What is the value of clinical trials?

An early stocktake of randomised controlled trials (RCT) in nursing identified 522 trials, including 375 published in nursing journals (Cullum, 1997). The design was clearly a method of interest and utility to nurses. But what is the value of trials? Simply, they are the best design for answering questions about the effect of interventions; no other design can establish the causal relationship necessary to address the question, “Is this treatment or intervention effective?” There are many different trial designs: parallel group trials, N-of-1 trials, cluster trials, stepped wedge trials, within-participant trials, cross-over trials, and factorial trials to name but a few. Each is suited to a different purpose.

However, trials are not the best design full stop. Trials cannot answer questions about diagnosis, prognosis, manifestation of disorder, or experience of a condition. There may still be critics of or adherents to trials who believe that randomised designs are the gold standard in research. But this view is underinformed and people with such views do not understand that for each type of question (aetiology, diagnosis, prognosis, therapy, and experience), different designs best answer the different questions. The hierarchy of evidence varies depending on the questions being asked and the RCT is not at the top of the pile for every question.

RCTs produce reliable data for evaluating interventions, when conducted properly. That caveat means that all nurses need to be able to critically read papers reporting RCTs so as to implement beneficial interventions and disinvest from harmful or ineffective interventions. However, not all RCTs are high quality (Jull & Aye, 2015), and being able to differentiate higher quality from lower quality trials is an important skillset for both the reader and the designer of trials - a skillset that comes from training.

Establishing a career as a triallist

My career should be seen as developing within a milieu, one that will differ to today’s context. The 1990s were a big decade for evidence-based practice, a movement that aimed to ensure health workers were able to find and appraise evidence. It was the decade where many would develop clinical guidelines, to summarise what was known to work rather than what was opined to work; the decade when abstract journals were started to provide regular quick summaries of new quality assessed evidence (one of which I co-edited); and the decade where systematic reviews of RCTs came to the fore in healthcare. The state of review science in leading medical journals was poor; study selection processes were not articulated; assessments of internal validity were largely absent; studies were rarely combined to provide an aggregated summary statistic; and three out of every 10 reviews did not even include a conclusion (Mulrow, 1987). Reviews at that time had more in common with op-eds (opinion pieces) than the systematic reviews we see published today.

The founding of the Cochrane Collaboration in 1993 sought to change review science. It built on the work of the Oxford Database of Perinatal Trials and the collection of systematic reviews that became the book, Effective Care in Pregnancy and Childbirth (Chalmers et al., 1989). The Cochrane Collaboration systematised the process of reviewing under the aegis of review groups, which were editorial centres that established priorities and guided volunteer reviewers to produce systematic reviews to a specified standard. One of those review groups was the Wound Review Group, led by Dame Nicky Cullum. And it was Nicky who invited me, then a clinical nurse consultant at Auckland Hospital, to be the Criticism Editor for the group in 1997.

There had been growing interest in evidence-based practice in Aotearoa New Zealand, including Auckland Hospital, with senior staff and academics being trained in guideline development. Mia Carroll, the then Director of Nursing at Auckland Hospital, was eager that nurses have those skills and that nurses be involved or lead guideline teams. It was she who urged me to lead the development in 1998 of what was to become a watershed document in my research career – the New Zealand Guidelines for the Management of People with Chronic Leg Ulcers (Jull et al., 2000, 2001). This guideline not only exposed me to a body of evidence composed mostly of randomised controlled trials, but it led me, for the first time, to people in Aotearoa New Zealand who were engaged in designing and conducting clinical trials. These clinicians and academics would become future collaborators in my own randomised trials.

It was the evidence gaps identified in the guideline that focused my long-held desire to be involved in research. One evidence gap became my Master’s thesis (pentoxifylline for treating venous leg ulcers), a systematic review published first in the Cochrane Library and then in Lancet (Jull et al., 2002). I saw another need too; all the nurses I knew were heading down a qualitative route for their research, despite my belief that nursing needed both quantitative and qualitative researchers. Two mentors simultaneously shone a light on that path for me; Professor Maralyn Foureur at Victoria University of Wellington, School of Nursing and Midwifery and Dr Natalie Walker, a research fellow leading the Auckland Leg Ulcer Study (Walker et al., 2002) at what was then the Clinical Trials Research Unit (CTRU) in the University of Auckland. Maralyn prompted, prodded, and then pushed me to apply for the HRC Foxley Fellowship in 2001, which gave me a one year research sabbatical from clinical practice. Natalie introduced me to the CTRU, provided some of the data I was to work on in my Fellowship year and became my supervisor for the year. Finally, I was in a trials training environment, surrounded by research fellows, PhD students, statisticians, data managers, and trial managers, many of whom were friends and collaborators with some of the world’s leading triallists, whose names I knew from reading about evidence-based practice. I felt at home.

That year was a creative one as I was able to pursue any interest I wished as well as my planned projects. On top of that I had time to write my first successful grant application applying for funding for a clinical trial of honey for treating venous leg ulcers (Jull et al., 2008). I still did not have a PhD, but getting that funding put paid to the notion that you had to have a PhD first to start an independent research career. Maybe that is the case for bench scientists, but it is less so for clinicians. With the trial team I was able to bring together within the CTRU as well as outside of the unit, it would be very hard to fail.

That RCT became the basis for my doctoral degree and opened a door to my leading a further five RCTs of different interventions for treating venous leg ulcers (aspirin, exercise, hypochlorous acid, a novel oligonucleotide, and a keratin dressing) as well as being co-investigator on 20 other trials, in addition to other studies. Trial methodology became, and remains, a passion.

How to support nurses as triallists

My path is but one way in which nurses can become triallists. A recent review by the Australasian Nursing and Midwifery Clinical Trials Network (Eckert et al., 2023) found 21 other registered nurses in Aotearoa New Zealand had been the principal investigator for a trial since 2006. But only myself and one other nurse have led more than one trial (although some RCTs may not have been included). This is woefully inadequate if nurses are going to use and lead trial designs.

There are very real barriers to running RCTs. They are expensive designs and many of the questions best answered by RCTs may only be fundable through public good sources, which makes funding hard to obtain without the right infrastructure and the right team. Those who have already been research nurses and research managers will have a step up when it comes to the necessary networks, but those roles need not be the starting point. Working across disciplines with those already experienced in trial design and conduct is necessary for new researcher seeking to lead a trial. It is also necessary to build support with the end users of the intended research, including Māori and Pasifika populations.

The key issue in becoming a triallist is building support. Research these days is all about relationship. Science no longer advances through the work of single iconoclasts, but through the work of research teams. However, in a small country, such support may not be easy to find especially outside academic centres. This barrier is one reason why the Australasian Nursing and Midwifery Clinical Trials Network (ANMCTN) was formed with the support of most of the universities in Aotearoa New Zealand. The intent of the Network is to support the growth in trial research capacity in each country through mentoring, training, and facilitating high quality RCTs to gain funding. If you have an interest in RCTs, have conducted or are conducting a clinical trial, or simply want to know more, you can join ANMCTN for free (https://anmctn.com.au); the Network is quite new, so get in on the ground floor! There will be events developing in Aotearoa New Zealand in the near future.