The World Health Organization (WHO) defines a ‘clinical trial’ as ‘any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes’. ¹ Since its articulation, the WHO definition has been adopted by governments and funding bodies worldwide (e.g., the US National Institutes of Health and the National Health and Medical Research Council of Australia) and has been used to develop grant funding guidelines and to govern clinical trial registration. We argue that the WHO definition of a clinical trial needs expansion to also be relevant to clinical trials in mental health.

Mental health problems often emerge during childhood and are now the leading cause of disability among children and young people worldwide. ^{Reference Erskine, Moffitt, Copeland, Costello, Ferrari and Patton2} These problems often persist into adulthood, creating long-term negative personal, social and economic burdens. ^{Reference Erskine, Moffitt, Copeland, Costello, Ferrari and Patton2} Despite major investment in mental healthcare, rates of mental health problems are not falling and may be rising. High-quality clinical trials are essential for understanding this crisis. To strengthen these trials and improve translation into practice across health fields, clinical trials networks (CTNs) are being established globally.

Growing Minds Australia ^{Reference Hawes, Dadds, Tully and Northam3} , one of the world’s first CTNs in child and youth mental health in Australia, was established to drive major reform in mental health research and systems. By fostering engagement and shared responsibility across stakeholders, the CTN operates as a learning health system (LHS), ^{Reference Hawes, Dadds, Tully and Northam3} characterised by continuous knowledge generation and implementation. Although the adoption of LHS in mental health research lags behind other health fields, ^{Reference Hawes, Dadds, Tully and Northam3} its integration is essential for addressing the current mental health crisis. As part of Growing Minds Australia’s efforts to support this shift, we examined the WHO definition of ‘clinical trials’.

The WHO definition has traditionally guided mental health research by focusing on testing new medical treatments, ¹ with an emphasis on efficacy. ^{Reference Glasgow, Harden, Gaglio, Rabin, Smith and Porter4} However, this narrow scope restricts the adoption of an LHS, as it excludes implementation science and innovative trial designs targeting broader outcomes such as social determinants of health or education, or other implementation processes. Furthermore, knowledge from trials is often not scaled or embedded into mental health systems, limiting its impact on policy and practice across contexts and countries. ^{Reference Brooks, Pilgram and Rogers5} As a result, consumers who use the service may not receive evidence-based support when needed.

Consultation with our diverse mental health stakeholders (including researchers, practitioners, people with lived and living experience, and policy advisors) highlighted the need to adopt more implementation science and innovative trial methodologies in mental health clinical trials. Expanding mental health clinical trial research to include implementation science and innovative trial designs will help to ensure evidence reaches broader community and population groups and does not remain limited to efficacy data from clinical populations. Therefore, we highlight a strong need to expand the WHO definition of ‘clinical trials’ as a priority for improving mental health clinical trial research.

Specifically, we argue that there is a need to expand the WHO definition for mental health clinical trials to include three new aspects: (a) trials that focus on implementation science, (b) innovative trial designs that may not include prospective assignment or individual randomisation, and (c) clinical trial outcomes that are broader than physiological and human health outcomes. The three proposed aspects are described in turn below.

First, our view is that the WHO definition for a ‘clinical trial’ needs to include implementation science to facilitate adoption of an LHS in CTNs for mental health research, as this is currently missing. Establishing the efficacy of clinical interventions is not enough to guarantee their uptake into routine care. Implementation science was developed to facilitate this and enhance public health impact. ^{Reference Bauer and Kirchner6} Established implementation science frameworks, such as the widely used RE-AIM, provide rigorous methods for identifying and addressing barriers and facilitators to translation of clinical trials evidence into practice. ^{Reference Glasgow, Harden, Gaglio, Rabin, Smith and Porter4}

Second, although traditional randomised controlled trials are the gold standard, they are costly, often inefficient, and typically limited to assessing efficacy. ^{Reference Brooks, Pilgram and Rogers5} Increasingly, mental health research is adopting alternative innovative trial methodologies that do not rely on prospective assignment or individual randomisation, offering more cost-effective, generalisable and real-world evidence. For example, adaptive platform trials allow simultaneous evaluation of multiple interventions within one protocol. ⁷ Stepped-wedge designs support population level evaluation and policy roll-outs by staggering entry into the intervention. ^{Reference Hussey and Hughes8} Pooling existing trial data increases power, reduces costs, advances personalised care and answers research questions not feasible for single studies. ^{Reference Bangdiwala, Bhargava, O’Connor, Robinson, Michie and Murray9}

Third, the current focus on physiological and human health outcomes only is narrow; including implementation science and other innovative designs will broaden the types of outcome that can be examined. ^{1,Reference Glasgow, Harden, Gaglio, Rabin, Smith and Porter4,Reference Bauer and Kirchner6} Other relevant mental health clinical trial outcomes include social determinants of health (e.g., housing, income, cost of living), education, and implementation, such as reach, effectiveness (including cost-effectiveness), adoption, and longer-term maintenance and sustainability at individual and population levels, as well as potential unintended negative effects (e.g., stigma). ^{Reference Glasgow, Harden, Gaglio, Rabin, Smith and Porter4}

We therefore propose expanding the WHO definition of a ‘clinical trial’ in mental health research as follows: ‘Additionally, ongoing advances in mental health research point to the need to consider clinical trials involving: (a) implementation science, (b) innovative trial designs and (c) broader outcomes. Accordingly, mental health clinical trials should include:

1. (a) research involving clinical or community populations in which prospective assignment or individual randomisation is not feasible (e.g., implementation science, innovative trial designs, analyses of existing data-sets); and

2. (b) research examining variables beyond health outcomes, including but not limited to, social determinants of health, education, and implementation (e.g., reach, effectiveness (including cost-effectiveness), adoption, attrition, acceptability, and maintenance and sustainability).’

We argue that an expanded WHO definition of ‘clinical trials’ in mental health research will pave the way toward funding of new types of innovative mental health clinical trial, as well as supporting stronger researcher–service partnerships and embedding of clinical trials within real-world services to address key unanswered mental health questions. In turn, this will support translation into practice across diverse contexts globally, reducing duplication and improving value for money on funding expenditure. This will enable better resource allocation by policy makers towards generalisable research that delivers real-world impact and contributes to improved long-term mental health outcomes.