Progress in clinical research in surgery and IDEAL.

The quality of clinical research in surgery has long attracted criticism. High-quality randomised trials have proved difficult to undertake in surgery, and many surgical treatments have therefore been adopted without adequate supporting evidence of efficacy and safety. This evidence deficit can adversely affect research funding and reimbursement decisions, lead to slow adoption of innovations, and permit widespread adoption of procedures that offer no benefit, or cause harm. Improvement in the quality of surgical evidence would therefore be valuable. The Idea, Development, Exploration, Assessment, and Long-term Follow-up (IDEAL) Framework and Recommendations specify desirable qualities for surgical studies, and outline an integrated evaluation pathway for surgery, and similar complex interventions. We used the IDEAL Recommendations to assess methodological progress in surgical research over time, assessed the uptake and influence of IDEAL, and identified the challenges to further methodological progress. Comparing studies from the periods 2000-04 and 2010-14, we noted apparent improvement in the use of standard outcome measures, adoption of Consolidated Standards of Reporting Trials (CONSORT) standards, and assessment of the quality of surgery and of learning curves, but no progress in the use of qualitative research or reporting of modifications during procedure development. Better education about research, integration of rigorous evaluation into routine practice and training, and linkage of such work to awards systems could foster further improvements in surgical evidence. IDEAL has probably contributed only slightly to the improvements described to date, but its uptake is accelerating rapidly. The need for the integrated evaluation template IDEAL offers for surgery and other complex treatments is becoming more widely accepted.

Sample size re-estimation in paired comparative diagnostic accuracy studies with a binary response.

BACKGROUND: The sample size required to power a study to a nominal level in a paired comparative diagnostic accuracy study, i.e. studies in which the diagnostic accuracy of two testing procedures is compared relative to a gold standard, depends on the conditional dependence between the two tests - the lower the dependence the greater the sample size required. A priori, we usually do not know the dependence between the two tests and thus cannot determine the exact sample size required. One option is to use the implied sample size for the maximal negative dependence, giving the largest possible sample size. However, this is potentially wasteful of resources and unnecessarily burdensome on study participants as the study is likely to be overpowered. A more accurate estimate of the sample size can be determined at a planned interim analysis point where the sample size is re-estimated. METHODS: This paper discusses a sample size estimation and re-estimation method based on the maximum likelihood estimates, under an implied multinomial model, of the observed values of conditional dependence between the two tests and, if required, prevalence, at a planned interim. The method is illustrated by comparing the accuracy of two procedures for the detection of pancreatic cancer, one procedure using the standard battery of tests, and the other using the standard battery with the addition of a PET/CT scan all relative to the gold standard of a cell biopsy. Simulation of the proposed method illustrates its robustness under various conditions. RESULTS: The results show that the type I error rate of the overall experiment is stable using our suggested method and that the type II error rate is close to or above nominal. Furthermore, the instances in which the type II error rate is above nominal are in the situations where the lowest sample size is required, meaning a lower impact on the actual number of participants recruited. CONCLUSION: We recommend multinomial model maximum likelihood estimation of the conditional dependence between paired diagnostic accuracy tests at an interim to reduce the number of participants required to power the study to at least the nominal level. TRIAL REGISTRATION: ISRCTN ISRCTN73852054 . Registered 9th of January 2015. Retrospectively registered.

Laparoscopic Excision Versus Ablation for Endometriosis-associated Pain: An Updated Systematic Review and Meta-analysis.

The aim of this study was to update the evidence on the surgical management of endometriosis-associated pain. Does laparoscopic excision offer any benefits over laparoscopic ablation? This is a systematic review and meta-analysis in which we searched MEDLINE, Embase, Institute for Scientific Information conference proceedings, the International Standard Randomised Controlled Trial Number registry, the Register and Meta-register for randomized controlled trials, the World Health Organization trials search portal, the Cochrane Library, and the British Library of electronic theses. Three randomized controlled trials were included, which enrolled 335 participants with a sample size per study ranging from 24 to 178 participants. Of these 3 studies, data from 2 could be pooled for meta-analysis. The primary outcome measure was the reduction in the visual analog scale score for dysmenorrhea. The secondary outcome measures included the reduction in the visual analog scale score for dyspareunia, dyschezia, and chronic pelvic pain and the reduction in Endometriosis Health Profile-30 core pain scores. The meta-analysis showed that the excision group had a significantly greater reduction in symptoms of dysmenorrhea (mean difference [MD] = 0.99; 95% confidence interval [CI], -0.02 to 2.00; p = .05) and dyschezia (MD = 1.31; 95% CI, 0.33-2.29; p = .009) compared with ablation. The symptoms of dyspareunia showed a nonsignificant benefit with excision (MD = 0.96; 95% CI, -0.07 to 1.99; p = .07). Data from 1 study showed a significant reduction in chronic pelvic pain (MD = 2.57; 95% CI, 1.27-3.87; p = .0001) and Endometriosis Health Profile-30 core pain scores (MD = 13.20; 95% CI, 3.70-22.70; p = .006) with the excision group compared with the ablation group. The limited available evidence shows that at 12 months postsurgery, symptoms of dysmenorrhea, dyschezia, and chronic pelvic pain secondary to endometriosis showed a significantly greater improvement with laparoscopic excision compared with ablation.

Role of corticosteroids in Functional Endoscopic Sinus Surgery--a systematic review and meta-analysis.

BACKGROUND: The aim of our study is to systematically review the existing evidence on the role of corticosteroids in patients undergoing functional endoscopic sinus surgery (FESS). METHODOLOGY: Systematic search of MEDLINE (1950- 2014), EMBASE (1980-2014), metaRegister, Cochrane Library and ISI conference proceedings was carried out. RESULTS: Eighteen randomised controlled trials with 1309 patients were included. Use of local and/or systemic corticosteroids with FESS was reported in four categories; operative, anaesthesia related, post-operative outcomes and risk of recurrence. Meta-analysis for operative outcomes demonstrated that, mean operative time (MD -10.70 minutes; 95% CI -15.86, -5.55; P <0.0001) and mean estimated blood loss (MD -28.32 mls; 95% CI -40.93, -15.72; P <0.0001) was significantly lower; and surgical field quality (MD -0.81; 95% CI -1.32, -0.30; P = 0.002) was significantly better in corticosteroid group. Meta-analysis showed that post-operative endoscopic scores (SMD -0.39; 95% CI -0.60, -0.17; P = 0.0004) were significantly better in corticosteroid group compared to no corticosteroid group. There was no increase in risk of sinusitis (RR 0.64; 95% CI 0.32, 1.30; P = 0.22) between use of corticosteroids and no corticosteroids; There was no significant difference in recurrence risk of chronic rhinosinusitis (CRS) in mixed population studies (RR 0.77; 95% CI 0.35, 1.70; P = 0.52) between the two groups but analysis of studies reporting on chronic rhinosinusitis with nasal polyps (CRSwNP) (RR 0.64;95% CI 0.45,0.91;P=0.01) showed significant difference in favour of the corticosteroid group. CONCLUSION: Pre-operative use of local and/or systemic corticosteroids in FESS, results in significantly reduced blood loss, shorter operative time and improved surgical field quality. Studies are limited on the intra-operative use of corticosteroids to reduce postoperative pain. Postoperative corticosteroids improve postoperative endoscopic scores in CRS and recurrence rates in cases of CRSwNP.

Early morning salivary cortisol and cortisone, and adrenal responses to a simplified low-dose short Synacthen test in children with asthma.

OBJECTIVE: To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels. DESIGN: Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min. RESULTS: A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%. CONCLUSION: Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.

Development and psychometric testing of the online Adolescent Diabetes Needs Assessment Tool (ADNAT).

AIM: To report on the development and psychometric testing of the Adolescent Diabetes Needs Assessment Tool. BACKGROUND: The UK has the fifth largest paediatric diabetes population in the world, but one of the poorest levels of diabetes control, highlighting the need for intervention development. DESIGN: Mixed methods following recommendations for questionnaire design and validation. METHODS: A total of 171 young people (12-18 years) participated between 2008- 2011. Methods included item selection using secondary framework analysis, item review, pre-testing, piloting and online transfer. Statistical tests assessed reliability using item-total correlations, interitem consistency and test-retest reliability; and validity using blood glucose (HbA1c) levels and the Self-Management of type 1 Diabetes in Adolescence questionnaire. RESULTS: The Adolescent Diabetes Needs Assessment Tool consists of 117 questions divided between six domains of educational and psychosocial support needs. It combines reflective questioning with needs assessment to raise self-awareness to support adolescent decision-making in relation to diabetes self-care. Thirty-six of the questions provide self-care and psychosocial health assessment scores. Face and content validity of the scoring items were all positively evaluated in terms of appropriateness and readability and tests for validity found significant correlations with Self-Management of type 1 Diabetes in Adolescence and weak correlation with HbA1c , which compared favourably with Self-Management of type 1 Diabetes in Adolescence, the only comparable (USA) tool. Item response analysis validated the use of simple additive scores. CONCLUSIONS: The Adolescent Diabetes Needs Assessment Tool combines reflective learning with needs assessment to support patient-centred clinical consultations.

Scalable Transdiagnostic Early Assessment of Mental Health (STREAM): a study protocol.

INTRODUCTION: Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant 'detection gap' where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions. METHODS AND ANALYSIS: The STREAM project will enrol and assess 4000 children aged 0-6 years from Malawi (n=2000) and India (n=2000). It integrates three established developmental assessment tools measuring motor, social and cognitive functioning using gamified tasks, observation checklists, parent-report and audio-video recordings. Domain scores for motor, social and cognitive functioning will be developed and assessed for their validity and reliability. These domain scores will then be used to construct age-adjusted developmental reference curves. ETHICS AND DISSEMINATION: Ethical approval has been obtained from local review boards at each site (India: Sangath Institutional Review Board; All India Institute of Medical Science (AIIMS) Ethics Committee; Indian Council of Medical Research-Health Ministry Screening Committee; Malawi: College of Medicine Research and Ethics Committee; Malawi Ministry of Health-Blantyre District Health Office). The study adheres to Good Clinical Practice standards and the ethical guidelines of the 6th (2008) Declaration of Helsinki. Findings from STREAM will be disseminated to participating families, healthcare professionals, policymakers, educators and researchers, at local, national and international levels through meetings, academic journals and conferences.

Robotic-assisted laparoscopic vs abdominal and laparoscopic myomectomy: systematic review and meta-analysis.

Herein is presented a systematic review and meta-analysis of evidence related to operative outcomes associated with robotic-assisted laparoscopic myomectomy (RLM) compared with abdominal myomectomy (AM) and laparoscopic myomectomy (LM). Outcome measures included estimated blood loss (EBL), blood transfusion, operating time, complications, length of hospital stay (LOHS), and costs. Meta-analysis 1 compared RLM vs AM, and meta-analysis 2 compared RLM vs LM. Studies scored moderately well on the Newcastle-Ottawa Quality Assessment Scale. No significant differences were found in age, body mass index, or number, diameter, and weight of myomas. In meta-analysis 1, EBL, blood transfusion, and LOHS were significantly lower; risk of complications was similar; and operating time and costs were significantly higher with RLM. In meta-analysis 2, no significant differences were noted in EBL, operating time, complications, and LOHS with RLM; however, blood transfusion risk and costs were higher. It was concluded that insofar as operative outcomes, RLM has significant short-term benefits compared with AM and no benefits compared with LM. Long-term benefits such as recurrence, fertility, and obstetric outcomes remain uncertain.

Development and preliminary validation of the challenges of living with cystic fibrosis (CLCF) questionnaire: a 46-item measure of treatment burden for parent/carers of children with CF.

OBJECTIVE: Treatments for cystic fibrosis (CF) are complex, labour-intensive, and perceived as highly burdensome by caregivers of children with CF. An instrument assessing burden of care is needed. DESIGN: A stepwise, qualitative design was used to create the CLCF with caregiver focus groups, participant researchers, a multidisciplinary professional panel, and cognitive interviews. MAIN OUTCOME MEASURES: Preliminary psychometric analyses evaluated the reliability and convergent validity of the CLCF scores. Cronbach's alpha assessed internal consistency and t-tests examined test-retest reliability. Correlations measured convergence between the Treatment Burden scale of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the CLCF. Discriminant validity was assessed by comparing CLCF scores in one vs two-parent families, across ages, and in children with vs without Pseudomonas aeruginosa (PA). RESULTS: Six Challenge subscales emerged from the qualitative data and the professional panel constructed a scoresheet estimating the Time and Effort required for treatments. Internal consistency and test-retest reliability were adequate. Good convergence was found between the Total Challenge score and Treatment Burden on the CFQ-R (r=-0.49, p = 0.02, n = 31). A recent PA infection signalled higher Total Challenge for caregivers (F(23)11.72, p = 0.002). CONCLUSIONS: The CLCF, developed in partnership with parents/caregivers and CF professionals, is a timely, disease-specific burden measure for clinical research.

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.

Development and validation of a short form psychometric tool assessing the caregiving Challenge of Living with Cystic Fibrosis (CLCF-SF) in a child.

OBJECTIVE: Caring for a child with cystic fibrosis (CF) is a rigorous daily commitment for caregivers and treatment burden is a major concern. We aimed to develop and validate a short form version of a 46-item tool assessing the Challenge of Living with Cystic Fibrosis (CLCF) for clinical or research use. DESIGN: A novel genetic algorithm based on 'evolving' a subset of items from a pre-specified set of criteria, was applied to optimise the tool, using data from 135 families. MAIN OUTCOME MEASURES: Internal reliability and validity were assessed; the latter compared scores to validated tests of parental well-being, markers of treatment burden, and disease severity. RESULTS: The 15-item CLCF-SF demonstrated very good internal consistency [Cronbach's alpha 0.82 (95%CI 0.78-0.87)]. Scores for convergent validity correlated with the Beck Depression Inventory (Rho = 0.48), State Trait Anxiety Inventory (STAI-State, Rho = 0.41; STAI-Trait, Rho = 0.43), Cystic Fibrosis Questionnaire-Revised, lung function (Rho = -0.37), caregiver treatment management (r = 0.48) and child treatment management (r = 0.45), and discriminated between unwell and well children with CF (Mean Difference 5.5, 95%CI 2.5-8.5, p < 0.001), and recent or no hospital admission (MD 3.6, 95%CI 0.25-6.95, p = 0.039). CONCLUSION: The CLCF-SF provides a robust 15-item tool for assessing the challenge of living with a child with CF.

Protocol for validation of the Global Scales for Early Development (GSED) for children under 3 years of age in seven countries.

INTRODUCTION: Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age. The GSED includes three measures for population and programmatic level measurement: (1) short form (SF) (caregiver report), (2) long form (LF) (direct administration) and (3) psychosocial form (PF) (caregiver report). The primary aim of this protocol is to validate the GSED SF and LF. Secondary aims are to create preliminary reference scores for the GSED SF and LF, validate an adaptive testing algorithm and assess the feasibility and preliminary validity of the GSED PF. METHODS AND ANALYSIS: We will conduct the validation in seven countries (Bangladesh, Brazil, Côte d'Ivoire, Pakistan, The Netherlands, People's Republic of China, United Republic of Tanzania), varying in geography, language, culture and income through a 1-year prospective design, combining cross-sectional and longitudinal methods with 1248 children per site, stratified by age and sex. The GSED generates an innovative common metric (Developmental Score: D-score) using the Rasch model and a Development for Age Z-score (DAZ). We will evaluate six psychometric properties of the GSED SF and LF: concurrent validity, predictive validity at 6 months, convergent and discriminant validity, and test-retest and inter-rater reliability. We will evaluate measurement invariance by comparing differential item functioning and differential test functioning across sites. ETHICS AND DISSEMINATION: This study has received ethical approval from the WHO (protocol GSED validation 004583 20.04.2020) and approval in each site. Study results will be disseminated through webinars and publications from WHO, international organisations, academic journals and conference proceedings. REGISTRATION DETAILS: Open Science Framework https://osf.io/ on 19 November 2021 (DOI 10.17605/OSF.IO/KX5T7; identifier: osf-registrations-kx5t7-v1).

Baseline and Peak Cortisol Response to the Low-Dose Short Synacthen Test Relates to Indication for Testing, Age, and Sex.

Context: Meta-analyses report that the low dose short Synacthen test (LDSST) is more sensitive but less specific than the standard dose test for the diagnosis of adrenal insufficiency, and there are concerns regarding the accuracy of dosing in the LDSST. Objective: Perform a retrospective, observational study to review the outcomes of LDSSTs performed in a tertiary endocrine service from 2008 to 2014 (N = 335) and 2016 to 2020 (N = 160), and examine for relationships between cortisol measurements and indication for testing, age and sex. Methods: LDSST were performed by endocrine nurses. Synacthen 500 ng/1.73m2 administered as IV bolus, sampling at 0, 15, 25, and 35 minutes. Results: Mean (± 1SD) baseline cortisol was 221 ± 120 nmol/L, peak 510 ± 166 nmol/L and increment 210 ± 116 nmol/L. 336 (70%) patients had a normal response (baseline cortisol >100 nmol/L, peak >450 nmol/L), 78 (16%) a suboptimal response (peak cortisol 350-450 nmol/L) and were prescribed hydrocortisone to during periods of stress only, 67 (14%) an abnormal response (baseline <100nmol/L or peak <350nmol/L) and were prescribed daily hydrocortisone. Basal, peak, and incremental increases in cortisol were higher in females (P = .03, P < .001, P = .03, respectively). Abnormal results occurred most frequently in patients treated previously with pharmacological doses of glucocorticoids or structural brain abnormalities (P < .001). Conclusion: The low prevalence and strong association of abnormal results with indication for testing, suggests that over diagnosis occurred infrequently in this clinical setting.

A population-based investigation of behavioural and emotional problems and maternal mental health: associations with autism spectrum disorder and intellectual disability.

BACKGROUND: While research indicates elevated behavioural and emotional problems in children with autism spectrum disorders (ASD) and decreased well-being in their parents, studies do not typically separate out the contribution of ASD from that of associated intellectual disabilities (ID). We investigated child behavioural and emotional problems, and maternal mental health, among cases with and without ASD and ID in a large population-representative sample. METHODS: Cross-sectional comparison of child behavioural and emotional problems and maternal mental health measures among 18,415 children (5 to 16 years old), of whom 47 had an ASD, 51 combined ASD with ID, 590 had only ID, and the remainder were the comparison group with no ASD or ID. RESULTS: The prevalence of likely clinical levels of behavioural and emotional problems was highest among children with ASD (with and without ID). After controlling for age, gender, adversity, and maternal mental health, the presence of ASD and ID significantly and independently increased the odds for hyperactivity symptoms, conduct, and emotional problems. Emotional disorder was more prevalent in mothers of children with ASD (with or without ID). The presence of ASD, but not ID, significantly increased the odds for maternal emotional disorder. As has been found in previous research, positive maternal mental health was not affected by the presence of ASD or ID. CONCLUSIONS: ASD and ID are independent risk factors for behavioural and emotional problems. ASD (but not ID) is positively associated with maternal emotional disorder. Approaches to diagnosing hyperactivity and conduct problems in children with ASD may need to be reconsidered.

Accounting for bias due to a non-ignorable tracing mechanism in a retrospective breast cancer cohort study.

We consider the analysis of competing risks in a retrospective breast cancer cohort study where tracing of patients is dependent on survival to a pre-specified truncation time. We demonstrate that if ignored, the observed cause-specific hazards will become distorted before the truncation time. Two approaches to account for the tracing bias are considered. First, a likelihood-based method using piecewise constant transition intensities under a Markov assumption. Second, a pseudo-likelihood method using inverse probability of tracing weights. For the breast cancer example, both methods improve the precision of estimates compared with a conventional approach based on excluding patients.

Pilot and feasibility studies for pragmatic trials have unique considerations and areas of uncertainty.

BACKGROUND AND OBJECTIVE: Feasibility studies are increasingly being used to support the development of, and investigate uncertainties around, future large-scale trials. The future trial can be designed with either a pragmatic or explanatory mindset. Whereas pragmatic trials aim to inform the choice between different care options and thus, are designed to resemble conditions outside of a clinical trial environment, explanatory trials examine the benefit of a treatment under more controlled conditions. There is existing guidance for designing feasibility studies, but none that explicitly considers the goals of pragmatic designs. We aimed to identify unique areas of uncertainty that are relevant to planning a pragmatic trial. RESULTS: We identified ten relevant domains, partly based on the pragmatic-explanatory continuum indicator summary-2 (PRECIS-2) framework, and describe potential questions of uncertainty within each: intervention development, research ethics, participant identification and eligibility, recruitment of individuals, setting, organization, flexibility of delivery, flexibility of adherence, follow-up, and importance of primary outcome to patients and decision-makers. We present examples to illustrate how uncertainty in these domains might be addressed within a feasibility study. CONCLUSION: Researchers planning a feasibility study in advance of a pragmatic trial should consider feasibility objectives specifically relevant to areas of uncertainty for pragmatic trials.

Progression from external pilot to definitive randomised controlled trial: a methodological review of progression criteria reporting.

OBJECTIVES: Prespecified progression criteria can inform the decision to progress from an external randomised pilot trial to a definitive randomised controlled trial. We assessed the characteristics of progression criteria reported in external randomised pilot trial protocols and results publications, including whether progression criteria were specified a priori and mentioned in prepublication peer reviewer reports. STUDY DESIGN: Methodological review. METHODS: We searched four journals through PubMed: British Medical Journal Open, Pilot and Feasibility Studies, Trials and Public Library of Science One. Eligible publications reported external randomised pilot trial protocols or results, were published between January 2018 and December 2019 and reported progression criteria. We double data extracted 25% of the included publications. Here we report the progression criteria characteristics. RESULTS: We included 160 publications (123 protocols and 37 completed trials). Recruitment and retention were the most frequent indicators contributing to progression criteria. Progression criteria were mostly reported as distinct thresholds (eg, achieving a specific target; 133/160, 83%). Less than a third of the planned and completed pilot trials that included qualitative research reported how these findings would contribute towards progression criteria (34/108, 31%). The publications seldom stated who established the progression criteria (12/160, 7.5%) or provided rationale or justification for progression criteria (44/160, 28%). Most completed pilot trials reported the intention to proceed to a definitive trial (30/37, 81%), but less than half strictly met all of their progression criteria (17/37, 46%). Prepublication peer reviewer reports were available for 153/160 publications (96%). Peer reviewer reports for 86/153 (56%) publications mentioned progression criteria, with peer reviewers of 35 publications commenting that progression criteria appeared not to be specified. CONCLUSIONS: Many external randomised pilot trial publications did not adequately report or propose prespecified progression criteria to inform whether to proceed to a future definitive randomised controlled trial.

Validation of the Infant and Young Child Development (IYCD) Indicators in Three Countries: Brazil, Malawi and Pakistan.

BACKGROUND: The early childhood years provide an important window of opportunity to build strong foundations for future development. One impediment to global progress is a lack of population-based measurement tools to provide reliable estimates of developmental status. We aimed to field test and validate a newly created tool for this purpose. METHODS: We assessed attainment of 121 Infant and Young Child Development (IYCD) items in 269 children aged 0-3 from Pakistan, Malawi and Brazil alongside socioeconomic status (SES), maternal educational, Family Care Indicators and anthropometry. Children born premature, malnourished or with neurodevelopmental problems were excluded. We assessed inter-rater and test-retest reliability as well as understandability of items. Each item was analyzed using logistic regression taking SES, anthropometry, gender and FCI as covariates. Consensus choice of final items depended on developmental trajectory, age of attainment, invariance, reliability and acceptability between countries. RESULTS: The IYCD has 100 developmental items (40 gross/fine motor, 30 expressive/receptive language/cognitive, 20 socio-emotional and 10 behavior). Items were acceptable, performed well in cognitive testing, had good developmental trajectories and high reliability across countries. Development for Age (DAZ) scores showed very good known-groups validity. CONCLUSIONS: The IYCD is a simple-to-use caregiver report tool enabling population level assessment of child development for children aged 0-3 years which performs well across three countries on three continents to provide reliable estimates of young children's developmental status.