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 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),
International Council for Harmonisation of Technical requirements for Pharmaceuticals for Human Use (ICH)-Good Clinical Practice (2016).
World Medical Association (2013). Declaration of Helsinki.