Introduction to Clinical Research and

Good Clinical Practice

Ahmed Abdelmabood ZeeneldinMD Medical Oncology, Egypt

Master of Clinical Research, UK

Items to be covered

• Clinical Research• GCP

Scientific Research

• Observations• Relations

• Workers• temperature• car-oil change

Clinical Research• Observations• Relations

• Question? Is there a relation between the time of car-oil change and temperature?

• Hypothesis? Increasing temperature decreases the time of car-oil change and temperature?

•

• Define measurement scales: – Temp: degrees centigrade– Time in minutes

• Collect data• Test hypothesis

• Conclusion: -increasing temp form 0-25 oC decreases time -while increase above 25 oCincreases the time

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0 10 20 30 40 50

Tem

pera

ture

(oC)

Time (min)

Scientific research

• Systematic investigation of hypothetical propositions about the presumed relationsamong observed phenomena.

Clinical research

• Scientific research • On

– humans or – materials or – data of human origin

Clinical research• Is there a relationship

between Eczema and number of car-oil change in workers?

• Number of car-oil change in workers – Limits: 16/day

• Eczema– Limits: non-invasive

(inspection and not biopsy)– Eczema score: area in CM x

severity (0, 1, 2 3)

Clinical and preclinical research

Clinical and preclinical research

• Preclinical Research:ØNot in humansØBut will serve humansØLABØAnimal

Why we do research?

– To gain knowledge• treat, prevent, diagnose diseases • Human welfare• Current and future patients

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Contributions to knowledge

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Why subjects engage in research?

– To help their diseases– To help other patients– Other benefits:

• e.g. payment

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Is research beneficial to patients?

• WE DO NOT KNOW:– It could be beneficial

(Hopefully)– It could prove harmful– It could prove of no

benefit

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Research vs. routine practice • Practice:

– Standard– approved– benefit

• Research: may not always benefit:– Non-standard– Non-approved– Benefit?

• May receive highest care• May directly benefit• May be harmed

• Research gives Knowledge for better health• Individual: respect, safety and dignity

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Study designs in health research

• Observational: – No intervention

• Experimental: – Intervention and outcome

• Semi-experimental• True-Experimental

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Study designs in Clinical Research

• Observational: – Research– Not clinical trials

• Experimental: – Research– As well as clinical trials

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Observational studies

• Cross-sectional• Case-control• Cohort

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Cross-sectional studies

• Example: – Obesity and Skin cancer

• .

Total SKIN cancer

Obese 350 (70%)Non-Obese 150 (30%)Total 500 (100%)

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Case-control studies

• Example: – Lung cancer and smoking in Gharbia

Lung cancer No-lung cancerSmoking 450 (90%) 150 (30%)No-smoking 50 (10%) 350 (70%)Total 500 500

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Cohort studies جماعة

• Example: – Skin cancer following chest wall irradiation for

Breast cancer

Breast CA+RT Breast CA- RT

Skin cancer 10 (10%) 4 (1.3%)No-SKIN cancer 90 (90%) 296 (98.7%)Total 100 300

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Experimental ResearchInterventional Research

• Phase I• Phase II• Phase III:

– Randomized controlled trial (RCT)

• Phase IV

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Experimental ResearchInterventional Research

• Phase I• Phase II• Phase III:

– Randomized controlled trial (RCT)

• Phase IV

• Semi experimental• Semi experimental• True experimental

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Example of clinical trials

• Use of Nigella Sativa oil in treatment of metastatic malignant melanoma

• استخدام زیت حبة البركة في عالج سرطان الجلد الصبغي المنتشر

Question?

• Why not going ahead and using this in all patients ? ~ 100, 000

Steps• Preclinical R

– Lab: manufacturing and purification, solubility and preservation

– Cell lines• Effective or not

– Animals• Safe or not?

– Dose and frequency and duration AND Route• Efficacious or not?

• Clinical R– Safe or not? à phase I– Efficacious or not? à phase II– More effective than current

chemotherapy? à phase III• What is next?

Phases of clinical trials

Why we use trials?

• Animal and human trials• Predictability of safety and efficacy• Animals:

– Safety prediction– Diseases are different in animals: X efficacy

• Humans:– Safety and efficacy prediction

• Prediction is never perfect

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Drug development cycle

Ethics in research

Preclinical Lab research

• New viruses• New war weapons• Resistant microbes

Pre-clinical animal research

• How long will guinea pig live in atmospheric temperature below 0°?

• How long will a guinea pig live without food or water?

• Carcinogenicity of car-oil on guinea pig skin?

Clinical research• How long will a human live in

atmospheric temperature below 0°?

• How long will a human live under a collapsed house without food or water?

• This will decide the time rescuers will spend on searching?

• Carcinogenicity of car-oil on human skin?

Clinical research

• Are these trials acceptable?

• Is this clinical research practice bad or good ?

• BCRP• GCRP= GCP

Good Clinical Practice (GCP)

• By GCP we mean:– Set of standards for clinical research – From design àconduct àmonitoring/auditing à recording à analysis à reporting

• Aspects of GCP– Science– Ethics– Quality

GCP1 Value (science), القیمة،2 Validity (quality), صالحیة3 Fairness (justice), العدالة4 Risk– benefit ratio

(beneficence), والمنافعالمخاطرنسبة

)المنفعة( 5 Protocol and its

Independent review, البروتوكول

المراجعة المستقلة6 Consent, الموافقة المستنیرة7 Respect االحترام

(Emanuel et al. 2000)Belmont report, 1979.

GCP rules• Social and scientific Value:

– respond to health needs and – provide a sound question whose answers will advance

knowledge for the good of science and society. • Validity (Quality):

– data generated from CR should be valid and interpretable through proper design, endpoints and methodology.

• Fair subject selection: – being non-biased and based of scientific grounds.

• Favorable risk– benefit ratio: – through minimization of vulnerability and risk as well as

maximization of benefits.

• Independent review: – to ensure adherence to the ethical guidelines in design, conduct

and analysis. • Informed consent:

– the process that provides adequate information allows only voluntary participation.

– Consent withdrawal should be allowed anytime in the research.– Consent does not deprive subjects from any of their rights nor

does it alleviate researchers from their responsibilities in protecting safety, rights and welfare of subjects.

• Respect for the enrolled subject’s: – autonomy, right and welfare both during and after research.– Individual’s rights and welfare should precede that of science

and society

BCP (Bad Clinical Practice)• Does skin exposure to car-

oil leads to skin cancer?

• Orphan house• Deal with manager• Paint their skin with car-oil

daily for 8 hours then wash• Do regular punch biopsied

of the skin each month• Follow them without

treatment for the rest of their lives

Good or badPoint Fulfill

mentBad Good

Value √ Skin cancer following exposure to car-oil

Skin cancer following exposure to car-oil

Validity (design) X Artificial exposure Spontaneous natural exposure

Fair X Orphan house Oil station workers

risk– benefit ratio X No Tx allowed Tx allowed

Independent review X No Yes

Consent X NoKids

YesAdults

Respect X Withdrawal not allowed Withdrawal allowed

Historical background of GCP460 BC Oath of Hippocrates1930's U.S. Food, Drugs and Cosmetic Act1947 Nuremberg Code (following Nazi experiments in WWII)1948 Declaration of Human Rights1964 Declaration of Helsinki1979 The Belmont Report1982 International Guidelines for Biomedical

Research Involving Human Subjects1996 ICH-GCP guidelines issued1997 ICH-GCP guidelines becomes law in some countries

Goals of GCP

• To protect the rights, safety and welfare of humans participating in research

• To assure the quality, reliability and integrity of data collected

• To provide standards and guidelines for the conduct of clinical research

The 13 principles of ICH-GCP

• Ethics: 1. Ethical conduct of clinical trials 2. Benefits justify risks 3. Rights, safety, and well-being of subjects prevail

• Protocol and science: 4. Nonclinical and clinical information supports the trial 5. Compliance with a scientifically sound, detailed protocol

The 13 principles of ICH-GCP

• Responsibilities: 6. IRB/IEC approval prior to initiation 7. Medical care/decisions by qualified physician 8. Each individual is qualified (education, training, experience) to perform his/her tasks

• Informed Consent: 9. Freely given from every subject prior to participation

The 13 principles of ICH-GCP

• Data quality and integrity: 10. Accurate reporting, interpretation, and verification 11. Protects confidentiality of records12. Investigational Products Conform to GMP’s and used per protocol

• Quality Control/Quality Assurance 13. Systems with procedures to ensure quality of every aspect of the trial

Parties involved in research

Parties involved in research• Investigator • Subject• Sponsor• CRO• Ethics

committee• Regulatory

authorities

Summary

• Scientific research• Clinical research• Clinical trials

– Phase I, II, III and IV• Ethics in research• GCP: standards or guidelines to ensure research is

scientific, ethical and of good quality• Parties involved in research and their role and

responsibilities

Thank You

Ahmed A ZeeneldinDirector of Research Center (RCENCI)

Tel: 01111 000 943Email: azeeneldin@gmail.com

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