Clinical Research Ethics

Clinical Research

• research on human biology/physiology

• safety/efficacy of new medical interventions (clinical trials)

• new medical devices, pharmaceuticals, diagnostic tests, studies of disease processes

• happens on both health volunteers and studied/treated conditions

Landmark Cases

• Tuskegee Syphilis Trials (1930s-1970s)

  • study of untreated syphilis despite available treatments

• Thalidomide (1950s-1960s)

  • global use of sedative given in pregnancy that caused birth defects

  • result = enhanced FDA regulations requiring side effect disclosure

• HIV/AIDS Research (1980s-1990s)

  • pressure from activists including NIH protests

  • requesting funding for research on HIV/AIDS and treatment

• Alder Hey Scandal (1980s-1990s)

  • organs collected from diseased infants

  • without family knowledge/consent in UK

  • result = legislation on human tissue

• Theranos (2010)

  • company promised to offer more effect and less painful blood testing

  • case was brought to court → company could not deliver

Emmanuel, Wendler & Grady 2000

7 requirements for Clinical Research

• Value = must enhance scientific knowledge or human health

• Scientific validity = methodically rigorous

• Fair subject selection = recruitment is scientifically sound (not biased)

• Favorable risk/benefit ratio = degree of risk matches potential benefit

• Independent review = people not on research team must vet the work

• Informed consent = participants agree freely/voluntarily without coercion

• Respect for subjects = subject identities kept private, free to withdraw, and well-being monitored

Declaration of Helsinki (1964, 2024)

• for human subjects research

• not a binding set of laws → commonly accepted code of ethics

• made by the World Medical Association

• many national research regulations based on it

• people’s right to (ongoing) self-determination about research participation

  • surrogates for people who cannot consent

  • participant welfare as a priority over scientific progress/advancement

  • ethics superseding laws/regulations

  • IRBs or mechanism of accountability present

Informed Consent

• participation is voluntary

• participants given information to make informed choice to participate or not

• different participants may want different amounts/types of information

• complicated scientific information must be communicated clearly

• risks/benefits important

  • highly experimental treatments

  • significant potential adverse effects

Therapeutic Misconception (McCormick 2018)

• misconception amongst participants in clinical research

• assumption that experimental treatment is meant to benefit them directly

• may be to collect data on efficacy and adverse effects

• therapeutic optimism = sharing enthusiasm/hope for an experimental therapy to work

• communicate clearly/explicitly what is known

• avoid anecdotal/speculative claims

Risk and Benefit

• high risk research needs potential for great benefit

• evidence that benefit is possible even if not guaranteed

• end study early if significant risks are discovered

• end study early if initial data reveals clear evidence that one treatment is superior to another

• challenging to inform participants about risks/adverse effects discovered months/years later

Participant Selection

• maximally inclusive studies

  • women were historically excluded from clinical trials

  • fear of thalidomide scandal

• ensure most robust and widely applicable data to be generated

• trial may be relevant only to a certain group

  • reproductive health interventions

  • particular age group drug

Placebos

• non-active substance given as a control to compare against variable (novel intervention)

• used when there is no known effective treatment

• participants made aware during informed consent that they may either receive a placebo or new treatment

• must be sound scientific reasons to use a placebo

• risk of denying participants a potentially effective treatment/cure

Nardini 2014

• Declaration of Helsinki’s rules

• placebo use is acceptable if no proven treatment exists

• must have compelling and scientifically sound methodological reasons

• used to determine efficacy or safety of an intervention

• ensure patients receiving placebo or no treatment are not subjected to any risk of serious or irreversible harm

Participant Harm

• negligence → research team/clinicians sued for malpractice

• research team/clinicians partially protected by informed consent document

  • if risks are accurately described

  • participant was fully informed

  • participant had ability to withdraw from research

• participant health insurance may cover medical harm from clinical trial

• participants may sue for payment of medical bills related to harm

Conflicts of Interest (COI)

• competing interest must be disclosed

  • when research on a medication is funded by pharmaceutical company manufacturing it

• persons with significant direct financial interest prohibited from carrying out the research

  • owners of large stocks in company

  • IRB prohibits persons from serving as researcher on drug manufactured by the company

Weigmann 2015

Global Clinical Trials

• easier to enroll participants in poverty with no other access to care

• concern of coercion and exploitation

• fewer regulations/protections to protect people

• participants in control group may only be entitled to interventions available locally (standard of care)

• questions if country where research is conducted sees benefits

• different barriers/understandings of informed consent between culture