Ethics and Cluster trials

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Ethics and Cluster trials

• Dr Sarah JL Edwards
• Senior Lecturer, Research Ethics and Governance

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• Cluster randomized trials are increasingly being
  used in health and health services research
• Illustrate the types of CRTs
• Identify some ethical issues in review
• Refer to literature and guidance

Ethics and study design Cluster randomized
trials in health research
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• Cluster randomized trials
• Complex studies
• Units of randomization are clusters or groups
• Study intervention may be delivered to
• the cluster as a unit (cluster-cluster trial)
• health professionals (professional-cluster trial)
• individual cluster members (individual-cluster
  trial)
• Outcomes are measured on individuals.

Ethics and study design Cluster randomized
trials in health research
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• COMMIT trial (cluster-cluster trial)
• Unit of randomisation US and Canadian
  Communities
• Intervention Multimodal community-level
  intervention to reduce cigarette consumption
  including media and billboard campaign and
  targeted messaging toward smokers from health
  professionals
• Data collection Interviews with a random sample
  of smokers in each community, the amounts of
  tobacco purchased by people living in the
  intervention and control communities.
• Result Intervention led to an improved quit rate
  for mild to moderate smokers, with no effect on
  the quit rate of heavy smokers.

Ethics and study design Cluster randomized
trials in health research
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• Improving primary care prescribing
  (professional-cluster trial)
• Unit of randomisation General practitioners in
  Ireland
• Intervention Personalized summary by mail of
  prescribing practices of antiplatelet and lipid
  lowering drugs plus an educational visit versus
  personalized summary of prescribing practices
  alone
• Data collection Data on prescribing practices
  from the national pharmacy insurance program
  database. Data on prescribing practices were
  aggregated by physician and contained no
  identifiable information
• Result Both interventions led to similar
  improvements.

Ethics and study design Cluster randomized
trials in health research
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• Cleansing of the umbilical stump in neonates
  (individual-cluster trial)
• Unit of randomisation Geographical areas in
  Nepal
• Intervention Community health workers provide
  cleaning the umbilical stump with chlorhexidine
  versus soap and water versus dry stump care
• Data collection Incidence of infection through
  clinical examination during household visits
  (15,000 infants), neonatal mortality,
  questionnaires about the household and infant
  care
• Result Chlorhexidine reduced infection of the
  umbilical stump by 75 and neonatal mortality by
  24.

Ethics and study design Cluster randomized
trials in health research
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• Rationale important
• Test how generalisable previous results have been
  
• Test cluster level intervention
• Avoid contamination between trial arms e.g.
  educational or behavioural interventions
• Capture herd or group effects e.g. vaccines
• Speed up community roll out of experimental
  medicine

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• Right to health and prior evidence of efficacy
  might render cluster trial unjustified
• Treatment Action Campaign and Others v. Minister
  of Health and Others Constitutional Court of
  South Africa 2002

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• In whose interests?
• Choice and size of cluster
• Moral status of social groups is not well
  understood
• Determine group interests average, aggregate?
• Individual interests each and every best
  interests?

Ethics and study design Cluster randomized
trials in health research
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• Who is research subject?
• CRTs are complex and have multiple levels e.g.,
  hospitals are randomized, health care workers
  receive experimental intervention, and patient
  outcomes are assessed
• Complicates the identification of research
  participants
• From whom is informed consent required, if
  anyone?

Ethics and study design Cluster randomized
trials in health research
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• Who represents group?
• In a CRT, clusters may be randomized prior to the
  identification of individual cluster members
• Is consent to randomization required? If so from
  whom ought it be sought?
• May gatekeepers provide consent to randomization?
• Person politically represent group anyway?
• What are his/her duties?

Ethics and study design Cluster randomized
trials in health research
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• Consent to receive intervention
• In a CRT, the study intervention may be directed
  at the individual or the cluster or both
• Cluster level interventions (e.g., public
  educational messages or fluoridation of water
  supply) may be difficult for individual cluster
  members to avoid
• In such cases, refusal of study participation may
  be meaningless.

Ethics and study design Cluster randomized
trials in health research
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• 5. Consent to submit data on outcomes
• In a CRT, the outcomes relate to individuals
  within clusters
• Individuals may not have consented to
  randomisation of group or to receive experimental
  intervention especially if in control group
• Risk of contamination may be rationale for using
  cluster design.

Ethics and study design Cluster randomized
trials in health research
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MRC 2001

• Ethical and methodological issues following BMJ
  paper 1999 by Edwards et al.

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Ethics and study design Cluster randomized
trials in health research
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Acknowledgements

• HTA for funding in 1999
• Canadian NIH, Ottowa Statement
• MRC PhD candidate, Sapfo Lignou, for work on
  ideas of community
• Wellcome Trust PhD candidate, Elizabeth Oduwo,
  right to health
• UCL BRC funded work on use of cluster designs
  during pandemic
• WHO conference 6th June 2014