In this blog, Andy Clegg, Senior Lecturer at Leeds University and Consultant Geriatrician at Bradford Royal Infirmary, expands on a recent Age & Ageing paper, looking at the use of the innovative cohort multiple randomised controlled trial (cmRCT) design to increase participation of older people in research studies
There are many challenges involved in recruitment of older people to research studies, particularly randomised controlled trials. Study exclusion criteria and refusal rates are a major issue and the presence of cognitive impairment and ethical decisions adds complexity. Concerns with study information and consent procedures are the most common reasons given for not participating in clinical trials. Understanding and weighing up the complex information about randomisation and control groups is not easy, particularly in the presence of sensory and cognitive impairment.
An extra problem in many randomised controlled trials is that it is not possible to achieve blinding of participants and assessors. This can mean that participants randomised to the control arm may be disappointed and perform less well in assessments or may be more likely to drop out of the trial. Additionally, if assessors are unblinded this may influence decisions when performing assessments.
The cohort multiple randomised controlled trial
The cohort multiple randomised controlled trial (cmRCT) design has been developed to address some of the problems of existing trial designs. This design may be especially appealing in research into conditions of ageing, for example frailty, falls and dementia. The cmRCT design has some key features:
- A large cohort of people with the condition of interest (e.g. frailty) is established
- Participants give assent for involvement in future trials of treatment options for the condition of interest when they join the cohort
- Participants are regularly assessed for outcomes that are also relevant for clinical trials
For subsequent trials, eligible participants are selected at random and offered the intervention/treatment. The outcomes for these participants are then compared with those who were not offered the treatment:
Example of a trial using a cmRCT design
A team of researchers establish a cohort of 500 older people with frailty, who are followed up at 6, 12 and 18 months. The team then develop an exercise programme that they would like to test in a pilot randomised trial requiring 100 participants. Eligible participants in the cohort are randomised, but only those who are randomised to the exercise programme are offered treatment. The ‘control’ group simply continues to be followed up in the cohort as usual. Once the trial is finished, results from those who received the exercise programme are compared with those in the ‘control’ group.
A cmRCT design is considered particularly relevant in situations in which the aim is to inform healthcare decisions in routine practice, the clinical condition is chronic and several trials are needed, and for studies where previous trials have struggled with recruitment. The design may therefore be useful in research into many of the chronic conditions of ageing.
- The process of offering treatment is more closely aligned with the method of offering and providing treatment in routine healthcare, potentially increasing generalisability of results
- Although recruitment rates in clinical trials for common conditions in older age have often been low, recruitment to cohort studies involving older people has remained relatively high, usually above 50%.
- The design enables better alignment of observational research; qualitative studies and clinical trials
- Very large cohorts may be needed to test a series of interventions, which has considerable cost implications. However, use of more efficient methods such as postal questionnaires, telephone interviews and linkage to routine clinical data may help sustain the cohort
- For a successful cmRCT, consensus is required on the assessments and follow-up schedule. This is relatively well established in some conditions, for example dementia, but less so in others, for example sarcopenia.
The cmRCT design has considerable potential to improve the recruitment of older people with a range of conditions to clinical trials. However, there are possible limitations that first require consideration, potentially through pilot work. If successful, it is possible that this innovative design could help improve the participation of older people in research studies across a range of common conditions in older age that have major impact on health and social care systems internationally.