Development of decision-making considerations to support equitable patient selection in paediatric haemophilia trials

Recommended selection methods: Random selection or prioritising patients who are most vulnerable

‘First come, first served’ may not be equitable as patients with connections may learn about and join trials earlier

Allocation method may be arrived at through stakeholder discussions

Health inequities: Implicit bias and structural barriers to participation should be identified and minimised, possibly with the use of a blinded scoring system

Allocation method determined through group discussions and consultations

Recommended selection methods: Regardless of participation in early-phase trials, patients who could give consent and met inclusion criteria were put into a random selection algorithm, then contacted in that random order until recruitment slots were filled

Implementation and outcomes: Regardless of outcome, participants/caregivers reported that the use of random chance was fair

Recommended selection methods: Does not necessarily require resources to be evenly distributed, but that they be distributed without coercion or domination

Health inequities: Marginalised groups (including women, the elderly, people with a history of drug use, or people with HIV) should not be unnecessarily excluded from clinical trials if they otherwise fit

Recommended selection methods: Main factors to consider are fair inclusion of participants, fair burden-sharing and risk assumption amongst subjects, fair opportunity for a subject to participate in research that may benefit them, and fair distribution of risks to third parties and surrounding community members

Health inequities: Benefits and risks of the research should be distributed fairly

Interacting priorities: Fair inclusion is prioritised over fair opportunity and fair burden-sharing. Fair distribution of third-party risks should be prioritised over fair inclusion, fair opportunity, or fair burden-sharing, except in cases where including a subject puts them at unacceptable risk

Recommended selection methods: Should mainly consider the scientific goals of the research, with the exclusion of any patient/group being scientifically or medically justified

Subjects should be selected to minimise risks and maximise benefits to individuals and to society

Health inequities: Those who bear the risks of the research should have access to benefits of the research, while those who are likely to benefit should share some of the risks

Health inequities: In response to Dobra et al. [6], the author suggests using the national registry of patients with cystic fibrosis to select participants, as geographic proximity to a cystic fibrosis treatment centre could be a barrier to participating in a clinical trial even though many cystic fibrosis patients show a willingness and ability to travel for treatment

Recommended selection methods: Participants should not be excluded or treated differently simply because they may face greater risks than others during the trial, unless their inclusion places them at undue harm or will not help facilitate the scientific goals of the study

Interacting priorities: Deliberately excluding those at greater risk under the principle of beneficence contradicts the principle of justice, while attempting to solely maximise good and minimise bad outcomes may lead to counterintuitive selection processes

Recommended selection methods: Prioritisation of the most vulnerable, prioritisation of those who would gain the greatest number of life-years, prioritisation of those with ‘instrumental value’ ^[12] such as essential workers, prioritisation based on random lottery, ‘first come, first served’, or prioritisation based on minimising outbreaks

Random lottery or ‘first come, first served’ is not recommended because this strategy is inequitable and unlikely to reduce morbidity, mortality, or health disparities

Interacting priorities: Conflicts and synergies may arise when one of the above distribution methods is chosen. Those at the intersection of any one of the above groups should be vaccinated first, with further decisions being made based on empirical data

Recommended selection methods: The suggested ranking of priority for distribution is healthcare professionals in immediate patient care, followed by recipients of organ transplants undergoing immunosuppressive therapy, and then all other people ordered from oldest to youngest regardless of medical insurance

This order is based on the principle that “those who are most needed come first, followed by those most in need.” ^[13]

Interacting priorities: Interacting priorities were not considered, as “any granularity in the criteria would render them less transparent and actionable.” ^[13]

Recommended selection methods: Prioritising the number of lives saved or life years gained, prioritising the most vulnerable groups, prioritising instrumental personnel, or by random lottery

‘First come, first served’ is not advised as it prioritises those who can access resources quickly and makes no attempt to maximise benefits

Developing a ‘clinical triage team’ to form an allocation framework may be advisable

Interacting priorities: Multiple tactics should be used, and some trade-offs may be necessary as determined by the clinician's own reasoning

Decision-making should always consider the four fundamental principles of beneficence, non-maleficence, autonomy, and justice

Suggested methods of selection: Decision-making criteria were formed through iterative discussions with a team of diverse professionals. A semi-quantitative score-assigning method was used to evaluate possible solutions, but each criterion's comparative importance was left up to clinicians’ judgement

Ethical criteria considered included the four pillars, ^[4] alongside medical criteria such as medical need, availability of alternative treatments, and wait times

Implementation and outcomes: Ethical concerns in the decision-making method or the decisions made were revised once noticed

Involving a multidisciplinary team was important in order to obtain a range of perspectives