PRELIMINARY FINDINGS: resolution of barriers to implementing early phase trials in parallel with routine care.

A report by Dr Sarah Markham (Visiting Researcher, Dept Biostatistics, IoP, KCL)

BARRIER: Lack of motivation/competency/skills/experience in clinical care staff in care settings: Attitudes

According to Paul Watts, Head of Mental Health Nursing at Somerset Foundation Trust “There is a lack of research knowledge within the workforce. In general the BSc in Nursing only covers basic research methods but we also need to recognise that the vast majority of the workforce still do not have degree level qualifications and it will be some time before they are in the majority. It is only when this occurs or that we make research modules more freely available to all staff that we will engage staff more readily. I also think there remains a mystique around research and the language that we use, breaking down this barrier is crucial, but I am not sure how we can achieve this. I am currently involved in several pieces of research as the Chief Researcher and Principle Researcher and although I think I took time to explain to staff the processes and requirements it has still been a struggle to engage people. Finally, it also about how we enable people to translate research results into practice. We have attempted this in our own organisations through regular research seminars and through the use of practice development where research needs to be used and evidenced. This has changed the culture slightly, but again we are not engaging with the majority of staff and research informed change remains slow.”

Eneida Mioshi (Clinical Research Associate at Department of Psychiatry, University of Cambridge) believes that lack of confidence in clinical care staff may be inhibiting their support for the implementation of clinical trials. “My experience to date is that most health professionals (I am referring here to nurses and AHPs) do not have confidence in running research in practice. This seems to stem from lack of appropriate training and/or lack of appropriate support/supervision within their teams. I also do not think all professionals are bound to be excited by research, but we should create mechanisms to support and nurture those who would like to try/learn and also find ways to work well with those who are "apparently" not keen on it.”

However a seeming lack of enthusiasm and experience of clinical teams in terms of engagement in clinical research may not always be lack of knowledge about trials rather that they just don't seem a priority when there is so much else going on and also concerns that they (care staff as well as nurses) would be held responsible if things went wrong. According to David Heron (Matron KCH) “it isn't necessarily that there is an enormous lack of interest in research per se, I think often it just comes down to priorities. Often clinical teams have a primary focus on clinical practice and meeting the physical or other health needs. Research of course feeds into this in the sense that we want to deliver evidence based medicine, but is often an add on that takes buy in from leaders and managers. I think nurses are becoming more research aware, nursing now being a graduate profession and often courses of study may they be pre-reg or add-on specialist courses have a research component. I think nurses often are in nursing to care and may have less of an interest in research. Possibly primarily due to lack of knowledge but often as clinical research in settings I've worked in trials are led by the medical team and nurses

can feel intimidated by the jargon and more complex quantitative research methods which are almost like a foreign language for the untrained. So some further training at pre-registration stage would certainly better equip nurses to get involved in research.”

Belinda Theis (Clinical Research Delivery Manager UCHL) has experienced significant difficulty in implementing clinical research trials in secondary care settings. “Our experience is that it's much easier to implement clinical trials in primary rather than secondary care settings. GP staff will refer patients and introduce them to what the trial involves and give researchers access to their patient database. The research team will do the rest of the work.” She also adds that collaborations with industry are advisable as this can lead to sufficient funding for trained CRNs to be deployed in routine care settings to perform the trials implementation instead of the clinical care staff.

Anna Massey (Associate Clinical Researcher, Institute of Neuroscience, University of Newcastle) opines that PIs have to be confident they can delegate responsibility to nurses and other clinical team members. She claims it is unrealistic to expect clinical team members to be involved beyond liaising with, passing information to and referring patients. Anna points to the need to protect trial participants from harm, hence the need for those who implement the trials to be (GCP) competant.

Linda Purandare (CRN) has experienced varying degrees of engagement from clinical teams. “Within some specialities where clinical trials teams are well established we have fairly good engagement with the clinical side, with some ward nurses being GCP trained and actively participating in clinical trials. We have developed a new streamlined management structure for our clinical trials team and have discussed engagement with

the clinical teams and are developing strategies for this. I am also negotiating with Bournemouth University for student placement with our clinical research teams. We also have two of our nurses currently undertaking NIHR MRes programmes and are looking at how to utilise their new skills.

Alison Jenkins (CRF Research Nurse Manager NIHR) also questions the competency of untrained clinical care staff to be involved in implementing a research protocol. “Regarding implementing Phase I trials into routine care. In my personal opinion, Phase I trials are safest implemented in appropriately set up units rather than in routine care. Phase I studies being offered to cancer patients happens in very specific circumstances. The delivery of the early phase compounds usually happens in badged Experimental Cancer Medicine Centres or in centres where there are appropriate safety measures in place. Other diseases where patients are offered Phase I or early phase trial participation, again usually receive the compound and care from a dedicated research team in an area with appropriate safety measures are in place. Regarding clinical ward or outpatient staff delivering trial compounds or being delegated trial specific tasks, as I’m sure you’re aware, GCP states that all trial team members must be “fit for purpose” with regard to education, training and experience. In practice this would have to include regularly updated GCP training and study specific training and education. This carries with it a significant cost implication. In addition ward managers and the nursing hierarchy would need to be in agreement that the ward team had time resource available to them to carry out trial specific tasks at the time they were due to ensure accuracy. There is also the challenge of ensuring staff working on the wards maintain competence over time. These challenges exist across the nursing spectrum not only in mental health nursing.”

Wendy L. Osborne (Neurology Research Manager, Clinical Research Facility, Salford Royal NHS Foundation Trust) also emphasizes the importance of GCP training for all staff involved in the implementation of clinical trials. “Research in clinical areas is often seen as an extra and not a core responsibility. The ward environments are already under pressure to deliver safe care and as an ex ward nurse (10 years experience) the paperwork involved had also increased therefore actual time to do research activities is even farther away than ever before. You also need to consider GCP in the equation as all study procedures should be carried out by someone in possession of a valid GCP certificate- to address this in the clinical areas would be costly (both in time and financially) requiring each nurse to be taken out of the ward for a day to attend GCP training. I have also found during my 8 years in research that studies (especially academic) are often set up without input from experienced NHS research staff with clinical experience therefore immediately are starting off unlikely to meet the Researchers targets or expectations. It is essential to know how a clinical area operates prior to running a study in the area.”

Dylan Wright (Ward Manager, The Chichester Centre Sussex) also highlights time pressures on the ward and increasing audit and other administrative demands on staff time. “We have so many audits to do; for the CQC, to ensure CQUIN targets are met etc., we're hard pressed to find the time for the patients let alone research.

Alison's and Belinda's concerns are echoed by

Alyson Moyes (Biomedical CPD Co-Ordinator, University of Chester) “It is sometimes hard to motivate the nurses to help as they lack the understanding as to why they are doing it, and simply see it as a burden of more work.”

Julia Boyle (Director of Surrey Clinical Research Centre) has experienced difficulty in recruiting CRNs. “We are an accredited Phase I Unit and we notice that when we are recruiting for new nurses many applicants have had limited exposure to clinical research. Those nurses that have had experience have tended to be involved in later Phase trials.” There seems to be a need to train more CRNs.

David Richards (Professor of Mental Health Services Research and NIHR Senior Investigator, University of Exeter Medical School) has a more positive view of nurses' research potential and competency “There are multiple trials that have used mental health trained staff, including nurses, to deliver therapy to a protocol when the researchers have applied proper training and supervision, e.g. http://bjp.rcpsych.org/content/198/1/66.abstract?ck=nck. If any clinicians cannot follow a research protocol then my advice would be to examine the protocol and its likely future tractability in health care.”

Education

Although most B.Sc. Nursing courses include basic research methods (focusing on social science methodology - qualitative and quantitative analysis, criteria for patient inclusion/exclusion, etc.) and may touch on the methodological framework around the implementation of clinical trials, in real terms a student nurse will probably not gain experience of implementing a clinical research protocol unless they go on to pursue a M.Res. or Ph.D. course.

However over the last 2 years there has been a growing awareness of the need to train pre-registration nurses to have a greater understanding and appreciation of the importance of clinical research and its impact on treatment. The RCN is working on this and

acting to provide more provision for students to have placements in research facilities and gain direct experience of how clinical trials work in practice. In the UK there are currently approximately 14,000 CRNs working in supportive roles in clinical trials, however many Trusts still struggle to recruit qualified clinical research nurses. Most Trusts now employ a Lead CRN who will act to standardise research training placements for students. Many Nursing and Health Science Faculties e.g. that at the University of Brighton (with support from SPNFT nurse consultant Anita Green), are looking very vigorously into how to expose students to research and active researchers (nurse and AHP led research).

Many Clinical Research Facilities, BRC’s and BRU’s now offer placements for student nurses and secondments for staff nurses to their units. These placements and secondments has been that they are oversubscribed and feedback is extremely positive.

Wendy Fraser (Head of Clinical Research at Surrey Clinical Research Centre) is currently working with the University of Surrey School of Health and Social Care to try and get trainee nurses more exposed to Phase I clinical research. “We would like to do this in a number of ways – lectures as part of their undergraduate degree and placements at our Phase I Unit with mentorship from our experienced clinical research nurses.”

Professor Tony Fryer (R&D Director, University Hospital of North Staffordshire NHS Trust) is reports that his hospital is involved in similar work. “UHNS have found a number of challenges around this area, particularly in filling research nurse posts with suitably qualified staff. This is partly because there is little training in the core curriculum for nursing. Consequently, our Lead Nurse for Clinical Trials, Beryl Alcock has been exploring the opportunities for placements for trainee nurses with the R&D department here. I am pleased to say that this has

been supported locally and will commence with the next intake. While it will take some time to move through the system, it is a positive start not only in providing the spark to ignite interest in research as a career option for nurses, but also in facilitating secondment opportunities to fill shorter term gaps. In my view, if we are to truly recognise research as a core NHS activity, then this should be reflected at the training curriculum level and reinforced with CPD requirements.

Caveat: Dr Ian Taylor (University of Brighton) is aware that a fair proportion of students struggle with the academic level set by the pre-registration degree course and indeed the entire concept of clinical trials. He is keen to introduce a more hands on approach to the optional 'Careers in clinical research' module with students gaining practical experience of clinical trial implementation. However it has proved difficult to persuade BSUH and SPNFT to accommodate this and practical experience has only occurred at an individual student level when a suitable a hub and spoke opportunity has occurred. Anita Green is planning to set up a pilot for mental health student nurses to gain experience of clinical research but it is still very much in the planning stage.

There are also concerns that it would not be practicable to modify current pre-registration nursing curricula to accommodate clinical research training. Ben Hannigan (Reader in Mental Health Nursing, School of Healthcare Sciences, College of Biomedical and Life Sciences, Cardiff University) is of the opinion that “Nursing curricula are jam-packed and have to reflect NMC standards, and this can leave little room for anything extra. In any case, a more suitable preparation for practitioners might be for them to know more of their obligations and responsibilities as practitioners when any kind of research is proposed in the workplace (trials being one, but not the only, example).”

The NIHR are currently doing their best to influence HE so there are more opportunities for undergraduate nurses to experience the delivery of clinical trials and are planning to hold a national seminar on the subject in the autumn 2014. As Dr Susan Hamer (Organisational and Workforce Development Director NIHR) reports, “We have a work group active in this area and have been in conversation with the Council of deans for health care. We are already sharing best practice across our network and raising the issue with directors of Nursing. There are many facets to our strategy in this area but we are gathering momentum. However as the nurse workforce only replaces itself slowly we also have to have a strategy for existing staff as they are so influential on culture and there too we are making progress with a campaign of awareness raising and influencing key opinion leaders. The DH have also been very supportive to us funding a range of activities and the workforce of CRNs is growing.

However not everyone is quite so optimistic about the future. Ben Hannigan opines “Even at MSc level the opportunities to carry out research are less than they once were, for all sorts of reasons (e.g. unfunded MSc research is not eligible for portfolio entry, and can attract NHS demands for NHS research costs to be covered). I think this situation also reflects the idea that the majority of nurses are (and if they're students, will be) research consumers but not producers.” Brendon McCormack (Professor of Nursing Research and Director of the Institute of Nursing and Health Research (INHR) at University of Ulster) suggests some more immediate measures. “The undergraduate curriculum for mental health nursing (as with all the pre-registration curricula) is extremely packed and so giving space to this area when it is not a universal requirement/practice would be largely seen as an unnecessary burden. It may be the case that centres and universities where there are a lot of trials happening could find a way to have something in the

curriculum specifically on this. The role of ‘everyday nurses’ in Phase 1 trials in my view is largely one of providing care in a specific situation but under research conditions – so in may ways it is/should be no different to the way that everyday practice happens anyway and so maybe the issue is about ‘emphasis’ rather than a separate/different training.”

David Lewis (Professor of Clinical Vaccine Immunology,Clinical Research Centre, University of Surrey), believes that “one practical way to ensure more student nurses get experience is to require them to identify an ongoing trial during their ward placements. Most trusts will have some trials ongoing. The student could then at least write a short essay on it, or discuss with the research nurses. They might also then understand better that being a research nurse is not so daunting, and does not necessarily require specialist statistical or scientific knowledge (often a false perception), just good nursing skills and excellent record keeping - essential basic skills for any nurse.”

Caroline Murphy (CTU Manager, King's College, London) believes CRN training needs to be introduced at the post-graduate and specialist nurse training level (a 6 month full time lecture and practice based training course for registered nurses) and for it to be focused on the research needs of the specific specialism. “The evaluation and appraisal of research can have very little meaning to pre-registration nurses and soon be forgotten.” She also thinks clinical research training should be mandatory for all medical doctors in order that they understand at the very least the importance of referring appropriate patients to appropriate trials. Caroline also questions the competency of many clinical research trainers. “Research methods are often taught by clinicians who lack the qualifications and experience to be able to teach the subjects well.” As for poor nursing attitudes towards engaging in the

implementation for clinical trials she suggests secondments for more senior nurses to CRFs to allow them to gain an appreciation for the nature and importance of clinical trials.”They will then be in a position to disseminate it to their own teams and authorise staff time to recruit and refer patients for clinical trials etc.

Career Development

According to Gordon Hill (Associate Director at the Edinburgh Academy of Clinical Research Education) pressures and priorities of clinical care teams mean routine clinical tasks take precedence over (imposed) clinical trials. Furthermore over recent years the number of trained staff on shift has been reduced so that staff struggle to provide regular clinical care let alone support the implementation of clinical trials. Therefore independent clinical trial units CTUs have been set up as regional hubs to train and deploy CRN (clinical research nurses) in routine care settings as needed to support clinical trials and other research.

NIHR Clinical Research Networks are also working to engage student interest in careers in clinical research. Claire Hall (DeNDRoN) has been involved with input into nursing education locally with Oxford Brookes University and University of Bedfordshire. “We offered day visits to nursing students and also longer term (4-6 week placements) for nursing students to get a more in-depth understanding of what's involved in the recruitment and delivery of clinical trials. Our feedback has been really positive, and students seem really interested. Students perceive research to be all about the modules on methods, data analysis etc. and they just don't think of the practicalities and reality of working in clinical research. We've disseminated our programmes nationally amongst research nursing colleagues, and I'm aware there are many different areas that are now taking on nursing students in this way. Obviously this impacts nurses qualifying at the moment, and I think there is a lot

more work to do with nurses who have already been qualified for a while in order to break down some of their perceptions about what we do, but it's a start.”

Support is also beginning to come from the regional Academic Health Science Networks. Andrew Rose (Head of Programmes WMAHSN (West Midlands Academic Health Science Network)) who was involved in setting up the MHRN is determined to make clinical research a priority for his region and, along with his colleagues is gathering economic data support funding research. The WMAHSN plan to promote clinical research education and training and set up multi-agency collaborations between academia, the NHS and industry involving placements for employees with various partner organisations in order to share and develop skills and resources. Another priority is to recruit science graduates to perform certain CRN duties thereby freeing up time for clinical research nurses to focus on using their more specialist skills.

Gillian Hornzee (Team Leader, Cancer Clinical Trials, NCRN, St mary's hospital, London) believes that engagement in research activity should be a feature of every nurse's contract of employment. “Our experience is that most nurses shy away from helping with recruitment and implementation of clinical trials, mostly because they perceive their workload doesn't allow for it. For example the breast care nurses could well help to recruit to clinical trials and participate in performing trial related activities, but in spite of having received training, refuse to do so. The reason it does not happen in oncology is that for the last ten years there has been a dedicated team in each hospital (part of the National Cancer Research Network) which often includes research nurses who are specifically tasked with recruiting to cancer trials. However this has not been the case for other specialities. I think the only way to rectify this is to include participation in research activity in the nurses' job specification so they can not refuse to participate.”

Gordon Hill (Associate Director Edinburgh Academy of Clinical Research Education) is encouraged by the progress that is currently being made in clinical research education for nurses. “More and more undergraduate courses are incorporating a clinical research component and many are offering elective placements with clinical research nurses. In addition there are more post registration courses available. At Edinburgh Napier we offer a 'top up' degree in clinical research (for nurses with diploma level qualifications) and PG Cert in Clinical Research for students with a degree. Both courses are aimed at Clinical Research Nurses and relate very closely to running clinical trials.”

CRN/SN dyad

Anne Croudass (Lead CRN Cancer Research UK) holds that it can be an advantage for CTUs etc. to train potential CRNs themselves selecting for enthusiasm, dedication and ability. Belinda Theis (Research Delivery Manager at UCHL) recommends recruiting from the nurse practitioner pool rather than staff nurses as they are more likely to have the necessary organisational and mental processing skills. For a CRN working alongside clinical care nurses the principle challenges are 1) mistrust or misunderstanding or the work they do (the irregular hours, the undisclosed duties they perform do outside the care environment) and 2) problems of delays in handover from out of hours staff to the CRN regarding the trial participants. The most effective means of ensuring a successful collaboration between CRNs and clinical care staff is for the CRN to become integrated into the wider MDT allowing for them and their work to become embedded into the care environment over time.

Sandie Wellman (Consultant Nurse, Oxford Radcliffe Hospitals) experience has been that in terms of

implementing clinical trials the principal challenge has been liaising with clinicians in the primary and secondary care settings from which trial participants are drawn. Certain GPs appear reluctant to refer their patients and may actively discourage them from doing so.

Sandie has also encountered reluctance from healthcare educators to allocate pre-registration nursing students to placements at the CTU. In order to promote mutual communication Sandie has been in direct contact with medical health educators to encourage more student engagement with the CTU. She has also been trying to raise the profile of the CTU and educate fellow clinicians and clinical staff about the exact nature of the research work that is carried out there. The CTU's profile on the Trust's website has been reworked and posters placed in waiting rooms and reception areas. The CTU is now a regular presence at hospital open days and the CTU staff now have their own logo.

Sandie is keen to point out that patients who participate in trials receive a great deal of care and information about their illness and also what is available to them in primary and secondary care.

BARRIER: Cultural resistance in the NHS (Poor relational dynamics between academics and clinicians) :

Rather than researchers and clinicians being allies sharing a purposeful approach to development of evidence, there seems to be cultural resistance to

research. This is likely grounded in contextual complexities (including physical and emotional distance between R&D departments and the clinical ‘frontline’, and the burden and demands of clinical work). The reported resistance may in part be grounded in the redirection of funding from clinical services to establish the NIHR to increase research capacity within services. It may also reflect a lack of fit between services and clinicians and the approaches taken by funding bodies e.g. NIHR, MRC and research support networks e.g. MHRN.

At a practical level, respect and reciprocity can be promoted by effective communication. Ensuring that the right information reaches the right people in a timely manner, and that clinicians are provided with progress reports and study findings, is essential. Offers of publication involvement, though potentially encouraging activity, should be made only as they align with ethics of authorship and the mixed messages around incentives mean that these should carefully be considered on a case-by-case basis.

Justin Watts (Clinical Trials Manager, Qunitiles) emphasizes the need for research to be ingrained in the culture of the healthcare environment for research to succeed. “Qunitiles works with a quarter of a million research sites worldwide, including primary, secondary and tertiary care. We tend to work to strict protocols and form strong collaborations with Principle Investigators. The principle barriers to implementation tend to be of an ethical or administrative nature; sponsors taking too long to review documents etc. Motivation can be a problem but only if research isn't embedding in the culture of the site. At teaching hospitals we don't have a problem and very often patients are matched to trials when they're given their treatment options on admission. Skill sets are also easy to provide through training. If you're trying to embed research into the working ethos of a healthcare environment, start small with say one

department. Set realistic goals and time targets. It is more of a slow-burn process, but medics are notoriously competitive and as long as they have a sense of ownership or at least a stake in the process they will want to be on board.”

Professor Tony Charman (Professor of Clinical Child Psychology KCL) advocates that academic researchers 'putting in the time on the ground' talking to and working alongside clinicians and other clinical staff helps to develop mutual respect and support, open communication and mutual confidence which will be of benefit to current and future trials.

Embedding new practices in clinical settings requires a team based approach focused on research implementation and the trial participants. Identifying and adopting an innovative health technology, or a new way of organizing professional work such as implementing clinical trials in parallel with routine clinical care involves policy-makers, managers, academics and clinicians facing two important problems as they try to get innovations into practice: 1) Process problems i.e. the implementation of new ways of thinking, acting and organising in health care, 2) Structural problems i.e. the integration of new systems of practice into existing organisational and professional settings. To understand implementation and integration, one must focus on the dynamic processes that lead to innovations becoming embedded in everyday work. Carl May's Normalization Process Theory is an explanatory model that helps managers, clinicians, and researchers understand these processes. NPT starts with the formal proposition that: Complex interventions become routinely embedded (implemented and integrated) in their organizational and professional contexts as the result of people working, individually and collectively, to implement them. The routine embedding of a complex intervention is the product of action (the things that people

do), not necessarily people's attitudes (how they feel about what they do), or their intentions (what they say they are going to do). The work of implementation is put into operation through four generative mechanisms (coherence - people making sense of the work of implementing and integrating a complex intervention; cognitive participation -how they engage with it; collective action - how they enact it) and reflexive monitoring (how they appraise its effects). The work of integration of a complex intervention requires continuous investment by people in ensembles of action that carry forward in time and space. It is not enough to adopt and diffuse a complex intervention, people need to keep investing in it or it will atrophy. Continually investing in sense-making, commitment, effort, and appraisal is part of the embedding of a complex intervention. A complex intervention that is routinely embedded in practices ceases to be a 'complex intervention' at all, and instead disappears into the everyday world of normal activities, the things that people just get on and do. Normalization Process Theory focuses attention down on how the work gets done - the everyday business of getting on with the job in hand - and the often very creative work that managers, academics and clinical staff do to normalize a set of tasks in a health care setting.

Magda Martinez, a CRN at the BRC, Guy's Hospital is keen for the implementation of clinical trials in parallel with routine clinical care to be the norm and not the exception. “Clinical research has to become embedded into clinical care otherwise it will remain very much a niche area of nursing practice which occurs in isolation and of which little is understood or appreciated.” Magda recommends the following steps to embedding a clinical trial into routine care:

1) Build relationships with the clinical team Engage the clinical staff so that they come to

understand and believe in the trials. This involves observing and working alongside the clinical staff to learn how they work and who their patients are. It is important to acknowledge the experience and expertise of the clinical team and to seek and make use of their advice whenever an opportunity arises. In doing so the CRN will gain the trust of her clinical colleagues and become seen as an integral part of the the clinical team and not as an unhelpful or meaningless add-on. The clinical team are the ones to consult as to how to approach their patients and of course the ones to refer patients to the trial. In short they are essential to the success of the trial. If their interest seems to be flagging at any point in the trial, then motivate them e.g. with friendly but purposeful emails congratulating them on their successes and urging them on when the need arises!

2) Create inviting, meaningful and trial materials Materials used in the clinical trial e.g. information sheets and other forms used in patient recruitment and the PIS (patient information sheet) need to be patient friendly – written in plain English and suitably embellished with e.g. picture and other illustrations if for minors. Ideally feedback/outcome/observation sheets should gather qualitative as well as quantitative data to give a more complete picture of the effects of the intervention on trial. When seeking participants do emphasize the positives e.g. that travel expenses will be paid and whether there is flexibility as to when/where patients participate.

3) Document everything Create comprehensive confidential databases in line with GCP which capture any relevant patient information. This may be of use when e.g. seeking participants for further or follow-up trials.

4) Beware of social media Staff need to be cautioned against posting confidential trial information or anything else that might compromise a trial's integrity or success on social media websites, e.g. Twitter. Similarly it is advisable

to monitor what patients are posting themselves and if necessary advise them on the possible consequences of what they are doing.

5) Feedback At all stages gather feedback from everyone involved (clinicians and patients) and as a result do make any necessary alterations to the trial.

6) Fruits of success One of the outcomes of successfully embedding a clinical trial into routine clinical care is that it opens the gate at all levels for further research to take place.

At research intensive centres (like SLaM and UCL) a degree of research fatigue may develop and researchers may often be at fault in not feeding back results to the clinicians who have helped us with recruitment and other aspects of carrying out research studies.

Use of motivational levers such as 1) the sense of satisfaction of engaging in a noble shared purpose or organisational goal, e.g. to do what is best for our patients. 2) to satisfy self-interest – provide financial or career based incentives for achieving targets. 3) to earn respect from colleagues and the Trust; this can be a powerful inducement to improve co-operation and performance. 4) to embrace medical tradition by promoting standards to align behaviours and make adherence a requirement for peer respect and acceptance.

The most important predictor of success in a group is the amount - not the content - of social interaction. Bruce Lloyd (Professor of Strategic Management South Band University) advocates the power and positive team building efficacy of 'quality conversations' . Recent research that has not been widely published throws some fascinating light on the power of conversation. Having a friendly conversation can boost your cognitive ability and improve team performance by increasing the amount of face-to-

face communication regardless of the topic of conversation. (Friends (and Sometimes Enemies) With Cognitive Benefits - What Types of Social Interactions Boost Executive Functioning? By Oscar Ybarra, Piotr Winkielman, Irene Yeh, Eugene Burnstein, Liam Kavanagh http://spp.sagepub.com/content/2/3/253) Talking with people in a friendly way can make it easier to solve common problems. But conversations that are competitive in tone, rather than cooperative, have no cognitive benefits. (Why is conversation so easy? By Simon Garrod; Martin J. Pickering http://www.bcs.rochester.edu/courses/crsinf/261/ARCHIVES/ S07 /GarrodPickering2004.pdf, Group Discussion as Interactive Dialogue or as Serial Monologue: - The Influence of Group Size - By Nicolas Fay; Simon Garrod; Jean Carletta - http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.8.4 348&rep=rep1&type=pdf) In small, 5-person groups, the communication is like dialogue and members are influenced most by those with whom they interact in the discussion. However, in large, 10-person groups, the communication is like monologue and members are influenced most by the dominant speaker. (Evidence for a Collective Intelligence Factor in the Performance of Human GroupsBy Anita Williams Woolley, Christopher F. Chabris, Alexander Pentland, Nada Hashmi,Thomas W. Malonehttp://advance.njit.edu/doc/Gender,%20Collaboration%20&% 20Group%20Intelligence.pdf) Performance is not strongly correlated with the average or maximum individual intelligence of group members but is correlated with the average social sensitivity of group members, the equality in distribution of conversational turn-taking, and the proportion of females in the group. (The New Science of Building Great Teams By Alexander Pentland April 2012 Harvard Business Reviewhttp://www.timgroup.ethz.ch/education/Courses_at_TIMGROUP/sp ring_2013/pentland_team.pdf)

BARRIER: Patient Participant Recruitment:

Research studies in the UK has indicated that in the mental health context, researcher access to potential trial participants is multiply influenced. Gate-keeping clinicians are faced with competing priorities and resources constrain research activity. As gatekeepers, clinicians may seek to protect people for whom they provide care from the perceived burden of research participation and/or an intervention perceived to be futile for an intractable condition. It seems that environmental adjustment predicated on equitable resource allocation is needed if clinicians in NHS mental health services are to fully support the conduct of randomised controlled trials. Whilst cultural transformation, requiring changes in assumptions and values, is complex, findings suggest that attention to practical matters can support this and highlight issues requiring careful consideration.

Symptom profiles also influence referral to studies and sub-groups of the population may be under-represented.

Despite government declaring a commitment to making research core business of the NHS this may not be facilitated at the clinical level. Rather than being enabled to enact the pledge in the NHS constitution to inform patients of studies in which they may be eligible to participate, the majority of mental health clinicians charged with gate-keeping access are struggling to cope with competing demands and unable to prioritise research.

Given recruitment is essentially a social activity, with success dependent in part on interpersonal connection between recruiting researchers and clinicians, it may well be that some of the challenges described reflect personal rather than systemic concerns. The key message is that rapprochement between the NHS R&D and clinical service factions and

academia is needed to support clinicians to participate fully in research activity. Whilst cultural transformation, requiring changes in assumptions and values, is complex, attention to practical matters can support this and highlight issues requiring careful consideration.

Reciprocity, relevance, respect and realistic feasibility studies are fundamental to ensuring that recruitment to trials is to be efficient and clinician-related selection bias is minimized. Rather than feeling ‘put upon’ by disinterested researchers, gatekeepers should be involved in the research process from the beginning and have their contributions valued. It behoves researchers and research support networks, e.g. MHRN to work actively to support clinician and service engagement and minimise the burden of research activity. In relation to relevance, the onus is on investigators and NHS leaders to engage collaboratively with clinicians to develop research questions and design studies which have face validity and will garner support.

On a practical level flexibility about the location of the trials will encourage participation from referred patients e.g. if the participants are children some parents may prefer a local institution around the corner rather than an academic or clinical trials facility several miles away distance away. Travel expenses should be funded and/or pre-paid taxis booked. Experienced investigator will budget for this in funding applications.

Susan Paterson (Senior Lecturer RMIT) believes that the “implementation of trials (at whatever stage) in routine practice (in mental health) is fraught by the vexed and uncertain nature of psychiatric diagnoses, (esp the absence of clear causative explanations), the complex nature of conditions and the associated disability and disadvantage, uncertain status of people with mental illness in society, (esp around protectiveness) personal issues.” Furthermore the

elusiveness of clinical gains amongst many mental health service users, the fragility of these gains given the high rates of relapse and the reality that when gains are achieved they often require treatment over the long term, may generate a conservative and cautious approach to gate-keeping amongst mental health workers who when invited to judge the potential positive and negative consequences of participation may see the scales tipped to often towards the negative. In response to this Prof D. Lewis of the Surrey Research Centre advocates a more “nuanced” pre-registration nursing education with regard to gaining consent for clinical trials and the nurse's role of allowing the patient to make informed decisions and not taking that choice away from them. “Looking at registered nurses I have also noticed some perceived conflict between the nurse's identification as "the patient's advocate" and clinical research. As you know research protocols often require that people are randomised to different regimes which may seem inferior, or to placebo, or be in studies with no actual benefit. I have noticed that many nurses are deeply uncomfortable with the idea that a particular patient may not be getting the "best" care, and as a result will not engage in research and may even advise the patient not to engage either. Doctors in my experience do not have this issue as they do not identify as strongly with the "Patient's Advocate" concept. I think more nuanced education on what it means to be an advocate to any individual patient while balancing the benefits to future and other patients, would strengthen nurse training and encourage more nurses to participate in research. As it stands too many nurses seem to identify with just the patient in front of them and then see their responsibility to advocate just narrowly for what seems to be in that patient's best interests at the time.”

BARRIER: Pressure of Time and Resources:

Protected time for clinical staff to engage in research duties. Alternately recruit CRNs who are contracted to partition their time between research and clinical duties.

Adaptive use of research resources is critical. Because the absence of dedicated resources (such as clinical time) or return on investment (such as allocation of accrual funding to team training) not only constrains the capacity of clinicians to undertake research activity but undermines belief in policy and sense that their roles are respected, research resources must be seen to make a difference.

Peter Brown (Professor of Experimental Neurology at the Nuffield Department of Clinical Neurosciences, University of Oxford) points to the administrative and organisational barriers of implementation in routine clinical care settings. “The enormous work involved in getting ethics in place, insurance/sponsorship, trial governance and documentation. Then there are issues of consistency/reproducibility of observations made in these environments ...”

BARRIER: Suspicion of 'Big Pharma' (due to past cases of lack of transparency around adverse reactions)

There are also long-standing concerns that the methods and results of many trials currently remain hidden from public view. This lack of transparency, say campaigners, undermines public trust, breaks the ethical pact between scientists and those participating in trials and leads to clinical decisions being made on the basis of incomplete evidence, potentially leading to poorer outcomes for patients. The topic of clinical trial transparency received renewed attention in late 2012 with the publication of Bad Pharma, a book by Dr Ben Goldacre that accused the pharmaceutical industry of deliberately suppressing unfavourable trial results from public view.

There are current calls on government to ensure all data from all clinical trials is published to foster greater openness in medical research. This degree of transparency would help to dissipate negative perceptions of the pharmaceutical industry.

There have been efforts by some members of the pharmaceutical industry, particularly GSK, to increase clinical trial transparency and hope fully other companies will act in the same spirit in implementing industry-wide principles for responsible clinical trial data sharing.

Clinical staff awareness and training days and similar provision in pre-registration nurse training would help to address negative perceptions of the pharmaceutical industry.

Trusts need to do far more to educate patients about the benefits, both to them and to the wider community, of participating in research and allowing properly controlled sharing of patient data.

Conclusion

Overcoming the barriers to the implementation of early phase clinical trials in parallel with routine clinical care will require a radical transformation, moving from a system organized around individual CIs and PIs to a team-based approach focused on patients. Such engagement requires more than mere cooperation, i.e. an agreement not to sabotage and aims to achieve full collaboration.

The leitmotif that runs through so much of the information gathered is that the implementation of clinical trials in parallel with routine clinical care is best facilitated when academic researchers make determined efforts to win over heart, minds and hands. In a more formal sense this is the application of Carl May's NPT (Normalisation Process Theory) which explains how to embed complex interventions into healthcare and other

organisational services. NPT encompasses the following 4 elements:

coherence (i.e. comprehension - defines and organizes the components of a practice)

cognitive participation (i.e. engagement - defines and organizes the people implicated in a complex intervention)

collective action (i.e. team enactment - defines and organizes the enacting of a practice)

reflexive monitoring (defines and organizes assessment of the outcomes of a practice)

The production and reproduction of a practice requires continuous investment by agents in ensembles of action that carry forward in time and space.

Academic researchers need to develop an understanding of behavioural economics and social capital and be ready to put in the ground work talking and listening to their clinical colleagues as they work alongside them to develop robust, open trusting working relationships.

To help academics engage clinicians and clinical staff in the pursuit of clinical research one approach is to use motivational tools to drive engagement and social action (that is, action in response to others’ behaviour), such as a sense of shared purpose, self-interest, respect for each other and the pursuit of good standards of practice. Academics can use these levers to win over clinical teams hearts minds and hands to induce the change the system so urgently needs.

To help clinical staff to gain an appreciation of the impact and practicalities involved in implementing clinical trials and make them more ready to engage make research modules more freely available to all staff. There also seems to be a need to train more CRNs and for student nurses to gain direct experience of what is involved in implementing clinical trials.

PIs and CIs need to be aware that it may take a significant degree of time and effort to explain to clinical staff the processes and requirements of the clinical trial and to engage them. Engagement can be encouraged by translating research results into practice, e.g. through active practice development and regular research seminars.

For a CRN working alongside clinical care nurses the principle challenges are 1) mistrust or misunderstanding or the work they do (the irregular hours, the undisclosed duties they perform do outside the care environment) and 2) problems of delays in handover from out of hours staff to the CRN regarding the trial participants. The most effective means of ensuring a successful collaboration between CRNs and clinical care staff is for the CRN to become integrated into the wider MDT allowing for them and their work to become embedded into the care environment over time.

Clinical teams have a primary focus on clinical practice and meeting the healthcare needs of their patients. Ward managers and the nursing hierarchy would need to be in agreement that the ward team had time resource available to them to carry out trial specific tasks at the time they were due to ensure accuracy.

Research studies in the UK has indicated that in the mental health context, researcher access to potential trial participants is multiply influenced. Gate-keeping clinicians are faced with competing priorities and resources constrain research activity. As gatekeepers, clinicians may seek to protect people for whom they provide care from the perceived burden of research participation and/or an intervention perceived to be futile for an intractable condition. Rather than feeling ‘put upon’ by disinterested researchers, gatekeepers should be involved in the research process from the beginning and have their contributions valued.

There are also long-standing concerns that the methods and results of many clinical trials currently remain hidden from public view. This lack of transparency, say campaigners, undermines public trust, breaks the ethical pact between scientists and those participating in trials and leads to clinical decisions being made on the basis of incomplete evidence, potentially leading to poorer outcomes for patients.

Collaboration with industry can bring in extra funding which can be used to recruit trained CRNs to implement the trials rather than the clinical team. This obviates the need and cost of facilitating GCP training for the clinical team. There are current calls on government to ensure all data from all clinical trials is published to foster greater openness in medical research. This degree of transparency would help to dissipate negative perceptions of the pharmaceutical industry.

According to one experienced CRN, embedding clinical trials successfully in routine care settings involves the following steps:1) Build relationships with the clinical team Engage the clinical staff so that they come to understand and believe in the trials. This involves observing and working alongside the clinical staff to learn how they work and who their patients are. It is important to acknowledge the experience and expertise of the clinical team and to seek and make use of their advice whenever an opportunity arises. In doing so the CRN will gain the trust of her clinical colleagues and become seen as an integral part of the the clinical team and not as an unhelpful or meaningless add-on. The clinical team are the ones to consult as to how to approach their patients and of course the ones to refer patients to the trial. In short they are essential to the success of the trial. If their interest seems to be flagging at any point in the trial, then motivate them e.g. with friendly but purposeful emails congratulating them on their successes and urging them on when the need arises!

2) Create inviting, meaningful and trial materials Materials used in the clinical trial e.g. information sheets

and other forms used in patient recruitment and the PIS (patient information sheet) need to be patient friendly – written in plain English and suitably embellished with e.g. picture and other illustrations if for minors. Ideally feedback/outcome/observation sheets should gather qualitative as well as quantitative data to give a more complete picture of the effects of the intervention on trial. When seeking participants do emphasize the positives e.g. that travel expenses will be paid and whether there is flexibility as to when/where patients participate.

3) Document everything Create comprehensive confidential databases in line with GCP which capture any relevant patient information. This may be of use when e.g. seeking participants for further or follow-up trials.

4) Beware of social media Staff need to be cautioned against posting confidential trial information or anything else that might compromise a trial's integrity or success on social media websites, e.g. Twitter. Similarly it is advisable to monitor what patients are posting themselves and if necessary advise them on the possible consequences of what they are doing.

5) Feedback At all stages gather feedback from everyone involved (clinicians and patients) and as a result do make any necessary alterations to the trial.

6) Fruits of success One of the outcomes of successfully embedding a clinical trial into routine clinical care is that it opens the gate at all levels for further research to take place and creates a clinical team who are open to this happening.

A report by Dr Sarah Markham (Visiting Researcher, Dept Biostatistics, IoP, KCL)