The concept of grouping subjects for randomization is called cluster randomized trials (CRT) – this concept is becoming increasingly common when randomizing large groups. However, when CRTs involve interventions at a cluster level, informed consent from participants may not always be possible to obtain.

As informed consent is a fundamental ethical requirement for clinical trials, this presents a serious challenge for CRTs. Furthermore, the need for these types of trials is likely to increase, with growing demand to evaluate the delivery of health services, public education and policy on social care.

The George Institute is currently conducting a study known as HeadPost – a study to compare the effects of a patients head position after suffering a stroke – which has been designed as a CRT. The HeadPost study is the largest nursing care trial ever conducted, with a target sample size of over 19,000 patients. The study will determine whether lying flat with a head position of zero degrees is superior to sitting up with the head positioned greater than or equal to a 30 degree angle.

The HeadPost study has been clustered by sites, and its objective is to reach 120 sites for it to be effective. This is a challenging feat for an academic study with limited funding, however as all patients in the cluster are eligible for the study, a larger and more diverse population of the disease group is included (as opposed to a typical randomized clinical trial in stroke).

One of the challenges in HeadPost was obtaining informed consent. Informed consent is a critical step where potential participants are given information about the key facts of a clinical trial before deciding whether or not to take part. As the study intervention is delivered at a cluster level, individuals in the cluster may find it difficult to avoid the intervention. For example, if the intervention was health advice through a radio program, individuals would not be aware that the radio broadcast was an intervention and the ability for each individual to consent participation would be lost. Obtaining consent for such large clusters is indeed a challenge to CRTs; therefore, innovative solutions is needed when consent for individuals cannot be obtained.

One of the recommendations is that a study “gatekeeper” or “cluster representation mechanism” is appointed – a person or body charged with making decision on behalf of the entire cluster. In HeadPost, the informed consent for the intervention was signed by the head of department of the site, and approved by the ethics committee. As the intervention in HeadPost was lying flat or sitting up, both considered to be usual care, ethics committees were agreeable to this. The consent can also be delayed for data collection and follow-up.  This reduces delay in the intervention which reduces pressure on site staff, allows for consecutive enrolment to the study, and reduce selection bias to a degree.

In Australia, the “Opt-out” consent method was added, which meant that all patients are automatically in the study during the study period and may opt-out of the study at any time up until the end of the study period.  This has been shown to reduce selection bias in registries and low-risk studies, and the opt-out rate is typically between 2-3%.

Conclusions

CRTs are widely recognised as an appropriate method for evaluating interventions such as family-based dietary interventions, community-based health promotion initiatives or educational interventions that target health professionals rather than individual patients. To an extent, the traditional approach of gathering individual informed consent for subjects is impractical for CRTs. This is because consent is acquired in clusters where there are large numbers of subjects, and the intervention has to be applied to the entire cluster. Therefore, it is vital that consenting process be designed such that it is obtained at the earliest opportunity from a representative or ‘gatekeeper’ that can make decisions on behalf of the cluster. In HeadPost, the study team sought the consent of the head of department of the hospital site, which was the cluster in this study. In Australia, the team also incorporated an “opt-out” method for subjects which enabled them to opt-out at any time. These solutions fulfilled ethics committee requirements and enabled this important study to be conducted around the world.