Internal Pilot Study Research Articles

Early Intervention after Rape to prevent post-traumatic stress symptoms (the EIR-study): an internal pilot study of a randomized controlled trial

BackgroundRape is one of the trauma incidents with the highest risk of subsequent post-traumatic stress disorder. Early interventions, such as prolonged exposure therapy (PE), have shown promise in preventing PTSD following a sexual assault. The primary objective of this internal pilot trial was to examine the feasibility of the EIR study protocol, which used modified prolonged exposure therapy (mPE) as a preventive intervention after rape.MethodsThis parallel two-arm clinical pilot study involved three sexual assault centers (SACs) in Trondheim, Oslo, and Vestfold, with data collected between June 2022 and March 2023. Women seeking assistance at one of these three SACs within 72 h after rape or attempted rape received acute medical treatment and forensic examinations. Women who wanted further psychosocial treatment were, if eligible and consenting, recruited to complete baseline assessments and a clinical interview before being randomized to one of two study arms. The intervention group prescribed up to five sessions of modified PE (mPE) in addition to treatment as usual (TAU), starting within the first 14 days after the rape incident, followed by weekly sessions. The other group received TAU.The present pilot evaluation is based on 22 participants, i.e., nine mPE + TAU and 13 TAU alone. Primary outcomes were predefined progression criteria regarding recruitment, retention, intervention implementation, a harm reporting system, and applying biological measurements and actigraphy.ResultsDuring the 6-month recruitment period, 235 women visited the three SACs. After eligibility screening and consent, 22 (9.4%) women were randomized. Three months later, 14 (63.6%) participants completed the final assessments. Intervention implementation was successful using trained SAC personnel to deliver mPE. The harm reporting system was used according to the study’s plan, and adverse and serious adverse events were detected during the trial. The biological measurements and actigraphy had substantial missing data but were still considered usable for statistical analyses.ConclusionIt may be feasible to conduct a full-scale RCT of early intervention after rape by comparing mPE + TAU to TAU alone. Minor design refinements were made to the protocol to enhance the main study outcome.Trial registrationClinicalTrials.gov Identifier: NCT05489133. Registered on 15 July 2022, retrospectively.

Sample Size Reestimation in Stochastic Curtailment Tests With Time-to-Events Outcome in the Case of Nonproportional Hazards Utilizing Two Weibull Distributions With Unknown Shape Parameters.

Stochastic curtailment tests for Phase II two-arm trials with time-to-event end points are traditionally performed using the log-rank test. Recent advances in designing time-to-event trials have utilized the Weibull distribution with a known shape parameter estimated from historical studies. As sample size calculations depend on the value of this shape parameter, these methods either cannot be used or likely underperform/overperform when the natural variation around the point estimate is ignored. We demonstrate that when the magnitude of the Weibull shape parameters changes, unblinded interim information on the shape of the survival curves can be useful to enrich the final analysis for reestimation of the sample size. For such scenarios, we propose two Bayesian solutions to estimate the natural variations of the Weibull shape parameter. We implement these approaches under the framework of the newly proposed relative time method that allows nonproportional hazards and nonproportional time. We also demonstrate the sample size reestimation for the relative time method using three different approaches (internal pilot study approach, conditional power, and predictive power approach) at the interim stage of the trial. We demonstrate our methods using a hypothetical example and provide insights regarding the practical constraints for the proposed methods.

Individual supported work placements (ReISE) for improving sustained return to work in unemployed people with persistent pain: an internal pilot study of a cohort randomised controlled approach

BackgroundPersistent pain is a frequent cause of sick leave and work disability in Norway. A return-to-work intervention featuring supported work placements, developed in the UK, demonstrated feasibility, and a return-to-work rate of 20% within 6 months was observed in the sample. We sought to adapt the intervention for delivery in Norway and to confirm feasibility prior to a full-scale trial.MethodsIn this internal pilot, we used a pragmatic cohort randomised controlled approach with national recruitment in Norway. We recruited people who were unemployed (for at least 1 month), having persistent pain (for at least 3 months), aged between 18 and 64, and wanting to return to work. We initially recruited people to an observational cohort study of the impact of being unemployed with persistent pain. After baseline measurement, we randomly sub-sampled participants to whom we offered the intervention, which featured individual case management and support, work-familiarisation sessions, and the offer of a 6-week part-time unpaid work placement. We assessed recruitment rates (aiming to recruit 66, and sub-sample 17 within 6 months); optimal recruitment pathways; intervention acceptance rates; the feasibility of data collection; using video links for work-familiarisation sessions and remote case manager support.ResultsThe pilot ran from June to November 2022. Of 168 people expressing interest, 94 consented. Recruitment posts on Facebook yielded the most ‘expressions of interest’ (66%, n = 111). After screening for eligibility, we included 55 participants. Of these, 19 were randomised to be offered the intervention. Of these, less than half (n = 8) consented to intervention participation. Remote case manager and work-familiarisation sessions appeared feasible. Following a delay in identifying placements, three participants received offers of work placements, with one starting and completing during the pilot period. Data collection methods were feasible, and no adverse events were reported.ConclusionsRecruitment and logistical processes, such as remote management by video link, are feasible. However, delivery of the intervention is challenging. In particular, sourcing placements and the time required for identifying appropriate placements was more challenging than anticipated. A full-scale trial is feasible but will require improvements to the placement identification processes.Trial registrationISRCTN85437524 (Referring to the ReISE trial, of which this internal pilot was a part), Registered 31 of May 2022 https://doi.org/10.1186/ISRCTN85437524Trial fundingNorwegian Research Council.

Delayed cold-stored vs. room temperature stored platelet transfusions in bleeding adult cardiac surgery patients—a randomized multicentre pilot study (PLTS-1)

BackgroundPlatelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP.MethodsThis protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product).DiscussionDCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study.Trial registrationNCT 06147531 (clinicaltrials.gov).

Prevalence of Keratoconus in the Young Eastern Population of Saudi Arabia.

Keratoconus (KCN) is a progressive corneal ectasia that manifests at a young age and significantly impacts vision and quality of life. Early diagnosis allows for effective treatment with corneal collagen crosslinking, yet there is a lack of screening methods. This research aims to screen adolescents and young adults for this sight-threatening disease using quick corneal tomography mapping. This prospective cross-sectional study is being conducted at Johns Hopkins Aramco Healthcare in Saudi Arabia, focusing on subjects aged 13-23. We are presenting the data from our study as internal pilot study data. Bilateral corneal imaging with Pentacam HR (Oculus, Wetzlar, Germany), utilizing Scheimpflug corneal tomography, was performed. Historical data on allergies, eye rubbing, KCN, family history, previous eye surgery, and contact lens use were collected. The Belin Ambrosio Enhanced Ectasia Display total D value served as an objective criterion for suspect KCN (SKCN) diagnosis. In this study with 110 participants, KCN was identified in 2.75% of participants and SKCNin 11.93%. Systemic allergies or eczema were reported by 2.80%, with no cases in the KCN or SKCN groups. Eye rubbing behavior was observed in 5.50%, with the highest prevalence (33.30%) in the KCN group. A family history of KCN was found in 21.10%, with SKCN having the highest prevalence (30.80%). This restricted population study reveals a significant KCN rate of 2.75%. The condition, easily detected and treatable with corneal collagen crosslinking, highlights the need for larger population studies to determine the disease's true prevalence. Efficient screening programs tailored to regional data are essential for early detection and intervention.

A randomized trial evaluating the utility of non-targeted biopsies for colorectal neoplasia detection in adults with inflammatory bowel disease: a pilot study protocol

BackgroundPersons with inflammatory bowel diseases are at increased risk of developing colorectal cancer and require frequent colonoscopy surveillance. Guidelines recommend taking 30 to 40 non-targeted biopsies throughout the colorectum to detect “invisible” neoplasia in this setting, despite a lack of evidence supporting this practice. We sought to assess the utility of this practice through a randomized controlled trial. We first propose an internal pilot study to assess recruitment potential, protocol adherence and data capture to guide the full trial.MethodsWe have designed a multi-centre, parallel-group, non-inferiority randomized controlled trial to test the utility of non-targeted biopsies as an adjunct to colonoscopy surveillance for neoplasia detection in persons with inflammatory bowel disease involving the colorectum in routine clinical practice. Participants are randomized 1:1, stratified by study site, to either standard of care high-definition white-light colonoscopy with 32 to 40 non-targeted biopsies of non-neoplastic-appearing mucosa along with a sampling of abnormal-appearing mucosa (control group) or modified colonoscopy with targeted sampling alone (intervention group). The primary outcome for the full trial will be the proportion of persons with ≥ 1 neoplastic focus detected during colonoscopy. For the pilot phase, we will assess the feasibility of recruiting a minimum of 15% of the estimated sample size within 1 year, under identical conditions as the full trial, while maintaining ≥ 90–95% rate of protocol adherence and data capture. These participants will contribute data to the full trial. The trial is being conducted at 12 centres across Canada, with a total sample size of 1952 persons.DiscussionsThe trial protocol has been approved by the ethics committees of all participating sites, and the pilot study has received funding through the Canadian Institutes of Health Research (PJT 159607). If feasibility metrics are met during the pilot phase, we will complete the full trial. The trial outcomes will contribute to update the practice guidelines in this area.Trial registrationClinicalTrials.gov, NCT04067778.

Improving self-management behaviour through a digital lifestyle intervention: An internal pilot study.

Self-management is a key component of successful chronic kidney disease (CKD) management. Here, we present the findings from the internal pilot of a multicentre randomised controlled trial (RCT) aimed to test the effect of a digital self-management programme ('My Kidneys & Me' (MK&M)). Participants (aged ≥18 years and CKD stages 3-4) were recruited from hospital kidney services across England. Study processes were completed virtually. Participants were randomised 2:1 to either intervention (MK&M) or control group. The first 60 participants recruited were included in a 10-week internal pilot which assessed study feasibility and acceptability against pre-specified progression criteria: 1) eligibility and recruitment, acceptability of 2) randomisation and 3) outcomes, 4) MK&M activation, and 5) retention and attrition rates. Semi-structured interviews further explored views on trial participation. Of the 60 participants recruited, 41 were randomised to MK&M and 19 to control. All participants completed baseline measures and 62% (n=37) completed post-intervention outcome measures. All progression criteria met the minimum thresholds to proceed. Nine participants were interviewed. The themes identified were satisfaction with study recruitment processes (openness to participate, reading and agreeing to "terms and conditions"), acceptability of study design (remote study participation, acceptability of randomisation, completion of online assessment(s)), and methods to improve recruitment and retention (personalised approach, follow-up communication). This internal pilot demonstrated the feasibility and acceptability of a virtually run RCT. Progression criteria thresholds to proceed to the definitive RCT were met. Areas for improvement were identified and protocol amendments were made to improve trial delivery.

The Promotoer, a brain-computer interface-assisted intervention to promote upper limb functional motor recovery after stroke: a statistical analysis plan for a randomized controlled trial

BackgroundElectroencephalography (EEG)-based brain-computer interfaces (BCIs) allow to modulate the sensorimotor rhythms and are emerging technologies for promoting post-stroke motor function recovery. The Promotoer study aims to assess the short and long-term efficacy of the Promotoer system, an EEG-based BCI assisting motor imagery (MI) practice, in enhancing post-stroke functional hand motor recovery. This paper details the statistical analysis plan of the Promotoer study.MethodsThe Promotoer study is a randomized, controlled, assessor-blinded, single-centre, superiority trial, with two parallel groups and a 1:1 allocation ratio. Subacute stroke patients are randomized to EEG-based BCI-assisted MI training or to MI training alone (i.e. no BCI). An internal pilot study for sample size re-assessment is planned. The primary outcome is the effectiveness of the Upper Extremity Fugl-Meyer Assessment (UE-FMA) score. Secondary outcomes include clinical, functional, and user experience scores assessed at the end of intervention and at follow-up. Neurophysiological assessments are also planned. Effectiveness formulas have been specified, and intention-to-treat and per-protocol populations have been defined. Statistical methods for comparisons of groups and for development of a predictive score of significant improvement are described. Explorative subgroup analyses and methodology to handle missing data are considered.DiscussionThe Promotoer study will provide robust evidence for the short/long-term efficacy of the Promotoer system in subacute stroke patients undergoing a rehabilitation program. Moreover, the development of a predictive score of response will allow transferring of the Promotoer system to optimal clinical practice. By carefully describing the statistical principles and procedures, the statistical analysis plan provides transparency in the analysis of data.Trial registrationClinicalTrials.gov NCT04353297. Registered on April 15, 2020.

A randomized controlled trial comparing conservative versus surgical treatment in patients with foot drop due to peroneal nerve entrapment: results of an internal feasibility pilot study

BackgroundBased on the lack of literature to support any treatment strategy in patients with foot drop due to peroneal nerve entrapment, a prospective study randomizing patients between surgery and conservative treatment is warranted. Since studies comparing surgery to no surgery are often challenging, we first examined the feasibility of such a randomized controlled trial.Methods/designAn internal feasibility pilot study was conducted to assess several aspects of process, resource, management, and scientific feasibility. The main objective was the assessment of the recruitment rate. The criterion to embark on a full study was the recruitment of at least 14 patients in 6 participating centers within 6 months. Cross-over rate, blinding measures, training strategies, and trial assessments were evaluated. The trial was entirely funded by the KCE Trials public funding program of the Belgian Health Care Knowledge Centre (ID KCE19-1232).ResultsThe initial duration was prolonged due to the COVID-19 pandemic. Between April 2021 and October 2022, we included 19 patients of which 15 were randomized. Fourteen patients were treated as randomized. One drop-out occurred after randomization, prior to surgery. We did not document any cross-over or accidental unblinding. Training strategies were successful. Patients perceived the quality of life questionnaire as the least relevant assessment. Assessment of ankle dorsiflexion range of motion was prone to interobserver variability. All other trial assessments were adequate.DiscussionRecruitment of the anticipated 14 patients was feasible although slower than expected. The Short-Form Health Survey (SF-36) and assessment of ankle dorsiflexion range of motion will no longer be included in the full-scale FOOTDROP trial.ConclusionThe FOOTDROP study is feasible.Trial registrationClinicalTrials.gov, identifier NCT04695834. Registered 4 January 2021.

Midline Compared With Peripheral Intravenous Catheters for Therapy of 4 Days or Longer in Pediatric Patients

Peripheral intravenous catheters (PIVCs) frequently fail during treatment causing therapy interruption, pain, recatheterization, and additional health care costs. Midline catheters (MCs) may improve functional dwell time and reduce failure compared with traditional PIVCs. To compare device failure of MCs with PIVCs. This was a pragmatic, randomized clinical superiority trial with an embedded internal pilot study conducted from July 2020 to May 2022. The study took place in a quaternary pediatric hospital in Brisbane, Queensland, Australia. Inclusion criteria were patients aged 1 to 18 years requiring peripherally compatible intravenous therapy for 4 days or longer. Patients were randomly assigned 1:1 to receive a PIVC or MC, stratified by age (≤5 years, >5 years). One catheter was studied per patient. The primary outcome was all-cause device failure, defined as premature cessation of device function. Secondary outcomes included number of insertion attempts, insertion failure, pain (on insertion), procedural time, patient/parent satisfaction (with insertion), device dwell time, device complications during dwell time, additional vascular access devices required to complete treatment, clinician satisfaction (at removal), and health care costs. Of the 128 patients randomly assigned to study groups, 127 patients (median [IQR] age, 7 [2-13] years; 71 male [56%]) had a device inserted, with 65 (51.2%) in the PIVC group and 62 (48.8%) in the MC group. All patients were included in the intention-to-treat analysis. Device failure was lower in patients in the MC group (10 [16.1%]) compared with those in the PIVC group (30 [46.2%]; odds ratio [OR], 0.22; 95% CI, 0.10-0.52; P <.001). MCs were associated with fewer insertion attempts (mean difference [MD], -0.3; 95% CI, -0.5 to 0; P = .04), increased dwell time (MD, 66.9 hours; 95% CI, 36.2-97.5 hours; P <.001), and fewer patients required additional vascular access devices to complete treatment in the MC group (4 [6.5%]) and PIVC group (19 [29.2%]; OR, 0.17; 95% CI, 0.05-0.52; P = .002). Compared with PIVCs, use of MCs was associated with greater patient (9.0 vs 7.1 of 10; P = .002) and parent (9.1 vs 8.2 of 10; P = .02) satisfaction and lower health care costs (AUS -$151.67 [US -$101.13] per person; 95% credible interval, AUS -$171.45 to -$131.90 [US -$114.20 to -$87.95]). Findings suggest that MC insertion for patients requiring peripherally compatible intravenous therapy for 4 days or longer should be prioritized to reduce the resource intensive, expensive, and burdensome sequelae of device failure. Australia New Zealand Clinical Trials Registry, ACTRN12620000724976.

The Growth Hormone Deficiency (GHD) Reversal Trial: effect on final height of discontinuation versus continuation of growth hormone treatment in pubertal children with isolated GHD—a non-inferiority Randomised Controlled Trial (RCT)

Background Growth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64–82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved.Methods/designEvidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH < 6.7 mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (primary outcome; inferiority margin 0.55 SD), target height (TH) minus near FH, HRQoL, bone health index and lipid profiles (secondary outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario.DiscussionIf this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8–4.6 million (€2.05–5.24 million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects.Trial registrationEudraCT number: 2020-001006-39

Sample size reestimation and Bayesian predictive probability for single-arm clinical trials with a time-to-event endpoint using Weibull distribution with unknown shape parameter

ABSTRACT This manuscript consists of two topics. Firstly, we explore the utility of internal pilot study (IPS) approach for reestimating sample size at an interim stage when a reliable estimate of the nuisance shape parameter of the Weibull distribution for modeling survival data is unavailable during the planning phase of a study. Although IPS approach can help rescue the study power, it is noted that the adjusted sample size can be as much as twice the initially planned sample size, which may put substantial practical constraints to continue the study. Secondly, we discuss Bayesian predictive probability for conducting interim analyses to obtain preliminary evidence of efficacy or futility of an experimental treatment warranting early termination of a clinical trial. In the context of single-arm clinical trials with time-to-event endpoints following Weibull distribution, we present the calculation of the Bayesian predictive probability when the shape parameter of the Weibull distribution is unknown. Based on the data accumulated at the interim, we propose two approaches which rely on the posterior mode or the entire posterior distribution of the shape parameter. To account for uncertainty in the shape parameter, it is recommended to incorporate its entire posterior distribution in our calculation.

Pilot and feasibility studies: extending the conceptual framework

In 2016, we published a conceptual framework outlining the conclusions of our work in defining pilot and feasibility studies. Since then, the CONSORT extension to randomised pilot and feasibility trials has been published and there have been further developments in the pilot study landscape. In this paper, we revisit and extend our framework to incorporate the various feasibility pathways open to researchers, which include internal pilot studies. We consider, with examples, when different approaches to feasibility and pilot studies are more effective and efficient, taking into account the pragmatic decisions that may need to be made. The ethical issues involved in pilot studies are discussed. We end with a consideration of the funders’ perspective in making difficult resource decisions to include feasibility work and the policy implications of these; throughout, we provide examples of the uncertainties and compromises that researchers have to navigate to make progress in the most efficient way.

964. Physicians' acceptable treatment failure rates and interpretation of antibiogram for Gram-negative infections: A pilot survey study of infectious diseases specialists

Abstract Background The recommendations of many clinical guidelines include an antibiogram as a key component when making empiric therapy decisions. However, little is known about how clinicians interpret antibiograms. We aim to characterize the threshold of the acceptable risk of selecting inappropriate antibiotics among clinicians through clinical case-based questionnaires. Methods We conducted an online survey of infectious diseases (ID) specialists at the University of Iowa, as an internal pilot study. We created realistic clinical case scenarios and asked clinicians to provide the desired minimum percentage of susceptible isolates on an antibiogram for them to feel comfortable with selecting that agent for empiric therapy. We included four scenarios in the questionnaire: i) a patient with urinary tract infection (UTI) in an outpatient setting, ii) a patient with UTI in an inpatient setting, iii) a patient with Gram-negative rod bloodstream infection (GNR-BSI) in an intensive care unit (ICU) setting, iv) a patient with GNR-BSI in a non-ICU setting. Results Of the 16 of 26 providers (62%) who responded, 15 were considered effective responses. ID Physicians reported wide ranges in thresholds of minimum percentage to feel comfortable with prescribing a hypothetical antibiotic and higher thresholds for patients with more severe illnesses (outpatient with UTI: 85% [range: 75-100%]; inpatient with UTI: 95% [range: 50-99%]; inpatient with GNR-BSI in non-ICU settings: 90% [range: 80-95%]; inpatient with GNR-BSI in ICU: 95% [range: 88-100%]) (Figure 1). Figure 1.The distribution of physicians’ acceptable likelihood of susceptibility in four realistic clinical case-scenarios. Abbreviations: GNR-BSI, Gram-negative rod bloodstream infection; ICU, intensive care unit; UTI, urinary tract infection. Conclusion There were wide ranges in thresholds for interpretation of antibiogram among frontline clinicians, especially for less severe infections. Understanding physicians’ antibiogram usage can be helpful to determine how and if antibiogram guides clinicians toward more appropriate empiric therapy decisions. As this was a preliminary study, we plan to conduct a study with a larger sample size to better characterize the use of antibiogram among clinicians from diverse practice settings. Disclosures Michihiko Goto, MD MSCI, Merck &amp; Co.: Grant/Research Support.

Online Parent Training for The Initial Management of ADHD referrals (OPTIMA): the protocol for a randomised controlled trial of a digital parenting intervention implemented to support parents and children on a treatment waitlist

BackgroundChildren referred for attention-deficit/hyperactivity disorder (ADHD) often present with a broader pattern of conduct problems including oppositionality and defiance. This combination can be extremely stressful to parents, lower parents’ self-esteem and negatively impact family life. The National Institute for Health and Care Excellence (NICE) recommends that families receive support as soon as possible after their referral. However, as clinical services are overstretched, and traditional in-person parenting intervention programmes are expensive, families often must wait times a long time prior to receiving this vital input. To address this, we have created a digital parenting programme called STEPS. It is delivered as a mobile phone app providing a set of tools and resources that can be easily accessed at parents’ convenience. This study aims to evaluate the clinical and cost-effectiveness of STEPS in supporting parents of children with high levels of hyperactivity/impulsivity, inattention and conduct problems, who are waiting to be assessed by specialist children’s clinical services.MethodsOnline Parent Training for The Initial Management of ADHD referrals (OPTIMA) is a two-arm superiority parallel randomised controlled trial with an internal pilot study. We aim to recruit 352 parents and their children, who have been accepted onto a waitlist in Child and Adolescent Mental Health Services or similar child health services. Parents who consent will be randomised 1:1 to either the STEPS or wait-as-usual (WAU) group. The trial will be conducted remotely (online and telephone) with measures taken at baseline and 3, 6, 9 and 12 months post-randomisation. The primary objective is to evaluate whether STEPS reduces the severity of children’s oppositional and defiant behaviour, as rated by parents, measured at 3 months post-randomisation compared to WAU.DiscussionDigital solutions, such as mobile phone apps, have potential for delivering psychological support for parents of children with clinical-level needs in a timely and inexpensive manner. This trial will provide data on the clinical and cost-effectiveness of the STEPS app, which could support the implementation of this scalable parenting intervention programme into standard clinical care and, ultimately, improve the outcomes for families of children referred to specialist child and adolescent health services.Trial registrationISRCTN 16523503. Prospectively registered on 18 November 2021. https://www.isrctn.com/ISRCTN16523503

Induction of labour for predicted macrosomia: study protocol for the ‘Big Baby’ randomised controlled trial

IntroductionLarge-for-gestational age (LGA) fetuses have an increased risk of shoulder dystocia. This can lead to adverse neonatal outcomes and death. Early induction of labour in women with a fetus suspected...

An internal pilot study of a novel rectal mucocellular sampling device to allow next-generation sequencing for colorectal disease.

BackgroundThe ORI-EGI-02 study was designed to test the hypothesis that rectal mucus collected using a novel rectal sampling device (OriCol™), contains sufficient human deoxyribonucleic acid (DNA) of the required quality for Next Generation Sequencing (NGS), for colorectal disease genetic signature discovery.MethodsUsing National Institute for Health and Care Research methodology, an internal pilot study was performed in January 2020–May 2021, at four sites in the United Kingdom, to assess the process of recruitment, consent, specimen acquisition and viability for analysis. Following an OriCol™ test, the sample was stabilized with a buffer solution to preserve the material, which was posted to the laboratory. Samples were processed using QIAamp® DNA Blood Midi kit to extract DNA and Quant-iT™ PicoGreen® dsDNA Reagent to quantify the retrieved DNA. DNA integrity was measured by Agilent TapeStation system. 25 ng of human amplifiable DNA was prepared for Next Generation Sequencing (NGS), which was performed on an Illumina NextSeq550 sequencer using the 300-cycle high output kit v2.5.ResultsThis study assessed the first 300 patients enrolled to the ORI-EGI-02 Study (n = 800). 290/300 (96.67%) were eligible to undergo OriCol™ sampling procedure and 285/290 (98.27%) had a successful OriCol™ sample taken. After transportation, extraction and quantification of DNA, 96.20% (279/290) of the samples had NGS successfully performed for bioinformatic analysis.ConclusionsOur internal pilot study demonstrated that the OriCol™ sampling device can capture rectal mucus from unprepared bowel in subjects who could undergo a digital rectal examination. The technique could be applied irrespective of age, frailty, or co-morbidity. Completion of the study to 800 patients and analysis of NGS data for colorectal cancer mutations will now proceed.

A Preliminary Study on Factors Influences the Design of Soccer Shoes Among Malaysian Soccer Players

Soccer is a contact sport, so a soccer shoe's design is important because it affects the kick's accuracy, speed, and ability to avoid foot injuries. A research study with an appropriate experimental design and precise execution is necessary to produce high-quality results. A pilot study can be conducted as an external pilot study apart from the main study or as an internal pilot study integrated into the main study's research plan. This paper will review the research conducted from a pilot project to identify the design factors such as anatomy, anthropometry, biomechanics and physical characteristics for a soccer shoe popular amongst Malaysian soccer players. The objectives of this research are to determine the accuracy of the questionnaire items. The initial sample consisted of 50 Men soccer players from Peninsular Malaysian states are randomly selected from various levels of the game and have at least one year of playing experience. This study used the quantitative method, whereby questionnaires were applied to obtain information from respondents and findings were analyzed using SPSS software version 23.0 to calculate the Cronbach's Alpha reliability index. The validation of the instrument involves a total of two expert panels. A total of 84-item survey is divided into 4 sections, covering the demographic information of the respondents, their professional backgrounds, their opinions on soccer shoes, and their perceptions on shoe design elements. This study has shown that 81 items were appropriate to be utilized to measure the selection of soccer shoes design. Overall, these results indicate that the analysis has statistically proved that the items in this instrument has a high degree of validity and reliability and can be used for study’s actual sample. The high value of the alpha coefficients suggest that the instruments is very reliable and capable of determining the accuracy of the questionnaire items.

Blindrecalc - An R Package for Blinded Sample Size Recalculation

Besides the type 1 and type 2 error rate and the clinically relevant effect size, the sample size of a clinical trial depends on so-called nuisance parameters for which the concrete values are usually unknown when a clinical trial is planned. When the uncertainty about the magnitude of these parameters is high, an internal pilot study design with a blinded sample size recalculation can be used to achieve the target power even when the initially assumed value for the nuisance parameter is wrong. In this paper, we present the R-package blindrecalc that helps with planning a clinical trial with such a design by computing the operating characteristics and the distribution of the total sample size under different true values of the nuisance parameter. We implemented methods for continuous and binary outcomes in the superiority and the non-inferiority setting.

Physiotherapy interventions encouraging frequent changes of the body position and physical activity for infants hospitalised with bronchiolitis: an internal feasibility study of a randomised control trial

BackgroundThe effect of a treatment that includes frequent changes of the body position for infants with bronchiolitis has not been evaluated, although it is often used in Swedish hospitals. Because of this, a randomised control trial (RCT) has begun with the aim to evaluate this treatment, comparing the effect of an individualised physiotherapy intervention, a non-individualised intervention, and standard care in a control group. The objective of this internal pilot study was to address uncertainties concerning the ongoing RCT and to determine whether the trial is feasible or not, possibly with adjustments to the protocol.MethodsDescriptive analyses of the recruitment, retention, data supply for the primary end point, and the usability of the primary outcome measure in the full RCT were performed. A safety analysis was conducted by an independent analysis group.ResultsNinety-one infants were included, 33 (36.3%), 28 (30.8%), and 30 (33.0%) in the respective allocation groups. Fifty-nine (64.8%) were boys. The median age was 2.5 (min–max 0.2–23.7) months. They remained in the study for a median of 46 hours (min–max 2–159). The recruitment rate was 19%. The data supply for the primary end point and for the primary outcome measure was lower than anticipated in the original sample size calculation. Difficulties concerning utilising the primary outcome measure were identified. The safety analysis detected no risks of harm related to participation in the study.ConclusionsIt is feasible to continue the RCT with modifications of the analysis plan. Participation in the study was not associated with any safety risks.Trial registrationClinicalTrials.gov NCT03575091. Registered 2 July 2018. Retrospectively registered.