Reporting and communication of sample size calculations in adaptive clinical trials: a review of trial protocols and grant applications.

Background: An adaptive design allows modifying the design based on accumulated data while maintaining trial validity and integrity. The final sample size may be unknown when designing an adaptive trial. It is therefore important to consider what sample size is used in the planning of the study and how that is communicated to add transparency to the understanding of the trial design and facilitate robust planning.

Exploring the barriers to, and importance of, participant diversity in early-phase clinical trials: an interview-based qualitative study of professionals and patient and public representatives.

Objectives: To explore the importance of, and barriers to achieving, diversity in early-phase clinical trials.

Design: Qualitative interviews analysed using thematic analysis.

Setting And Participants: Five professionals (clinical researchers and methodologists) and three patient and public representatives (those with experience of early-phase clinical trials and/or those from ethnic minority backgrounds) were interviewed between June and August 2022.

Outpatient paracentesis for the management of ovarian hyperstimulation syndrome: study protocol for the STOP-OHSS randomised controlled trial.

Introduction: Ovarian hyperstimulation syndrome (OHSS) is the most significant short-term complication of pharmacological ovarian stimulation. Symptoms range from mild abdominal discomfort to rare complications such as renal failure, thromboembolism and respiratory distress syndrome.Currently, clinical practice typically involves monitoring the patient until the condition becomes severe, at which point they are admitted to hospital, where drainage of ascitic fluid (paracentesis) may take place.

Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance.

The CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. The CONSORT Dose-finding Extension (DEFINE) extends the guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such trials generally focus on safety, tolerability, activity, and recommending dosing and scheduling regimens for further clinical development.

Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study.

Background: Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials.

SPIRIT and CONSORT extensions for early phase dose-finding clinical trials: the DEFINE (DosE-FIndiNg Extensions) study protocol.

Introduction: Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials.

Practical guidance for planning resources required to support publicly-funded adaptive clinical trials.

Adaptive designs are a class of methods for improving efficiency and patient benefit of clinical trials. Although their use has increased in recent years, research suggests they are not used in many situations where they have potential to bring benefit. One barrier to their more widespread use is a lack of understanding about how the choice to use an adaptive design, rather than a traditional design, affects resources (staff and non-staff) required to set-up, conduct and report a trial.

Costs and staffing resource requirements for adaptive clinical trials: quantitative and qualitative results from the Costing Adaptive Trials project.

Background: Adaptive designs offer great promise in improving the efficiency and patient-benefit of clinical trials. An important barrier to further increased use is a lack of understanding about which additional resources are required to conduct a high-quality adaptive clinical trial, compared to a traditional fixed design. The Costing Adaptive Trials (CAT) project investigated which additional resources may be required to support adaptive trials.

Self-managed, computerised word finding therapy as an add-on to usual care for chronic aphasia post-stroke: An economic evaluation.

Objective: To examine the cost-effectiveness of self-managed computerised word finding therapy as an add-on to usual care for people with aphasia post-stroke.

Design: Cost-effectiveness modelling over a life-time period, taking a UK National Health Service (NHS) and personal social service perspective.

Setting: Based on the Big CACTUS randomised controlled trial, conducted in 21 UK NHS speech and language therapy departments.

The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design.

Adaptive designs (ADs) allow pre-planned changes to an ongoing trial without compromising the validity of conclusions and it is essential to distinguish pre-planned from unplanned changes that may also occur. The reporting of ADs in randomised trials is inconsistent and needs improving. Incompletely reported AD randomised trials are difficult to reproduce and are hard to interpret and synthesise.

Computerised speech and language therapy or attention control added to usual care for people with long-term post-stroke aphasia: the Big CACTUS three-arm RCT.

Background: People with aphasia may improve their communication with speech and language therapy many months/years after stroke. However, NHS speech and language therapy reduces in availability over time post stroke.

Objective: This trial evaluated the clinical effectiveness and cost-effectiveness of self-managed computerised speech and language therapy to provide additional therapy.

Self-managed, computerised speech and language therapy for patients with chronic aphasia post-stroke compared with usual care or attention control (Big CACTUS): a multicentre, single-blinded, randomised controlled trial.

Background: Post-stroke aphasia might improve over many years with speech and language therapy; however speech and language therapy is often less readily available beyond a few months after stroke. We assessed self-managed computerised speech and language therapy (CSLT) as a means of providing more therapy than patients can access through usual care alone.

Methods: In this pragmatic, superiority, three-arm, individually randomised, single-blind, parallel group trial, patients were recruited from 21 speech and language therapy departments in the UK.

A Review of Perspectives on the Use of Randomization in Phase II Oncology Trials.

Historically, phase II oncology trials assessed a treatment's efficacy by examining its tumor response rate in a single-arm trial. Then, approximately 25 years ago, certain statistical and pharmacological considerations ignited a debate around whether randomized designs should be used instead. Here, based on an extensive literature review, we review the arguments on either side of this debate.

Development process of a consensus-driven CONSORT extension for randomised trials using an adaptive design.

Background: Adequate reporting of adaptive designs (ADs) maximises their potential benefits in the conduct of clinical trials. Transparent reporting can help address some obstacles and concerns relating to the use of ADs. Currently, there are deficiencies in the reporting of AD trials.

Appropriate statistical methods for analysing partially nested randomised controlled trials with continuous outcomes: a simulation study.

Background: In individually randomised trials we might expect interventions delivered in groups or by care providers to result in clustering of outcomes for participants treated in the same group or by the same care provider. In partially nested randomised controlled trials (pnRCTs) this clustering only occurs in one trial arm, commonly the intervention arm. It is important to measure and account for between-cluster variability in trial design and analysis.

Adaptive designs in clinical trials: why use them, and how to run and report them.

Adaptive designs can make clinical trials more flexible by utilising results accumulating in the trial to modify the trial's course in accordance with pre-specified rules. Trials with an adaptive design are often more efficient, informative and ethical than trials with a traditional fixed design since they often make better use of resources such as time and money, and might require fewer participants. Adaptive designs can be applied across all phases of clinical research, from early-phase dose escalation to confirmatory trials.

A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.

Background: Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment.

Recommendations for the analysis of individually randomised controlled trials with clustering in one arm - a case of continuous outcomes.

Background: In an individually randomised controlled trial where the treatment is delivered by a health professional it seems likely that the effectiveness of the treatment, independent of any treatment effect, could depend on the skill, training or even enthusiasm of the health professional delivering it. This may then lead to a potential clustering of the outcomes for patients treated by the same health professional, but similar clustering may not occur in the control arm. Using four case studies, we aim to provide practical guidance and recommendations for the analysis of trials with some element of clustering in one arm.

Researching Complex Interventions in Health: The State of the Art : Exeter, UK. 14-15 October 2015.

KEYNOTE PRESENTATIONS K1 Researching complex interventions: the need for robust approaches Peter Craig K2 Complex intervention studies: an important step in developing knowledge for practice Ingalill Rahm-Hallberg K3 Public and patient involvement in research: what, why and how? Nicky Britten K4 Mixed methods in health service research – where do we go from here? Gunilla Borglin SPEAKER PRESENTATIONS S1 Exploring complexity in systematic reviews of complex interventions Gabriele Meyer, Sascha Köpke, Jane Noyes, Jackie Chandler S2 Can complex health interventions be optimised before moving to a definitive RCT? Strategies and methods currently in use Sara Levati S3 A systematic approach to develop theory based implementation interventions Anne Sales S4 Pilot studies and feasibility studies for complex interventions: an introduction Lehana Thabane, Lora Giangregorio S5 What can be done to pilot complex interventions? Nancy Feeley, Sylvie Cossette S6 Using feasibility and pilot trials to test alternative methodologies and methodological procedures prior to full scale trials Rod Taylor S7 A mixed methods feasibility study in practice Jacqueline Hill, David A Richards, Willem Kuyken S8 Non-standard experimental designs and preference designs Louise von Essen S9 Evaluation gone wild: using natural experimental approaches to evaluate complex interventions Andrew Williams S10 The stepped wedge cluster randomised trial: an opportunity to increase the quality of evaluations of service delivery and public policy interventions Karla Hemming, Richard Lilford, Alan Girling, Monica Taljaard S11 Adaptive designs in confirmatory clinical trials: opportunities in investigating complex interventions Munyaradzi Dimairo S12 Processes, contexts and outcomes in complex interventions, and the implications for evaluation Mark Petticrew S13 Processes, contexts and outcomes in complex interventions, and the implications for evaluation Janis Baird, Graham Moore S14 Qualitative evaluation alongside RCTs: what to consider to get relevant and valuable results Willem Odendaal, Salla Atkins, Elizabeth Lutge, Natalie Leon, Simon Lewin S15 Using economic evaluations to understand the value of complex interventions: when maximising health status is not sufficient Katherine Payne S16 How to arrive at an implementation plan Theo van Achterberg S17 Modelling process and outcomes in complex interventions Walter Sermeus S18 Systems modelling for improving health care Martin Pitt, Thomas Monks

Adaptive designs undertaken in clinical research: a review of registered clinical trials.

Adaptive designs have the potential to improve efficiency in the evaluation of new medical treatments in comparison to traditional fixed sample size designs. However, they are still not widely used in practice in clinical research. Little research has been conducted to investigate what adaptive designs are being undertaken.

Physiotherapy for Patients with Sciatica Awaiting Lumbar Micro-discectomy Surgery: A Nested, Qualitative Study of Patients' Views and Experiences.

Background And Purpose: Sciatica is a common clinical condition that can be extremely painful, disabling and life-changing. Whether conservative or surgical treatment for sciatica secondary to an intervertebral disc prolapse is most effective is still much debated. An important component of conservative treatment is physiotherapy, which aims to promote physical and psychological health for the patient, whilst resorption of the disc takes place.