Table 2

A three-step ethical framework for evaluating existing regulatory protections for clinical research

Guiding questionsConcrete tasks
1. Do the regulatory protections have a sound ethical rationale?Determine whether the regulatory protections are prima facie ethically defensible.
Specifically, consider whether the protections are consistent with widely accepted ethical standards for clinical research; whether they protect participants’ rights and interests; and whether the protections meet other ethical criteria, such as a just and fair distribution of research benefits and burdens.
A negative answer to all these questions provides a strong indication that the protections should be revised or revoked. However, the next steps of the framework should still be followed in order to confirm this answer and decide whether and how the protections should be revised, all things considered.
2. What are the benefits and costs of implementing the regulatory protections?Survey all the relevant facts regarding the effects of implementing the regulatory protections.
Specifically, examine systematically who benefits from the protections and who incurs costs, including how significant the benefits and costs are. Have the affected people fared better or worse after the protections were introduced, as compared with how they would have fared if the protections had not been introduced?
Be sure to consider the benefits and costs for everyone affected, based on the list provided below. (Note that listed potential benefits can turn into potential costs when a given regulatory protection leads to a decline in clinical research activity and, consequently, to forgone benefits; conversely, listed potential costs can turn into potential benefits.)
Research participantsPotential clinical benefits from the research intervention (during and after the trial if post-trial access to proven beneficial interventions is provided)
Potential clinical benefits from improved clinical care as part of the research (‘inclusion benefits’)
Potential clinical benefits from ancillary care (eg, following up on diagnoses based on research tests, treating conditions unrelated to the study’s aims)
Potential clinical costs or harms (eg, research-related injuries)
Potential psychological benefits (eg, feelings of altruism)
Potential psychological costs (eg, anxiety from undergoing research procedures or receiving research results)
Potential social benefits (eg, social recognition)
Potential social costs (eg, stigma or discrimination)
Potential financial benefits from monetary compensation
Potential financial costs (eg, transportation costs, lost wages, treatment costs for research-related injuries)
PatientsPotential clinical benefits from access to new interventions
Potential clinical benefits from research-related improvements in the quality of routine clinical care
Potential clinical benefits from advances in scientific or medical knowledge that address local health needs or priorities (primarily fostered through local research capacity building)
Potential clinical costs or harms if qualified clinicians are diverted from routine clinical care to clinical research
Wider communityPotential financial benefits from cost savings for healthcare payers (if research sponsors cover study treatments)
Potential financial benefits from research-related economic activity (eg, research-related jobs or bonuses) and tax revenues
3. Are the regulatory protections justified, all things considered?Consider whether the regulatory protections are, all things considered, ethically justified.
Specifically, weigh the benefits against the costs of the regulatory protections, consider to what extent the distribution of benefits and costs across different population groups promotes or curtails justice, and judge whether the costs to individuals or certain groups amount to a violation of their rights.
If the benefits of the regulatory protections do not outweigh the costs, the protections create new injustices or exacerbate existing ones, or the protections violate the rights of individuals or certain groups, there is reason to revise or amend the protections.
If none of these ethical problems is evident and the protections’ benefits seem to outweigh the costs, then the regulatory protections are ethically justified.
  • Online supplementary appendix 1 provides a summary of how the framework can be applied to the Chilean Law 20.850. Online supplementary appendix 2 provides a slightly modified version of the framework for evaluating new regulatory protections under consideration (rather than existing regulatory protections).