The document provides an overview of the evolution of good clinical practices from unethical medical experiments and drug trials that occurred in the past. It discusses key events that led to the development of international guidelines like the Declaration of Helsinki and ICH GCP guidelines to protect human subjects. These include the Nazi war crimes trials, Tuskegee syphilis study, Thalidomide disaster, and others. The objective of the ICH GCP guideline is to provide a unified standard across regions to facilitate acceptance of clinical trial data.
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
An Institutional Review Board (IRB), also known as an Independent Ethics Committee (IEC), is a committee responsible for reviewing and approving the ethical aspects of research involving human subjects. IRBs/IECs play a crucial role in protecting the rights, welfare, and safety of research participants. Here are some key points about IRBs/IECs
“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”.
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
An Institutional Review Board (IRB), also known as an Independent Ethics Committee (IEC), is a committee responsible for reviewing and approving the ethical aspects of research involving human subjects. IRBs/IECs play a crucial role in protecting the rights, welfare, and safety of research participants. Here are some key points about IRBs/IECs
“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”.
Ethics in Clinical Research and Historical Perspective of Nazi Trials, Nuremb...ShantanuThakre3
What is Ethics ?
The word ‘ethics’ is derived from the Greek word,
ethos, which means custom or character. Ethics is
the systematic study of values, so as to decide
what is right and what is wrong. Ethics is concerned
with what is good for individuals and society.
What is Clinical Research ?
Clinical Research is a branch of healthcare science that determines the safety and effectiveness of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treatment, diagnosis or for relieving symptoms of a disease.
Importance of Ethics in Clinical Research :-
1. Ethics is important in clinical research because it keeps the researcher from committing errors while seeking knowledge and truth.
2. Ethical guidelines for clinical research were formulated only after discovery of inhumane behavior with participants during research experiments.
3. In clinical research human beings are involved, as opposed to animals, atoms or asteroids, as the object of study.
4. It focuses on improving human health and well-being, typically by identifying better methods to treat, cure or prevent illnesses.
5. The Ethics Committee stands as the bridge between the researcher and the ethical guidelines of the country
Regulations for drug approval in USA, E.U & India
Pharmaceutical industry is the most regulated of all the industries. Regulations are put in order to develop the most efficient and safe pharmaceutical products. It takes more than 8 to 15 years to develop a new drug product & costs more than $ 800 million.
FOMAT Medical Research is a site research network specializes in developing clinical. We offer a wide range of solutions for Sponsors, Clinical Contract Organizations (CROs), and Sites throughout the Americas. Visit here- https://www.fomatmedical.com
Roles and Responsibilities of sponsor, CRO, and investigator MOHAMMEDSALEEMJM
This slide mainly includes Roles and responsibilities of sponsor CRO and Investigator in Ethical conduct of Clinical Research as per ICH GCP Guidelines
Required mainly for Regulatory affairs students
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.
The Declaration of Helsinki is a set of ethical principles and guidelines for conducting medical research involving human subjects. It was adopted by the World Medical Association (WMA) in 1964 and has been revised multiple times since then, with the most recent revision occurring in 2013.
The Declaration of Helsinki outlines several key principles and considerations for researchers and physicians involved in human research, with a focus on protecting the rights, safety, and well-being of research participants. Some of the core principles and points covered in the Declaration of Helsinki include:
Informed Consent: Research participants must provide voluntary, informed, and written consent to participate in a study. They should be fully informed about the nature of the research, its purpose, risks, benefits, and alternatives.
Beneficence and Non-Maleficence: Researchers should aim to maximize the benefits of research while minimizing harm to participants. The well-being of the research subjects should be the primary concern.
Research Ethics Committee Review: All research involving human subjects should undergo ethical review by an independent committee. This review ensures that the study meets ethical and scientific standards.
Scientific Validity and Ethical Conduct: Research should be scientifically rigorous and designed to answer important questions. Researchers must conduct their work with integrity and honesty.
Privacy and Confidentiality: Participants' privacy should be protected, and their data should be kept confidential. Personal information should not be disclosed without informed consent.
Equitable Distribution of Benefits and Burdens: Research should benefit society, and the selection of research subjects should be fair, without exploitation or discrimination.
Continuing Review: Ethical review of research should continue throughout the duration of the study, with particular attention to any new information that may affect the research's ethical considerations.
Access to Medical Care: Participants should have access to medical care and treatment, and they should be compensated for any injuries resulting from their participation in research.
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.
Ethics in Clinical Research and Historical Perspective of Nazi Trials, Nuremb...ShantanuThakre3
What is Ethics ?
The word ‘ethics’ is derived from the Greek word,
ethos, which means custom or character. Ethics is
the systematic study of values, so as to decide
what is right and what is wrong. Ethics is concerned
with what is good for individuals and society.
What is Clinical Research ?
Clinical Research is a branch of healthcare science that determines the safety and effectiveness of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treatment, diagnosis or for relieving symptoms of a disease.
Importance of Ethics in Clinical Research :-
1. Ethics is important in clinical research because it keeps the researcher from committing errors while seeking knowledge and truth.
2. Ethical guidelines for clinical research were formulated only after discovery of inhumane behavior with participants during research experiments.
3. In clinical research human beings are involved, as opposed to animals, atoms or asteroids, as the object of study.
4. It focuses on improving human health and well-being, typically by identifying better methods to treat, cure or prevent illnesses.
5. The Ethics Committee stands as the bridge between the researcher and the ethical guidelines of the country
Regulations for drug approval in USA, E.U & India
Pharmaceutical industry is the most regulated of all the industries. Regulations are put in order to develop the most efficient and safe pharmaceutical products. It takes more than 8 to 15 years to develop a new drug product & costs more than $ 800 million.
FOMAT Medical Research is a site research network specializes in developing clinical. We offer a wide range of solutions for Sponsors, Clinical Contract Organizations (CROs), and Sites throughout the Americas. Visit here- https://www.fomatmedical.com
Roles and Responsibilities of sponsor, CRO, and investigator MOHAMMEDSALEEMJM
This slide mainly includes Roles and responsibilities of sponsor CRO and Investigator in Ethical conduct of Clinical Research as per ICH GCP Guidelines
Required mainly for Regulatory affairs students
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.
The Declaration of Helsinki is a set of ethical principles and guidelines for conducting medical research involving human subjects. It was adopted by the World Medical Association (WMA) in 1964 and has been revised multiple times since then, with the most recent revision occurring in 2013.
The Declaration of Helsinki outlines several key principles and considerations for researchers and physicians involved in human research, with a focus on protecting the rights, safety, and well-being of research participants. Some of the core principles and points covered in the Declaration of Helsinki include:
Informed Consent: Research participants must provide voluntary, informed, and written consent to participate in a study. They should be fully informed about the nature of the research, its purpose, risks, benefits, and alternatives.
Beneficence and Non-Maleficence: Researchers should aim to maximize the benefits of research while minimizing harm to participants. The well-being of the research subjects should be the primary concern.
Research Ethics Committee Review: All research involving human subjects should undergo ethical review by an independent committee. This review ensures that the study meets ethical and scientific standards.
Scientific Validity and Ethical Conduct: Research should be scientifically rigorous and designed to answer important questions. Researchers must conduct their work with integrity and honesty.
Privacy and Confidentiality: Participants' privacy should be protected, and their data should be kept confidential. Personal information should not be disclosed without informed consent.
Equitable Distribution of Benefits and Burdens: Research should benefit society, and the selection of research subjects should be fair, without exploitation or discrimination.
Continuing Review: Ethical review of research should continue throughout the duration of the study, with particular attention to any new information that may affect the research's ethical considerations.
Access to Medical Care: Participants should have access to medical care and treatment, and they should be compensated for any injuries resulting from their participation in research.
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.
This presentation explores the origin of good Clinical Practice, Need of GCP. Principals of Good Clinical Practices. Its a ICH guideline E6.This presentation is very useful to prepare for interviews in the field of Clinical Research.
Elite Institute of Pharma Skills gives quality Education to Pharmacy and Life Science graduates in the field of Regulatory Affairs, Clinical Research, Pharmacovigilance and Medical Coding.
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Ethical considerations in molecular & biotechnology researchDr Ghaiath Hussein
A lecture presented by Dr. Ghaiath Hussein in University of Khartoum for the students of the MSc programme in Genetics/Molecular Biology.
Session 1 (Introduction): Definition of ethics, bioethics and medical ethics.
What is an ethical issue?
International approaches to medical ethics
Islamic approaches to medical ethics
Ethical considerations in Clinical Research Dr Ankita.pptxClinosolIndia
Ethical considerations are paramount in clinical research to protect the rights, well-being, and confidentiality of participants, as well as to ensure data integrity and maintain public trust. Here are some key ethical considerations in clinical research:
Informed Consent: Obtaining informed consent from participants is crucial. Participants should receive clear, understandable information about the study purpose, procedures, potential risks and benefits, alternatives, confidentiality measures, and their right to withdraw at any time. Informed consent should be voluntary, free from coercion, and obtained prior to participation.
Institutional Review Board (IRB) Approval: All clinical research involving human participants must undergo review by an independent IRB or ethics committee. The IRB evaluates the study's ethical implications, participant protections, study design, and informed consent process to ensure that the benefits of the research outweigh the potential risks.
Participant Safety and Monitoring: Safeguarding participant safety is paramount. Researchers should monitor participants closely, promptly address any adverse events or risks, and have protocols in place for participant safety and medical care. Regular safety monitoring and data analysis should be conducted throughout the study.
Data Privacy and Confidentiality: Protecting participant privacy and ensuring data confidentiality are critical. Researchers must adhere to applicable data protection regulations and establish robust measures to safeguard participant data, including de-identification, encryption, secure data storage, and restricted access. Only authorized personnel should have access to identifiable participant information.
Data Integrity and Transparency: Maintaining data integrity is essential for reliable research outcomes. Researchers should accurately collect, record, and report data, adhering to Good Clinical Practice (GCP) guidelines. Data should be analyzed objectively and reported transparently, avoiding any selective or biased reporting that could compromise the scientific integrity of the study.
Equity and Fairness: Clinical research should be conducted in a manner that promotes equity and fairness. Participants should be recruited and selected based on scientifically justified criteria, without discrimination or bias. Efforts should be made to ensure diverse representation in research studies to avoid underrepresentation of certain populations.
Post-trial Access: Participants should have the opportunity to access the study intervention or any relevant follow-up care once the trial is completed, particularly if the intervention has demonstrated significant benefit. Researchers should consider post-trial access in the study design and communicate the availability of such access to participants during the informed consent process.
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.
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
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.
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!
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
3. PROTOCOL
• Nazi war crimes
• Tuskegee syphilis trial
• Thalidomide disaster
• Jews chronic disease trial
• Neuremberg trial code
• Declaration of helsinki
• Belmonte report
• ICH/GCP Guidelines
3
4. Good Clinical Practice (GCP): Meaning
4
Good Clinical Practice (GCP) is an international
ethical and scientific quality standard for designing,
conducting, recording and reporting trials that involve the
participation of human subjects.
Compliance with this standard provides public
assurance that the rights, safety and well-being of trial
subjects are protected, consistent with the principles that
have their origin in the Declaration of Helsinki, and that
the clinical trial data are credible.
5. • The objective of this ICH GCP Guideline is to
provide a unified standard for the European
Union (EU), Japan and the United States to
facilitate the mutual acceptance of clinical
data by the regulatory authorities in these
jurisdictions.
5
7. Nazi Medical War Crimes:
during World War II
• Experiments conducted by Nazi physicians
during World War II were unprecedented in
their scope and the degree of harm and
suffering to which human beings were
subjected
• Typically, the experiments resulted in
death, disfigurement or permanent disability,
and as such are considered as examples
of medical torture
8. Nazi Medical War Crimes
"Medical experiments" were performed on
thousands of concentration camp
prisoners and included deadly studies and
tortures such as-
Injecting people with gasoline and live
viruses
Immersing people in ice water
Forcing people to ingest poisons
10. Victim of a tuberculosis medical
experiment
10
11. Prisoner in a compression chamber
11
An experiment to
determine
altitudes at which
aircraft crews
could survive
without oxygen
12. Immersing people in ice water
• With the intent of discovering
means to prevent and treat
hypothermia.
• 280 to 300 victims
• One study forced subjects to
endure a tank of ice water for up
to five hours.
12
13. • In 1946, an American
military tribunal opened
criminal proceedings
against 23 leading German
physicians : Doctors' Trial
• Sixteen of the doctors were
found guilty
• Seven were sentenced to
death
• Development of
the Nuremberg
Code of medical ethics
13
THE DOCTORS TRIAL
14. The Tuskegee Syphilis Study
• Research participants was the long-term study of
black males conducted at Tuskegee, Alabama by the
United States Public Health Service.
• (1930s-1970) - examination of the natural history of
untreated syphilis
• More than 400 African-American men with syphilis
participated
• The men were recruited without informed consent
and, in fact, were misinformed that some of the
procedures done in the interest of the research (e.g.,
spinal taps) were actually "special free treatment."
15. The Tuskegee Syphilis Study
• In the 1940s, penicillin was found to be effective in the
treatment of syphilis.
• The study continued, however, and the men were neither
informed of nor treated with the antibiotic.
• The first accounts of this study appeared in the national
press in 1972.
• Belmont report 1978 (Ethical Principles and guidelines
for the protection of human subjects of research)-
Tuskegee syphilis study
16. The Jewish Chronic Disease Hospital
Study
• In 1963, studies were undertaken at New York's Jewish
Chronic Disease Hospital to understand whether the
body's inability to reject cancer cells was due to cancer or
debilitation.
• Previous studies had indicated that healthy persons
reject cancer cells promptly, and the researchers
allegedly believed that the debilitated patients would
also reject the cancers but at a substantially slower rate
compared to healthy participants.
17. The Jewish Chronic Disease Hospital
Study
• Further, patients were not told that they
would receive cancer cells, because the
researchers felt it would unnecessarily
frighten them
• It was found that the study had not been
presented to the hospital's research
committee and that the physicians
responsible for the patients' care had not
been consulted.
• The researchers were found guilty of fraud,
deceit, and unprofessional conduct.
18. The Willowbrook Study
• Institutionalized children, as participants in research
is demonstrated in a series of studies conducted
from 1963 through 1966 at the Willowbrook State
School, a New York institution for "mentally
defective" children.
• In order to gain an understanding of the natural
history of infectious hepatitis under controlled
circumstances, newly admitted children were
deliberately infected with the hepatitis virus.
• In some cases, parents found they were unable to
admit their children to Willowbrook unless they
agreed to their child’s participation in the studies.
19. The Willowbrook Study
This controversial case raised important
questions about the adequacy and
freedom of consent, inadequate disclosure
of the child's risk of later developing
chronic liver disease
20. The Milgram Study
• The ‘teachers’ were instructed to give the ‘learners’
electrical shocks in response to incorrect answers on
verbally given ‘tests’.
• Participants were deceived as to the nature of the
study, being told it was to test new teaching-learning
techniques.
21. Thalidomide tragedy
• Thalidomide was a widely used drug in the
late 1950s and early 1960s for the
treatment of nausea in pregnant women
• It became apparent in the 1960s that
thalidomide treatment resulted in severe
birth defects in thousands of children.
21
22. • Within a few years of
the widespread use of
thalidomide in
Europe, Australia, and
Japan, approximately
10,000 children were
born with
phocomelia, leading
to the ban of
thalidomide in most
countries in 1961
22
23. • The thalidomide tragedy marked a turning
point in toxicity testing, as it prompted
United States and international regulatory
agencies to develop systematic toxicity
testing protocols
• The thalidomide tragedy also brought into
sharp focus the importance of rigorous and
relevant testing of pharmaceuticals prior
to their introduction into the market place
(Kelsey, 1988).
23
Thalidomide tragedy
24. Nuremberg Code-1947
• On April 17, 1947, United States Counsel for War Crimes
came out with six points defining “legitimate research”.
• The verdict of August 19 reiterated almost all of these
points in a section entitled "Permissible Medical
Experiments" and revised the original six points into ten.
• Subsequently, the ten points became known as the
"Nuremberg Code."
24
25. Codes and Guidelines
Nuremberg Code (1947).
W.M.A’s Declaration of Helsinki (1964).
• Belmont Report (USA) (1979)-Tuskegee syphilis study
Council for International Organizations of Medical Sciences
(CIOMS) 1993.
International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for Human
Use (ICH), in 1996, Guideline on Good Clinical Practice,E6
(GCP).
26. Nuremberg Code (1947)
Voluntary and Informed consent-absolutely essential.
Anticipate scientific benefits, Useful.
Animal experimentation first.
Avoid physical and mental suffering.
Benefits outweigh risks.
No intentional death or disability.
Protection from harm.
Subject free to withdraw.
Qualified investigators.
Investigator will stop if harm occurs.
28. Is an international standard for the conduct of clinical
research adopted by International Conference on
Harmonization(ICH) Good Clinical Practice standards.
A global ethical standard for medical research and was
approved at the WMA General Assembly by a majority vote
of 75%.
It is the mission of the clinical research professionals to
safeguard the health of the people.
THE DECLARATION OF HELSINKI-1964
29. Historical Overview:-
Its origin has been found in the Nazi Disaster and has
undergone several modifications.
Prior to 1947 Nuremberg Code, there was no
accepted code of conduct governing the ethical
aspects of human research.
30. World Medical Association
It is an international organization of physicians,
established on September 17, 1947.
First general Assembly of WMA was held in Paris,
France.
Mission:- Serve humanity by endeavoring to achieve the
highest international standards in medical education,
science, ethics and health care for all peoples of the world.
31. Declaration of Helsinki 1964
Adapted from Nuremberg
Code by the World Medical
Association (WMA).
First adopted in Helsinki,
Finland, 1964
32. WORLD MEDICAL ASSOCIATION DECLARATION OF
HELSINKI- 2008
Ethical Principles for Medical Research Involving Human Subjects
Adopted by the 18th WMA
General Assembly, Helsinki,
Finland, June 1964, and amended
by the:
29th WMA General Assembly,
Tokyo, Japan, October 1975
35th WMA General Assembly,
Venice, Italy, October 1983
41st WMA General Assembly,
Hong Kong, September 1989
53th WMA General Assembly,
Washington 2002 (Note of
Clarification on paragraph 29
added)
55th WMA General Assembly,
Tokyo 2004 (Note of Clarification
on Paragraph 30 added)
59th WMA General Assembly,
Seoul, October 2008
33. Seven Ethical Pillars of Clinical
Research
AUTONOMY
BENEFICENCE
NON – MALFEASANCE
FIDELITY
TRUTHFULNESS
CONFIDENTIALITY
JUSTICE
34. Declaration of Helsinki
Autonomy
Consent
Para 20 The subjects must be volunteers and
informed participants in the research project.
Para 22 freely-given informed consent,
preferably in writing .
35. Declaration of Helsinki
Para 5 well-being of the human subject should
take precedence over the interests of science
and society.
Beneficence
36. Declaration of Helsinki
Para 16
• Preceded by careful assessment of
predictable risks and burdens
• Attempt to avoid any act or treatment
plan that would harm the patient
Non Malfeasance
37. Declaration of Helsinki
Para 11
Medical research involving human subjects must be based
on generally accepted scientific principles, thorough
knowledge of the scientific literature and on adequate
laboratory and, where appropriate, animal
experimentation.
Para 15
Conducted only by clinically competent medical person.
Fidelity – duty of care
38. Declaration of Helsinki
Para 27
Both authors & investigators are obliged to
preserve the accuracy of the results. Negative
as well as positive results should be published
Truthfulness - Honesty
39. Declaration of Helsinki
Para 21
Every precaution should be taken to
respect the privacy of the subject, the
confidentiality of the patient's information
Confidentiality
40. Declaration of Helsinki
Para 30
Every patient entered into the study should be assured of
access to the best proven prophylactic, diagnostic and
therapeutic methods identified by the study.
Para 9
Research Investigators should be aware of the ethical,
legal and regulatory requirements for research on human
subjects
Para 17
Physicians should cease any investigation if the risks
outweigh the potential benefits
Justice
41. DECLARATION OF HELSINKI :-
Basic Principles
1. Conform to accepted scientific principles.
2. Design formulated in experimental protocol, reviewed by IEC.
3. Conducted by qualified and trained persons.
4. Importance in proportion to inherent risk.
5. Assessment of risks vs. benefits.
6. Safeguard subject’s integrity (privacy).
7. Abstain unless hazards are predictable.
8. Preserve accuracy when publishing.
9. Adequately inform or right to withdraw.
10. Obtain true informed consent in writing.
11. Reliance on legal guardian.
12. State compliance with Declaration.
42. Ethical Principles and Guidelines for the
Protection of Human Subjects of Research
• Tuskegee Syphilis Study (1932–1972)
• Named the Belmont Report, for
the Belmont Conference Center, where the
National Commission met when first
drafting the report
42
Belmont Report: 1979
43. Belmont Report: 1979
Three ethical principles related to research on human
subjects:
1. Respect for Persons
2. Beneficence: "Do no harm" while maximizing benefits
for research project and minimizing risks to the research
subjects
3. Justice: ensuring reasonable, non-exploitative, and
well-considered procedures are administered
45. What is ICH?
• The International Conference on
Harmonisation of Technical Requirements
for Registration of Pharmaceuticals for
Human Use (ICH)- is unique in bringing
together the regulatory authorities and
pharmaceutical industry of Europe, Japan
and the US to discuss scientific and
technical aspects of drug registration.
45
46. What is ICH?
• Since its inception in 1990, ICH has
gradually evolved
• ICH's mission is to ensure that safe,
effective, and high quality medicines are
developed and registered in the most
resource-efficient manner
47. How did it evolve?
The need to harmonize
• Public disasters, serious fraud and abuse of
human rights.
• Trials of War criminals-Nuremberg code
1949
• Thalidomide- Declaration of Helsinki 1964
• Belmont report 1978 (Ethical Principles and guidelines
for the protection of human subjects of research)-Tuskegee syphilis
study
48. History
1962 US FDA IND Guidelines
1964 Declaration of Helsinki
1968 Committee on Safety of Medicines, uk
1978 GCP, US FDA
1991 GCP, Europe
1996 ICH GCP
1997 ICH GCP Guideline
49. When did it begin?
• Ist conf. in 1990 in Brussels
3 regions participated
• Representatives from
Industry
Academia
Ministry of
health
50. ICH parties
6 parties
• EU
• EFPIA European federation of pharmaceutical industries’ associations
• MHLW Ministry of health, Labor and welfare, Japan
• JPMA Japan Pharmaceuticals manufacturers Association
• US FDA
• PhRMA
• Observers : WHO, TPP(canada)
• International federation of Pharmaceutical manufacturer’s
association
51. Key objective
• To discuss and define the minimum
standards for the development and
registration of investigational products
52. The result?
Many guidelines made
• Most important- ICH GCP guidelines
• Evolved in several steps
• Consolidated guideline ICH E6 Sept 1997
53. ICH Guidelines: examples
• Efficacy:
– clinical trials etc
• Safety:
– pharmacovigilance, adverse drug reaction
reporting
• Quality:
– raw materials, impurities, residual solvents etc
• Multidisciplinary:
– common technical document, electronic
submission, coding systems
54. What is GCP?
A standard for the design, conduct,
performance, monitoring ,auditing,
recording, analyses and reporting of
clinical trials that provide assurance that
the data and the reported results are
credible, accurate and that the rights,
integrity and confidentiality of trial
subjects are protected.
55. Why is it needed?
• To ensure the rights, safety and well being
of the trial subjects are protected
• Ensure the credibility of clinical trial data
56. The ICH GCP guideline
• Provide a unified standard for the EU, Japan and
USA regions to facilitate mutual acceptance of
clinical trial data by the regulatory authorities in
these regions.
• 8 sections
57. ICH GCP guideline
1. Glossary
Common language for
investigators/sponsors/ethics committees
2.Principles of Good Clinical Practice
13 tenets of ICH GCP
3.Requirements for IRB/IEC
Roles responsibilities and composition
58. ICH GCP guideline
4.Responsibilities of the investigator
5.Responsibilities of the sponsor
6.Requirements for clinical trial protocol and
protocol amendments
7.Responsibility of the sponsor in the
development of investigator’s brochure.
8.Essential documents
59. Principles of ICH GCP
• Ethical conduct as per
Declaration of Helsinki
GCP
Regulatory Requirements
Risk- Benefit
Primary concern- Subject
60. Principles of ICH GCP
• Supportive data
• Protocol
Scientifically sound, clear, detailed
• Ethical Clearance
Study to be conducted in compliance
to the protocol which has received EC
approval
61. Principles of ICH GCP
• Subject Care
Medical decisions responsibility of
qualified physician
• Qualified staff
By education, training, experience in their
area of responsibility
• Informed Consent
62. Principles of ICH GCP
• Clinical Trial data
Recorded, handled and stored to enable
accurate reporting, interpretation and
verification
• Confidentiality
63. Principles of ICH GCP
• Investigational Product
Manufactured, handled and stored as per
GMP
64. Principles of ICH GCP
• Quality Assurance
Systems and procedures to ensure the
Quality of every aspect of the trial
65. Indian GCP guidelines
• Released in Dec 2001(Developed by CDCSO
and endorsed by DCGI)
• In general, in line with ICH GCP
• Has Revised Schedule Y (Jan 2005)
addressed discrepancies?
66. • SAFEGUARD PUBLIC HEALTH
• ASSURE CONSUMER PROTECTION STANDARDS
• FACILITATE AVAILABILITY OF SAFE AND EFFECTIVE
PRODUCTS
• ELIMINATE INCONSISTENT STANDARDS
INTERNATIONALLY
• FACILITATE MUTUAL ACCEPTANCE OF DATA FROM
CLINICAL TRIALS
GOALS OF INTERNATIONAL HARMONIZATION OF
REGULATORY REQUIREMENTS
67. Study Documentation
During the study
The investigator must keep:
– Source documents
• Medical records (including access to computer
records)
• Laboratory reports
• ECGs, X-rays, etc.
• Any other medical records, reports or notes
(hospital admissions and discharges)
– A subject identification list
– Copies of all study related documentation
68. Medical Records
• In particular, they should contain notes on:
– Sufficient information to support subject eligibility
– This should be well documented (signed and dated)
– Subject’s participation in the study
– Dates of visits
– Procedures, investigations done
– Observations, diagnoses
– Medications taken (including study medication)
– Adverse events
– Completion or withdrawal (reason) from the study
69. Study Documentation
After the study
The sponsor needs from the
investigator:
– Final drug accountability records
– All used and unused supplies and
medication
– All required documents completed