clinical contexts.
36.
37. PHASE 5
• A central question for Phase V research is whether the effects are
similar to those found in efficacy studies and to determine who
benefits from the treatment.
• It is during this phase of research that questions concerning the
cost-benefit ratio of the intervention can be addressed.
38. CRITICAL PATH INITIATIVE
• In 2004, a white paper, now known as the Critical Path Initiative
(CPI), is given by FDA that called attention to an alarming
decline in the number of innovative medical products being
submitted for FDA approval.
• This led to the new concept of adaptive phase clinical trials
39. ADAPTIVE PHASE CLINICAL TRIALS
• Study that includes a prospectively planned opportunity for
modification of one or more specified aspects of the study design
and hypotheses based on analysis of data (usually interim data)
from subjects in the study.
• The purpose is to make clinical trials more flexible, efficient and
fast. Due to the level of flexibility involved, these trial designs
are also termed as “flexible designs.”
40. NON INFERIORITY CLINICAL TRIALS
• Non-inferiority clinical trials aim to demonstrate that the test
product is no worse than the comparator by more than a
prespecified small amount. This amount is known as the non-
inferiority margin (M), or delta (Δ).