INTRODUCTION TO GOOD RESEARCH PRACTICE

GOAL
An enhanced awareness of the importance of health research ethics and an improved capacity for
participation in the research ethics review system as research stakeholders
An enhanced awareness of the importance of health research ethics and an improved capacity for
participation in the research ethics review system as research stakeholders
OBJECTIVES OF THIS SESSION
1. Trace the development of research ethics and international guidelines in health-related research
2. To familiarize medical students on the ethical principles in health research
Definitions
Research refers to a class of activity designed to develop or contribute to generalizable knowledge (e.g.
theories, principles or relationships, or the accumulation of information on which they are based that can
be corroborated by accepted scientific methods of observations and inference. (CIOMS, 2002)
Health Research medical and behavioral studies pertaining to human health. (CIOMS, 2002)
Health related Research studies that impact the well-being of individuals and communities
Ethics is doing the right thing (-deals with the concept of what is good as a goal and what is right "as
a course of action or s the justified claim or entitlement).
Research Ethics is setting good goals and defining right processes in the conduct of health research
Good Clinical Practice a standard for the design , conduct, performance, monitoring, auditing,
recording, analysis, 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,1996)
Good Research Practice standard for the design. Conduct, data recording and analysis and reporting of
research studies that ensures credibility of results and the protection of the rights of study participants
and other stakeholders. (MTR Proposal 7/17 2015)
Historical Notes in the Development of Research Ethics
1. The Nazi Experiments and the Nuremberg Trials
--Nuremberg Code 1947
---Helsinki
Declaration 1964.2013
2. The Willowbrook and Tuskegee Clinical Experiments
The Belmont Report 1974
3. Drug Trials in Developing Countries
CIOMS (Council for International Organizations of Medical Sciences)-WHO International Ethical Guidelines
for Biomedical Research Involving Human Subjects 19822002.
4. Inter-country Registration of Pharmaceutical Products
> ICH (International Conference for Harmonization)-GCP (Good Clinical Practice) Guidelines 1996
Requirement for Ethical Review, need for ERCs
WHO Operational Guidelines for Ethics Committees that Review Biomedical Research (Geneva 2000)
>WHO standards and Operational Guidelines for Ethics Review of Health-Related Research with Human
Participants (2011)
Nazi Experiments Exposed during the Nuremberg Trials (1946)
23 German doctors committed crimes against humanity for performing medical experiments upon
concentration camp inmates and other human subjects without their consent.
The Experiments
On limits of human endurance in high altitudes (Subjects placed in low-pressure chambers)
On the most effective means of resuscitating pilots who have been severely chilled/frozen after falling
into the sea: (Subjects forced to remain in ice water for 3 hours).
For diseases troubling German occupation forces
- malaria: Healthy subjects infested using mosquitos
- Infected wounds: Sulfanilamide clinical trial. (Subjects deliberately wounded, infected with bacteria,
circulation interrupted, aggravated by forcing wood shavings and ground glass).
For diseases troubling German occupation forces
- Feasibility and organ transplantation: Bone, muscle and nerves removed from one group and translated into
the other group.
On methods of sterilizing men and women --On the most efficient means of mass execution of useless
people ex. poisons
The Nuremberg Code of 1947
Focused on voluntary consent and human rights of human participants
Avoidance of unnecessary physical and mental suffering and injury.
Balancing risks and benefits
Termination of research participation by the human subject

Proper design and prior information

Code for Research and Experimentation (WMA) 1954

Qualification of researcher

Proxy consent for human participants who cannot give consent for themselves
The Helsinki Declaration (WMA) 1964, 1975, 1983,1989, 1996, 2000,2002, 2004,2008, 2013

Proxy Consent
Ethical Review by an independent committee
Standard of care

Universal Declaration of Human Rights 1966

(UN General assembly) International Covenant on Civil and Political Rights
ART. 7 No one shall be subjected to torture or to cruel , inhuman or degrading treatment or punishment. In
particular, no one shall be subjected without his (her) free consent to medical or scientific experimentation.
Willowbrook Hepatitis Expt
Objective: To determine the mode of infection of the hepatitis virus and course of the disease and to test
effectiveness of human globulin

Subjects: > 700 mentally retarded children

Therapeutic/Non-therapeutic Research
Placebo control

Methodology: deliberate infection with hepatitis

virus

Early subjects fed extracts of stools from infected individuals

Late subjects received purified virus preparations
Defense: Majority of the children will acquire the infection at Willowbrook so its better for them to be infected under
carefully controlled research conditions
Tuskegee Clinical Trial (1932-1972)
NIH (National Institute for Health ) sponsored, Alabama, USA
Objective: To determine the clinical course of untreated syphilis
Subjects: 600 men with syphilis
Methodology: 300 randomized to treatment
, 300 randomized to NO treatment
No clear endpoints, no information, no permission
Results: Untreated patients fared poorly, many died
(CNN, May 16, 1997: Public Apology from US Pres. Clinton, Support for lasting Bioethics reforms).
The Belmont Report (1974)
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
-mandated by Congress to provide an ethical foundation for a system of protections for human subjects
-identified 3 basic ethical principles relevant to research involving human subjects a) respect for persons (personal
autonomy), b). Beneficence; and c) justice
CIOMS-WHO International Ethical Guidelines for Biomedical Research Involving Human Subjects- 1982
1993, 2002
CIOMS- Council for International Organizations of Medical Sciences funded under the auspices of WHO and UNESCO
in 1949
21 Guidelines with commentaries including:
-Ethical justification and scientific validity of research
-Ethical review , informed consent, vulnerability of individuals, groups, communities and populations
-Women as research subjects
CIOMS-WHO International Ethical Guidelines for Biomedical Research Involving Human Subjects
-Equity regarding burdens and benefits
-choice of control in clinical trials
-Confidentiality, Compensation
-Strengthening of national or local capacity for ethical review and obligations of sponsors to provide health-care
services
ICH Guidelines for Good Clinical Practice (1996)
International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for
Human Use
Objective: To provide a unified standard for Europe, Japan and the US to facilitate the mutual acceptance of clinical
data by the regulatory authorities in these jurisdictions
ICH Guidelines for Good Clinical Practice (1996)
A standard for the design, conduct of the study, performance , monitoring, auditing, recording, analyses and
reporting of clinical trials that provides assurance
(1) that the data and reported results are credible and accurate
(2) That the rights, integrity and
confidentiality of trial subjects are protected
WHO Operational Guidelines for Ethics Committees that Review Biomedical Research (Geneva 2000)
Intended to facilitate and support ethical review in all countries around the world
Objective: To contribute to the development of quality and consistency in then ethical review of biomedical research
- To be used by national and local bodies in developing, evaluating and progressively refining SOPs for ethical review
of biomedical research.
Standards and Operational Guidelines for Ethics Review of Health-Relate research with Human
Participants (WHO 2011)
I. Standards for the Research Ethics Review System
II. Standards and Guidance for Entities that Establish research Ethics Committees (composition, resources,
independence, training, transparency, accountability and quality)
Standards and Operational Guidelines for Ethics Review of Health-Relate research with Human
Participants (WHO 2011
III. Standards and Guidance for members of the Ethics Review Committee (ethical basis for decision-making in
research ethics committee)
IV. Standards and Guidance or the Secretariat, Staff and Administration of the Research Ethics Committee).
V. standards and guidance for Researchers
Worst Examples of Research
Research driven by curiosity or ambition that treats the patients as means to an end.
Research that needlessly prolongs distress because of the protocol design
Research where researchers lose interest after the last day of the study
( Research that an investigator would not recommend to his or her own loved ones if they were similarly affected by
the illness)
Importance of Ethics in Research
1. Human subjects can be harmed or wronged as participants in health rsearch
2. Good Guys can sometimes be bad
3. Scientific/economic interest may trump individual persons interest.
4. Promote public credibility in research
5. Sustain public support.