Benefits & Risks in Research Involving Human Particpants

Ghaiath M. A. HusseinMBBS, MHSc. (Bioethics)

Acknowledgment

This presentation is based on presentations given by:• Henry Silverman• Naeema Abdallah

Outline of the presentation

• What is meant by benefits?• Types of Benefit• What is risk?• What are the types of risk?• How to assess risk?

Benefits

• Benefits to research subjects

• Benefits to societyoSpecific new, effective intervention oKnowledge which some time in the

future may lead to effective interventions

Benefits to Research Subjects• Direct Benefit

o arising from the intervention being studiedo information that can influence care, e.g., diagnostic

• Collateral Benefito Also called “indirect” benefito Arising from being a subject, even if one does not receive

the experimental interventiono extra supervision from being in the research study (?)o access to medical care not available for economic

reasonso unplanned or unanticipated benefits

Benefits to Research Subjects

• Inspirational

• Aspirationalo benefit to society (arises from the results of the study)

• Payments or incentives – benefits???• Should not be considered as benefits• Inappropriately skew judgments concerning risks

and potential benefits• Any level of research risk could be offset by such

gains if they were significant enoug

Benefits to Research Subjects

• No benefits from the researchoPhase I trials testing maximum tolerated

doseoNon-therapeutic research procedures

Mechanism of disease

Definition• Risk:Means any harm or injury that affect the subject or the participant under study.

• Risk:“ A state of uncertainty where some of the possibilities involve a loss, catastrophe, or other undesirable outcome. ” (1)

Types of risks

• Physical risks:1.Cold:As the Nazi Experiments used Tanks filled with cold water to submerge prisoners to determine how long German pilots would survive after parachuting into the cold North Sea.

Nazi Experiments

2. Pressure:

Low oxygen pressure as happened with the Nazi experiments when high altitude experiments where performed to test how long pilots would survive after being ejected from their planes.

High Altitude Experiments

3. Heat: Heat stroke; Burn; Exhaustion

4.Noise: High noise may lead to impairment or loss of hearing

5. Light:Dim light may affect the vision

• Medical Risks:1.Therapeutics: • As happened with black Americans

who's being prevented from syphilis treatment to study the disease natural course.

• Stop antibiotics from bacterial infected patients as happened with patients of Rheumatic Fever.

• Placebo that used in control groups of diseased participants.

2. Preventive:New vaccines e.g. Salk polio vaccine when a lump of a live polio vaccine given to children and most of them eventually developed polio.

3. Diagnostic:• Irradiation:

- Teratogenic effect to the fetus.- Carcinogenic effect.• Samplings:

- Biopsies: tissues that contain genetic information about the participant.- Surgical hazards.-Too risky procedures (under anesthesia)

• Social Risks:Stigma (As patients with HIV-AIDS, STDs).• Emotional Risks:On families when their children chosen for trial of new vaccine; research in war.• Psychological Risks:

Questionnaires with sensitive questions to participants in sensitive positions, as to ask poor people about there nutrition and houses.

The Forgotten Risks!

Risk to the Society:

• Manipulating environmental factors (Pathogenic organisms and toxic chemicals) which affect the community under that study.

• Legal risks:• Vulnerable groups, e.g., prisoners,

children, pregnant women.

Economic risk:

• - Burden of traveling cost as for diagnostic or therapeutic procedures conducted far from the participant residential area.

- Absentees, may loss their job or work.

Categorization of Risk

According to the severity of the risk, it can be categorized to:1.Minimal Risk: As routine blood sample , throat

swabs, vaginal swabs, sputum exams• Above Minimal Risk: That can be minimized, and

within the toleration of the participant. • Too Risky: the most dangerous type, and the

Researcher should not be allowed to conduct A research that endanger the life of the participants e.g. live cancer cells , live virus

Minimal Risk

• The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during routine performance of physical or psychological examination or tests

Clinical Equipoise• The start of the trial, there must be a state of

clinical equipoise regarding the merits of the regimens to be tested, and the trial must be designed in such a way as to make it reasonable to expect that, if it is successfully conducted, clinical equipoise will be disturbed."

Clinical Equipoise• Clinical equipoise means a genuine

uncertainty on the part of the expert medical community about the comparative therapeutic merits of each arm of a clinical trial.

• The tenet of clinical equipoise provides a clear moral foundation to the requirement that the health care of subjects not be disadvantaged by research participants.

-Adequate facilities ,procedures and personnel for dealing with emergencies .-Arrangement made for monitoring and detecting adverse out comes .-All trials should be reviewed by a Data Safety Monitoring Board (DSMB).-All potential toxins, mutagens or teratogens used should be justified.-The National Committee for Atomic Energy should completed risk assessment for the use of the radiation and radioactive substances .

Minimization of Risk

• For Drugs:- Registration, its trade name, chemical name and pharmacological class .- Recommended dose, form of administration in the study.- Known or possible interaction with other drugs, side effects and adverse reactions.- Placebo should be justified.

Minimization of Risk

• Social Risks:- The research should have potential to enhance the future health of the society .

• For vulnerable groups :- Additional safeguards needed to protect there rights and welfare .

• For recruitment materials:(posters, newspapers, T.V, videos ……).Should be acceptable if submitted .

Minimization of Risk

• For Psychological Risks :• Sensitive questions for sensitive group like those

with AIDS ,STDs,T.B, can be questioned through 3rd person or ask the help of psychologists .

• Economic Risks :• Traveling cost can be solved out.• Absentees issues should also be solved out.

Minimization of Risk

• Legal :- The risk should be reasonable in relation to the anticipated benefits to the subjects or society .- Privacy of subject should be adequately protected .- For tissue samples containing genetics information the subject should have option to withdraw at any time .

Minimization of Risk

References

1.Douglas Hubbard "How to Measure Anything: Finding the Value of Intangibles in Business" pg. 46, John Wiley & Sons, 2007.

2.National Guidelines for Health Research involving Human subjects (Sudan, 2008)