Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Design and reporting characteristics of clinical trials investigating sedation practices in the paediatric intensive care unit: a scoping review by SCEPTER (Sedation Consortium on Endpoints and Procedures for Treatment, Education and Research).

OBJECTIVES: To conduct a scoping review of sedation clinical trials in the paediatric intensive care setting and summarise key methodological elements. DESIGN: Scoping review. DATA SOURCES: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature and grey references including ClinicalTrials.gov from database inception to 3 August 2021. STUDY SELECTION: All human trials in the English language related to sedation in paediatric critically ill patients were included. After title and abstract screening, full-text review was performed. 29 trials were eligible for final analysis. DATA EXTRACTION: A coding manual was developed and pretested. Trial characteristics were double extracted. RESULTS: The majority of trials were single centre (22/29, 75.9%), parallel group superiority (17/29, 58.6%), double-blinded (18/29, 62.1%) and conducted in an academic setting (29/29, 100.0%). Trial enrolment (≥90% planned sample size) was achieved in 65.5% of trials (19/29), and retention (≥90% enrolled subjects) in 72.4% of trials (21/29). Protocol violations were reported in nine trials (31.0%). The most commonly studied cohorts were mechanically ventilated patients (28/29, 96.6%) and postsurgical patients (11/29, 37.9%) with inclusion criteria for age ranging from 0±0.5 to 15.0±7.3 years (median±IQR). The median age of enrolled patients was 1.7 years (IQR=4.4 years). Patients excluded from trials were those with neurological impairment (21/29, 72.4%), complex disease (20/29, 69.0%) or receipt of neuromuscular blockade (10/29, 34.5%). Trials evaluated drugs/protocols for sedation management (20/29, 69.0%), weaning (3/29, 10.3%), daily interruption (3/29, 10.3%) or protocolisation (3/29, 10.3%). Primary outcome measures were heterogeneous, as were assessment instruments and follow-up durations. CONCLUSIONS: There is substantial heterogeneity in methodological approach in clinical trials evaluating sedation in critically ill paediatric patients. These results provide a basis for the design of future clinical trials to improve the quality of trial data and aid in the development of sedation-related clinical guidelines.

Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III.

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.

Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations.

ABSTRACT: Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

The interplay between residency program culture and feedback culture: a cross-sectional study exploring perceptions of residents at three institutions.

BACKGROUND: Giving and receiving feedback that changes performance is influenced significantly by the clinical learning environment. This environment is multi-dimensional but includes both organizational and feedback specific dimensions. OBJECTIVE: The objectives of this research were to investigate the relationship between residents' perceptions of residency program culture and feedback culture; and whether there were differences in resident perceptions of their programs' and feedback cultures based on their disciplines and institution. We hypothesized that residents preferred certain program culture types and that certain aspects of a residency program's culture were related to the feedback culture. DESIGN: Residents from six specialties at three institutions voluntarily completed two validated survey instruments (Organizational Culture Assessment Instrument [OCAI] and Feedback in Medical Education [FEEDME]-Culture survey) to assess the residency program and feedback cultures, respectively. Descriptive statistics were calculated and non-parametric tests were used to analyze the data. RESULTS: The overall response rate was 37.9% (116/306 residents). 'Clan' culture was both the current and preferred culture by 49.3% and 56.8%, respectively, of the residents overall. There were differences across programs with more current 'clan' culture in pediatrics than in surgery (P = 0.01). Multiple regression analysis showed the Hierarchy Now culture type was significantly related to the feedback culture mean score (p = <.01). For every one unit increase in the Hierarchy Now culture type, the FEEDME-Culture mean score decreases by 0.023 units. CONCLUSIONS: The findings of this study add to the literature by describing residents' preferences of their residency program's culture, and providing insights into the interplay between the residency program and feedback cultures.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Academic Anesthesiology Career Development: A Mixed-Methods Evaluation of the Role of Foundation for Anesthesiology Education and Research Funding.

BACKGROUND: In 1986, the American Society of Anesthesiologists created the Foundation for Anesthesiology Education and Research (FAER) to fund young anesthesiology investigators toward the goal of helping launch their academic careers. Determining the impact of the FAER grant program has been of importance. METHODS: This mixed-methods study included quantitative data collection through a Research Electronic Data Capture survey and curriculum vitae (CV) submission and qualitative interviews. CVs were abstracted for education history, faculty appointment(s), first and last author peer-reviewed publications, grant funding, and leadership positions. Survey nonrespondents were sent up to 3 reminders. Interview questions elicited details about the experience of submitting a FAER grant. Quantitative data were summarized descriptively, and qualitative data were analyzed with NVivo. RESULTS: Of 830 eligible participants, 38.3% (N = 318) completed surveys, 170 submitted CVs, and 21 participated in interviews. Roughly 85% held an academic appointment. Funded applicants were more likely than unfunded applicants to apply for National Institutes of Health funding (60% vs 35%, respectively; P < .01), but the probability of successfully receiving an National Institutes of Health grant did not differ (83% vs 85%, respectively; P = .82). The peer-reviewed publication rate (publications per year since attending medical school) did not differ between funded and unfunded applicants, with an estimated difference in means (95% confidence interval) of 1.3 (-0.3 to 2.9) publications per year. The primary FAER grant mentor for over one-third of interview participants was a nonanesthesiologist. Interview participants commonly discussed the value of having multiple mentors. Key mentor attributes mentioned were availability, guidance, reputation, and history of success. CONCLUSIONS: This cross-sectional data demonstrated career success in publications, grants, and leadership positions for faculty who apply for a FAER grant. A FAER grant application may be a marker for an anesthesiologist who is interested in pursuing a physician-scientist career.

Efficacy Outcome Measures for Pediatric Procedural Sedation Clinical Trials: An ACTTION Systematic Review.

Objective evaluations comparing different techniques and approaches to pediatric procedural sedation studies have been limited by a lack of consistency among the outcome measures used in assessment. This study reviewed those existing measures, which have undergone psychometric analysis in a pediatric procedural sedation setting, to determine to what extent and in what circumstances their use is justified across the spectrum of procedures, age groups, and techniques. The results of our study suggest that a wide range of measures has been used to assess the efficacy and effectiveness of pediatric procedural sedation. Most lack the evidence of validity and reliability that is necessary to facilitate rigorous clinical trial design, as well as the evaluation of new drugs and devices. A set of core pediatric sedation outcome domains and outcome measures can be developed on the basis of our findings. We believe that consensus among all stakeholders regarding appropriate domains and measures to evaluate pediatric procedural sedation is possible and that widespread implementation of such recommendations should be pursued.

Trainees' Perceptions of Feedback: Validity Evidence for Two FEEDME (Feedback in Medical Education) Instruments.

Construct: Medical educators consider feedback a core component of the educational process. Effective feedback allows learners to acquire new skills, knowledge, and attitudes. Learners' perceptions of feedback are an important aspect to assess with valid methods in order to improve the feedback skills of educators and the feedback culture. BACKGROUND: Although guidelines for delivering effective feedback have existed for several decades, medical students and residents often indicate that they receive little feedback. A recent scoping review on feedback in medical education did not reveal any validity evidence on instruments to assess learner's perceptions of feedback. The purpose of our study was to gather validity evidence on two novel FEEDME (Feedback in Medical Education) instruments to assess medical students' and residents' perceptions of the feedback that they receive. APPROACH: After the authors developed an initial instrument with 54 items, cognitive interviews with medical students and residents suggested that 2 separate instruments were needed, one focused on the feedback culture (FEEDME-Culture) and the other on the provider of feedback (FEEDME-Provider). A Delphi study with 17 medical education experts and faculty members assessed content validity. The response process was explored involving 31 medical students and residents at 2 academic institutions. Exploratory factor analysis and reliability analyses were performed on completed instruments. RESULTS: Two Delphi consultation rounds refined the wording of items and eliminated several items. Learners found both instruments easy and quick to answer; it took them less than 5 minutes to complete. Learners preferred an electronic format of the instruments over paper. Factor analysis revealed a two- and three-factor solution for the FEEDME-Culture and FEEDME-Provider instruments, respectively. Cronbach's alpha was greater than 0.80 for all factors. Items on both instruments were moderately to highly correlated (range, r = .3-.7). CONCLUSIONS: Our results provide preliminary validity evidence of 2 novel feedback instruments. After further validation of both FEEDME instruments, sharing the results of the FEEDME-Culture instrument with educational leaders and faculty may improve the culture of feedback on specific educational rotations and at the institutional level. The FEEDME-Provider instrument could be useful for faculty development targeting feedback skills. Additional research studies could assess whether both instruments may be used to help learners receive feedback and prompt reflective learning.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

Evaluation of the Foundation for Anesthesia Education and Research Medical Student Anesthesia Research Fellowship Program Participants' Scholarly Activity and Career Choices.

BACKGROUND: The Foundation for Anesthesia Education and Research Medical Student Anesthesia Research Fellowship (MSARF) program is an 8-week program that pairs medical students with anesthesiologists performing anesthesia-related research. This study evaluated the proportion of students who published an article from their work, as well as the percentage of students who entered anesthesiology residency programs. METHODS: A list of previous MSARF participants (2005 to 2012), site, and project information was obtained. Searches for publications were performed using PubMed. The primary outcome was the publication rate for MSARF projects. The MSARF abstract-to-publication ratio was compared with the percentage of abstracts presented at biomedical meetings that resulted in publication as estimated by a Cochrane review (44%). For students who had graduated from medical school, match lists from the students' medical schools were reviewed for specialty choice. RESULTS: Forty-two percent of the 346 MSARF projects were subsequently published. There was no difference between the MSARF abstract-to-publication ratio and the publication rate of articles from abstracts presented at scientific meetings (P = 0.57). Thirty percent (n = 105; 95% CI, 25 to 35%) of all the MSARF students were authors on a publication. Fifty-eight percent of the students for whom residency match data (n = 255) were available matched into anesthesiology residencies (95% CI, 52 to 64%). CONCLUSIONS: The MSARF program resulted in many students being included as a co-author on a published article; the majority of these students entered anesthesiology residency programs. Future research should determine whether the program has a long-term impact on the development of academic anesthesiologists.

A Randomized, Prospective, Double-Blinded Study of Physostigmine to Prevent Sedation-Induced Ventilatory Arrhythmias.

BACKGROUND: Physostigmine, a centrally acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the postanesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep-disordered breathing. We investigated whether physostigmine was effective in decreasing the frequency of ventilatory arrhythmias produced during moderate sedation with midazolam and remifentanil during the conditions of breathing room air or 2 L/min nasal O2. METHODS: Ten healthy male volunteers participated in this randomized, double-blind control trial of physostigmine (0.24 µg·kg·min) versus placebo. Moderate sedation was achieved with infusions of midazolam and remifentanil and monitored with full and processed electroencephalogram. Analgesia was quantified with subjective pain score to thermal stimulation. Ventilatory arrhythmias, as measured by the sedation apnea-hypopnea index (S-AHI), were scored as the number of apneas and hypopneas during two 1-hour periods on room air or 2 L/min nasal O2. RESULTS: All subjects tolerated the sedation and physostigmine without significant adverse effects. Sedation during placebo infusion resulted in clinically significant (S-AHI > 15) ventilatory arrhythmias in 5 conditions in 3 subjects (2 on room air and then O2, and 1 on O2 only). Physostigmine did not significantly (P > 0.46) reduce the total number of ventilatory arrhythmias on either room air or O2 (13.4 ± 18.8 events/h [mean ± SEM], 95% confidence interval [CI] = -9.9 to 62.7; and 6.2 ± 8.0, 95% CI = -3.1 to 28.7, respectively). Physostigmine did reduce the S-AHI in all 5 instances of clinically significant ventilatory arrhythmias (S-AHI decreased by 67.0 ± 22.2; CI = 29.2-111.7; P = 0.04). CONCLUSIONS: Physostigmine does not appear to be useful as a pretreatment to prevent ventilatory arrhythmias during moderate sedation. However, it may be useful as a treatment for clinically significant ventilatory arrhythmias during moderate sedation.

A sustainable course in research mentoring.

In this report, we describe a six-year experience (2007-2012) in a single CTSA awardee institution on the development, implementation and evaluation of a hybrid online mentoring curriculum that is applicable to CTSA trainees at various levels (graduate, medical students, and junior faculty) of career training. The curriculum offers convenience, engagement, and financial sustainability. Overall, we found high levels of satisfaction with the curriculum and mentoring experience among both protégés and mentors. Qualitative data showed remarkable consensus of 14 of the 15 domains of mentoring that form the framework of the mentoring curriculum: (1) accessibility, (2) selectivity, (3) engagement/support, (4) teaching/training, (5) clarity of performance/expectations, (6) sponsorship/sharing power judiciously, (7) demystifying the system (academia), (8) challenging/encouraging risk taking, (9) affirming, (10) providing exposure/visibility, (11) being an intentional role model, (12) protecting, (13) providing feedback, (14) self-disclosure, and lastly (15) counseling, with the fifteenth domain "counseling" being the most controversial. Quantitative survey data of both mentors and protégés indicated a high degree of overall satisfaction in their mentor-protégé dyad with 86% (59) of protégés and 86% (55) of mentors responding good or excellent to the "quality of time spent." Mentors and protégés were most satisfied in the area of research, with 93% (62) of protégés and 96% (57) of mentors finding discussions in research very to somewhat useful for their own career advancement. Along with wide acceptability, this format is a useful option for institutions where face-to-face time is limited and education budgets are lean.

Engaging students and faculty: implications of self-determination theory for teachers and leaders in academic medicine.

BACKGROUND: Much of the work of teachers and leaders at academic health centers involves engaging learners and faculty members in shared goals. Strategies to do so, however, are seldom informed by empirically-supported theories of human motivation. DISCUSSION: This article summarizes a substantial body of motivational research that yields insights and approaches of importance to academic faculty leaders. After identification of key limitations of traditional rewards-based (i.e., incentives, or 'carrots and sticks') approaches, key findings are summarized from the science of self-determination theory. These findings demonstrate the importance of fostering autonomous motivation by supporting the fundamental human needs for autonomy, competence, and relatedness. In turn, these considerations lead to specific recommendations about approaches to engaging autonomous motivation, using examples in academic health centers. SUMMARY: Since supporting autonomous motivation maximizes both functioning and well-being (i.e., people are both happier and more productive), the approaches recommended will help academic health centers recruit, retain, and foster the success of learners and faculty members. Such goals are particularly important to address the multiple challenges confronting these institutions.

Validation of a measurement to predict upper airway collapsibility during sedation for colonoscopy.

Techniques to quantify the effects of sedation on upper airway collapsibility have been used as research tools in the laboratory and operating room. However, they have not been used previously in the usual clinical practice environment of colonoscopy sedation. The propensity for upper airway collapsibility, quantified as the critical pharyngeal pressure (P(crit)), was hypothesized to correlate with the need for clinical intervention to maintain ventilation. Twenty patients scheduled for colonoscopy with sedation were prospectively recruited to undergo measurement of upper airway collapsibility using negative airway pressure (NAP) provocation with a minimum pressure of -18 cmH(2)O. The P(crit) was the negative pressure that collapses the airway, either directly or by extrapolation from the pressure-flow relationship. An exponential transformation was applied to the P(crit) data for statistical analysis. A clinical intervention score (CIS) was used to quantify required interventions by the sedation nurse. The measurement of the P(crit) during sedation was significantly larger (less negative) than both the baseline ("awake") (P = 0.0029) and late recovery (P = 0.01) values. The CIS was not predicted by the transformed baseline or sedated P(crit) with or without including demographics associated with sleep apnea syndrome. Although the NAP technique showed the expected changes with sedation in this clinical situation, we did not find that it predicted the need for clinical intervention during endoscopy. Our study was not large enough to test for subpopulations in which the test might be predictive; further studies of these particular groups are needed to determine the clinical utility of the NAP measurement.

Process of discovery: a fourth-year translational science course.

BACKGROUND: The Liaison Committee on Medical Education notes the importance of educating medical students on clinical and translational research principles. PURPOSE: To describe a fourth-year course, "Process of discovery," which addresses teaching these principles, and to discuss students' perceptions of the course. METHODS: Core components and pedagogical methods of this course are presented. Course assessment was performed with specific pre- and post-course assessments. RESULTS: During academic years 2004 to 2009, 562 students were enrolled, with assessment response rate of 94% pre-course and 85% post-course. The students' self-assessment of their current understanding of clinical and translation research significantly increased, as well as their understanding of how clinical advances will take place over the next decade. CONCLUSIONS: A fourth-year course teaching clinical and translational research is successful, is seen as a positive experience and can meet the requirements for including clinical and translational research in the medical school curriculum.