From evidence to guidance on patient recruitment to clinical research in intensive care units

Clinical research in intensive care units (ICUs) is essential for improving treatments for critically ill patients. However, being invited to consider research participation in this situation is far from straightforward. ICU studies frequently take place within a narrow time window and patients will often be unconscious and unable to consent. Consent must therefore be sought from representatives, usually the patient's relatives. However, conversations about research particiation may seem peripheral to relatives, who, overwhelmed and struggling to absorb information, will want the focus to be on the clinical care of the patient. Relatives may also feel uneasy about making decisions on behalf of their loved ones. Given that a quarter of ICU patients do not survive and many others will experience long-term health problems, there is also the possibility that a patient's poor outcome may be associated with their participation (or non participation) in research, bringing the risk of blame and regret.

Further challenges arise in studies of emergency treatments for ICU patients, where any delay in seeking consent before enroling the patient (and implementing the treatment being studied) could have serious consequences for the patient, and potentially invalidate the study. In such circumstances, legislation allows doctors to give the treatment that is under investigation and seek consent later, a process known as 'deferred consent'. Unfortunately some patients will die after being entered into a study but before the research has been discussed with relatives. For grieving relatives, learning that a deceased loved one has received treatment as part of a research study could be intensely distressing. For the doctors and nurses who have the responsibility for explaining the research to bereaved relatives, such encounters will be daunting, yet there is little systematic knowledge for them to drawn on in approaching bereaved relatives about research in these circumstances.

The recruitment of patients to ICU studies therefore poses numerous and intense challenges. Despite these challenges, there is little good quality evidence and guidance on patient and other stakeholder perspectives to inform how recruitment and consent is carried out in ICU studies. Among the many questions facing those who design and conduct ICU studies are: what are the most appropriate methods and timing for seeking consent; which staff members should be involved and how should they be trained; what information should be provided to patients/relatives and how should health practitioners support their decisions?

For these and other questions, knowledge of stakeholder perspectives is needed if we are to avoid continuing to base recruitment and consent processes on presumptions about how people experience ICU research. Our project will use established social science research methods to investigate the perspectives of stakeholders who have recent first-hand experience of ICU treatment and research. We will explore their views of research, the different methods for recruiting patients and seeking consent, and examine how their perspectives can inform approaches to the challenges outlined above.

Once we have collected and analysed this information we will use it to inform good practice guidance on recruitment and consent to future ICU studies. We will draw on methods, called empirical ethics, to ensure that this guidance is well justified and balances the interests of the various stakeholders. However, there are questions about how knowledge of stakeholder perspectives should be used to inform guidance. To address these we will involve a team of researchers and an expert Advisory Group of key stakeholders (to include patients, relatives, and other stakeholders) who bring different perspectives to interpreting the evidence and carefully document how the different perspectives inform the guidance.

Our impact objectives are to:

1) Inform social scientific knowledge on clinical research practices: We describe how the project will address this objective in the 'Academic Beneficiaries' section above.

2) Inform and influence the clinical research community, including critical care researchers and practitioners and the research ethics community: Our study will provide trustworthy knowledge about psychological and social processes in recruitment to ICU studies and insights into the views of stakeholders, particularly patients and relatives. Building on the considerable enthusiasm that already exists for our project (see Pathways to Impact), we will engage with research-practitioners (who design ICU clinical research), frontline practitioners (who communicate with patients/relatives in the course of enrolment to such studies) and the ethics and regulatory communities (who approve ICU studies) to inform and influence policy and practice. Our previous work on paediatric clinical research processes has been cited in influential policy documents (7, 8) which is indicative of our success in disseminating findings to relevant clinical-academic communities. While our impact strategy for the current project will include disseminating the findings via relevant practice-based journals and conferences, academic outputs rarely achieve impact simply by being disseminated (9). Therefore, to inform practice in ICU studies, as outlined in our "Case for Support", we will also go beyond dissemination of findings to develop and publish good practice guidance on ICU clinical study recruitment and consent based on our findings. We will involve members of the clinical research and ethics communities in the guidance development process to ensure the guidance is credible and useful to the relevant communities. To do this, we will establish an Advisory Group comprising members of these communities (including patients and relatives - see below) and work with them in drafting the guidance. We have identified specific organisations that will be influential in ensuring uptake of the guidance, which includes the NHS Research Ethics Service and the Intensive Care Society. We will use our existing links to ensure members of these organisations are involved in the study Advisory Group. We will also work to build new links with other influential organisations, such as the Intensive Care Foundation, Health Research Authority and the Research Society of the Royal College of Nursing. Finally, we will work with these organisations to identify ways that findings from our project could be incorporated into recruitment and consent training for members of the clinical research and ethics communities.

3) Inform patients, their relatives, PPI advocates and the public: We regard ICU patients and relatives and PPI advocates as key stakeholders for our work and will involve members of these groups in our Advisory Group to ensure the patient perspective is prominent as we develop the guidance. As outlined in our 'Pathways to Impact' document we will also produce a resource for patients and relatives about research in ICUs and will involve the Advisory Group in its development and dissemination. The wider public will have a strong interest in learning about our findings, not least because some will experience ICU care in the future (as a patients or relatives). We will develop a strategy to publicise the findings via media organisations. However, blanket media coverage could have potential to misrepresent or sensationalise work in this area. We will therefore develop a carefully targeted publicity strategy involving media organisations, journalists and bloggers with a track-record of balanced and accurate coverage of controversial health issues. We will liaise closely with the public relations teams at the University of Liverpool and partner NHS Trusts to develop this strategy in good time for the launch of our guidance.