Engaging GPs and primary care patients in research: implications of the ASPREE trial for future studies

A clinical research network would facilitate routinely including primary care patients in large clinical trials

Although aspirin‐containing medications prevent cardiovascular events,1 meta‐analyses of randomised trials have found that, overall, they do more harm than good when used for primary prevention.2 The recently published ASPREE trial3,4,5 confirmed that this holds true for older people without cardiovascular disease, dementia or physical disability. The well conducted trial — with 19 114 participants, the largest ever undertaken in Australia — found no benefit for treatment with low dose aspirin (compared with placebo) in terms of disability‐free survival,3 cardiovascular disease4 or fatal cancer.5 However, there was evidence of harm, with an increased risk of death and bleeding among participants receiving aspirin.4,5

The results of this trial confirm the recommendations of clinical guidelines,6,7 which advise caution when considering prescribing aspirin for the primary prevention of cardiovascular disease. They also highlight the importance of recruiting a population representative of the patients who would be targeted for intervention in routine care. The cardiovascular disease event rate in the ASPREE trial was 11.3 per 1000 patient‐years;4 this was about half the rate projected in the original trial protocol (22.4 per 1000 patient‐years),8 an estimate based on prevention trials predominantly conducted in secondary care settings. The lower than anticipated event rate resulted in a less precise estimate of the treatment effect, and suggests that any observed reduction in cardiovascular disease risk would translate to a very small reduction in absolute risk in a primary care setting. This is critical when assessing the relative benefits and harms of treatment, and underscores the importance of a representative study population.

Pragmatic, primary care‐based trials are often perceived to be challenging because of the complex nature of general practice. In this issue of the MJA, Lockery and colleagues9 describe the strategy taken by investigators in Australia to engage GPs and recruit primary care patients for the ASPREE study. The 2717 contributing GPs ultimately recruited 16 035 participants. To encourage recruitment activity, ASPREE investigators remunerated GP practices for their involvement, recognised participating GPs as associate investigators, and analysed local population data to identify geographic areas with high numbers of older people, and therefore of potential participants. Of particular interest is the suggestion that participating GPs were motivated by their interest in the research question, which indicates that engaging them early in the research process is important for defining relevant and important topics for investigation. GPs in areas of higher socio‐economic status were more likely to recruit participants, perhaps reflecting differences between practices that are better funded and those serving more disadvantaged areas.

In the United Kingdom, investment in the Clinical Research Network (CRN) has addressed a number of challenges similar to those faced by the ASPREE trial investigators. The CRN enables large scale clinical studies to be rolled out across the UK, providing a single portal for approval processes and a standardised approach to engaging and working with individual practices. Local CRN facilitators build on existing relationships with GP investigators to introduce studies and help with electronic health record searches, and they often also assist with recruitment and follow‐up. The network is supported by national funding, and works by providing nurses and facilitators, as well as direct payments to GPs involved in enrolling participating patients. In some respects, the ASPREE investigators needed to develop their own CRN capability and to inspire enthusiasm for research among primary care providers. Establishing a national CRN in Australia could ensure that the dividend of such investment continues to be reaped after an individual trial is completed.

A further step would be to embed trials such as ASPREE in routine care by utilising existing electronic record systems to alert clinicians to potential trial participants and to facilitate follow‐up. Incorporating these capabilities into the establishment of platform trials would allow real world estimates of the effectiveness of interventions to be rapidly fed back to investigators.10 Platform trials are based on a master protocol that allows evaluation of several interventions, both simultaneously and in series; analysis is undertaken continuously rather than only once a predefined sample size has been reached, and data already accumulated are used to assess both current and subsequently introduced interventions. This approach holds great promise, but is yet to be realised in a primary care setting because of technical and regulatory barriers.

The ASPREE study reminds us that methods for primary care research must be refined, and that standing infrastructure is needed to more efficiently and routinely include primary care patients in large scale clinical trials. Such infrastructure would enable critical information, such as that generated by ASPREE, to be continuously updated and associated questions to be answered more efficiently.