Pragmatic trials aim to generate timely evidence while ensuring feasibility, minimizing practice burden, and maintaining real-world conditions. We conducted rapid-cycle qualitative research in the preimplementation period of a trial evaluating a community paramedic program to shorten and prevent hospitalizations. Between December 2021 and March 2022, interviews (n = 30) and presentations/discussions (n = 17) were conducted with clinical and administrative stakeholders. Two investigators analyzed interview and presentation data to identify potential trial challenges, and team reflections were used to develop responsive strategies. Solutions were implemented prior to the commencement of trial enrollment and were aimed at bolstering feasibility and building ongoing practice feedback loops.

Pragmatic or practice-oriented comparative effectiveness trials may be conducted to fill the evidence gaps that are revealed after the private sector has performed the trials needed for bringing their product to the market. A tool of increasing importance to identify such evidence gaps is resulting from health technology assessments (HTA) whereby the data derived from clinical research are examined in a systematic manner with reference to effect, safety, as well as additional parameters. Practice-oriented trials are informative for healthcare decision makers, practice-changing and may even be cost-saving for the healthcare payers. There are however only a limited number of funding sources for such trials. Public and private healthcare payers should stimulate the conduct of practice-oriented trials in their effort to maximize patient benefit within the limitation of the available resources. Pragmatic randomized trials can be performed at low cost when based on existing coded electronic health records and as well health registries. Public health decision makers are increasingly taking advantage of results from health technology assessments to support priority setting. In accordance with this it would appear reasonable that decision makers should get more involved in priority setting and funding also in the field of clinical research in order to provide further evidence needed for assessments, reassessments, and subsequent qualified decisions and resource allocations in health care. A closer dialogue and collaboration between the clinical research and HTA communities would facilitate a more efficient utilization of such opportunities.

Although long-acting antipsychotics are widely used in individuals with psychotic disorders, it is unclear which long-acting preparation should be considered as first-line treatment in clinical practice. In this commentary, the main strengths and weaknesses of a recently published pragmatic randomised study comparing long-acting paliperidone palmitate v. long-acting haloperidol decanoate are briefly analysed.

This Editorial addresses the crucial issue of which research methodology is most suited for capturing the complexity of psychosocial interventions conducted in ‘real world’ mental health settings. It first examines conventional randomized controlled trial (RCT) methodology and critically appraises its strengths and weaknesses. It then considers the specificity of mental health care treatments and defines the term ‘complex’ intervention and its implications for RCT design. The salient features of pragmatic RCTs aimed at generating evidence of psychosocial intervention effectiveness are then described. Subsequently, the conceptualization of pragmatic RCTs, and of their further developments – which we propose to call ‘new generation’ pragmatic trials – in the broader routine mental health service context, is explored. Helpful tools for planning pragmatic RCTs, such as the CONSORT extension for pragmatic trials, and the PRECIS tool are also examined. We then discuss some practical challenges that are involved in the design and implementation of pragmatic trials based on our own experience in conducting the GET UP PIANO Trial. Lastly, we speculate on the ways in which current ideas on the purpose, scope and ethics of mental health care research may determine further challenges for clinical research and evidence-based practice.

Having first introduced the pragmatic health care trial, the discussion then focuses on a selected list of technical problems that are important for the design, analysis and inference from such trials. The first is lack of independence of participants’ outcomes do to clustering either arising from a cluster randomized design or to the way treatment is delivered (therapist and group effects). The second and third concern the implications of non-adherence to treatment and subsequent loss to follow-up, particularly, when non-adherence is associated with missing outcome data. Finally, it is argued that pragmatism and a desire for a scientific explanation should not be regarded as mutually exclusive.