The impact of the COVID-19 pandemic on ICU clinical trials: a description of one research team's experience.

BACKGROUND: Disruptions to clinical trials conducted in the intensive care unit (ICU) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2; coronavirus disease 2019 [COVID-19]) pandemic included fewer new trials activated and more trials stopped. While a number of ongoing, non-COVID-19 clinical trials remained open to enrollment, the direct impact of the pandemic on ICUs instilled chaos in this already challenging environment. The numerous challenges need to be reported so investigators can proactively plan and manage these myriad challenges. Thus, the purpose of this study was to describe the impact of the COVID-19 pandemic on screening and accrual for a non-COVID-19 parent clinical trial enrolling critically ill ICU patients receiving mechanical ventilatory support. METHODS: A descriptive, retrospective design using quantitative data from detailed screening logs and qualitative observations with field notes from a parent clinical trial were used to address the objectives. The primary aims of the two-site parent clinical trial (n = 190) are to test the efficacy of self-administration of sedative therapy by mechanically ventilated ICU patients on anxiety and delirium occurrence. ICUs from two academic medical centers [names removed for blinding] plus a community hospital in Minnesota were screened daily for alert patients (Richmond Agitation Sedation Scale [RASS] - 2 to + 1), following commands, hemodynamically stable with sufficient hand grip strength to depress a push-button device. Screening data were summarized based on the primary reason patients were not enrolled (screen failures, declinations of consent). Descriptive statistics (frequencies, percentages), chi-square, and Fisher's Exact test were used to describe the data and to determine any differences among distributions of screening failures and recruitment declinations during the defined pre-pandemic (August 27, 2018-March 15, 2020, 2976 screened patients) and pandemic timeframes (March 16, 2020-February 28, 2022, 3912 screened patients). Qualitative data from varied sources such as screening logs, institutional email communications, staff field notes, and research team meeting minutes were summarized into themes. RESULTS: Despite significantly fewer screen failures due to hypotension, cognitive impairment/dementia, coma, or chemical paralysis with 938 additional patients on the screening log, more were accrued pre-pandemic (n = 55) than during the pandemic period (n = 45); declination reasons were non-significant. Pandemic burdens experienced by study personnel, ICU care providers, and patients/families were revealed that attributed to decreased accrual. CONCLUSIONS: While the parent clinical trial remained opened, cumulative factors adversely impacted the trial during the pandemic period with fewer patients accrued. The human toll of the pandemic on research staff, clinicians, and patients/family members demands that investigators be proactive in managing these challenges to conduct ICU clinical trials successfully, including careful oversight of human and financial resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT#02,819,141 Registered 29 June 2016.

Study protocol to test the efficacy of self-administration of dexmedetomidine sedative therapy on anxiety, delirium, and ventilator days in critically ill mechanically ventilated patients: an open-label randomized clinical trial.

BACKGROUND: Administration of sedative and opioid medications to patients receiving mechanical ventilatory support in the intensive care unit is a common clinical practice. METHODS: A two-site randomized open-label clinical trial will test the efficacy of self-management of sedative therapy with dexmedetomidine compared to usual care on anxiety, delirium, and duration of ventilatory support after randomization. Secondary objectives are to compare self-management of sedative therapy to usual care on level of alertness, total aggregate sedative and opioid medication exposure, and ventilator-free days up to day 28 after study enrolment. Exploratory objectives of the study are to compare self-management of sedative therapy to usual care on 3- and 6-month post-discharge physical and functional status, psychological well-being (depression, symptoms of post-traumatic stress disorder), health-related quality of life, and recollections of ICU care. ICU patients (n = 190) who are alert enough to follow commands to self-manage sedative therapy are randomly assigned to self-management of sedative therapy or usual care. Patients remain in the ICU sedative medication study phase for up to 7 days as long as mechanically ventilated. DISCUSSION: The care of critically ill mechanically ventilated patients can change significantly over the course of a 5-year clinical trial. Changes in sedation and pain interventions, oxygenation approaches, and standards related to extubation have substantially impacted consistency in the number of eligible patients over time. In addition, the COVID-19 pandemic resulted in mandated extended pauses in trial enrolment as well as alterations in recruitment methods out of concern for study personnel safety and availability of protective equipment. Patient triaging among healthcare institutions due to COVID-19 cases also has resulted in inconsistent access to the eligible study population. This has made it even more imperative for the study team to be flexible and innovative to identify and enrol all eligible participants. Patient-controlled sedation is a novel approach to the management of patient symptoms that may be able to alleviate mechanical ventilation-induced distress without serious side effects. Findings from this study will provide insight into the efficacy of this approach on short- and long-term outcomes in a subset of mechanically ventilated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02819141. Registered on June 29, 2016.

Iterative development and pilot testing of an intervention fidelity monitoring plan for the enhanced, electronic health record-facilitated pragmatic clinical trial: Implications for training and protocol integrity.

Fidelity monitoring is the degree to which a clinical trial intervention is implemented as intended by a research protocol. Consistent implementation of research protocols supported with extant fidelity monitoring plans contribute rigor and validity of study results. Fidelity monitoring plans should be comprehensive yet practical to accommodate the realities of conducting research, particularly a pragmatic clinical trial, in dynamic settings with heterogeneous patient populations. The purposes of this paper are to describe the (1) iterative development and implementation of protocols for intervention fidelity monitoring, (2) pilot testing of the fidelity monitoring plan, (3) the identification of interventionist training deficiencies, and (4) opportunities to enhance protocol rigor for a cancer symptom management intervention delivered through the electronic health record patient portal and telephone as part of a complex, multi-component pragmatic clinical trial to uncover training deficits and bolster protocol integrity. The intervention focuses on prominent symptoms reported among medical oncology patients including sleep disturbance, pain, anxiety, depression, low energy (fatigue) and physical function. In this pragmatic trial, the role of interventionist is a registered nurse symptom care manager (RN SCM). A three-part fidelity monitoring plan with checklists audit: Part-1 RN SCM role training activities in research components, clinical training components, and protocol simulation training; Part-2 RN SCM adherence to the intervention core components delivered over the telephone; and Part-3 maintenance of adherence to core intervention components. The goal is ≥ 80% adherence to components of each of the three checklists. An initial pilot test of the fidelity monitoring plan was conducted to evaluate the checklists and the RN SCM adherence to core protocol components. RN SCM skills and training deficits were identified during the pilot phase, as were opportunities to improve protocol integrity. Overall, approximately 50% of the audited RN SCM telephone calls had ≥80% fidelity to the core components. There remains on-going need for RN SCM training and skill building in action planning. The content presented in this paper is intended to begin to fill the gap of fidelity monitoring plans for complex interventions tested in pragmatic clinical trials and delivered remotely in an effort to strengthen protocol integrity.