Good Clinical Practice is a part of pharmaceutical quality assurance in pharmaceutical industry and its about the clinical trials of drugs for patients . New drug research starts by studying how the body functions at its most basic levels. The first series of tests

1. Introduction to GCP and Ethical
considerations in clinical trials
Dr. Mwaka Erisa, PhD
Orthopaedic surgeon and Senior lecturer
College of Health Sciences
Makerere University
NDA 08/12/2017

2. Outline
• Objective
• Introduction
• GCP principles 1 to 5
• Case studies on unethical research practice
• Physician-patient relationship in research

3. Objective
• To understand and appreciate the importance
of GCP guidelines in research

4. Introduction
• GCP is an international ethical and scientific quality
standard for designing, conducting, recording and
reporting trials that involve the participation of
human subjects.
• 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. GCP Principles
Clinical trials should be conducted in
accordance with the ethical principles that
have their origin in the Declaration of Helsinki,
and that are consistent with GCP and the
applicable regulatory requirement(s)
• Adopted by WMA in 1964
• Revised 7 times, latest 2013

6. IMPORTANT!!
• ‘‘The health of my patient will be my first
consideration,’’
• ‘‘A physician shall act only in the patient’s
interest when providing medical care which
might have the effect of weakening the
physical and mental condition of the patient.’’
Helsinki Declaration 2016

7. Clauses in the Declaration of Helsinki
• General principles
• Risks, Burdens and Benefits
• Vulnerable groups and Individuals
• Scientific requirements and research protocols
• Research Ethics Committees
• Privacy and confidentiality
• Informed Consent
• Use of placebo
• Post-trial provisions
• Research registration and publication and dissemination of
results
• Unproven interventions in clinical practice.

8. Before a trial is initiated, foreseeable risks and
inconveniences should be weighed against the
anticipated benefit for the individual trial subject and
society. A trial should be initiated and continued only
if the anticipated benefits justify the risks
• Beneficence
• Non-malefiscence
• Responsibility of the researcher and regulatory
bodies e.g., REC, UNCST,NDA

9. The rights, safety, and well-being of the trial
subjects are the most important considerations
and should prevail over interests of science and
society.
The available nonclinical and clinical
information on an investigational product
should be adequate to support the proposed
clinical trial.
Clinical trials should be scientifically sound, and
described in a clear, detailed protocol.

10. Unethical research cases studies
Epidemic outbreak of bacterial meningitis in Kano
• Bacterial (meningococcal) meningitis epidemic in
a slum area in Kano, Nigeria (1996)
• An estimated 15 000 people died and thousands
of children were permanently disabled
• RCT where Trovan (IP- 100 Children) and
Ceftriaxone (100 children) where compared.
• Ceftriaxone administered at 33% of
recommended dose
• 5 children (Trovan) and 6 (Ceftriaxone) died
• Trial conclusion Trovan 94.4% and Cetriaxone
90% survival rate

11. Trovan case …
• Falsified REC approval
• No evidence of informed consent
• Nigerian government called the trial "an illegal
trial of an unregistered drug."
• Long standing court case that was settled in
2009 out of court.
• Nigerian Government conducted investigation,
kept in secret for 5 years and files later
disappeared.

12. Trovan
• Who didn’t do their job?
• Relating to Uganda who would have been
responsible for the protection of the very sick
vulnerable children?
• What do we learn from this case as
researchers and research regulators?

13. Case 2: Informed consent
Professor ZN is a well-respected researcher and PI
of a phase IIa clinical trial on Ovarian cancer.
• Participants recruited from Cancer ward
• Many patients refuse to consent because of fear
of side effects.
• Trial sponsor is unhappy about the slow
recruitment rate.
• RA decide to recruit without proper informed
consent without PI’s knowledge and is happy with
their improved rate.

14. Informed consent …
• Whistle blower writes anonymously to PI what
is happening.
• PI calls for meeting, rebukes the RA, institutes
remedial measures but says nothing about the
data and samples collected without IC.
• PI doesn’t report to the REC but REC
eventually finds out.
• Trial suspended and investigations are
instituted

15. Discussion
• How should the PI have handled this
situation?
• What are the ramifications of the PI’s decision
• What do we have to learn about the
responsibilities of the researcher.

16. Physician-patient relationship in
research
• Patients are increasingly seeking treatment
through research participation instead of, or
as an adjunct to, standard clinical care.
• Physicians are likely to be asked by their
patients for advice about whether to enrol in
clinical trials
• Avoid abuse of this relationship in research.
Chen et al

17. Physicians’ role
• Hope and desperation, frequently motivate
people to participate in a clinical trial can
predispose patients and their families to make
decisions based on unrealistic hope.
• Helping patients understand the difference
between clinical research and clinical practice
• Combating “therapeutic misconception” and
other distortions in decision making about clinical
trial participation
• Physicians to can refer patients to a clinical trial
out of desperation e.g., Oncology research

18. Ethical Issues
• Undue influence
• Coercion
• Conflict of interest e.g., Pharma sponsors
• Physicians should not recommend
participation in a clinical trial if they believe
that participation would unduly compromise
patient care or if they have unmanageable
conflicts of interest

19. Conclusion
• ‘‘The health of my patient will be my first
consideration,’’
• ‘‘A physician shall act only in the patient’s
interest when providing medical care which
might have the effect of weakening the
physical and mental condition of the patient.’’

20. References
• Chen, D. T., Miller, F. G., & Rosenstein, D. L.
(2003). Clinical research and the physician–
patient relationship. Annals of Internal
Medicine, 138(8), 669-672.
• International Council for Harmonisation of
Technical requirements for Pharmaceuticals for
Human Use (ICH)-Good Clinical Practice (2016).
• World Medical Association (2013). Declaration of
Helsinki.