L8 - Ethical Challenges in SCI (spinal cord injury) Clinical Trials

Spinal Cord Injuries

Review of ethics - discuss the following terms :

• The Declaration of Helsinki

• The Belmont Report

• Tri-Council Policy Statement

• FOUR principles of ethics

Main focus of the following document

• The Declaration of Helsinki = global document for ethical principles regarding human experimentation & research ethics oversight

• The Belmont Report = important biomedical ethics principles

• Tri-Council Policy Statement = canadian policy for research involving human participants

FOUR principles of ethics

• Autonomy = informed consent, respect for persons

• Beneficence = maximize benefits

• Nonmaleficence = minimize risks

• Justice = fairness and equity

What are the ethics in clinical research (8) + give examples for each

Voluntariness

• particpant’s choice to join a study

Informed Consent

• participant is given details about the study, such as data collection, potential risks, privacy of data

Right to withdraw

• participant’s ability to change their mind and leave the study without any consequences

Confidentiality

• privacy of information / who has access to the information of the participant

Accessibility

• participation is open to large population by accounting for different cultural backgrounds

Values and Priorities

• focus on the outcome that matters to both the researcher and the participant

Follow up

• check in with the participant after a study has ended to monitor effects

Safety

• ensuring that side effects of a study are monitored and terminating the research if any serious risks are detected

What is the damage of spinal cord injury depending on the location of injury (3)

Cervical

• difficulty breathing

• shoulder movement

Thoracic

• trunk stability

• temperature regulation

Lumbar & Sacral

• bladder and bowel control

• leg function

What are some consequences of spinal cord injury - INTERNAL (5)

• Paralysis → loss of motor and sensory function

• Loss of control over bowel & bladder function

• Pain

• Susceptibility to infection

• Affect other physiological functions → EX: cardiovascular / respiratory

What are some consequences of spinal cord injury - EXTERNAL (5)

• Loss of independence

• Limited employment opportunities

• Altered purpose / meaning of life → EX: dancer loses their ability to move and so lose their identity

• Personal and financial burden on the individual & caregiver

• Societal cost (economic burden on healthcare system)

Explain the statement “Time is Spine” (pathophysiology of SCI)

Damage due to SCI evolves over time and early intervention is necessary to prevent irreversible destruction

Acute = seconds to days after incident

• perfect timing where early intervention (stabilize blood flow) can prevent further damage

  • internal hemorrhage (bleeding)

  • inflammation

  • swelling due to extra fluid buildup

Intermediate = days to week after incident

• still have time to intervene by focusing on supporting recovery

  • axons retracting SO leading to gaps between nerves

  • molecules released by astrocytes start to accumulate around injury site & prevent axon growth

Chronic = weekS to months after incident

• low chance of recovery from damage SO shift focus to rehabilitation

  • physical scar is formed at injury site prevent aoxnal growth

  • loss of neuronal connections

Discuss the clinical trial phases of SCI (4) + some limitations ?

LIMITATIONS: financial reasons (too expensive to continue), enrollment issues (small population), low power (poor study design)

Phase I = safety

• safest dose that is tolerable

• closely monitoring side effects

• testing on smaller population

Phase II = efficacy

• aiming for most effective dose

• measuring outcomes

• testing on larger population

Phase III = confirmation

• compare with other treatments (confirming effectiveness & safety)

• monitor adverse events

• involving control group

Phase IV = follow-up

• detect long term side effects

• put on the market

→ BUT lots of interventions do not make it to the market due to financial reasons

Discuss the distribution of SCI clinical trial intervention (depending on the stages)

Later phases of clinical trial intervention involve pharmaceutical companies more heavily as the focus has shifted from basic safety testing to larger scale production and commercialization of a product

Why might a SCI clinical trial be stopped? (4)

• Safety → adverse events occur

• Poor study design → low enrollment

• Efficacy → results are insignificant

• Commercial reasons → money is not enough

What are some commercial reasons for stopping SCI clinical trial + is it ethical to do so?

• research budgets reduce

• competitive products emerge

• supply failures

• pressure to terminate unproductive programs

What are some types of intervention for SCI? (5) + What is a combination intervention?

• Drugs => reducing secondary damage after injury such as inflammation, pain, axon health

• Stem cells => repair and replace damaged cells (regeneration & cell replacement)

• Devices => exoskeletons used to support or restore physical abilities (rehabilitation)

• Biomaterial => physically guiding axonal regrowth

• Surgical => prevent further damage and relieve pressure

Effective intervention for SCI involve combination of different approaches since SCI is not caused by one problem

Discuss the Mend the Gap intervention + what type of intervention is it?

• It is a proposed approach to spinal cord repair promoting axon regeneration => bridge the gap in spinal cord tissue

• combination of

  • biomaterial injected into spinal cord injury site

  • drug delivered by biomaterials to eliminate scar tissue

  • surgical robot visualize tissue structure & guide the injection of biomaterials

Discuss the difference in values & priorities depending on severity of the SCI

Differ in their technology adoption behaviours

MAJORITY of people with chronic cervical SCI = late adopters

• less willing to take risks

• afraid to lose the current functions that they have

MAJORITY of people with chronic thoracic SCI = early adopters

• higher tolerance to risk

• see more gain from risky interventions

What is medical tourism - why are people seeking for it - what are the ethical implications

• People traveling to other countries to receive medical interventions / healthcare services

• Reasons:

  • cost savings

  • faster access / shorter wait times

  • access unapproved services in their home country

  • better expertise & quality

  • combine with tourism

• Ethical implications

  • resource allocation → wealthy foreign patients are prioritized over local population

  • risk of complications when returning home

  • consent issues due to cultural differences

  • vulnerable to false → clinics offering treatments with limited scientific evidence

  • legal concerns across countries