Are some feasibility studies more feasible than others? A review of the outcomes of feasibility studies on the ISRCTN registry

Background Feasibility studies are often conducted before committing to a randomised controlled trial (RCT), yet there is little published evidence to inform how useful feasibility studies are, especially in terms of adding or reducing waste in research. This study attempted to examine how many feasibility studies demonstrated that the full trial was feasible and whether some feasibility studies were inherently likely to be feasible or not feasible, based on the topic area and/or research setting. Methods Keyword searches were conducted on the International Standard Randomised Controlled Trials Number (ISRCTN) registry to identify all completed feasibility studies which had been conducted in the UK. Results A total of 625 records from the 1933 identified were reviewed before it became evident that it would be futile to continue. Of 329 feasibility studies identified, 160 had a known outcome (49%), 133 (83%) trials were deemed to be feasible and only 27 (17%) were reported to be non-feasible. There were therefore too few studies to allow the intended comparison of differences in non-feasible studies by topic and/or setting. Conclusions There were too few studies reported as non-feasible to draw any useful conclusions on whether topic and/or setting had an effect. However, the high feasibility rate (83%) may suggest that non-feasible studies are subject to publication bias or that many feasible studies are redundant and may be adding waste to the research pathway.

Evaluating Registered Reports Funding Partnerships: a feasibility study

Background: We studied a novel initiative – Registered Reports Funding Partnerships (RRFPs) – whereby research funders and journals partner in order to integrate their procedures for funding applications and Registered Reports submissions into one process. We investigated the feasibility of conducting a randomised controlled trial (RCT) of the impact of RRFPs on (1) research quality and (2) the efficiency of the research process, from funding to publication. Methods: We conducted 32 semi-structured interviews and follow-up questionnaires with stakeholders (funders, editors, authors, and reviewers) across six different RRFPs. Results: A RCT of RRFPs appears to be feasible in principle. The partnership concept seems worthwhile to pursue further and is adaptable to the needs of various funders and publishers, and across disciplines. Three primary outcomes of interest should be measurable, and participant randomisation could conceivably be done in a number of ways. In practice, however, the current volume of submissions going through existing partnerships is too low to support a full trial. Conclusions: Although a RCT of RRFPs is conceptually feasible, it will only be possible if organisations are willing to form new partnerships, scale up existing ones, and incorporate a trial (i.e., randomisation) into these partnerships.

A Feasibility and Pilot Randomised Dismantling Trial of the Efficacy of Self-As-Context During Acceptance and Commitment Therapy

The comparative clinical utility of the components of the psychological flexibility model of acceptance and commitment therapy (ACT) have not been equally evaluated. This study therefore conducted a feasibility and pilot two-arm dismantling trial by quarantining the self-as-context component. Sixteen participants were randomised to either 8 sessions of protocol-based ACT (Full-ACT) or 8 sessions of protocol-based ACT minus self-as-context (ACT-SAC). Process measures (flexibility and decentring) were taken at start of treatment, end of treatment, and at 6-week follow-up. Clinical outcome measures (functioning, anxiety, and depression) were collected on a session-by-session basis. Randomisation was well tolerated, all measures were completed, both interventions were competently delivered, and one adverse effect occurred in the full-ACT arm. Ten participants attended all 8 sessions creating a dropout rate of 37.50%. Clinical change appeared linear in both treatments and that treatment gains were maintained. Findings suggest that a full trial is possible and sample size calculations and methodological improvements are provided for this.

PP32 Pathway to portfolio: from idea to full trial funding

BackgroundNIHR funding is provided to studies which will produce evidence to inform policy and practice in healthcare. Exploratory or feasibility work can be difficult to find funding for. We present the timeline and steps in the process from first having an idea for research through to gaining funding for a definitive trial.ObjectiveTo determine costs and effects of Fascia Iliaca Compartment Block delivered by paramedics at the scene of injury for suspected hip fracture.MethodsLiterature reviewDevelopment and testing of tool to support identification of hip fracture by paramedicsFeasibility trial (RAPID 1)Proposal for definitive trial (RAPID 2)ResultsFunding was gained from local NHS ‘Pathway to Portfolio’ resources to carry out the first stages of the programme; then a grant was won through the Welsh ‘Research for Patient and Public Benefit’ scheme to undertake a feasibility study. Finally, NIHR HTA funding was awarded to carry out a definitive trial, in five ambulance services.2015 – 16: A systematic review of the literature found that the effectiveness of FICB carried out by paramedics at the scene of injury is unknown, although nurse practitioners have been found to deliver this intervention safely in the Emergency Department.2015 – 16: A tool for identifying hip fracture at the scene of injury was developed by orthopaedic clinicians and tested by ambulance service staff. Sensitivity and positive predictive value were high.2015 – 18: Feasibility trial progression criteria related to methods and intervention safety and acceptability were met.2019 – 20: A full trial proposal was submitted, shortlisted, rejected, amended, resubmitted and funded.2020 – 2025: The RAPID 2 trial is now underway, with paramedic training and patient recruitment due to start in June 2021.ConclusionsResearch funding systems can work to help to progress from idea to full trial, although timescales can be lengthy.

A day at the races

Two major barriers to conducting user studies are the costs involved in recruiting participants and researcher time in performing studies. Typical solutions are to study convenience samples or design studies that can be deployed on crowd-sourcing platforms. Both solutions have benefits but also drawbacks. Even in cases where these approaches make sense, it is still reasonable to ask whether we are using our resources – participants’ and our time – efficiently and whether we can do better. Typically user studies compare randomly-assigned experimental conditions, such that a uniform number of opportunities are assigned to each condition. This sampling approach, as has been demonstrated in clinical trials, is sub-optimal. The goal of many Information Retrieval (IR) user studies is to determine which strategy (e.g., behaviour or system) performs the best. In such a setup, it is not wise to waste participant and researcher time and money on conditions that are obviously inferior. In this work we explore whether Best Arm Identification (BAI) algorithms provide a natural solution to this problem. BAI methods are a class of Multi-armed Bandits (MABs) where the only goal is to output a recommended arm and the algorithms are evaluated by the average payoff of the recommended arm. Using three datasets associated with previously published IR-related user studies and a series of simulations, we test the extent to which the cost required to run user studies can be reduced by employing BAI methods. Our results suggest that some BAI instances (racing algorithms) are promising devices to reduce the cost of user studies. One of the racing algorithms studied, Hoeffding, holds particular promise. This algorithm offered consistent savings across both the real and simulated data sets and only extremely rarely returned a result inconsistent with the result of the full trial. We believe the results can have an important impact on the way research is performed in this field. The results show that the conditions assigned to participants could be dynamically changed, automatically, to make efficient use of participant and experimenter time.

The ASCEND Study: Protocol for a Feasibility Study to Evaluate an Early Social Communication Intervention for Young Children with Down Syndrome

Background: Down syndrome is the most common cause of learning disability, affecting approximately 1 in every 700 babies. Children with Down Syndrome have particular difficulties with speech and language. This makes it challenging for them to participate fully in life, access health care services and educational opportunities. Improving the language skills of young children with Down Syndrome is vital for their future social and emotional well-being and behaviour, and consequently contribution to society. As Down Syndrome is detected before or at birth, we can provide support from early on. There are currently no standard interventions for improving the language skills of children with Down Syndrome under the age of 36 months. Evidence suggests that early parent-based interventions may be effective in improving language outcomes. In partnership with parents and speech and language therapists, we have co-developed an intervention focusing on early social communication skills and our preliminary work shows that it can lead to better language in children with Down Syndrome. Our aim is to carry out a feasibility study which will inform a future pilot/full trial to test whether the intervention is effective in improving language skills before children with Down Syndrome start school. Methods: This is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site comparing the intervention (plus standard NHS speech and language therapy) with no intervention (standard NHS speech and language therapy only). We aim to recruit between 25 and 30 children with Down Syndrome aged between 12 and 30 months. Sites are defined by the geographical boundaries of three National Health Service (NHS) Trusts. Recruitment is from NHS Speech and Language Therapist caseloads within the 3 Trusts and self-referral. In the intervention arm parents/guardians will receive brief training on the parent-based intervention and a manual to follow with their child for 10 weeks. The children’s language and early communication skills and family health outcomes will be assessed by a blinded assessor at baseline, post-intervention and 6 month follow up. Questionnaire and semi-structured interviews will explore the acceptability of the intervention to parents and SLTs.Discussion: The feasibility study’s outcomes will determine whether it would be viable to progress to a full-trial and whether adjustments need to made to the procedures, data collection methods, intervention delivery, and the intensity of support needed. We want to assess whether our early intervention can be delivered and rolled out through NHS Speech and Language Therapy Services. We anticipate that NHS services will need to make ongoing changes due to the COVID19 pandemic, so it is likely we will need to make adjustments for the definitive trial. We will also calculate descriptive statistics of the language outcome measure which will we use for any future sample size calculation. Trial registration: ISRCTN13902755. Registered on 25th August 2020. http://www.isrctn.com/ISRCTN13902755

Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial

Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.

An ADePT evaluation for incorporating the TIPPS periodontal health intervention into primary care antenatal programmes to enhance infant birth weight in Palestine: a feasibility study

Background A feasibility study was conducted to implement the Talk, Instruct, Practice, Plan and Support (TIPPS) intervention for pregnant women to enhance infant birth weight in a conflict area in Low- and Middle-Income Countries (LMIC). The decision tool, A process for Decision-making after Pilot and feasibility Trials (ADePT), examines the methodological factors identified in a feasibility study, that may require modification for a full trial. Thus, this study aimed to use the ADePT decision tool to evaluate if the feasibility study had achieved its objectives and to identify the need for intervention, clinical context and trial design modification. Methods A one-arm, pretest–posttest feasibility study recruited 25 pregnant women in their first trimester and clinic staff from a primary healthcare clinic located in Gaza City, Palestine. The TIPPS periodontal health intervention was delivered by antenatal care nurses to the pregnant women during their regular follow-up appointments. The ADePT framework was applied to evaluate the findings from the feasibility study. The ADePT checklist demonstrated sample size estimation, recruitment, consent, intervention adherence, intervention acceptability, costs and duration, completion and appropriateness of outcome assessments, retention, logistics, and synergy between protocol components. Results All recruited pregnant women (25, aged 16–35 years old) consented to participate in the study, and the adherence to the intervention was 88% (22 women). The TIPPS intervention was acceptable, but there was ambivalence over who should deliver it in the clinic. Only the cost of toothbrushing and TIPPS information materials was calculated, while the cost of nurses’ time was not included. The missing values of data were few (12% of gingival bleeding data and 22% from infant birth weight data). This intervention significantly reduced the mean percentage of plaque and bleeding scores after 3 months. The sample size for future randomised controlled trial was estimated around 400 participants. The participants stated the value of the intervention. The clinic staff voiced concerns regarding time and the cost of nurses providing the TIPPS intervention. This allowed suggestions to be made regarding the modification of trial design and context of implementation. Conclusions The ADePT evaluation showed it was possible to progress to full trial with modifications in the trial design.

An ADePT evaluation for incorporating the TIPPS periodontal health intervention into primary care ante-natal programmes to enhance infant birthweight in Palestine: a feasibility study.

Background: A feasibility study was conducted to implement the T alk, I nstruct, P ractice, P lan and S upport (TIPPS) intervention for pregnant women to enhance infant birthweight in a conflict area in L ow and M iddle I ncome C ountries ( LMIC). The decision tool, A process for De cision-making after P ilot and feasibility T rials (ADePT) examines the methodological factors identified in a feasibility study, that may require modification for a full trial. Objectives: To use the ADePT decision tool to evaluate if the feasibility study had achieved its objectives and to identify the need for intervention, clinical context and trial design modification. Basic research design: Feasibility study: a one-arm, pre-test-post-test design. The ADePT framework was applied to evaluate the findings from the feasibility study. Clinical setting: Primary healthcare clinic located in Gaza City, Palestine. Participants: 25 pregnant women in their first trimester and clinic staff. Interventions: The TIPPS periodontal health intervention delivered by ante-natal nurses. Main outcome measures: ADePT checklist: sample size estimation, recruitment, consent, intervention adherence, intervention acceptability, costs and duration, completion and appropriateness of outcome assessments, retention, logistics and synergy between protocol components. Results: 25 pregnant women (aged 16-35 years old) attended the baseline and 22 (88%) completed the second follow-up appointment. This intervention significantly reduced (P<0.001) the mean percentage of plaque and bleeding scores from the baseline to Time 2. The participants stated the value of the intervention. The clinic staff voiced concerns regarding time and the cost of nurses providing the TIPPS intervention. This allowed suggestions to be made regarding the modification of trial design and context of implementation. Conclusions: The ADePT evaluation showed it was possible to progress to full trial with modifications in the trial design.

Judgements Without Trial in Civil Proceedings in Malaysia: A Brief Analysis on the Burden of Proof Required

Civil proceedings involve a complex procedure with various interlocutory applications before the matter is set for trial. Some of the interlocutory applications, namely applications to enter judgment in default, to strike out pleading and for summary judgment, may result in the plaintiff obtaining early judgment or disposal of the case without a full trial. Interestingly, these applications require a different burden of proof for the plaintiff to satisfy. This article seeks to explore the burden of proof necessitated in those applications in order to evaluate the likelihood of the plaintiff obtaining judgment without trial. In achieving this objective, the process of civil proceedings in Malaysia is briefly explained. This is followed by an analysis on the burden of proof required in the said applications. It is observed that although judgment in defaults or summary judgment may be entered against the defendant upon the plaintiff’s satisfaction of mere procedural requirements, it is equally ‘easy’ for the defendant to set aside or oppose such judgment or application. A conclusion can be derived that civil procedure in Malaysia allows the defendant a sufficient right or opportunity to have ‘his day in court’ by placing a low threshold for him set aside judgment in default or oppose summary judgment application. Further, it is also observed that a stringent burden of proof is needed for the plaintiff to be able to strike out the defendant’s defence and enter judgment on his behalf. This is, arguably crucial so as to cloth the defendant with the right to a fair trial which includes the right to be heard and present their cases sufficiently.