Standard Protocol Items : Recommendations For Interventional Trials Research Articles

A Modern Flexitarian Dietary Intervention Incorporating Web-Based Nutrition Education in Healthy Young Adults: Protocol for a Randomized Controlled Trial.

BackgroundThe trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens.ObjectiveThe aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being.MethodsA cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood samples of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t0), week 5 into the intervention (t5), and post intervention (t10).ResultsThe protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health’s Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication.ConclusionsTo our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet.Trial RegistrationClinicalTrials.gov NCT04869163; https://clinicaltrials.gov/ct2/show/NCT04869163International Registered Report Identifier (IRRID)PRR1-10.2196/30909

Evaluation of the efficacy and safety of conventional and biportal endoscopic decompressive laminectomy in patients with lumbar spinal stenosis (ENDO-B trial): a protocol for a prospective, randomized, assessor-blind, multicenter trial

BackgroundRecent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial.MethodsThis study will include 120 patients (60 per group, aged 20–80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols.DiscussionIt is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery.Trial registrationThe ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr) (KCT0006057; April 52,021).

A study protocol for the development of a SPIRIT extension for trials conducted using cohorts and routinely collected data (SPIRIT-ROUTINE)

Background: Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Initiative in 2013. Presently, there is increasing use of cohorts and routinely collected data (RCD) for RCTs because these data have the potential to improve efficiencies by facilitating recruitment, simplifying, and reducing the cost of data collection. Reporting guidelines have been shown to improve the quality of reporting, but there is currently no specific SPIRIT guidance on protocols for trials conducted using cohorts and RCD. This protocol outlines steps for developing SPIRIT-ROUTINE, which aims to address this gap by extending the SPIRIT guidance to protocols for trials conducted using cohorts and RCD. Methods: The development of the SPIRIT-ROUTINE extension comprises five stages. Stage 1 consists of a project launch and a meeting to finalise the membership of the steering group and scope of the extension. In Stage 2, a rapid review will be performed to identify possible modifications to the original SPIRIT 2013 checklist. Other key reporting guidelines will be reviewed to identify areas where additional items may be needed, such as the Consolidated Standards of Reporting Trials (CONSORT) extension for trials conducted using cohorts and RCD (CONSORT-ROUTINE). Stage 3 will involve an online Delphi exercise, consisting of two rounds and involving key international stakeholders to gather feedback on the preliminary checklist items. In Stage 4, a consensus meeting of the SPIRIT-ROUTINE steering group will finalise the items to include in the extension. Stage 5 will involve the publication preparation and dissemination of the final checklist. Conclusion: The SPIRIT-ROUTINE extension will contribute to improving design of trials using cohorts and RCD and transparency of reporting.

Developing Specific Reporting Standards in Artificial Intelligence Centred Research.

Developing Specific Reporting Standards in Artificial Intelligence Centred Research.

Deprescribing to reduce polypharmacy: study protocol for a randomised controlled trial assessing deprescribing of anticholinergic and sedative drugs in a cohort of frail older people living in the community

BackgroundTargeted deprescribing of anticholinergic and sedative medications in older people may improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community.Methods and analysisThe standard protocol items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomized controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients.Study populationCommunity-dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly.InterventionNew Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend anticholinergic and sedative medications that could be deprescribed to the participant’s general practitioner. The total use of anticholinergic and sedative medications will be quantified using the Drug Burden Index (DBI).OutcomesThe primary outcome will be the change in total DBI between baseline and 6-month follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalization, and death.Data collection pointsData will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3).Ethics and disseminationEthical approval has been obtained from the Human, Disability and Ethics Committee: ethical number (17CEN265).Trial registrationClinicalTrials.gov ACTRN12618000729224. Registered on May 2, 2018, with the Australian New Zealand Clinical Trials Registry

Inconsistencies in the Methodological Framework Throughout Published Studies in High-Impact Orthopaedic Journals: A Systematic Review.

Both the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines recommend that clinical trials follow a study framework that aligns with their objective to test the relative efficacy or safety (equality) or effectiveness (superiority, noninferiority, or equivalence) between interventions. We conducted a systematic review to assess the proportion of studies that demonstrated inconsistency between the framing of their research question, sample size calculation, and conclusion and those that should have framed their research question differently based on the compared interventions. We included studies from 5 high-impact-factor orthopaedic journals published in 2017 and 2019 that compared at least 2 interventions using patient-reported outcome measures. We included 228 studies. The sample size calculation was reported in 60.5% (n = 138) of studies. Of these, 52.2% (n = 72) were inconsistent between the framing of their research question, sample size calculation, and conclusion. The majority (n = 137) of sample size calculations were for equality, but 43.8% of these studies concluded superiority, noninferiority, or equivalence. Studies that framed their research question as equality (n = 186) should have been framed as superiority (n = 129), equivalence (n = 52), or noninferiority (n = 3). Only 2 studies correctly framed their research question as equality. Studies published in high-impact journals were inconsistent between the framing of their research question, sample size calculation, and conclusion. Authors may be misinterpreting research findings and making clinical recommendations solely based on p values. Researchers are encouraged to state and justify their methodological framework and choice of margin(s) in a publicly published protocol as they have implications for sample size and the applicability of conclusions. The results of clinical research must be interpreted using confidence intervals, with careful consideration as to how the confidence intervals relate to clinically meaningful differences in outcomes between treatments. The more typical practice of relying on p values leaves the clinician at high risk of erroneous interpretation, recommendation, and/or action.

An efficient randomised trial design for multi-cancer screening blood tests: nested enhanced mortality outcomes of screening trial.

Screening aims to detect cancer at an early, curable stage, and is currently recommended for breast, lung, colorectal, and cervical cancers in some countries. Prostate cancer screening might be considered for some men. Individual screening programmes for most other cancer types are unlikely to be worthwhile, mainly because each of these cancers has relatively low incidence and mortality. Leveraging external data in the design and analysis of clinical trials in neuro-oncologyIntegration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions). Based on a series of presentations at the 2020 Clinical Trials Think Tank hosted by the Society of Neuro-Oncology, we provide an overview on the use of external control data representative of the standard of care in the design and analysis of clinical trials. Full-Text PDF Basket clinical trial design for targeted therapies for cancer: a French National Authority for Health statement for health technology assessmentDuring the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial. Full-Text PDF Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extensionThe 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and molecular pathology practices within trials have not been codified or formalised. We developed international consensus reporting guidelines for cellular and molecular pathology content in clinical trial protocols (the SPIRIT-Path extension) using an international Delphi process, which assesses candidate items generated from a previous systematic review, followed by an expert consensus meeting. Full-Text PDF Late phase 1 studies: concepts and outcomesOver the past two decades, targeted therapies have become cornerstone treatments for numerous cancers with oncogene addiction. Unfortunately, their effectiveness reduces over time and most patients who receive targeted therapies relapse within 12 months. The emergence of drug-resistance mechanisms in tumours paved the way for next-generation inhibitors. However, insufficient concentration of targeted therapy is a frequent but poorly explored mechanism of treatment failure. Additionally, the maximum tolerated dose (MTD) is not always reached in phase studies, and the recommended phase 2 dose is mostly based on benefit–risk ratio and pharmacokinetic considerations, which could result in a suboptimal dose. Full-Text PDF Correction to Lancet Oncol 2021; 22: 1360–62Hackshaw A, Berg CD. An efficient randomised trial design for multi-cancer screening blood tests: nested enhanced mortality outcomes of screening trial. Lancet Oncol 2021; 22: 1360–62—In this Comment the affiliation details for Christine D Berg have been updated. This correction has been made to the online version as of Nov 1, 2021. Full-Text PDF

Integration of Health Information Technology and Promotion of Personhood in Family-Centered Dementia Care: Intervention Trial.

PLWD and their care partners. Use of AAC Plus to promote communication and personhood for PLWD. AAC Plus will provide PLWD and care partners a way to communicate PLWD's daily preferences and provide clinical data for health care providers. Determine whether enhanced communication of daily preferences of PLWD will improve quality of life of PLWD and their care partners. ClinicalTrials.gov Identifier: NCT04571502 (Date of registration October 1, 2020). [Research in Gerontological Nursing, 14(5), 225-234.].

A study protocol for the development of a SPIRIT extension for trials conducted using cohorts and routinely collected data (SPIRIT-ROUTINE).

Background:Protocols are an essential document for conducting randomised controlled trials (RCTs).However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Initiative in 2013. Presently, there is increasing use of cohorts and routinely collected data (RCD) for RCTs because these data have the potential to improve efficiencies by facilitating recruitment, simplifying,and reducing the cost of data collection. Reporting guidelines have been shown to improve the quality of reporting, but there is currently no specific SPIRIT guidance on protocols for trials conducted using cohorts and RCD. This protocol outlines steps fordevelopingSPIRIT-ROUTINE,which aims to address this gap by extending the SPIRIT guidance to protocols for trials conducted using cohorts and RCD. Methods:The development of the SPIRIT-ROUTINE extension comprises five stages. Stage 1 consists of a project launch and a meeting to finalise the membership of the steering group and scope of the extension. In Stage 2, a rapid review will be performed to identify possible modifications to the original SPIRIT 2013 checklist. Other key reporting guidelines will be reviewed to identify areas where additional items may be needed,such as theConsolidated Standards of Reporting Trials(CONSORT)extension fortrialsconductedusingcohorts andRCD(CONSORT-ROUTINE). Stage 3 will involve an online Delphi exercise, consisting of two rounds and involving key international stakeholders to gather feedback on the preliminary checklistitems. In Stage 4, a consensus meeting of the SPIRIT-ROUTINE steering group will finalise the items to include in the extension. Stage 5 will involve the publication preparation and dissemination of the final checklist. Conclusion:The SPIRIT-ROUTINE extension will contribute to improving design of trials using cohorts and RCD and transparency of reporting.

‘Give Us The Tools!’: development of knowledge transfer tools to support the involvement of patient partners in the development of clinical trial protocols with patient-reported outcomes (PROs), in accordance with SPIRIT-PRO Extension

Objectives(a) To adapt the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-patient-reported outcome (PRO) Extension guidance to a user-friendly format for patient partners and (b) to codesign a web-based tool...

Reporting quality of trial protocols improved for non-regulated interventions but not regulated interventions: A repeated cross-sectional study

ObjectivesTo investigate the adherence of randomised controlled trial (RCT) protocols evaluating non-regulated interventions (including dietary interventions, surgical procedures, behavioural and lifestyle interventions, and exercise programmes) in comparison with regulated interventions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement. MethodsWe conducted a repeated cross-sectional investigation in a random sample of RCT protocols approved in 2012 (n = 257) or 2016 (n = 292) by research ethics committees in Switzerland, Germany, or Canada. We investigated the proportion of accurately reported SPIRIT checklist items in protocols of trials with non-regulated as compared to regulated interventions. ResultsOverall, 131 (24%) of trial protocols tested non-regulated interventions. In 2012, the median proportion of SPIRIT items reported in these protocols (59%, interquartile range [IQR], 53%-69%) was lower than in protocols with regulated interventions (median, 74%, IQR, 66%-80%). In 2016, the reporting quality of protocols with non-regulated interventions (median, 75%, IQR, 62%-83%) improved to the level of regulated intervention protocols, which had not changed on average. ConclusionsReporting of RCT protocols evaluating non-regulated interventions improved between 2012 and 2016, although remained suboptimal. SPIRIT recommendations need to be further endorsed by researchers, ethics committees, funding agencies, and journals to optimize reporting of RCT protocols.

Academy of Nutrition and Dietetics Nutrition Research Network: The Saqmolo' Project Rationale and Study Protocol for a Randomized Controlled Trial Examining the Influence of Daily Complementary Feeding of Eggs on Infant Development and Growth in Guatemala

Adequate nutrition during the complementary feeding period is critical for optimal child growth and development and for promoting long-term educational attainment and economic potential. To prioritize limited public health resources, there is a need for studies that rigorously assess the influence of multicomponent integrated nutrition interventions in children younger than age 2 years in different contexts. This study aimed to describe the rationale and protocol for the Saqmolo’ Project using the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. The Saqmolo’ (ie, “egg” in the Mayan language, Kaqchiquel) Project is an individually randomized, partially blinded, controlled comparative effectiveness trial to evaluate the influence of adding delivery of a single whole egg per day to local standard nutrition care (ie, growth monitoring, medical care, deworming medication, multiple micronutrient powders for point-of-use food fortification [chispitas], and individualized complementary and responsive feeding education for caregivers) for 6 months, compared with the local standard nutrition care package alone, on child development, growth, and diet quality measures in rural indigenous Mayan infants aged 6 to 9 months at baseline (N = 1,200). The study is being executed in partnership with the Wuqu’ Kawoq/Maya Health Alliance, a primary health care organization located in central Guatemala. Primary outcomes for this study are changes in global development scores, assessed using the Guide for Monitoring Global Development and the Caregiver Reported Child Development Instruments. Secondary outcomes include changes in infant hemoglobin, anthropometric measures (including z scores for weight for age, length for age, weight for length, and head circumference for age), and diet quality as measured using the World Health Organization’s infant and young child feeding indicators. The results of the Saqmolo’ Project may help to inform public health decision making regarding resource allocation for effective nutrition interventions during the complementary feeding period.

Recommendations for cellular and molecular pathology input into clinical trials: a systematic review and meta-aggregation.

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology‐related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE‐GRS (Appraisal of Guidelines for REsearch & Evaluation – Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE‐CERQual (Grading of Recommendations Assessment, Development and Evaluation–Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta‐aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full‐text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology‐related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology‐related parameters; (5) transparent reporting of pathology‐related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research.

Community-Based Rehabilitation for Persons with Severe Mental Illness in a Rural Community of Karnataka: Methodology of a Randomized Controlled Study.

Background:Task shifting has been recommended as a strategy to reach out to persons with mental illness and bridge the treatment gap. There is a need to explore task-shifting using existing health staff like Accredited Social Health Activists (ASHAs).Aim and Context:ASHAs are involved in ongoing community-based rehabilitation (CBR) program run with a public–private partnership over the last 5 years at Jagaluru Taluk (an administrative block) in Davanagere district (Karnataka, India). This article aims to summarize a randomized controlled trial (RCT) to examine whether CBR delivered by ASHAs is more effective than treatment as usual (TAU) control group in reducing disability associated with severe mental illness (SMI).Method:A group of proactive ASHAs is already working with us for a follow-up of persons with SMI. For the study, we would allocate areas that are currently not being covered proactively by ASHAs randomly in a 1:1 ratio via computer-generated randomization list to receive either ASHAs delivered CBR arm or TAU control group. A sample size of about 100 in each arm is enough to identify an effect size of 0.5 in total IDEAS score between the intervention and control arms with a power of 90% and an alpha of 0.05. We use the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement to describe the methods of the trial.Result:The study has been approved by the institute ethics committee and registered with CTRI (CTRI/2019/08/020585 dated 6th August 2019). The recruitment of subjects is ongoing. The patients will be followed up for 1 year and assessed. The trial is funded by the Indian Council of Medical Research, Government of India.Discussion:The results of the study will be helpful from a public health perspective in delivering cost-effective and replicable CBR for persons with SMI through ASHAs. If the model turns successful, this could be expanded throughout the state/country. This would go a long way in bridging the huge treatment gap.

Impact Evaluation of VKN-NIMHANS-ECHO Model of Capacity Building for Mental Health and Addiction: Methodology of Two Randomized Controlled Trials.

Background:Bridging the alarming treatment gap for mental disorders in India requires a monumental effort from all stakeholders. Harnessing digital technology is one of the potential ways to leapfrog many known barriers for capacity building.Aim and Context:The ongoing Virtual Knowledge Network (VKN)–National Institute of Mental Health and Neurosciences (NIMHANS)–Extension of Community Health Outcomes (ECHO) (VKN–NIMHANS–ECHO: hub and spokes model) model for skilled capacity building is a collaborative effort between NIMHANS and the University of New Mexico Health Sciences Centre, USA. This article aims to summarize the methodology of two randomized controlled trials funded by the Indian Council of Medical Research (ICMR) designed to evaluate the effectiveness of the VKN–NIMHANS–ECHO model of training as compared to training as usual (TAU).Methods:Both RCTs were conducted in Karnataka, a southern Indian state in which the DMHP operates in all districts. We compared the impact of the following two models of capacity building for the DMHP workforce (a) the VKN–NIMHANS–ECHO model and (b) the traditional method. We use the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement to describe the methods of these two trials.Trial 1 is to evaluate the “Effectiveness of addition of Virtual-NIMHANS–ECHO tele-mentoring model for skilled capacity building in providing quality care in alcohol use disorders by the existing staff of DMHP districts of Karnataka.” Hub for trial 1 was set up at NIMHANS and the spokes were psychiatrists and other mental health professionals headquartered in the district level office. Trial 2 assesses the implementation and evaluation of the NIMHANS–ECHO blended training program for the DMHP workforce in a rural south-Indian district of Karnataka state. The hub for trial 2 was set up in the district headquarter of Ramanagaram. Hub specialists are DMHP psychiatrists, whereas spokes are the non-doctor workforce (including auxiliary nurse midwives [ANMs] and accredited social health activists [ASHA] workers) medical officers of primary health centers. The location of the HubHub differs in these two studies. Both trials are funded by the ICMR, Government of IndiaDiscussion:Both these trials, though conceptually similar, have some operational differences which have been highlighted. If demonstrated to be effective, this model of telementoring can be generalized and widely merged into the Indian health care system, thus aiding in reducing the treatment gap for patients unable to access care.

Developing a core outcome set for future infertility research: an international consensus development study† ‡.

STUDY QUESTIONCan a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed?SUMMARY ANSWERA minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility.WHAT IS KNOWN ALREADYComplex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret.STUDY DESIGN, SIZE, DURATIONA three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries).PARTICIPANTS/MATERIALS, SETTING, METHODSHealthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods.MAIN RESULTS AND THE ROLE OF CHANCEThe core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable.LIMITATIONS, REASONS FOR CAUTIONWe used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold.WIDER IMPLICATIONS OF THE FINDINGSEmbedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.STUDY FUNDING/COMPETING INTEREST(S)This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form.TRIAL REGISTRATION NUMBERCore Outcome Measures in Effectiveness Trials Initiative: 1023.

Assessing effectiveness and implementation of a perioperative enhanced recovery protocol for children undergoing surgery: study protocol for a prospective, stepped-wedge, cluster, randomized, controlled clinical trial

BackgroundPerioperative enhanced recovery protocols (ERPs) have been found to decrease hospital length of stay, in-hospital costs, and complications among adult surgical populations but evidence for pediatric populations is lacking. The study is designed to evaluate the adoption, effectiveness, and generalizability of a 21-element ERP, adapted for pediatric surgery.MethodsThe multicenter study is a stepped-wedge, cluster-randomized, pragmatic clinical trial that will evaluate the effectiveness of the ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) intervention while also assessing site-specific adaptations, implementation fidelity, and sustainability. The target patient population is pediatric patients, between 10 and 18 years old, who undergo elective gastrointestinal surgery. Eighteen (N = 18) participating sites will be randomly assigned to one of three clusters with each cluster, in turn, being randomly assigned to an intervention start period (stepped-wedge). Each cluster will participate in a Learning Collaborative, using the National Implementation Research Network’s five Active Implementation Frameworks (AIFs) (competency, organization, and leadership), as drivers of facilitation of rapid-cycle adaptations and implementation. The primary study outcome is hospital length of stay, with implementation metrics being used to evaluate adoption, fidelity, and sustainability. Additional clinical outcomes include opioid use, post-surgical complications, and post-discharge healthcare utilization (clinic/emergency room visits, telephone calls to clinic, and re-hospitalizations), as well as, assess patient- and parent-reported health-related quality of life outcomes. The protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.DiscussionThe study provides a unique opportunity to accelerate the adoption of ERPs across 18 US pediatric surgical centers and to evaluate, for the first time, the effect of a pediatric-specific ENRICH-US intervention on clinical and implementation outcomes. The study design and methods can serve as a model for future pediatric surgical quality improvement implementation efforts.Trial registrationClinicalTrials.gov NCT04060303. Registered on 07 August 2019.

Active and passive work breaks during simulated laparoscopy among laparoscopic surgeons: study protocol for a controlled, randomised cross-over laboratory trial

IntroductionLaparoscopy has partially replaced open surgery due to the lower infection rate for the patient and hence better and shorter recovery. However, the surgeon’s physical load is higher due to...

Rationale and design of repeated cross-sectional studies to evaluate the reporting quality of trial protocols: the Adherence to SPIrit REcommendations (ASPIRE) study and associated projects

BackgroundClearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain.Objectives and methodsAims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries.We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results.We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; and the use of routinely collected data for RCTs.DiscussionThe ASPIRE study and associated substudies will provide important information on the impact of measures to improve the reporting of RCT protocols and on multiple aspects of RCT design, trial registration, premature discontinuation, and non-publication of RCTs observing potential changes over time.

An Evaluation of Reporting Guidelines and Clinical Trial Registry Requirements Among Addiction Medicine Journals.

Robust methodology and ethical reporting are paramount for quality scientific research, but recently, that quality in addiction research has been questioned. Avenues to improve such research quality include adherence to reporting guidelines and proper usage of clinical trial registries. Reporting guidelines and clinical trial registries have been shown to lead researchers to more ethical and transparent methodology. To investigate the reporting guideline and clinical trial registration policies of addiction research journals and identify areas of improvement. We used Google Scholar Metrics' h-5 index to identify the top 20 addiction research journals. We then examined the instructions for authors from each journal to identify whether they required, recommended, or made no mention of trial registration and reporting guidelines, including the Consolidated Standards of Reporting Trials (CONSORT), Meta-Analysis of Observational Studies in Epidemiology (MOOSE), Quality of Reporting of Meta-analyses (QUOROM), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Standards for Reporting Diagnostic Accuracy Studies (STARD), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), Animal Research: Reporting of In Vivo Experiments (ARRIVE), Case Reports (CARE), Consolidated Health Economic Evaluation Reporting Standards (CHEERS), Standards for Reporting Qualitative Research (SRQR), Standards for Quality Improvement Reporting Excellence (SQUIRE), Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), Consolidated Criteria for Reporting Qualitative Research (COREQ), Transparent Reporting of a Multivariate Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the International Committee of Medical Journal Editors (ICMJE) guidelines. We performed the same analysis regarding requirements for clinical trial registration. Of the 20 journals included in this study, 10 journals (50%) did not require adherence to any reporting guidelines. Trial registration followed a similar trend; 15 journals (75%) did not mention any form of trial or systematic review registration, and ClinicalTrials.gov was only recommended by only 1 journal (5%). Among top addiction medicine journals, required adherence to reporting guidelines and clinical trial registry policies remains substandard. A step toward fulfilling the National Institute on Drug Abuses' call for improvement in transparency and reproducibility within addiction research should include all journals adopting a strict reporting guideline and clinical trial registry adherence policy.